A TEXT-BOOK 
/ OF 
PATHOLOGY 
With a Final Section on 
POST-MORTEM EXAMINATIONS AND THE METHODS OF 
PRESERVING AND EXAMINING DISEASED TISSUES 
BY 
FRANCIS DELAFIELD, M. D, LL. D. 
EMERITUS PROFESSOR OF THE PRACTICE OF MEDICINE, COLLEGE OF PHYSICIANS AND SURGEONS, 
COLUMBIA UNIVERSITY, NEW YORK 
AND 
T. MITCHELL PRUDDEN, M. D., LL. D. 
EMERITUS PROFESSOR OF PATHOLOGY, COLLEGE OF PHYSICIANS AND SURGEONS, COLUMBIA 
UNIVERSITY, NEW YORK 
Genth Edition 
REVISED WITH THE COOPERATION OF 
FRANCIS CARTER WOOD/M. D. 
DIRECTOR OF CANCER RESEARCH, COLUMBIA UNIVERSITY, NEW' YORK 
WITH FOURTEEN FULL-PAGE PLATES AND SIX HUNDRED AND NINETY- 
FOUR ILLUSTRATIONS IN THE TEXT, IN BLACK AND COLORS 
NEW YORK 
WILLIAM WOOD AND COMPANY 
MDCCCCXIV Copyright, 1914 
By WILLIAM WOOD & COMPANY PREFACE TO THE TENTH EDITION. 
It has been the aim in this edition to incorporate in the text some 
account of the more important advances in the knowledge of pathology 
which have been made during the past three years. These have taken 
place along many lines. Some of them involve changes in the point of 
view; a few are actual achievements of research; while some concern new 
technical procedures. 
The references have been freshened, and in places considerably 
increased. A few new cuts have been added, replacing or supplementing 
the old. 
The general aims of the book and the acknowledgments which are 
due to earlier friendly cooperation are set forth in the preface to the former 
edition which has been retained. 
T. MITCHELL PRUDDEN 
FRANCIS CARTER WOOD PREFACE TO THE NINTH EDITION. 
In this, as in former editions of this work, it is aimed, first, to give 
to students and practitioners of medicine the knowledge necessary for 
the making of autopsies, the preservation of tissues and their prepara- 
tion for microscopic examination; second, to consider the characters 
of the general processes which underlie the various manifestations of dis- 
ease; third, to set forth the nature of infection and immunity, and to de- 
scribe concisely, with such illustrations as seem necessary, the lesions of 
the acute infectious diseases and, so far as they are known, the micro- 
organisms inciting them, the various phases of degeneration and inflam- 
mation, the characters of tumors, and the lesions of the general diseases, 
of poisoning, and of violent deaths; and, finally, to describe briefly the 
special lesions of different tissues and organs of the body. 
In this edition, the section devoted to general pathology has been re- 
written and expanded, and various phases of pathological physiology have 
received more attention than formerly. Also, in this, still more than in 
the last editions, stress has been laid upon the relationships of pathology 
to the allied phases of biological science, and, where it might be done 
without hazard to the more urgent practical aims of the work, disease 
has been considered as an adaptive process, and pathology viewed as one 
aspect of the diverse manifestations of life and energy, rather than 
as belonging to a special and exclusively human domain. 
Dr. Delafield no longer shares in the preparation of the work: so 
that the writer, deprived of the wise counsel and large experience of 
the senior author, is alone responsible for such alterations and additions 
as have been made in this as in the last three revisions. 
The great and rapid accumulation of data in the wide field which 
this book covers has made necessary the exclusion in large measure 
of those phases of clinical diagnosis and practical bacteriology which are 
now more adequately covered in special and in larger treatises. The 
limitations of the book have made it necessary also to omit the con- 
sideration of many suggestive facts and recent alluring speculations 
bearing upon various aspects of pathological physiology, the significance 
and value of which are not yet adequately determined. 
The book has been largely revised. A few of the older illustrations 
have been discarded, while over forty new ones have been added. 
The references in foot-notes have been revised and considerably 
increased, the intention in these has been in part to indicate special 
studies or reviews relating to the theme under consideration; but more 
particularly to point out here and there publications in which a fuller 
V VI 
PREFACE TO THE NINTH EDITION 
bibliography may be found than is consistent with the scope and limi- 
tations of this work. 
The chapter on the Blood and the Blood-forming Organs and the 
chapter on Tumors have been rewritten, and the section on Malaria 
revised, by Professor Francis Carter Wood. My obligation to Professor 
Wood is very great, not only for the revisions of the text indicated, 
but for many helpful suggestions embodied throughout the work and 
for counsel and aid without which the preparation of this edition 
would have been impracticable. 
For assistance in the preparation of material brought forward from 
the last edition I wish to express my continuing indebtedness to Drs. 
F. R. Bailey, Edward Learning, and W. C. Clarke, and to Professors 
F. C. Wood, Philip Hanson Hiss, John H. Larkin, and Augustus B. 
Wadsworth. 
To Professors Hiss, Wadsworth, Zinsser, and Wright, and to Drs. 
Flexner, Noguchi, and Terry I am indebted for the privilege of repro- 
ducing photographs and for many helpful suggestions. 
I wish, finally, to record my appreciation of the skilful service and 
invaluable cooperation of Miss S. M. Wood in the final preparation for 
the press of the material for this edition, in correcting the proof, and in 
indexing the work. 
T. MITCHELL PRUDDEN CONTENTS. 
PART first. 
GENERAL PATHOLOGY. 
Introduction, 3. 
The Conditions of Disease, 8.-External conditions of disease, 9.-Internal condi- 
tions of disease, 13. 
CHAPTER II. 
Changes in the Circulation of the Blood: General conditions, 15.-Hyperaemia 
and anaemia, 16.-Haemorrhage and transudation, 20.-Resorption and absorp- 
tion, 23.-Thrombosis and embolism, 24.-Experimental study of disturbances 
of the circulation, 34. 
CHAPTER I. 
CHAPTER III. 
Regressive Tissue Changes: General considerations, 35.-Atrophy, 36.-Degen- 
eration, 39.-Pigmentation, 53.-Necrosis, 56. 
Progressive Tissue Changes: Hypertrophy and hyperplasia, 61.-Metaplasia, 62.- 
Reversion, 63.-Regeneration, 64.-Modes of cell division, 64.-General char- 
acters and limitations of cell regeneration, 68.-Regeneration of special tissues, 
69.-Transplantation of tissue, 77.-The impulse to cell regeneration, 79. 
CHAPTER IV. 
CHAPTER V. 
Inflammation: General considerations, 81.-Types of inflammatory reaction of the 
body to injury, 82.-The healing of wounds, 91.-Hyperplasia and interstitial 
inflammation, 96.-Special phases of inflammation, 97.---The disposal of foreign 
and dead substances-phagocytosis-autolysis, 98.-Survey of the inflammatory 
process and its significance, 107.-Characterization of the inflammatory process, 
110.-The experimental study of resorption of foreign material, phagocytes, etc., 
in inflammation, 110.-Practical study of exudative inflammation in the living 
frog, 111. 
CHAPTER VI. 
Animal Parasites: Protozoa, 114.-Worms, 123.-Arthropoda, 131. 
VII VIII 
CONTENTS 
CHAPTER VII. 
Plant Parasites: Bacteria, morphology, physiology, and distribution, 133.-Clas- 
sification of bacteria, 142.-Modes of morphological study of bacteria, 143.- 
Artificial cultivation of bacteria, 145.--Collection of material for bacterial cul- 
tures, 145.-Yeasts, 146.-Moulds, 147.-Methods of studying yeasts and moulds, 
149. 
CHAPTER VIII. 
The Relations of Micro-organisms to Disease-Infection and Immunity: The 
presence of bacteria and other micro-organisms in the body; its protective mech- 
anism, 150.-Action of bacteria and their products in the body, 152.-Proofs 
of the infective nature of bacteria found in the body, 153.-Conditions influencing 
the occurrence of infectious diseases, 155.-Infection and immunity; infectious 
diseases and the nature of infection, 156.-Incubation period, 156.-Forms of 
infection, 157.-Communicability of infectious diseases, 158.-Immunity; nature 
and forms of immunity, 160.-Artificial immunization, 162.-Antitoxic im- 
munity, 163.-Ehrlich's "side-chain" hypothesis, 165.-Bactericidal or antibac- 
terial immunity (bacteriolytic immunity), 169.-Cytolytic substances-Cytolysis 
171.-Agglutinative substances, 179.--Precipitating substances, 181.-Opsonic 
substances-opsonins, 183.-Leucocyte extract, 188.-Diversion of comple- 
ment, 189.-Fixation of complement, 189.-Allergy and anaphylaxis, 190.- 
Technique, 193.-Bibliography, 196. 
CHAPTER IX. 
The Infectious Diseases: General considerations, 197.-Suppurative and allied 
forms of inflammation, 198.-The pyogenic bacteria, 205.-Septic sore throat, 
211.-Erysipelas, 211.-Infectious pseudo-membranous inflammation of mucous 
membranes, 212.-Other bacteria which are frequent excitants of suppuration, 
213.-Acute lobar pneumonia and other infectious diseases induced by the 
Diplococcus pneumoniae, 217.-Gonorrhoea and other inflammatory lesions in- 
duced by the Micrococcus gonorrhoeae, 221.-Acute cerebro-spinal meningitis, 
223.-Glanders, 226.-Anthrax, 228.-Actinomycosis, 230.-Influenza, 233.- 
Typhoid fever, 234.-Dysentery, 247.-Asiatic cholera, 247.-Tuberculosis, 251. 
-Lepra, 269.-Syphilis, 270.--Wassermann test, 277.-Luetin test, 281.- 
Rhinoscleroma, 282.-Diphtheria, 282.-Tetanus, 286.-Malta fever, 287.- 
Bubonic plague, 288.-Haemorrhagic septicaemia, 289.-Malignant oedema, 291. 
-Meat poisoning, 291.-Botulism, 291.-Relapsing fever, 292.-Tick fever, 
293.-Vincent's angina, 293.-Yaws, 293.-Hydrophobia, 294.-Acute anterior 
poliomyelitis, 299.-Typhus fever, 300.-Mexican typhus, 301.-Rocky Mountain 
spotted fever, 301.-Yellow fever, 301.-Variola, 303.-Scarlet fever, 306.- 
Trachoma, 307.-Measles, 309.-Malaria, 310.-Whooping-cough, 317.-Acute 
rheumatism, 317.-Beri-beri, 318.-Pellagra, 318.-Infectious diseases of un- 
known origin, 318.--The infectious diseases of animals, 319.-Bibliography 
of the infectious diseases, 319. 
CHAPTER X. 
Malformations: General considerations, 320.-Malformations involving single in- 
dividuals, 321.-Normal and pathological conditions in which two or more in- 
dividuals develop together, 327. CONTENTS 
IX 
CHAPTER XL 
Tumors: The nature and characters of tumors in general, 336.-Etiology of tumors, 
344.-The intrinsic excitants of tumors; " Biological origin," 350.-The need of 
new research in tumors, 353.-The transplantation of tumors, 354.-Classification 
of tumors, 357.-Tumors formed by various combinations of tissue types, 358. 
-Complex congenital growths, teratoma, 358.-Special tumor types, 359.- 
Cysts, 359.-Special forms of tumors, 362.-Bibliography of tumors, 416. 
CHAPTER XII. 
The Lesions Induced by Poisons: Forms of poisons, 417.-The lesions induced by 
exogenous poisons, 417.-Lesions induced by endogenous poisons-auto-intoxi- 
cations, 426. 
CHAPTER XIII. 
General Diseases, 429.-Cachexia strumipriva, myxcedema, 429.-Exophthalmic 
goitre, 432.-Addison's disease, 433.-Diabetes mellitus, 435.-Gout, 436.-Sun- 
stroke, 437.-Scorbutus, 437.-Acromegalia, 438.-Purpura, 439.-Lymphatic 
constitution, 439.-Fever, 440. 
CHAPTER XIV. 
The Lesions in Certain Forms of Death from Violence: Sudden Death; Suffo- 
cation; asphyxia, 442.-Death from strangulation; hanging, 443,-Death from 
drowning, 443.-Sudden death, 446. 
PART SECOND. 
SPECIAL PATHOLOGY. 
General Considerations, 451. 
CHAPTER I. 
The Blood and the Blood-forming Organs: Changes in the composition and struc- 
ture of the blood, 452.-The red blood cells, 456.-The white blood cells, 459.- 
Leucocytosis, 462.-Methods of examination of the blood, 466.-Foreign bodies 
in the blood, 469.-General diseases involving the blood and blood-forming 
organs, 471.-Chlorosis, 471.-Secondary anaemia, 472.-Pernicious anaemia, 
473.-Leukaemia, 475.-Chloroma, 478.-Pseudo-leukaemia, 479.-Anaemia in- 
fantum pseudo-leukaemica, 479.-Splenic anaemia, 479. 
CHAPTER II. 
The Lymph-Nodes: General characteristics of the lymph-nodes, 481.-Atrophy. 
481.-CEdema, 482.-Degeneration, 482.-Pigmentation, 483.-Inflammation, 
483.-Hyperplasia of the lymph-nodes, 488.-Pseudo-leukaemia, 489.-Tumors, 
498.-Parasites, 498.-Haemolymph nodes, 498. X 
CONTENTS 
CHAPTER III. 
The Spleen and Thymus: General characteristics of the spleen, 499.-Malformations 
and displacements, 499.-Wounds, rupture, and haemorrhage, 500.-Atrophy, 
500.-Degeneration, 500.-Pigmentation, 501.-Disturbances of the circulation, 
501.-Inflammation, 504.-Chronic endothelial hyperplasia of the spleen, 508. 
-Alterations of the spleen in leukaemia, and pseudo-leukaemia, 509.-Tumors, 
510.-Parasites, 511.-The thymus; malformation and hypertrophy, 511.- 
Haemorrhage, 511.-Inflammation, 511.-Tumors, 511. 
CHAPTER IV. 
The Thyroid and Adrenals: The thyroid; malformations, 512.-Degeneration, 
512.-Disturbances of circulation, 512.-Inflammation, 512.-Struma, 513.- 
Tumors, 514.-Parasites, 514.-Parathyroid glands, 514.-The adrenals; malfor- 
mations, 515.-Atrophy and degeneration, 515.-Thrombosis and haemorrhage, 
516.-Inflammation, 516.-Tumors, 517.-The carotid gland, 517. 
CHAPTER V. 
The Circulatory System: The pericardium; injuries, 518.-Haemorrhage, 518.- 
Hydropericardium, 518.-Pneumopericardium, 518.-Inflammation, 518.- 
Tumors, 522.-The heart; malformations and malpositions, 522.-Wounds and rup- 
tures, 526.-Atrophy, 528.-Aneurism of the heart and valves, 529.-Thrombosis 
of the heart, 531.-Degeneration, 533.-Segmentation and fragmentation of the 
myocardium, 536.-Lesions of the coronary arteries, 537.-Sclerosis and throm- 
bosis, 537.-Inflammation; myocarditis, 538.-Endocarditis, 542.-Stokes- 
Adams' disease, 549.-Hypertrophy and dilatation of the heart, 550.-Lesions 
of the heart valves in relation to hypertrophy and dilatation, 552.-Aortic 
insufficiency and stenosis, 552.-Mitral insufficiency and stenosis, 553.-In- 
sufficiency and stenosis in the right heart, 553.-Summary of conditions leading 
to hypertrophy of the ventricles, 554.-Dilatation of the heart, 555.-Tumors, 
556.-Parasites, 556.-The blood-vessels; hypoplasia, atrophy, and hyper- 
trophy, 556.-The arteries; rupture and wounds, 557.-Degeneration, 557.- 
Inflammation, 559.-Periarteritis nodosa, 566.-Aneurism, 567.-Aneurisms 
of the different arteries, 570.-Stenosis and obliteration of the aorta, 571.- 
Tumors of the arteries, 571.-The veins; dilatation, 572.-Wounds-rupture, 
573.-Thrombosis, 573.-Degeneration, 573.-Inflammation, 573.-Tumors, 575. 
-Parasites, 575.-The capillaries, 575.-The lymph-vessels, general characters. 
576.-Lymphangiectasis, 576.-Lymphorrhagia, 576.-Thrombosis, 576.-In- 
flammation, 577.-Tumors, 577. 
CHAPTER VI. 
The Respiratory System: The nose and its associated cavities, 579.-Malformations, 
579.--Haemorrhage, 579.-Inflammation, 579.-Tumors, 581.-The pharynx, 
581.-The larynx and trachea; malformations, 581.-Haemorrhage, 582.-(Edema 
of the glottis, 582.-Inflammation, 582.-Tumors, 585.-The bronchi and lungs; 
the bronchi, haemorrhage, 586.-Inflammation, 586.-Bronchiectasia, 589.- 
Tumors, 591.-Lesions of the tracheal and bronchial lymph-nodes, 592.-The 
lungs; malformations, 593.-Injuries; perforations, 593.-Disturbances of circu- 
lation, 593.-Hyperaemia, 593.-(Edema of the lungs, 595.-Haemorrhage and 
infarctions, 595.--Atelectasis, 596.-Emphysema, 597.-Gangrene 59; .-In- 
flammation, 600.-Acute lobar pneumonia, 603.-Lobular pneumonia and bron- 
cho-pneumonia, 608.--Interstitial pneumonia, 614.-Tuberculous pneumonia, CONTENTS 
XI 
618.-Focal tuberculosis, 619.-Tuberculous broncho-pneumonia, 624.-Com- 
plex forms of nodular and diffuse tuberculous lesions, 627.-Formation of cavities 
in pulmonary tuberculosis, 628.-Secondary lesions in pulmonary tuberculosis, 
629.-Distribution of lesions, 630.- Concurrent infection, 631.-Artificial pul- 
monary tuberculosis in animals, 631.-Syphilitic pneumonia, 633.-Tumors, 
634.-The mediastinum, 636.-The pleura; hydrothorax, 636.-Hydropneumo- 
thorax, 637.-Haemorrhage, 637.-Inflammation, 637.-Tumors, 641. 
CHAPTER VII. 
The Digestive System: The mouth; malformations, 643.-Inflammation, 643.- 
Tumors, 645.-The tongue; malformations, 645.-Hypertrophy and inflamma- 
tion, 646.-Tumors, 646.-Micro-organisms of the mouth, 646.-The pharynx; 
malformations, 647.-Inflammation, 648.-Tumors, 650.-The oesophagus; mal- 
formations, 651.-Perforation and rupture, 651.-Haemorrhage, 651.--Dilatation, 
651.-Stenosis, 652.-Inflammation, 653.-Tumors, 653.-The stomach, 654.- 
Malformations, 654.-Cadaveric changes, 655.-Injuries, 655-Haemorrhage, 655. 
-Atrophy and degeneration, 656.-Inflammation, 656.-Ulcers of the stomach, 
660.-Dilatation, 662.-Tumors, 662.-Foreign bodies, 667.-The intestines; 
malformations, 667.-Incarceration, 668.-Intussusception, 669.-Hernia, 670. 
-Wounds-ruptures, 671.-Disturbances of the circulation--haemorrhage, 
671.-Degeneration, 671.-Inflammation, 672.-The caecum, 682.-The rectum, 
683.-The appendix vermiformis, 684.--Tumors of the intestine, 688.-In- 
testinal concretions, 690.-Parasites, 691.-Actinomycosis, 691.-The peri- 
toneum; malformations, 691.-Haemorrhage, 692.-Ascites, 692.-Inflamma- 
tion, 692.-Tumors, 696.-Cysts, 699.-Parasites, 699.-The salivary glands: 
Parotid, submaxillary, and sublingual; inflammation, 699.-Tumors of the sali- 
vary glands, 700.-The pancreas; malformations and displacements, 701.- 
Atrophy, degeneration, and necrosis, 702.-Haemorrhage, 705.-Inflammation, 
705.-Tumors, 706. 
CHAPTER VIII. 
The Liver: Malformations, 708.-Wounds, rupture, and haemorrhage, 708.-Anaemia 
and hyperaemia, 709.-Lesions of the hepatic vessels, 711.-Atrophy of the liver, 
714.-Necrosis, 714.-Degeneration, 716.-Pigmentation of the liver, 721.-Cal- 
cification, 722.-Inflammation, 722.-Hyperplasia of lymphatic tissue in the liver 
734.-Tumors of the liver, 734.-Cysts of the liver, 737.-Parasites, 738.-Lesions 
of the biliary passage and the gall-bladder, 740.-Tumors of the gall-bladder and 
larger gall-ducts, 743.-Biliary calculi, 743. 
CHAPTER IX. 
The Urinary Organs: The kidneys; malformations, 746.-Changes in position, 747. 
-Compensatory hypertrophy of the kidney, 747.-Disturbances of circulation, 
748.-Albuminuria and casts, 749.-Necrosis, 750.-Degeneration, 751.-In- 
flammation, 753.-Suppurative pyelitis and pyelo-nephritis, 771.-Hydronephro- 
sis, 772.-Perinephritic suppuration, 772.-Cysts in the kidneys, 772.-Renal 
calculi, 774.-Tumors, 776.-Parasites, 781.--The urinary bladder; malforma- 
tions, 781.-Changes in size and position, 782.-Wounds, rupture, perforation, 
782.-Disturbances of circulation, 783.-Inflammation, 783.-Tumors, 786.- 
Parasites, foreign bodies and calculi, 789.-The urethra; malformations, 790.- 
Changes in size and position, 790.-Wounds, rupture, perforation, 791.-In- 
flammation, 791.-Tumors, 792. XII 
CONTENTS 
CHAPTER X. 
The Reproductive Organs of the Female: The vulva; malformations, 793.- 
Haemorrhage, hyperaemia, etc., 793.-Inflammation, 793.-Tumors, 794.-The 
vagina; malformations, 795.--Changes in size and position, 795.-Wounds; 
perforations, 796.--Inflammation, 796.-Tumors, 797.-Parasites, 797.-The 
uterus; congenital malformations, 797.-Changes in size, 798.-Changes in posi- 
tion, 800.--Rupture and perforation, 802.-Hyperaemia; uterine and peri-uterine 
haemorrhage, 802.-Atrophy, degeneration, etc., 803.-Inflammation, 804.- 
Tumors, 809.-Chorionepithelioma of pregnancy, 820.-Chorionepithelioma with 
teratoma, 822.-Parasites and cysts, 822.-Lesions of the placenta, 822.-Degen- 
eration, 823.-Haemorrhage, 823.-Inflammation, 823.-Tumors, 824.-The 
ovaries; malformations, 826.-Changes in size and position, 826.-Hyperaemia 
and haemorrhage, 826.-Inflammation, 827.-Tumors, 829.-The Fallopian tubes; 
malformations, 838.-Changes in position and size, 838.--Haemorrhage, 839.-In- 
flammation, 839.--Tumors, 841.-Extra-uterine pregnancy, 841.-The mamma; 
malformations, 842.-Haemorrhage, 842.-Inflammation, 843.-Tumors, 847. 
CHAPTER XI. 
Reproductive Organs of the Male: The penis; malformations, 853.-Injury and 
haemorrhage, 854.--Inflammation, 854.-Tumors, 854.-The scrotum, 855.-- 
Tumors, 855.-The testicles; malformation, 855.-Varicocele, 856.-Hydrocele, 
856.-Haematocele, 857.-Spermatocele, 857.-Atrophy, 857.-Inflammation, 
857.-Tumors, 860.-Parasites, 863.-The seminal vesicles, 863.-Tumors, 863. 
-The prostate; degeneration, atrophy, and hypertrophy, 863.-Inflammation, 
864.-Tumors, 866.-Parasites and concretions, 866.-Cowper's glands, 867.- 
The male mamma, 867. 
CHAPTER XII. 
Voluntary Muscle: Necrosis, 868.-Atrophy and hypertrophy, 868.-Degeneration, 
871.-Injuries, haemorrhage, and infarction, 873.--Inflammation, 873.-Tumors, 
875.-Parasites, 875. 
CHAPTER XIII. 
The Bones and Joints: The bones; general considerations, 876.-Atrophy, 876.- 
Disturbances of circulation, 877.-Healing of wounds and fractures of bone, 877. 
-Inflammation, 878.-Necrosis, 889.-Caries, 891.-Rachitis, 891.-Osteo- 
malacia, 896.-Alterations of the bone-marrow in leukaemia and anaemia, 897.-- 
Tumors, 899.-The joints, 903.-Degeneration, 903.-Inflammation, 903.- 
Tumors, 906. 
CHAPTER XIV. 
The Nervous System: The membranes and the ventricles; the dura mater cere- 
bralis, 908.-Haemorrhage, 908.-Thrombosis, 908.-Inflammation, 909.-Tu- 
mors, 911.-The pia mater cerebralis; general characters, 912.-(Edema, 913.- 
Hyperaemia and haemorrhage, 913.-Inflammation, 914.-Tumors, 919.-Para- 
sites, 921.-The dura mater spinalis, 921.-Haemorrhage, 922.-Inflammation, 
922.-Tumors, 922.-Parasites, 922.-The pia mater spinalis, 922.-Haemor- 
rhage, 922.-Inflammation, 923.-Tumors, 923.-Parasites, 923.-The ventricles 
of the brain. The ependyma and choroid plexus; general considerations, 924.- CONTENTS 
XIII 
Inflammation, 924.-Tumors, 927.-Parasites, 927.-The brain and spinal cord; 
malformations of the brain, 927.-Malformations of the spinal cord, 928.-In- 
juries of the brain, 930.-Injuries of the cord, 931.-Injuries of the nerve?, 931.- 
Hypertrophy and atrophy of the brain, 931.-Pigmentation of the brain, 933.- 
Circulatory and vascular changes in the brain and spinal cord, 933.-Hypersemia 
and anaemia, 934.-GEdema, 934.-Haemorrhage, 935.-Thrombosis and embo- 
lism, 940.-Lesions of the vessel walls, 942.-Degeneration and inflammation in 
the brain, spinal cord, and nerves, 942.-Degeneration, 946.-Secondary degen- 
erations, 953.-Primary degenerations, 955.-Inflammation, 964.-Lesions of the 
brain in general paresis of the insane, 972.-Tuberculous lesions in the nervous 
system, 974.-Syphilitic lesions of the nervous system, 975.-Actinomycosis, 976. 
-Leprous inflammation, 976.-Tumors, 976.-Parasites, 979.-Holes and cysts 
in the brain, 979.-Pineal gland, 980.-Hypophysis cerebri, 980.-Methods of 
preparation of nerve tissue for microscopical study, 980. 
PART THIRD. 
THE METHOD OF MAKING POST-MORTEM EXAMINATIONS AND THE 
METHODS OF PRESERVING AND EXAMINING 
PATHOLOGICAL TISSUES. 
The Method of Making Post-mortem Examinations: General considerations, 985. 
-External inspection, 986.-Internal examination, 990.-The head, 991.-The 
spinal cord, 999.-The thorax and abdomen, 1001.-The closure of the body after 
the post-mortem examination, 1021.-Bacterial examination of post-mortem 
specimens, 1021.-Autopsies in medico-legal cases, 1022.-Autopsies in cases of 
suspected poisoning, 1022.-Examination of the bodies of new-born children, 
1023. 
CHAPTER I. 
CHAPTER II. 
General Methods of Preserving Pathological Specimens and Preparing them 
for Study, 1027.-The study of fresh tissues, 1027.-Rapid fixation and frozen 
sections, 1028.-Fixation, hardening and preservation, 1029.-Decalcifying, 
1031.-Embedding and section-cutting, 1031.-Methods of staining, 1035.- 
Methods of preserving specimens for gross demonstration and for museums, 1039. 
-Kaiserling's method of fixing natural colors in museum specimens, 1039.-The 
importance of careful fixation and preservation, 1040. LIST OF ILLUSTRATIONS. 
Fig. Page 
1. Caisson disease, 12 
2. Hypersemia of the blood-vessels near a bronchus, 17 
3. Diagram illustrating the establishment of collateral circulation in obstruc- 
tion of a vein-after Ribbert, 18 
4. Occluding thrombus of the iliac, 24 
5. Portion of red thrombus, 25 
6. Lamellated thrombus, . . 26 
7. Organized thrombus, 28 
8. Embolus lodged at the point of division of an artery, 29 
9. Fat emboli in the blood-vessels of the lung, 30 
10. Infarcts of the spleen, 30 
11. Diagram illustrating the formation of a haemorrhagic infarct, 31 
12. Diagram illustrating the formation of an anaemic infarct, 32 
13. Schematic illustration of embolism-after Ribbert, 33 
14. Atrophy of muscle, . . 36 
15. Atrophy and distortion of the liver from tight-lacing-female, 37 
16. Atrophy of liver cells, 38 
17. Albuminous degeneration-kidney, 39 
18. Fatty degeneration-kidney, 41 
19. Fatty degeneration of epithelium in the kidney, 42 
20. Fatty infiltration of the heart, 43 
20A. Lipoid globules, 44 
21. Glycogen infiltration of epithelial cells, 44 
22. Serous infiltration of epithelial cells, 45 
23. Mucous degeneration of epithelial cells, 45 
24. " Beaker cells," 46 
25. Mucous degeneration of fibrous tissue of mamma, 46 
26. Hyaline degeneration in the walls of small blood-vessels, 48 
27. Hyaline degeneration of muscle cells, 48 
28. Amyloid degeneration of capillary blood-vessels of a glomerulus of the 
kidney, 49 
29. Corpora amylacea, 50 
30. Calcification of epithelial cells of the kidney, 51 
31. Calcareous infiltration of the kidney, 52 
32. Pigmentation of lungs, 53 
33. Hsematogenous pigment, 54 
34. Melanotic pigment, 55 
35. Pigmentation of lungs, 55 
36. Necrosis of epithelium-kidney, 57 
37. Gangrene of foot, 57 
38. Coagulation necrosis in cells, 58 
39. Coagulation necrosis in tuberculous tissue, 59 
40. Cheesy degeneration in tubercle, 59 
41. Phases of mitosis, 66 
XV XVI 
ILLUSTRATIONS 
Fig. Page 
42. Abnormal phases of mitosis, 67 
43. Regeneration of striated muscle after injury, 70 
44. Regeneration of epithelium, 71 
45. Regeneration of epithelium, 72 
46. Mitosis in granulation tissue, . . . . ( 73 
47. Regeneration of connective tissue, 74 
48. Developing blood-vessels in new-formed tissue, showing plasma cells. . 75 
49. Regeneration of fat tissue, 77 
50. Healing of a wound of the cornea, 82 
51. Emigration of leucocytes, 84 
52. Exudative inflammation, 85 
53. Fibrin in inflammatory exudate, 86 
54. Fibrin forming around dead cells, 87 
55. Bacterial embolus in the liver, 88 
56. Bacterial embolus in the liver, with necrosis, 89 
57. Necrosis and suppuration in the liver, 90 
58, Granulation tissue, 91 
59. Granulation tissue, 92 
60. Fibroblasts of new connective tissue, 93 
61. Healing wound in the tongue of a dog, 93 
62. Cicatricial tissue, 94 
63. Exuberant granulations, 94 
64. Regeneration of epithelium, 95 
65. Phagocytes, 100 
66. Giant cells, 101 
67. Fragment of sponge in healing wound, 101 
68. Giant cells and new-formed fibrous tissue around a foreign body, . . . 102 
69. Giant cells around foreign bodies, 103 
70. Osteoclasts, 104 
71. Fragments of necrotic muscle, 104 
72. Thoma's frog-plates, 112 
73. Entamoeba histolytica, 116 
74. Trypanosoma brucei, 117 
75. Treponema pallidum, 118 
76. Trichomonas vaginalis, 119 
77. Balantidium coli, 120 
78. Coccidium oviforme, 121 
78A. Sarcocystis muris 121 
79. Distoma hepaticum, 123 
80. Head of Taenia solium, 123 
81. Taenia mediocanellata. Head and proglottides, 124 
82. Cuticula of echinococcus cyst, 125 
83. Scolices of Taenia echinococcus, 125 
84. Hooklets from scolex of Taenia echinococcus, 126 
85. Ascaris lumbricoides, 127 
86. Eggs of nematode worms, 127 
87. Oxyuris vermicularis, 128 
88. Trichocephalus dispar, 128 
89. Trichina spiralis, 129 
90. Filaria sanguinis hominis, 130 
91. Sarcoptes hominis, 132 
92. Pediculus capitis, 132 
93. Bacteria with flagella, 133 lymph-vessel, 240 
142. Endothelial cell proliferation in the liver, 241 
143. Hyperplasia of the endothelium in the liver, 242 
144. Typhoid bacilli in the spleen, 244 
145. Spirillum cholerse Asiatic®, 249 XVIII 
Fig. Page 
146. Small miliary tubercle, 253 
147. Miliary tubercle with giant cells, 253 
148. Miliary tubercle in the lung, 254 
149. Tuberculosis-exudative form, 256 
150. Tubercle bacilli in sputum, 257 
151. Tubercle-bacillus culture-from man, 258 
152. Tubercle-bacillus culture-from bird, 258 
153. Lesion of dead tubercle bacilli, 261 
154. Lupus of face, 268 
155. Bacilli of leprosy, 269 
156. Syphilitic inflammation, 270 
157. Syphilitic condyloma, 271 
158. Syphilitic nodule, 272 
159. Syphilitic inflammation, ' 273 
160. Syphilitic gumma-liver, 273 
161. Treponema pallidum (India ink stain), 275 
162. Treponema pallidum (silver stain), 276 
163. Rhinoscleroma 282 
164. Fibrin in diphtheritic membrane, 282 
165. Diphtheritic inflammation, 283 
166. Bacillus diphtherias, 284 
167. Bacillus tetani, 286 
168. Spirochaete Obermeieri, 292 
169. Hydrophobia, 294 
170. Negri bodies, 296 
170A. Organism isolated from case of poliomyelitis 299 
171. Smallpox vesicle, 303 
172. Trachoma bodies, 308 
173. Trachoma bodies, 309 
174. Abrachius, 321 
175. Facial fissure, 322 
176. Double harelip, 322 
177. Synophthalmia, agnathia, and synotia, 323 
178. Abdominal fissure, 324 
179. Craniorrhachischisis, 325 
180. Myelomeningocele sacralis, 326 
181. Encephalocele, • 327 
182. Cranioschisis, 328 
183. Horseshoe kidney, 329 
184. Foetus, with cord around neck and leg, 330 
185. Partial intra-uterine amputation of leg, 331 
186. Twins, 332 
187. Thoracopagus, 333 
188. Thoracopagus-pig, 334 
189. Child with acardiac parasite, 335 
190. Multiple nodular sarcomata, 339 
191. Sarcoma of forearm, 339 
192. Polypoid fibroma, 340 
193. Tumor-cell embolus, 341 
194. Plimmer's bodies, 348 
195. Epithelial cell " inclusions," 349 
196. Dermoid cyst of skin, 361 
197. Fibroma durum, 362 
ILLUSTRATIONS XIX 
Fig. Page 
198. Fibroma molle, 363 
199. Papilloma of skin, 363 
200. Mucous polyp of nose, 364 
201. Myxoma of larynx, 365 
202. Sarcoma-large spindle-celled, 367 
203. Sarcoma-spindle-celled, 368 
204. Sarcoma-spindle-celled, 369 
205. Sarcoma-small round-celled, 369 
206. Sarcoma-large round-celled, 369 
207. Melano-sarcoma, 370 
208. Melano-sarcoma, _ 370 
209. Sarcoma-giant-celled, 371 
210. Sarcoma-giant-celled, 371 
211. Osteo-sarcoma, 372 
212. Epulis, 373 
213. Angio-sarcoma, 374 
214. Angio-sarcoma, 374 
215. Angio-sarcoma, 374 
216. Myxo-sarcoma, 375 
217. Adeno-sarcoma, 376 
218. Endothelioma, 377 
219. Endothelioma, 378 
220. Endothelioma, psammomatous form, 378 
221. Endothelioma, psammomatous form, 379 
222. Endothelioma, 380 
223. Endothelioma, 381 
224. Endothelioma, 382 
225. Epithelioma, 383 
226. Sacrococcygeal chordoma, 384 
227. Endothelioma, 385 
228. Lipoma, 386 
229. Chondroma, 386 
230. Glioma, 387 
231. Neuroglia from glioma, 387 
232. Myoma uteri, 388 
233. Fibro-myoma uteri, 389 
234. Neuroma ganglioniforme, 390 
235. False neuroma, 391 
236. Multiple fibromata, 391 
237. Multiple fibromata, 392 
238. Angioma telangiectoides, 393 
239. Angioma cavernosum, 394 
240. Congenital lymphangioma, 394 
241. Carcinoma molle, 396 
242. Intracanalicular fibro-adenoma, 397 
243. Adenoma, 397 
244. Foetal adenoma of thyroid, 398 
245. Sebaceous adenoma, 399 
246. Adenoma, 400 
247. Infiltrating cancer cells, 401 
248. Carcinoma cells in lymph-vessel, 401 
249. Metastatic carcinoma, 402 
ILLUSTRATIONS ILLUSTRATIONS 
XX 
Fig. Page 
250. Mitosis in carcinoma, 403 
251. Metastatic carcinoma, 403 
252. Carcinoma of hand, 404 
253. Exudative inflammation in carcinoma, 405 
254. Epithelioma, 406 
255. Epithelioma, 407 
256. Epithelioma, 408 
257. Epithelioma, 409 
258. Epithelioma, 409 
259. Congenital nsevus, 410 
260. Epithelioma, basal-celled,. 411 
261. Small epithelioma of face, 412 
262. Small superficial epithelioma of face, 412 
263. Epithelioma, giant cells, .■ 413 
264. Epithelioma, giant-celled, 413 
265. Carcinoma, 414 
266. Carcinoma durum, 414 
267. Carcinoma gelatinosum, 415 
268. Carcinoma myxomatodes, 415 
269. Adamantinoma, 416 
270. Myxcedema, 430 
271. Cretin, 431 
272. Thyroid gland in myxcedema, 432 
272A. Island of Langerhans in case of diabetes 435 
272B. Island of Langerhans in case of diabetes 435 
273. Lesions of gout, 436 
274. Hyperplasia of lymphoid tissue, 439 
275. Enlarged thymus, 445 
276. Enlarged thymus, 446 
277. Suffocation from lodgment of meat in larynx, 447 
278. Megakaryocytes, 465 
279. Megakaryocytes, 466 
280. Bone marrow, 472 
281. Leukaemic infiltration of kidney 476 
282. Liver in lymphatic leukaemia, 477 
283. (Edema of lymph-node, 482 
284. Pigmentation of lymph-node, 483 
285. Hyperplastic inflammation of lymph-node, 484 
286. Endothelial cells in hyperplasia of lymph-nodes, 485 
287. Hyperplasia of Peyer's patch, 485 
288. Chronic inflammation of lymph-node, 486 
289. Lymph-node in lymphatic leukaemia, 490 
290. Bone marrow in Hodgkin's disease, 491 
291. Hodgkin's disease, 492 
292. Hodgkin's disease, 493 
293. Hodgkin's disease, 493 
294. Hodgkin's disease, 494 
295. Hodgkin's disease, 495 
296. Hodgkin's disease, 496 
297. Hodgkin's disease, 496 
297A. Endothelioma of lymph-node . 497 
298. Amyloid degeneration of spleen, 501 ILLUSTRATIONS 
XXI 
Fig. Page 
299. Hyperaemia of spleen, 502 
300. Infarction of spleen, 503 
301. Chronic indurative splenitis, 505 
302. Chronic interstitial splenitis, 506 
303. Malarial spleen, 506 
304. Tuberculosis of spleen, 507 
305. Hyperplasia of spleen, 508 
306. Hodgkin's disease, 509 
307. Lymphatic leukaemia, 510 
308. Colloid struma, 513 
309. Fatty degeneration in adrenal, 515 
310. Haemorrhage into adrenal, 516 
311. Fibrinous pericarditis, 519 
312. Adhesions of pericardium, 520 
313. Obliteration of pericardial sac, 521 
314. Tuberculous pericarditis, 522 
315. Reptilian heart, 523 
316. Stenosis of pulmonary artery, 524 
317. Interventricular foramen, 525 
318. Fenestration of semilunar valves, .526 
319. Abnormal chordae tendineae, 527 
320. Rupture of heart, 528 
321. Atrophic pericardial fat tissue, 529 
322. Aneurism of heart, 530 
323. Polypoid thrombus in auricle, 531 
324. Globular thrombus in ventricle, 532 
325. Globular thrombus in auricle, 533 
326. Thrombi among heart trabeculae, 534 
327. Thrombus on edge of mitral valve, 535 
328. Fatty degeneration of heart muscle, 535 
329. Fatty infiltration of heart, 536 
330. Bacterial embolus in heart muscle, 539 
331. Chronic interstitial myocarditis, 540 
332. Chronic interstitial myocarditis, 540 
333. Chronic interstitial myocarditis, 541 
334. Ulcerative endocarditis, 542 
335. Bacteria in vegetation of heart valve, 543 
336. Chronic endocarditis, 544 
337. Chronic endocarditis, 545 
338. Vegetation on aortic valve, 546 
339. Chronic endocarditis, 546 
340. Verrucous endocarditis, 547 
341. Stenosis of aortic valves, 548 
342. Chronic endocarditis with calcification of valves, 549 
343. Hypertrophy of heart, 551 
344. Transverse rupture of aorta, 558 
345. Chronic arteritis, 560 
346. Chronic arteritis, 560 
347. Obliterating endarteritis, 560 
348. Connective tissue in intima, 561 
349. Chronic arteritis, 561 
350. Atrophy of elastic tissue in wall of aorta, 562 XXII 
ILLUSTRATIONS 
Fig. Page 
351. Atheroma of aorta, 562 
352. Chronic inflammation of aorta, 563 
353. Chronic arteritis, 563 
354. Tuberculous arteritis, 566 
355. Aneurism of arch of aorta, 568 
356. Aneurism of popliteal artery, 569 
357. Tuberculous phlebitis, 574 
358. Catarrhal inflammation, . . 579 
359. Mucous polyp of nose, 580 
360. Mucous polyp of nose, 581 
361. Hyperplasia of epithelium of false vocal cords, 583 
362. Diphtheria of larynx and trachea, . . 584 
363. Tuberculous laryngitis, 585 
364. Papilloma of larynx, 586 
365. Acute catarrhal bronchitis, 587 
366. Chronic bronchitis, 588 
367. Chronic fibrinous bronchitis, 589 
368. Muitiple bronchiectasiae, 590 
369. Adenoma of bronchi, 591 
370. Lung stones, 591 
371. Tuberculous lymph-nodes, 592 
372. Chronic congestion of lung, 594 
373. Vesicular emphysema, 597 
374. Interlobular emphysema of lung, 598 
375. Interstitial emphysema of lung, 599 
376. Lung showing tubercles with pigmentation in pleura, 602 
377. Acute lobar pneumonia, 604 
378. Acute lobar pneumonia, 604 
379. Acute lobar pneumonia, 605 
380. Exudate from lung, 606 
381. "Organizing" pneumonia, 608 
382. Broncho-pneumonia, 609 
383. Broncho-pneumonia, 610 
384. Broncho-pneumonia, 610 
385. Broncho-pneumonia, 611 
386. Broncho-pneumonia, chronic, 612 
387. Air vesicle in broncho-pneumonia with streptococci, 613 
388. Interstitial pneumonia, 614 
389. Chronic interstitial pneumonia, 615 
390. Anthracotic pigmentation of lung, 616 
391. Anthracosis of lung, 617 
392. Miliary tubercle of lung, 620 
393. Miliary tubercle of lung, 621 
394. Miliary tubercle of lung, 622 
395. " Healed tubercle " of lung, 623 
396. " Healed tubercle " of lung, 623 
397. Tuberculous inflammation of lung, 624 
398. Tuberculous broncho-pneumonia, 625 
399. Tuberculous broncho-pneumonia, 625 
400. Tuberculous broncho-pneumonia, 626 
401. Acute pulmonary tuberculosis, 628 
402. Chronic pulmonary tuberculosis, 629 ILLUSTRATIONS 
^IG- Page 
403. Experimental tuberculosis-rabbit, 632 
404. Experimental tuberculosis-rabbit, 632 
405. Experimental tuberculosis-rabbit, 633 
406. Secondary carcinoma of lung, 634 
407. Endothelioma of pleura, 635 
408. Endothelioma of pleura, 635 
409. Endothelioma of lung, 641 
410. Wall of branchial cyst, 647 
411. Wall of branchial cyst, 648 
412. " Adenoid " polyp of pharynx, 650 
413. Carcinoma of oesophagus, 654 
414. Degeneration of gastric epithelium in phosphorus poisoning, 656 
415. Acute catarrhal gastritis, 657 
416. Chronic gastritis, 657 
417. Chronic gastritis, 658 
418. Chronic gastritis, 658 
419. Ulcer of stomach, 660 
420. Perforating ulcer of stomach, 661 
421. Papillary adenoma of stomach, 663 
422. Carcinoma of stomach, 664 
423. Gelatinous carcinoma of stomach, 665 
424. Hair-balls from human stomach, 666 
425. Diverticulum of small intestine, 667 
426. Multiple false diverticula of intestine, 668 
427. Intussusception, 669 
428. Intussusception, 669 
429. Inguinal hernia-intestinal, 670 
430. Inguinal hernia-omental, 670 
431. Acute catarrhal enteritis, 672 
432. Nodular enteritis, 673 
433. Tuberculous ulcers of intestine, 673 
434. Tuberculous ulcer of intestine, 674 
435. Subserous tubercles, 674 
436. Tuberculous ulcers in intestine, 675 
437. Acute catarrhal colitis, 676 
438. Amoebic colitis, 677 
439. Nodular colitis, 678 
440. Nodular colitis with ulceration, 678 
441. Nodular colitis, 679 
442. Croupous colitis, 679 
443. Necrotic colitis, 680 
444. Chronic ulcerative colitis, 681 
445. Chronic colitis with ulceration, 682 
446. Haemorrhoids, 684 
447. Acute appendicitis, 685 
448. Acute suppurative appendicitis, 686 
449. Chronic appendicitis, 687 
450. Obliteration of lumen and appendix, 687 
451. Small polyp of mucous membrane of small intestine, 688 
452. "Lymphomata"of intestine in pseudo-leukaemia 689 
453. Adeno-carcinoma of rectum, ' 689 
454. Adenoma of rectum, . . 690 
XXIII XXIV 
ILLUSTRATIONS 
Fio. Pa«e 
455. Acute cellular peritonitis, 693 
456. Peritoneal adhesions between liver and intestine, 695 
457. Miliary tubercles of omentum, 696 
458. Papillary fibroma of peritoneum, 697 
459. Cystic papilloma of omentum, 698 
460. Endothelioma of parotid, 701 
461. Fatty infiltration of pancreas, 702 
462. Fat necrosis in mesentery, 703 
463. Fat necrosis in pancreas, 704 
464. " Nutmeg liver," , "09 
465. Chronic congestion of liver, 710 
466. Chronic congestion of liver, <11 
467. Infarction of liver, 713 
468. Acute yellow atrophy of liver, 717 
469. Fatty infiltration of liver, <18 
470. Fatty infiltration of liver cells, 719 
471. Fatty degeneration of liver cells, 719 
472. Amyloid degeneration of liver capillaries, 720 
473. Malarial pigmentation of liver, 721 
474. Abscesses in liver containing bacilli, 723 
475. Chronic interstitial hepatitis, 724 
476. Chronic interstitial hepatitis, 725 
477. Chronic interstitial hepatitis, 726 
478. New formed gall-ducts in cirrhosis, 727 
479. Hypertrophic cirrhosis of liver, 729 
480. Gumma of liver, "31 
481. Syphilitic hepatitis, "32 
482. Miliary tubercle of liver, 733 
483. Cavernous angioma of liver, 735 
484. Secondary carcinoma of liver, 736 
485. "Foamy liver," "38 
486. Echinococcus multilocularis of liver, <39 
487. Cholangitis, "40 
488. Cholangitis, "41 
489. Adenoma of gall-duct, "42 
490. Biliary calculi, 744 
491. Horseshoe kidney, '46 
492. Foetal lobulation of kidneys in adult, 747 
493. Hyaline globules in uriniferous tubule, 749 
494. Hyaline casts in uriniferous tubule, 750 
495. Albuminous degeneration of kidney, 751 
496. Fatty degeneration of epithelium in kidney, 752 
497. Amyloid degeneration of capillaries in kidney, 752 
498. Glycogen degeneration of epithelium in kidney, <53 
499. Suppurative nephritis, 755 
500. Acute diffuse nephritis, "56 
501. Acute diffuse nephritis, 757 
502. Acute diffuse nephritis, "58 
503. Acute diffuse nephritis, "59 
504. Diffuse nephritis, 760 
505. Atrophied glomerulus of kidney, "61 
506. Chronic diffuse nephritis, "63 ILLUSTRATIONS 
XXV 
Fig • Page 
507. Chronic diffuse nephritis, 764 
508. Chronic diffuse nephritis, 765 
509. Chronic diffuse nephritis, 766 
510. Chronic diffuse nephritis, .J .... * 767 
511. Chronic diffuse nephritis, 768 
512. Chronic obliterating endarteritis in nephritis, 769 
513. Tuberculous nephritis, 770 
514. Chronic pyelo-nephritis, 771 
515. Hydronephrosis, 773 
516. Congenital cystic kidney, 774 
517. Cyst of kidney, 775 
518. Calculus in pelvis of kidney, 775 
519. Adenoma of kidney, 776 
520. Adenoma of kidney-hypernephroma, 777 
521. Adenoma of kidney, 778 
522. Adenoma of kidney, papillary, 778 
523. Adenoma of kidney, alveolar, 779 
524. Hypernephroma, 779 
525. Hypernephroma, 780 
526. Diverticula of bladder, 780 
527. Hypertrophy of wall of bladder, 781 
528. Acute catarrhal cystitis, 783 
529. Hyperplasia of bladder epithelium, 784 
530. Hyperplasia of bladder epithelium, 785 
531. Papilloma of bladder, 787 
532. Carcinoma of bladder, 787 
533. Papillary carcinoma of bladder, 788 
534. Vesical calculus, 789 
535. Stricture of male urethra, 791 
536. Uterus bicornis, 798 
537. Hour-glass uterus, 799 
538. Retroflexion of uterus, 800 
539. Prolapse of uterus, 801 
540. Chronic endometritis, 804 
541. Chronic endometritis, 805 
542. Chronic endometritis, 806 
543. Hyperplasia of cervix uteri, 807 
544. Uterine phlebitis, 809 
545. Uterine polyp, 810 
546. Extramural myomata, 811 
547. Intraparietal myomata of uterus, 812 
548. Glandular myoma of uterus, 813 
549. Adenoma of uterus, 814 
550. Adenoma of uterus, 815 
551. Adenoma of uterus 815 
552. Adenoma of uterus, 816 
553. Adenoma of uterus, 817 
554. Carcinoma of uterus, 818 
555. Carcinoma of cervix uteri, 819 
556. Carcinoma of uterus, 819 
557. Chorionepithelioma, 820 
558. Large cells from chorionepithelioma, 821 XXVI 
Fig- Page 
559. Fragment of decidua, 824 
560. Curettings from uterine cavity, 824 
561. Hydatid mole, 825 
562. Hydatid mole, 825 
563. Chronic oophoritis, 827 
564. Chronic oophoritis, 828 
565. Papilloma of ovary, 829 
566. Papilloma of ovary, 830 
567. Sarcoma of ovary, 831 
568. Endothelioma of ovary, 831 
569. Cystadenoma of ovary, 832 
570. Cystadenoma of ovary, 833 
571. Cystadenoma of ovary, glandular, 834 
572. Cystadenoma of ovary, papillary, 834 
573. Papillary cysts of omentum, 835 
574. Follicular cysts of ovary, 836 
575. Dermoid cyst of ovary, 837 
576. Small pediculated cyst of broad ligament, 837 
577. Hydrosalpinx, 838 
578. Pyosalpinx, •. 839 
579. Pyosalpinx, 840 
580. Tuberculous salpingitis, 841 
581. Suppurative mastitis, 843 
582. Chronic inflammation of mammary gland, 843 
583. Carcinoma and tuberculosis of mamma, 844 
584. Hypertrophy of mamma, 845 
585. Hypertrophy of mamma, 846 
586. Hypertrophy of mamma, 846 
587. Intracanalicular fibroma of mamma, 847 
588. Fibro-adenoma of mamma, 848 
589. Pericanalicular fibroma of mamma, 849 
590. Adenoma of mamma, 849 
591. Papillary cystadenoma of mamma, 850 
592. Adenoma of mamma, 851 
593. Adenoma of mamma, 851 
594. Carcinoma of mamma, scirrhus, 852 
595. Varicocele, 856 
596. Chronic interstitial orchitis, 858 
597. Tuberculous orchitis, 859 
598. Chronic orchitis, 860 
599. Rhabdomyoma of testicle, . '. 861 
600. Teratoma of testicle, : 862 
601. Chorionepithelioma of testicle, 862 
602. Hypertrophy of prostate, 864 
603. Hypertrophy of prostate, 865 
604. Adenoma of prostate,, 865 
605. Glandular hyperplasia of prostate, 866 
606. Corpora amylacea in prostate, 867 
607. Progressive muscular atrophy, 868 
608. Progressive muscular atrophy, 869 
609. Pseudo-hypertrophy of gastrocnemius muscle, 870 
610. Hyaline degeneration of muscle, 872 
ILLUSTRATIONS XXVII 
Fig. Page 
611. Chronic interstitial myositis, 874 
612. Callus after fracture, 878 
613. Healed fracture, 879 
614. Ossifying periostitis, 880 
615. Ossifying periostitis, 880 
616. Ossifying periostitis, 881 
617. Tuberculosis of joint, 882 
618. Rarefying osteitis, 884 
619. Condensing osteitis, 885 
620. Tuberculous osteitis, 887 
621. Necrosis of bone, 890 
622. Caries of vertebrae, 891 
623. Rachitic bone, 892 
624. Rickets, 893 
625. Craniotabes, 894 
626. Thorax of rachitic child, 895 
627. Achondroplasia, 895 
628. Achondroplasia, 896 
629. Hyperplastic bone marrow, 898 
630. Normal bone marrow, 898 
631. Sarcoma of bone, • 901 
632. Myelogenic sarcoma of sternum, 902 
633. Pachymeningitis interna haemorrhagica, chronic, 909 
634. Brain sand, 910 
635. Psammoma of dura mater, 912 
636. Acute exudative meningitis, 915 
637. Acute exudative meningitis, 915 
638. Acute exudative meningitis, 916 
639. Fatty degeneration in pia mater, 917 
640. Miliary tubercle of pia mater, 918 
641. Miliary tubercle of ependyma of lateral ventricle, 919 
642. Endothelioma of cerebellum, 920 
643. Endothelioma of pia mater, 921 
644. Plates of bone in pia mater spinalis, 923 
645. Acute ependymitis, 925 
646. Congenital hydrocephalus, 926 
647. Hydromyelia, 929 
648. False heterotopia, 930 
649. Atrophy of brain convolutions, 932 
650. Diagram of circle of Willis, 933 
651. Large haemorrhage in brain, 937 
652. Section of cord showing haemorrhage into gray matter, 938 
653. Haematomyelopore, 939 
654. Degenerated brain tissue in embolic softening, 941 
655. Blood-vessels from embolic softening, 941 
656. Neurone from human cerebral cortex, 944 
657. Neurone from cerebellar cortex of guinea-pig, 945 
658. Neuroglia cell, 945 
659. Neuroglia cell, 946 
660. Neurone degeneration, 946 
661. Secondary descending degeneration, 953 
662. Secondary ascending degeneration, 954 
ILLUSTRATIONS XXVIII 
Fig. Page 
663. Amyotrophic lateral sclerosis, 956 
664. Tabes dorsalis, 959 
665. Tabes dorsalis, 960 
666. Posterior spinal sclerosis, 960 
667. Combined system disease, 962 
668. Degenerated tissue from acute myelitis, 966 
669. Poliomyelitis anterior, 967 
670. Acute anterior poliomyelitis, 968 
671. Perivascular infiltration in cord in acute anterior poliomyelitis, .... 968 
671A. Ganglion cell lesions in acute anterior poliomyelitis, 969 
672. Organism isolated from acute poliomyelitis, 969 
673. Landry's paralysis, 969 
674. Degeneration of nerve fibres, 970 
675. Multiple sclerosis in spinal cord, 973 
676. Solitary tubercle of cerebellum, 974 
677. Syringomyelia, 978 
678. Side view of human brain, 993 
679. Method of opening brain, 994 
680. Method of opening brain, 995 
681. Schematic picture of brain, 996 
682. Brain axis separated from brain mantle, 996 
683. Brain mantle seen from below, 997 
684. Outlines of sections of spinal cord, 1000 
685. Heart, showing lines for incision, 1006 
686. Heart opened, exposing aortic valves, 1007 
687. Special incisions for opening heart, 1008 
ILLUSTRATIONS PART I. 
GENERAL PATHOLOGY. INTRODUCTION. 
The successful pursuit of pathology-the science which treats of 
disease-depends largely upon the clearness and accuracy of the student's 
knowledge of normal anatomy and normal physiology. The possession 
of such knowledge by the reader is necessarily assumed in this epitomized 
presentation of a large and rapidly extending field of observation and 
research. 
The Nature of the Living Body.-Leaving aside as not indispensable, 
and at present not attainable, an accurate definition of life, it is impor- 
tant constantly to realize that the normal living body is a complex 
and delicate mechanism incapable of creating new forces, but able, by 
means of its cellular and molecular organization, to accumulate or store 
energy derived from without, releasing this under fixed and definite 
conditions. This storing of energy is possible by means of the capacity of 
living body-cells to build up complex molecular combinations. These, 
owing to their instability, may be readily resolved into less complex and 
more stable combinations with the release of the stored-up energy. 
This it is which makes possible all expression of life. 
The Chemistry of Life.-The complex molecular combinations through 
which energy is stored and released by cells during the processes of life 
areespecially characterized by their content of carbon, nitrogen, hydrogen, 
oxygen, and sulphur. Iron and phosphorus are found in some of them 
while numerous other elementary substances often share in their composi- 
tion. Such molecular combinations are called proteins. There is reason 
to believe that the proteid molecule is of great size and complexity, that 
during life it is capable of entering upon an exceedingly great variety of 
combinations and readjustments of its structure conditioned upon heredity 
and environment. 
While the chemist in his researches deals largely with dead protein, it 
has been found convenient by certain writers to embody a conception 
of the living proteid molecule in the terms biophore or biogen. 
It is inevitable that the proteins and their performances while sharing 
in the processes of life, and the various influences which determine these 
performances, should fix the storm centre of research into the nature of 
life and offer the highest promise of light upon the ultimate and funda- 
mental problems of biology. But we must be patient and not too eager 
to carry the formulae and the working hypotheses of the chemists, with- 
out due reserve, over into the domain of living things, whose story and 
performances, and limitations we are only just beginning to spell out. 
The details of the chemistry of the life processes, so far as they are 
known, and their relationship to protein substances and protein metab- 
3 4 
INTRODUCTION 
olism in general, to ferments and to enzymes, and a consideration of the 
successes, the hopes, and the dreams of the chemists within this borderland 
of living matter, belong in those studies in physiological chemistry and 
chemical physiology which naturally precede the consideration of the 
problems of pathology, and should be sought in special treatises. 
The Characters of Disease.-Many of the earlier views concerning life 
and death and health and disease, which have long since given way to 
more accurate conceptions, still hold a certain sway among the thought- 
less, perpetuated by traditional forms of speech. One of these is that 
disease is an entity, something foreign to the body which may enter from 
without, and with which the body may struggle and fight, which it may 
conquer or to whose ravages it may succumb. It will be wise for the 
student constantly to remember that disease is not a thing, but a process. 
It is an abnormal performance of certain of the functions of the body. 
This may or may not be associated with appreciable morphological altera- 
tions of the body structure. It is those agencies and conditions to which 
the body has not adapted itself, which, swaying its normal capacities now 
one way and now another, induce the functional aberrations and struc- 
tural alterations by which disease is manifested. 
It follows from this that the functional abnormalities and the struc- 
tural alterations which make up the signs, symptoms, and lesions of dis- 
ease involve the expression of no new functional capacities which the 
normal body does not possess. These may be diminished or exalted; 
they may be perverted or abolished; or the cells may now and then re- 
vert to forms and to phases of activity which the body has long since 
outgrown or largely suppressed in its slow adaptation to conditions of 
life which now constitute the normal. But the body in disease manifests 
no new functions, develops no new forms of energy, reveals no new 
capacities. 
The Significance of Cells in Pathology.-If pathology is to be for the 
student or the practitioner anything but a mass of more or less useful facts 
he must learn to correlate its data with the facts and laws of normal 
morphology and normal physiology. While he should be conscious 
always, on the one hand, of the invisible molecular changes which under 
lie the manifestations of energy, and, on the other, will not ignore the 
details of gross morphology, his attention will be most constantly drawn 
to the cells as the life units upon which ultimately both the form and 
function of living things depend. He will realize that as the cells of the 
normal body are what they are in form and in function because of the 
conditions under which they have been slowly evolved, and are at the 
moment placed; so when the conditions change and become abnormal, 
it is to the cells that he must look for an understanding of the aber- 
rations and disturbances by which we recognize disease. 
In normal physiology attention is most keenly centred to-day upon 
the structure and performances of cells as the field richest in the promise 
of significant revelations. So, also, in pathology by similar methods 
and with equal persistence must the structure and performances of cells 
under abnormal conditions be studied if we are to hope with reason for INTRODUCTION 
5 
a clearer comprehension of disease. This has long been recognized, and 
to the conception of the pathological processes as essentially cellular 
processes are due the great advances which this phase of biological science 
has made during the past few decades. But the newer knowledge of the 
cell, not as a membranous bag nor as a mere lump of protoplasm, but as 
a complex machine whose various structural features are of the utmost 
significance, has greatly widened the field of cellular pathology. 
Manifestations of heredity which are displayed in the body as a 
whole have long been known. To-day we may and must take account 
of the marks of heredity in individual cell life. Not a few of what we 
call the aberrances of cells in disease are but the expression of cell traits 
and capacities latent in the environment which has become the usual and 
therefore the normal, but finding expression as the sway of the body- 
organism is released under disturbances of its equilibrium. Thus cells 
thrown out of function may in a measure revert in character to less dif- 
ferentiated types, and cells long comparatively quiescent may, under 
varying stimuli, assume capacities and forms which they seemed to have 
outgrown. 
Of course, in the pursuit of pathological morphology it is the dead 
body and dead tissues with which we are most often engaged. But these 
are of special interest only as they reveal structures or indicate processes 
which were maintained during life. So that he who can most closely 
correlate the knowledge of the living cells with his observations upon 
those which are dead will gain most from his morphological studies. 
The Interrelationship of Cells and of Organs.-While the pathology of 
to-day is essentially a cellular pathology, while it is illuminating and con- 
venient to consider the cells as physiological and structural units, main- 
taining a certain independence of existence and function, it is neverthe- 
less true that beyond their mere juxtaposition in the body, beyond a close 
mutual dependence upon the common blood supply and nerve control, 
there is a subtle and as yet little understood transmission of physiological 
impulses from cell to cell. Whether this is often by protoplasmic con- 
tinuity or usually in some other way, we do not know. But it should not 
be left out of the account in some of the more complex and subtle prob- 
lems which, in health as in disease, the life of the cell and the life of the 
body present. 
The interrelationship of organs, and the innervation and circulation 
which they share in common, have most important bearings upon both 
the morphology and physiology of disease. This relationship will be 
considered briefly in the later chapters of this book, but should receive 
especial attention in the study of clinical pathology. 
The Excitants of Disease.-When we study the so-called causes of 
disease, we should remember always that, underlying the manifestations 
of disease, as well as sustaining the correlated processes which we name 
health, are the complex and ceaseless chemical transformations which in 
both health and disease alike supply the energy which sustains all ex- 
pression of life. So that what we are wont to call the causes, whether 
external or internal, of disease are really not primary causes, but liber- 6 
INTRODUCTION 
ating impulses or excitants which sway and modify the orderly transfor- 
mations of energy constituting health, with those manifestations of per- 
turbed function or altered structure, or both, on which our conceptions of 
disease are framed. 
Phases and Classifications of Pathology.-Pathology, then, deals with 
the disturbances of function and the alterations in structure in living 
beings, induced by unusual agencies and conditions. The functional 
disturbances thus induced are embraced as symptoms of disease in 
pathological physiology, which so largely dominates the scientific activi- 
ties of the physician and forms the basis for the practice of his art. The 
phenomena of pathological physiology are in no sense opposed to those 
of normal physiology, but are their inevitable correlatives when the 
living body is placed under sufficiently abnormal conditions. Patho- 
logical morphology is concerned with the structural alterations of the 
organism which may result from abnormal conditions. Pathological 
morphology deals with both the gross and the microscopic alterations of 
structure, and hence embraces both pathological anatomy and pathological 
histology. 
But alterations in structure are so closely associated with disturbances 
in function, and both are so constantly dependent upon the inciting fac- 
tors in disease, that an intelligent study of morphology necessitates a 
constant consideration of etiology and of certain phases of pathological 
physiology. 
It is customary and convenient in the study of pathology to consider 
together the general or elementary abnormal processes and conditions 
and the etiological factors in disease without reference to their special 
manifestations in particular organs or parts of the body. This division 
of the subject is called General Pathology. Special Pathology deals with 
the forms and details of lesions in individual organs or parts of 
the body. 
Correlated Sciences.-The human body is so complex in its organiza- 
tion that the student of pathology, like the student of normal morphology 
and physiology, is under the constant necessity of seeking light through 
the study of simpler organisms. In our extremely differentiated and 
intimately co-ordinated cells, many features fundamentally simple are 
veiled or modified; so that we can understand them only when we inter- 
pret them in the light of less advanced forms. 
Thus it is that in the lore of the zoologist and the botanist we may 
find the key to obscure and important manifestations of aberrant cell 
life. It is, in truth, through the pursuit of comparative pathology that 
some of our greatest advances in the conceptions of disease have been 
won, and in it lies the brightest promise for the future. In the light of 
embryology many obscure pathological processes become plain and many 
clews to fruitful research are secured. 
Furthermore, so much depends upon the metabolism of the body in 
health and disease that it is to chemistry, both in health and disease, 
that the scientific physician looks most eagerly for the solution of prob- 
lems which each day become more numerous and urgent. INTRODUCTION 
7 
Finally, we are daily realizing more clearly that in those complex and 
subtle processes which we are wont to call vital, such physical factors as 
molecular constitution, surface tension, osmosis and diffusion, gravitation, 
elasticity, and pressure are of the highest significance and in our studies 
cannot be wisely ignored. CHAPTER I. 
THE CONDITIONS OF DISEASE. 
Adaptation in Health and Disease.-The human body, like other 
living organisms, has acquired its present form and its varied functions 
through gradual adaptation to its environment. 
The maintenance of the normal life of the body involves a normal 
mechanism and impulse to start with, and a constant and successful 
adjustment to the conditions under which it is placed. While the 
continuance of the state which we call health depends upon the approxi- 
mate maintenance of the external conditions to which the body has 
become adapted, it should be borne in mind that the adaptive capacity 
of the body is in many ways so effective that it can maintain its normal 
structure and functions in spite of unusual surroundings and adverse 
influences. Thus, for example, the body can adapt itself, within the 
limits of what we call health, to alterations, deficiencies, or excesses of 
nutrient material; to varying extremes of heat or cold, moisture or dry- 
ness; to electrical tension; to animal and vegetable parasites; and to 
various poisons, both those which come from without and those which 
result from faulty metabolism. Beyond certain rather ill-defined limits, 
however, the adaptive capacity cannot go, and disease results. 
Disposition to Disease.-The adaptive capacity may vary greatly in 
different individuals, depending upon age, sex, race, etc., so that adverse 
conditions which one individual can sustain without marked functional 
disturbance or structural damage may induce in another more or less 
serious disease. There is thus disposition and relative immunity to dis- 
ease. For example, children are in general much more disposed to cer- 
tain diseases than are adults. This disposition to disease is not, however, 
always fixed, but may give way to immunity under conditions which we 
shall study especially in the acute infections. 
Disposition to disease may be inherited and find expression through 
obvious structural abnormalities or through subtle functional defects, 
difficult or impossible to define or detect. 
Classes of Disease Conditions.-The harmful conditions to which the 
body may be subjected and which incite disease may be divided into two 
classes, external and internal. We may thus speak of external and inter- 
nal conditions of disease. 
It does not fall within the scope of this book to enter upon a dis- 
cussion of the many and varied conditions under which disease occurs, 
nor to place in array the many and wearisome phases of classification 
which have been more or less imposing or useful in the earlier days of 
8 CONDITIONS OF DISEASE 
9 
pathology and medical practice. We shall consider here only some of 
the more general conditions of disease, referring for a study of the de- 
tails of the specific excitants to later chapters. 
External Conditions of Disease. 
Disturbances of Nutrition.-The body may suffer through excessive 
or deficient nourishment. Too much food may in certain, though not 
in all, persons lead to an abnormal accumulation of fat. Too much food 
or unsuitable food may lead to disorders of the digestive apparatus 
or it may lead to the production within the body of metabolic sub- 
stances which seriously damage important organs. There is much 
reason for believing that through such faulty metabolism forms of 
auto-intoxication may arise which damage the parenchyma of the 
liver and kidney, for example, so that structural as well as functional 
disorders arise. 
On the other hand, through insufficient nutriment the fat may 
disappear, the voluntary muscle substance diminish, and the blood 
deteriorate. Inanition may, however, occur in persons whose food 
supply is both abundant and suitable; for example, in structural or 
functional disorders of the digestive organs, in the insane, etc. Nutri- 
tion may suffer also in the absence of a sufficient amount of water or 
proteids or inorganic salts in the food.1 
Air Supply.-Through the function of respiration a supply of oxygen is 
furnished to the blood in the recesses of the lungs, and excretory prod- 
ucts are carried off. The failure of this function may be due to a lack 
of air bearing the oxygen or some interference with the respiratory 
channels or mechanism. The failure of oxygen to reach the lungs in 
proper condition and quantity is followed by forcible respiratory efforts 
which mark dyspnoea. A fatal suppression of respiration by the ex- 
clusion of air is called suffocation or strangulation. Asphyxia is a con- 
dition in which respiration is suspended, but the heart continues to beat. 
This condition is of frequent occurrence in the new-born, and is associ- 
ated with many forms of disease of the respiratory organs. For a more 
detailed consideration of asphyxia, suffocation, and strangulation see 
p. 442. 
Occupation.-Many diseases are closely dependent in origin upon 
unsanitary conditions associated with occupation. The dusty air 
prevalent in many stores, factories, theatres, court-rooms, prisons, 
schools, etc., may damage the lungs directly and render them more 
vulnerable in the presence of pathogenic micro-organisms. The high 
temperature and foul air common in many places of work or assembly 
may be serious preclisponents to disease. Finally, the abuse of alco- 
holic drinks and tobacco may be cited among many common excesses 
as agencies through which the conditions of disease are fulfilled. 
Damage from Excessive or Deficient Heat.-Through the heat-regu- 
1 Consult for details, Lusk. "Elements of the Science of Nutrition," 2d edition, 1911; and Wells, 
"Chemical Pathology," 2d edition, 1914. 10 
CONDITIONS OF DISEASE 
lating mechanism of the body a remarkable adaptation to moderate 
elevations of temperature is possible. But the maintenance of life is 
incompatible with very high temperatures. 
Local exposure to both extreme heat and extreme cold induces necro- 
sis and various phases of inflammation of the tissues. 
Death may be caused by the inspiration of smoke and flame; by the 
drinking of hot fluids; by the direct contact of flame or hot substances 
with the external surface of the body. It may be due to the direct effect 
of the agents, to secondary affections of the viscera, or to the exhaustion 
produced by long-continued inflammation and suppuration. Sudden 
death may occur after extensive burnings of the skin.1 
The burned skin divested of epidermis may present a peculiar red, hard, parchment- 
like appearance. If the patient have lived for some time, suppuration of the injured 
surface may ensue. Or there are small, bladder-like elevations of the epidermis. The 
base of these blisters is red, and they are surrounded by a red zone, or suppuration 
may have commenced. These appearances cannot be produced by heat applied to 
the skin after death. 
After death from severe burns there is apt to be congestion of the brain and the 
thoracic and abdominal viscera. The lymph-nodes and the lymphatic tissues through- 
out the body may be swollen and the seat of endothelial cell proliferation and necrosis. 
There is usually albuminous degeneration of the liver and kidneys; the spleen is 
swollen, and the seat of focal necrosis. Focal necrosis in the bone marrow has been 
noted. There may be capillary thromboses, interstitial haemorrhages in the kidney, 
and leucocytosis. These lesions indicate the presence of toxic substances in the body 
fluids, and thus the general condition may be regarded as an instance of auto-intoxi- 
cation.3 
Secondary lesions are not infrequent after severe burns. There may be oedema of 
the glottis, pseudo-membranous inflammation of the larynx and trachea, pneumonia, 
ulceration of the duodenum, and pyaemia with infarctions in the lungs, liver, spleen, 
and kidneys. 
Excessive cold may lead to the extinction of life in the body as a 
whole or in exposed parts, which cannot long resist freezing. 
Electricity.-Lightning.-Persons who are struck by lightning may die 
instantly, or may continue for several hours comatose or delirious, and 
then either die or recover; or they may die after some time from the effects 
of the burns and injuries received. 
The post-mortem appearances are very variable. Sometimes there 
are no marks of external violence or internal lesions. Sometimes the 
clothes are burnt and torn, while the skin beneath them is unchanged. 
Usually there are marks of contusion and laceration, or ecchymoses, 
or lacerated, punctured wounds, or fractures of the bones, or super- 
ficial or deep burns. The track of the electric current may sometimes 
be marked by dark red arborescent streaks on the skin. Fractures 
are rare. 
The internal viscera may be lacerated and disorganized from lightning. 
Artificial Electrical Currents.-In death from powerful artificial elec- 
trical currents, either by accident, as in linemen and others, or in elec- 
1 For a study of sudden death following severe burns, consult Silbermann, Virch. Arch., Bd. cix., 
p. 488, 1890, bib. 
2 For a study of the visceral changes following extensive burns, consult Bardeen, Jour. Exp. Med., 
vol. ii., p. 501, 1897, bib. McCrae, Trans. Ass. Am. Phys., vol. xvi., 1901, p. 153; also, Locke, Boston 
Med. and Surg. Jour., vol. cxlvii., p. 480, 1902, bib. CONDITIONS OF DISEASE 
11 
trical executions, there may be local burnings of varying degree where 
the wires or electrodes come in contact with the skin. The clothes may 
be pierced with holes at the point of exit of the current. Internally 
there appear to be no marked or characteristic lesions, either gross or 
microscopical, in this form of death. Van Gieson and others have ob- 
served the occasional, but not constant, occurrence of small haemor- 
rhages in the floor of the fourth ventricle, the significance of which is 
doubtful. Other petechial spots have been observed beneath the 
serous surfaces of the endocardium, pericardium, and pleura, and on the 
spleen.1 
Roentgen Rays and Radium.2-Exposure of the tissues to the x-rays or 
radium in sufficient quantity gives rise to a simple inflammation of the 
skin, which may be limited to a slight erythema, may cause a loss of the 
superficial epithelium, or may produce deep ulceration. The radiation 
of organs also causes destruction of the parenchymal cells with an increase 
in the connective tissue. As a rule, young and rapidly growing cells are 
more sensitive to the action of radium than are the mature cells; the lym- 
phoid and marrow tissues are especially sensitive; and tumor cells are 
also more easily affected than normal cells. This is apparently due 
chiefly to the action of the radium or the x-rays on the capillary blood- 
vessels, and not to an extreme sensitiveness of the tumor cell itself, for 
in cultures of cells in vitro there is but little difference in resistance be- 
tween embryonic growing cells, adult tissue cells, and tumor cells. The 
cellular changes are most marked at the end of about ten days after the 
exposure, and consist in an intercellular oedema, a shrinkage of the 
parenchymal cells of the organ or tumor, with the formation of syncytium, 
and a tendency to pycnosis of the nuclei. The blood-vessels often show a 
marked subendothelial hyperplasia, at times leading to almost complete 
closure. Thrombi are not infrequent in the smaller vessels with local 
haemorrhages. Some weeks later when the phagocytes have carried off 
the dead cells, the connective tissue will form a firm scar, poorly vas- 
cularized as a rule, though there may remain some distended venules 
under the surface of the skin. It is possible to destroy completely some 
superficial carcinomata of the skin by means of radium or the x-ray, but 
as yet there is no evidence to show that these agents have any permanent 
effect on rapidly growing glandular carcinomata or sarcomata. After 
prolonged exposure to the x-ray carcinomata of the skin frequently develop. 
In line with the marked effect on the bone marrow exerted by the x-ray is 
the occurrence of a number of cases of leukaemia in x-ray workers. 
Trauma.-The various forms of mechanical injury which the body 
may suffer need not be considered here in detail. The significance to 
life and health depends upon the extent of the injury and the part of 
the body affected. Thus, a concussion of the brain, even without 
1 Cunningham, "The Cause of Death from Industrial Electric Currents," New York Medical Journal, 
vol. Ixx., pp. 581 and 615, 1899. Jelliffe, Peterson and Haines' "Text-book of Legal Medicine," p. 245. 
2 For a study of lesions in x-ray examinations see Wolbach, Jour. Exp. Med., xxi, 415. 1909. 12 
CONDITIONS OF DISEASE 
obvious structural lesion, may be immediately fatal, while excessive 
laceration or crushing of a limb or muscle may be readily recovered 
from. 
Foreign Bodies.-We shall see later how the presence of lifeless 
foreign bodies, or of animal and vegetable parasites-bacteria, pro- 
tozoa, etc.-may be harmful to the organism, and the adaptive measures 
by which in favorable cases protection is secured. 
Poisons.-Certain forms of poisons are to be reckoned among the 
external agents harmful to the.body. These will be considered in a 
later section. 
Fig. 1.-Caisson Disease. 
Air in the vessels of the pia mater on the surface of the brain. 
Increased Atmospheric Pressure (Caisson Disease).-An extreme in- 
crease in atmospheric pressure, such as is often nowadays maintained 
in tunnels, caissons, and other construction works, is sometimes the 
occasion of death, especially when the pressure is relieved by a too sud- 
den return to normal conditions, that is, in what is technically called 
decompression. The danger seems to lie, apart from individual sus- 
ceptibility, in the rapidity of the decompression. 
When the pressure is relieved, susceptible individuals may breathe with difficulty, 
be cyanosed, and bleed from the nose, ears, eyes, and other mucous membranes. There 
may be pain in the joints, muscles, and abdomen. There may be paralyses, especially 
of the lower extremities. The bodies of the victims are often contorted from the 
muscular contraction, hence the common name of the condition, " the bends." All of 
these symptoms may be promptly relieved by recompression. On the other hand, 
susceptible persons may succumb within a few hours to the disorder.1 
The lesions in fatal cases are quite variable. During compression the blood ab- 
sorbs an abnormal quantity of the gases from the air. In decompression these escape, 
i For acute effects of caisson disease see Erdman, Am. Jour. Med. Sc., 1913, cxlv, 520. CONDITIONS OF DISEASE 
13 
and to this "frothing" of the blood in too rapid decompression the symptoms and 
lesions of caisson disease are, in part at least, due. On external inspection no lesion 
may be evident; or there may be marked cyanosis of the face and mucous membranes 
of the mouth, nose, etc. Crepitation of the skin may be elicited on light pressure, 
even though the skin be not obviously puffed up. The internal lesions are also vari- 
able. Of these, general venous congestion and frothy blood in the veins and capillaries 
are the most constant and characteristic. The gas in the vessels may be best seen in 
the pia mater cerebralis (Fig. 1) and in the omentum. Petechial haemorrhages may 
be found in the brain and cord. Also the gas sometimes accumulates in small blebs in 
the nerve tissue. 
In cases which recover from the primary- effects of the pressure there may be 
secondary degenerations in the nervous system, paralysis, emaciation, trophic ulcers, 
etc. 
Internal Conditions of Disease. 
In distinction to those external agencies which lead to disease, there 
are many conditions of the body itself which are incompatible with the 
maintenance of health. Thus, there are general conditions, due to dis- 
turbances of metabolism, such as diabetes and gout, which we shall con- 
sider separately later, in which abnormal amounts of sugar and uric acid 
are present, leading to many local and general disturbances. 
But by far the more common internal conditions associated with dis- 
ease are the structural and functional alterations of the various organs of 
the body, which may lead directly or indirectly to the most complex 
departures from the normal. Some of these will be considered more in 
detail in later sections of this book. We may note here, however, as 
examples, a few of these complex relationships between local lesions 
and the general welfare of the organism. 
Lesions of the heart valves lead to disturbances of the circulation of 
the blood in various parts of the body, so that, as we shall see later, 
both functional and structural changes harmful to the individual may 
occur in important viscera, for example, in the lungs, the kidney, liver, 
blood-vessels, etc., and secondarily in the walls of the heart itself. 
In the gastro-intestinal canal defective innervation, or trauma, or 
tumors, or constrictions may lead to the accumulation of ingested material, 
to innutrition, to intoxication through decomposition of the albuminous 
or other ingredients of the retained material. 
So in the liver, an insufficient production of bile or an occlusion of 
the gall-ducts may lead to digestive disturbances, to a deposition of 
bile pigment in various parts of the body-icterus; to the accumulation 
of bile in the blood-cholsemia. On the other hand, an overproduction 
of bile may take place in the destruction of abnormal quantities of red 
blood cells, leading to icterus. Furthermore, through disturbances in 
the glycogenic function of the liver, sugar may accumulate in the blood. 
These examples of the bearing of functional disturbances and struc- 
tural lesions of individual organs upon each other, and upon the welfare 
of the body as a whole, must suffice, since the scope of this book does 
not permit us to enter upon this wide field of pathological physiology, 
for the adequate consideration of which we must refer to systematic 
treatises on the practice of medicine. 14 
CONDITIONS OF DISEASE 
Race.-Examples of racial disposition to disease are not uncommon. 
Thus African negroes are less susceptible than are the whites to malaria. 
On the other hand, in this country the negro is especially vulnerable 
to tuberculosis. 
Age is an important factor in the liability to disease, though the 
reason for this is in very few instances at all clear. In childhood, for 
example, diseases of the digestive system are readily induced by un- 
suitable food. In advanced life, the vascular system is a vulnerable 
part of the body. This apparent predisposition of age may, however, 
be referred to the wearing out of the vascular mechanism. 
Sex appears to be a definite factor in disease disposition, for such 
maladies as diabetes, gout, general paralysis, tabes, etc., are more 
common in males than in females. But here, as in the age factor, many 
obvious external conditions, such as occupation, food, excesses in food 
and drink, syphilis, etc., may be invoked as elements of determining 
importance but not inherent in the condition of sex. The conditions 
incident to child-bearing, however, favor the occurrence of many more 
or less serious abnormalities of structure and function peculiar to the 
female. 
Heredity.-The relations of heredity to disease are extremely com- 
plex and subtle, and our knowledge of the subject is still too meagre to 
permit of a profitable exposition within the limits which this book im- 
poses. In certain infectious diseases, syphilis for example, the in- 
fective agent may be transmitted from the parents to the offspring. 
This, however, is not the conveyance of physiological or structural 
peculiarities, but only of an external disease excitant. 
For the sake of clearness of thought and correctness of observation it 
is well for the student and physician to remember that those features and 
capacities of the organism which are inherited, are those and those alone 
derived from the maternal and paternal germ plasm, or through the reac- 
tion of these upon each other. The many and varied external influences 
brought to bear upon the foetus during intrauterine life, may induce 
marked departures from the normal, but these abnormalities are not in a 
proper sense inherited. They are more correctly designated congenital.1 
Susceptibility to disease may be inherited, to tuberculosis, for 
example, though we are unable to define clearly either structural or 
functional traits to which this vulnerability may be attributed. 
There are numerous examples of hereditary anomalies or dispositions 
to disease. We cannot consider them here in detail, but we may men- 
tion as examples, haemophilia, color-blindness, myopia, neuroses of vari- 
ous types, polyuria, obesity, gout, and diabetes.2 
1 Many interesting examples of heredity in man have been collected by Bateson, Mendel's Principles 
of Heredity, 3d edition, Cambridge, 1913, and by Davenport, Heredity in Relation to Eugenics, New 
York, 1911. See also Adami, Inheritance and Disease, in Osler's Modern Medicine, i, 1907. Castle, 
Heredity, New York, 1913; and Morgan, Heredity and Sex, New York, 1913. 
2 For fuller exposition of the subjects considered in this chapter consult Adami, "Principles of 
Pathology," vol. i. 1908. Thoma, "Text-book of Pathology," English Trans., 1896. Chantemesse and 
Podwyssotsky, "Les Processus Generaux," 1901. Roger, "Introduction to the Study of Medicine," 
Eng. Trans., 1901. Aschoff, Pathologische Anatomie, 3d edition, Jena, 1913. CHAPTER II. 
CHANGES IN THE CIRCULATION OF THE BLOOD. 
General Conditions. 
The circulation of the blood in the body is maintained by a very 
efficient and delicate mechanism capable of prompt and effective ad- 
justment to changes in the local and general conditions under which 
the body is placed. 
The factors especially concerned in the maintenance of the normal 
circulation and in its adaptability to new and unfavorable conditions 
are the contractile heart with its valves, the elastic arteries, the innerva- 
tion of the heart and vessels, gravitation, and the various phases of 
pressure and suction upon the veins from external sources, direct mus- 
cular action, respiratory movements, etc., which promote the passage of 
the blood upon its rounds. Finally, the character of the blood itself may 
have an important bearing upon the efficiency of the circulatory mechan- 
ism. Alterations in any of these factors may involve disturbances of 
the circulation. 
We may glance briefly at some of these factors in the circulation, and 
first at the heart itself. The energy sustaining the circulation is primarily 
derived from the contractile heart, so that the condition of its muscle 
and innervation are of the first significance. Should the heart muscle 
be enfeebled, through lack of proper nutriment or innervation or by 
degeneration of the muscle for example, the circulation suffers in manner 
and degree, depending upon the part of the heart involved. Thus if 
the muscle of the right ventricle is enfeebled, blood is not properly 
drawn into the ventricle and is not sent with sufficient force into the 
lungs. The venous system then becomes overfilled with blood. If the 
muscle of the left ventricle be enfeebled, too little blood is sent into the 
arterial system and the pulmonary vessels are not properly emptied. 
Changes in the valvular openings of the heart or in the valves them- 
selves lead to disturbances of the circulation. Thus if the openings are 
narrowed, too little blood passes them; or if the valves fail to close 
properly, some of the blood flows backward through them. In this 
way both the pulmonary and the systemic veins become overfilled. 
The circulation may also suffer through alterations in the walls of 
the blood-vessels. The elasticity and contractility of the arterial walls 
are important factors in the maintenance of a normal circulation, since 
they sustain and reinforce the heart pressure in the blood and convert 
the pulsating movement imparted by that organ into a continuous, 
uniform flow through the capillaries and veins. If the arterial walls 
become stiffened and less elastic, or if their lumen becomes narrowed, 
15 16 
CHANGES IN THE CIRCULATION OF THE BLOOD 
more work is thrown upon the heart muscle. Thus the peripheral cir- 
culation is impaired unless, in a manner which we shall presently con- 
sider, the power of the heart muscle is increased by hypertrophy. Ob- 
struction of the veins may induce similar disturbances in the heart and an 
impaired local or general circulation. 
The circulation of the blood being controlled by the nervous system 
through the distribution of nerves to both the heart and the vessels, 
alterations in the central nervous system affecting the vagus or the 
sympatheticus, or severe traumatic injuries to the body involving re- 
flex disturbances, may induce serious local or general interference with 
the circulation of the blood. 
The respiratory movements of expiration and inspiration favor the 
circulation of the blood, so that interference with these may be of con- 
siderable importance. Thus pleuritic effusions, severe spasms of cough- 
ing, etc., may induce changes in the pulmonary circulation and the 
right heart as well as in the systemic circulation. 
The movements of the muscles of the trunk and extremities acting 
together with the valves of the veins contribute to the forces carrying 
the blood forward in circulation. Severe spasm of the muscle, as in 
epilepsy, tetanus, strychnine poisoning, etc., may induce stagnation of 
the blood in the veins of the trunk and the viscera so that it does not 
return properly to the heart. 
These are some of the more important of the changes which the 
general circulation suffers in conditions which interfere with the cir- 
culatory mechanism. 
The means by which the heart and the blood-vessels adapt themselves 
to various disturbing conditions through compensatory alterations will be 
considered in the chapters in "Special Pathology" dealing with these 
organs. 
We shall now consider in more detail the ocal effects of a disturbed 
circulation. 
Hyperaemia and Anaemia. 
Within physiological limits the amount of blood in a part may vary 
considerably under vasomotor control according to the functional necessi- 
ties of the part or vascular territory. Under a great variety of abnormal 
conditions the blood content suffers changes so excessive and so lasting as 
to be pathological. It is the latter alone which we are to consider here. 
A part of the body may contain an excess of blood, a condition called 
hypercemia (congestion). This is distinguished from plethora, which signi- 
fies a general excess of blood in the body. On the other hand, there may 
be too little blood in a part of the body, a condition which is called 
ancemia. 
HYPERAEMIA. 
Hyperaemia may occur either through increased arterial supply, 
active hypercemia (acute congestion), or through some hinderance to the 
venous outflow of the part, passive hypercemia (venous congestion). CHANGES IN THE CIRCULATION OF THE BLOOD 
17 
Active Hyperaemia.-This may occur through dilatation of the 
arteries by the action of various physical and chemical agents directly 
upon their muscular coats, or through the vasomotor nerves, or from 
the reduction of pressure upon the vessels from without. 
Thus, injuries or stimulation of the vasomotor nerves, heat, the 
sudden evacuation of large exudates, trauma, and the action on the 
vessels of a great variety of chemical irritants may lead to a dilatation 
Fig. 2.-Hyperemia of the Blood-vessels near a Bronchus. 
In chronic bronchitis. 
of the vessels, and, as friction is diminished with the dilatation of the 
lumen, to a more rapid flow of the blood. 
Under these conditions the affected region becomes redder, warmer, 
and may be more or less swollen, and under certain conditions the 
arterial characters of the blood and pulsation of the vessels may be 
extended into the venous trunks. 
Passive Hyperaemia (venous congestion).-In passive hypersemia 
due to obstruction to the outflow of blood from a part, there is an over- 
filling of the veins and capillaries (Fig. 2). The hinderance to the 18 
CHANGES IN THE CIRCULATION OF THE BLOOD 
outflow of blood may be due to compression of the vessels from without, 
as from tumor, aneurism, ligature, displacement, or from new interstitial 
tissues in various organs. It is frequently the result of thrombosis. 
One of the most fruitful determining causes of passive hyperaemia is 
the lesions of the heart which interfere with the regular entrance and 
exit of the blood from that organ. Thus, in incompetence or stenosis 
of the mitral valve the pulmonary vessels become congested; the right 
ventricle does not properly empty itself. So the systemic veins in vary- 
ing degrees suffer engorgement, and the viscera become involved in the 
secondary alterations due to chronic hyperaemia. 
The effect of venous obstruction varies greatly, depending upon its 
degree, the rapidity of its occurrence, and upon the structure and 
functional importance of the part involved. If, as in most instances 
is the case, venous anastomoses exist between the partially or wholly 
Fig. 3.-Diagram Illustrating the Establishment of Collateral Circulation in Obstruc- 
tion of a Vein-After Ribbert. 
The veins a and & at A are connected by a slender trunk, c. If a in B is occluded, as by a throm- 
bus, the blood cannot all pass out of the territory drained by a, so that the vessels here are dilated- 
congestion. If, however, the small anastomosing trunk widens as at C, the congestion is relieved_by 
the conveyance away of the blood through the vein b. 
occluded and other vessels, these may enlarge, and with the establish- 
ment of this collateral circulation a more or less complete adaptation 
to the changed conditions is secured (see Fig. 3). The collateral veins 
and even capillaries in the involved region widen and their walls thicken; 
and thus while for a time hyperaemia of varying intensity may exist, this 
gradually resolves. 
The possibilities of adaptation to venous obstruction are sometimes 
very great even when large trunks are concerned. Thus, a ligature of 
the femoral vein or a blocking of the inferior or superior vena cava may 
be compensated by the establishment of abundant collateral channels. 
On the other hand, after the blocking of the renal or splenic or of a main 
trunk of the portal vein, the circulation is re-established with difficulty. 
If a collateral circulation be not at once and readily established, 
and often even if this be the case, local venous obstruction leads to 
certain well-defined changes in the hyperaemic region. If the obstruction 
be partial, the flow of blood is slower than normal; the vessels are dilated; 
more or less fluid may transude into the surrounding tissues; and dia- 
pedesis (see page 86) of the red blood cells may occur. On the other 
hand, if the obstruction be complete in a large venous trunk, the capil- 
laries and veins in the involved region dilate; the axial stream of ery- CHANGES IN THE CIRCULATION OF THE BLOOD 
19 
throcytes in the veins disappears; the entire lumen is crowded with 
them; the blood pressure rises; the current wavers, slows, and stops. 
Then the red cells become packed into a homogeneous mass in the dilated 
vessel-this is stasis. Diapedesis and transudation now occur in the 
capillaries and veins of the involved region. Finally, if the circulation 
be not re-established, haemorrhagic infarction (see page 29) or death 
of the tissue-necrosis-may follow. 
If the venous obstruction be removed, as may be done in the tongue 
or mesentery of the experimental frog (see page 111), one may observe 
under the microscope the disappearance of the stasis and the re-establish- 
ment of the circulation. The homogeneous blood mass resolves itself 
into its component corpuscles; the blood moves at first fitfully and 
irregularly, then the current is established; the distention diminishes, 
and, after a longer or shorter time, the part, if the lesion has not been 
too extreme, assumes its normal appearance. 
In passive hyperaemia the tissue involved is more or less dark red in 
color-cyanotic-owing to the accumulation in the vessels of unaerated 
blood; the temperature may be lowered when the area concerned is 
extensive; it may also be swollen in part from the distention of the 
vessels, in part from the extravasation of fluid; finally, there may be 
pulsation and increased pressure in the veins. 
If the hypersemic condition be long continued-chronic congestion- 
the walls of the involved vessels may become thickened; there may be 
interstitial fibrous hyperplasia in the affected region; or there may be 
varying degrees of cell degeneration or of atrophy. Thus function may 
be interfered with or suspended. 
In many instances of diminished heart power or when for any reason 
the blood circulates with difficulty under favorable conditions, the effect 
of gravity may manifest itself in dependent portions of the body or of 
the organs, so that these become hyperaemic. This condition is called 
hypostatic congestion. The most marked example of this condition is in 
the lungs of debilitated persons, the dependent portions of which fre- 
quently become engorged with blood. This is often associated with 
oedema, atelectasis, and more or less cellular exudate in the air spaces. 
ANTE MIA. 
The word anaemia is used not only to denote the lack of blood in a 
part, but also to indicate a reduction or alteration in various constituents 
of the blood itself, a condition familiarly called "poverty" of the blood. 
General anaemia due to impoverishment of the blood will be considered 
in the chapter on the Special Pathology of the Blood and the Blood- 
forming Organs. We are here concerned only with local anaemia- 
ischaemia. 
Local anaemia may be due to the cutting off of the blood supply by 
the occlusion of the arteries in thrombosis and embolism; by ligatures; 
by the narrowing of the lumen through pathological processes in the 
wall of the vessel; by tumors, exudates, etc.; by contraction of the 20 
CHANGES IN THE CIRCULATION OF THE BLOOD 
vessels from nerve lesions as in Raynaud's disease; by the action upon the 
vessel of physical agents-cold-or by chemical substances or drugs 
which induce marked constriction-suprarenal extract and ergot. Fur- 
thermore, mechanical pressure upon the vessel from without or compres- 
sion of an entire organ or part may induce various grades of anaemia. 
The affected part or organ in anaemia becomes paler than normal, 
often with a yellowish tinge; the temperature is lowered; and the vol- 
ume may be diminished; finally, if the absence of blood persist, the 
function and nutrition of the involved part suffer, and atrophy, fatty 
degeneration and death of tissue may occur. 
If, however, the anaemia be only partial or if it be of short duration, 
in some organs the nutrition may not suffer in marked degree; in others, 
however, the brain, for example, extreme damage may follow even a 
temporary anaemia. 
The degree, duration, and results of local anaemia are largely dependent 
upon the cause of the shutting off of the blood supply, and the possi- 
bility of its restoration directly or through the establishment of a collao- 
eral circulation. Thus, for example, anaemia from compression at 
from an arterial ligature may at once resolve if the determining cause be 
removed. But even though an artery remain blocked, circulation may 
be in a measure restored by the dilatation of anastomosing capillaries or 
by the backflow of venous blood into the region deprived of its vascular 
pressure from the closed arteries. While a certain amount of fresh 
blood may reach the affected region in these ways, it is only when anas- 
tomoses exist between the branches of the closed and neighboring arterial 
trunks that a fairly complete collateral circulation can be established. 
For a further consideration of this subject see Embolism, p. 28. 
Haemorrhage and Transudation. 
HAEMORRHAGE. 
Haemorrhage is an escape of blood from the heart or vessels. It 
may occur from a rupture of the walls of the vessels, and is then called 
haemorrhage by rhexis. The rupture may be occasioned by injury,by 
lesion of the walls of the vessels which renders them too weak to resist 
the blood pressure from within, or it may occur from the blood pressure 
in the thin and incompletely developed walls of new-formed vessels as in 
granulation tissue, tumors, etc. The arrest of haemorrhage may take 
place through the contraction of the wall of the vessel or by the forma- 
tion of a clot. 
Under other conditions, without recognizable changes in the vessels, 
all the elements of the blood may become extravasated by passing, with- 
out rupture, through their walls, This is called haemorrhage by diape- 
desis. Such haemorrhages are usually small, but may be very extensive. 
They occur in the smaller veins and capillaries, the cells and fluids of the 
blood passing out through the cement substance between the endothelial CHANGES IN THE CIRCULATION OF THE BLOOD 
21 
cells. Although no marked morphological changes have as yet been 
detected which explain this extravasation, it is probable that some 
change in the nutrition of the walls does occur which renders them more 
permeable. Hsemorrhage by cliapedesis is apt to occur as a result of 
venous congestion, or when the flow of blood in the smaller vessels has 
been suspended for some time; or it may result from the action of some 
poison, or from an injury not leading to rupture; or it may occur in incom- 
pletely developed blood-vessels, in tumors and other new-formed tissues. 
In the extravasation of blood by cliapedesis the white blood cells may 
pass through the walls of the vessels, partly at least in virtue of their 
amoeboid movements; the red cells, on the other hand, having no power 
of spontaneous movement, are, according to Arnold, carried passively 
through the walls by minute currents of fluid which, under the changed 
condition, stream in increased force and volume through the endothelial 
cement substance into the tissue spaces outside. 
The altered condition of the blood-vessels leading to haemorrhage may 
be local or general, and in the latter case it may either be congenital, as 
in some cases of the haemorrhagic diathesis, or it may be the result of 
a general disease, such as scurvy, purpura, etc. The presence of bacteria 
in the vessels, or of bacterial or other poisons in the blood, as in malig- 
nant endocarditis and in haemophilia neonatorum, may induce changes in 
the walls of the vessels, leading to extravasation. 
Forms of Haemorrhage.-Very small haemorrhages are called petechice, 
larger, diffuse accumulations of blood in the interstices of the tissues 
are commonly called ecchymoses or suggillations. A complete infiltra- 
tion of a circumscribed portion of tissue with blood is called a hcemor- 
rhagic infarction. A collection of blood in a tumor-like mass is called a 
haematoma. Special names are given to haemorrhage in different parts of 
the body; thus, bleeding in the lungs is called haemoptysis; vomiting 
blood from the stomach, haematemesis; nosebleed, epistaxis; hemorrhage 
from the uterus, metrorrhagia; certain forms of brain haemorrhage, 
apoplexy. In the so-called hcematuria the blood may be derived from 
either the kidney or the bladder. Sometimes the elements of the tissue 
into which the blood escapes are simply crowded apart; sometimes, as 
in the brain, they are broken down. 
The extravasated blood in the tissues usually soon coagulates, al- 
though exceptionally it remains fluid for a long time. A certain num- 
ber of the white blood cells may wander into adjacent lymph-vessels, or 
they may remain entangled with the red cells in the meshes of the fibrin. 
The fluid is usually soon absorbed; the fibrin and a portion of the white 
blood cells disintegrate and are absorbed (see page 59). The red blood 
cells soon give up their hsemoglobin, which decomposes and may be 
carried away or be deposited either in cells or in the intercellular sub- 
stance at or near the seat of the hsemorrhage, either in the form of yellow 
or brown granules or as crystals of hsematoidin (see page 53). Some- 
times all trace of extravasations of blood in the tissues disappears, but 
frequently their seat is indicated for a long time by a greater or less 
amount of pigment or by new-formed connective tissue. Occasionally 22 
CHANGES IN THE CIRCULATION OF THE BLOOD 
the blood mass, in a more or less degenerated condition, becomes en- 
capsulated by connective tissue, forming a cyst. 
The action of phagocytes (see page 98) in the disposal of dead ma- 
terial is here, as it is under a great variety of conditions, an impor- 
tant factor in the restoration of the body, after lesion, to its normal 
conditions. 
Haemorrhages in the New-born. 
Haemorrhages, sometimes extensive, in various parts of the body- 
gastro-intestinal canal, mouth, nose, navel, or the viscera-are not infre- 
quent in the first few days of life. Aside from the occasional discovery 
of ulcers in the gastro-intestinal walls, the reason for these haemorrhages 
is not evident at autopsy.1 This condition has been called morbus macu- 
losus neonatorum. Haemorrhages from the skin, mucous membranes, 
or navel may take place in the syphilitic new-born. Haemoglobinuria 
may occur in epidemic form in young children. 
Haemophilia {Hcemorrhagic Diathesis'). 
This abnormal condition consists in a liability to persistent haemor- 
rhage on the slightest provocation, and is dependent upon some consti- 
tutional peculiarity which is unknown to us. It is usually hereditary. 
An uncommon thinness of the intima of the arteries has been noticed in 
some cases of ''bleeders," and other changes have been described; but 
there are no constant lesions associated with the haemorrhages, as yet 
discovered, which would satisfactorily account for their occurrence. 
The haemorrhages may be traumatic in origin, or they may occur spon- 
taneously from the mucous membranes. 
TRANSUDATION. 
Transudation is the passage, through the walls of the blood-vessels 
into the interstitial spaces outside, of fluid from the blood, with little or 
no admixture of its cellular elements. This occurs constantly, to a cer- 
tain extent, under normal conditions, and forms the commencement of 
the lymph circulation. But when the amount of fluid passing through 
the walls of the blood-vessels is increased, or its outflow into the larger 
lymph trunks is hindered so that it accumulates in undue quantity in 
the interstices and lymph channels of the tissues, the condition is 
pathological.2 
An accumulation of transudated fluid in the interstices of the tissues 
is called oedema; in the serous cavities, dropsy. Extensive cedematous 
infiltration of the subcutaneous tissue is called anasarca. If the trans- 
udate accumulates in the pleural cavity the condition is called hydro- 
thorax; in the pericardium, hydropericardium; in the ventricles of the 
brain, hydrocephalus. In similar fashion various other names are in 
1 For a study of haemorrhagic diseases of the new-born, with bibl., see Graham, Join-. Exper. Med., 
1912, xv, 307. 
2 For a study of oedema see Meltzer, Harrington Lectures, Univ, of Buffalo, 1904; American Medicine, 
July 2, 1904; also Pearce, Arch. Int. Med. iii, 422, 1909. CHANGES IN THE CIRCULATION OF THE BLOOD 
23 
common use for the accumulation of transudates in the body cavities; 
as hydroperitoneum (ascites), hydrarthrosis, hydrocele, etc. 
Its occurrence may depend upon some hinderance to the venous circu- 
lation or increase of capillary pressure, especially when associated with 
alterations in the walls of the blood-vessels, or upon changes in osmotic 
pressure induced by a reduction in the nutrient efficiency of the blood, 
by injuries, or in other ways which may affect the processes of filtration 
and osmosis, by which chiefly, it is believed, the normal transudation of 
fluids occurs. There is, furthermore, strong and increasing evidence that 
the endothelial cells of the capillaries possess active secretory or other 
functional capacities which should be taken account of in the attempt to 
comprehend transudation as well as many other pathological phenomena 
and lesions. A simple interference with the outflow of lymph does not 
usually alone suffice to induce transudation, although it may favor its 
occurrence. (Edema may depend upon little understood abnormalities 
of the nervous system, as in the so-called neuropathic oedemas. 
The transuded fluid, called transudate, is usually transparent and 
colorless or yellowish; it contains the same salts as the blood plasma, 
but less albumin. It may contain fat, mucin, urea, biliary acids, color- 
ing-matter of the bile; fibrinogen is usually present in variable quantity, 
and, rarely, fibrin. It may contain endothelial cells from the lymph 
spaces, and a variable number of red and white blood cells. The amount 
of fluid which may accumulate in the tissue varies greatly, depending 
upon whether they are loose or dense in texture. The fibres and cells of 
loose tissues may be crowded widely apart; the cells are apt to be more 
granular than normal, they may contain droplets of fluid or they may be 
atrophied. Transudates occurring in inflammation usually contain a con- 
siderable number of white blood cells and more or less fibrin, and differ 
in this from the non-inflammatory transudations; but in some cases there 
is no sharp distinction between them. The inflammatory transudates 
are often called exudations or exudates. 
Resorption and Absorption. 
Under many conditions, both normal and abnormal, fluids and solid 
particles are taken into the recesses of the tissues from without, or are 
gathered from one place in the tissues to be carried in the blood or 
lymph currents or by cells to other parts or to places of excretion. Thus 
from the intestinal contents both liquid substances and small solid 
particles, such as fat droplets, bacteria, etc., may be taken into the body 
fluids. In exudative inflammations, such as pleurisy or pneumonia, 
large quantities of fibrin, red and white blood cells, and fluids may 
accumulate in the cavities, to be presently removed. So also dead 
tissue, blood clots, etc., and foreign bodies may be removed through 
various processes of resorption. 
The absorption of fluid substances or the resorption of those which 
are rendered soluble takes place through the lymph channels, as we 
have seen, whence they may be eliminated through the excretory organs. 24 
CHANGES IN THE CIRCULATION OF THE BLOOD 
Solid material, such as fibrin, dead cells, etc., may be removed either 
through the action of fluids which render them soluble, lytic fluids 
(see p. 106), or they may be removed through the intervention of living 
cells, phagocytes (see p. 98). These processes will be considered in 
detail in a later section of this book. 
Thrombosis and Embolism. 
Thrombosis is the coagulation of the blood or the agglomeration or 
agglutination of the formed elements of the blood into a more or less 
coherent mass during life. The coagulum or mass is called a thrombus 
(Fig. 4). 
Thrombi may be composed of fibrin and of red and white blood cells 
intermingled in about the same proportion as in an ordinary extravascular 
blood clot (Fig. 5). These are called red 
thrombi and usually occur from some sudden 
stoppage of the circulation. Other thrombi, 
usually such as form while the blood is in 
motion, may consist almost entirely of white 
blood cells with a little fibrin, or of these in- 
termingled with blood platelets; or they may 
consist almost entirely of blood platelets; all 
of these forms are called white thrombi. Red 
thrombi, when decolorized by changes in the 
blood pigment, may somewhat resemble 
genuine white thrombi. Mixed thrombi arc 
usually lamellated (Fig. 6) and contain vary- 
ing proportions of fibrin, red and white blood 
cells, and platelets. The fibrin fibrils in 
thrombi, as elsewhere, often coalesce, forming 
hyaline masses. A similar change may take 
place in the blood platelets. Thrombi may 
consist almost wholly of red blood cells. 
Causes of Thrombosis.-Thrombi may 
occui' as the result of an injury to the wall of 
a vessel, or may follow its compression or 
dilatation; they may result from some altera- 
tion of the wall of the vessel by disease, or by 
the retardation of the circulation. So long 
as the endothelial lining of the vessels is 
intact, simple retardation of the circulation 
does not usually alone suffice to induce coagu- 
lation; but changes in the endothelium in a 
great variety of conditions, such as inflammation, degeneration, atheroma, 
calcification, and the presence of bacteria or their toxins, tumors, and 
foreign bodies, favor its occurrence, especially when associated with 
changes in the circulation or in the character and contents of the blood. 
THROMBOSIS. 
Fig. 4.-Occluding Thrombus 
of the Iliac. 
The vessel is laid open, showing 
the lamellated clot. CHANGES IN THE CIRCULATION OF THE BLOOD 
25 
Thrombi may develop from an embolus. Thrombosis is a not infrequent 
complication of the infectious diseases as well as of the cachetic conditions 
associated with various acute and chronic general diseases. 
One may conveniently class the various determining causes of 
thrombosis into: 1, those associated with a slowing of the blood current; 
2, those relating to changes in the walls of the blood channels; and 3, those 
involving such alterations in the blood itself as favor coagulation. These 
factors are frequently associated.1 
1. Disturbances of the circulation 
favoring thrombosis are frequently de- 
pendent upon enfeebled heart action, and 
thrombi may then form in the auricles 
behind the valves or among the trabeculae 
of the heart (Fig. 296), behind the valves 
of the veins, in the veins of the lower ex- 
tremities, in the great venous sinuses of 
the brain, or wherever by reason of ab- 
normal conditions the regular flow of the 
blood is interfered with-as in aneurisms, 
varices, etc. Such thrombi are sometimes 
called stagnation thrombi. When forming 
under marked asthenic conditions they 
are called marantic thrombi. In this class 
belong thrombi induced by pressure or 
ligature of the vessels. 
2. Thrombi associated with alterations in the walls of the blood- 
vessels may follow mechanical injuries to the vessels and may be con- 
servative in the control of haemorrhage. The action of various forms of 
pathogenic bacteria within or in the vicinity of blood-vessels inducing 
lesions of the walls is a fruitful determining factor in thrombosis. This 
is common in acute endocarditis, in septicaemia, in various forms of phle- 
bitis, and in tuberculosis. In chronic lesions of the walls of the heart 
and blood-vessels, associated with degeneration and necrosis (atheroma, 
calcification, etc), thrombi may form. The growth of tumors into the 
blood channels affords favorable conditions for the development of 
thrombi. 
3. The alterations of the blood itself favoring thrombosis are obscure. 
Such are the impoverishment of the blood in anaemia, the presence of 
bacterial toxins or of the bacteria themselves in various infectious 
diseases. Many of the so-called marantic thrombi are probably due to 
the presence of bacteria or of their toxins in the blood or in the walls 
of the vessels. Some cases of " white swelling" following parturition are 
probably of this nature. 
Among the less frequent alterations of the blood favoring thrombosis 
may be mentioned the presence of haemolytic substances, as in the 
Fig. 5.-Portion of Red Thrombus 
This shows red blood cells, fibrin, and 
a few leucocytes. 
1 For a study of the conditions relating to the occurrence of thrombosis, such as changes in the 
coagulability of the blood, power of agglutination, local and general condition of the blood flow, and 
endothelial damage, see Aschoff, Cartwright Lecture, Arch. Int. Med., 1913, xii, 503. 26 
CHANGES IN THE CIRCULATION OF THE BLOOD 
transfusion of alien blood and the artificial introduction of certain 
animal and vegetable extracts. 
Forms of Thrombi.-Various forms of thrombi, aside from those 
already described, have received special names. Thus thrombi are 
called primary or propagated, depending upon whether they are con- 
fined to the original site of formation or extend for some distance from 
the point of origin. Sometimes such extension is marked by variations 
in the color, density, and structure of the extending thrombus. A 
secondary thrombus is one formed upon an embolus or a pre-existent 
Fig. 6.-Lamellated Thrombus. 
This is an occluding thrombus. At the right and also above are masses of red blood cells, while the 
remainder is largely fibrin in layers, indicating successive deposits. 
thrombus. A thrombus may be obstructing or parietal; solid or canal- 
ized; simple or infective; it may be arterial or venous-all names whose 
significance is obvious. 
Agglutinative Thrombi.1-The recent studies on agglutination and 
haemolysis (see p. 171) have led to the belief that certain thrombi occur- 
ring in infectious diseases, as well as under other conditions, may arise 
from the development of agglutinative substances in the blood. Under 
the action of these substances the red blood cells may, without the 
formation of fibrin, clump together, leading to thrombosis. Such 
thrombi are called agglutinative thrombi. They have been observed 
repeatedly in typhoid fever and other infections. In such masses of 
agglutinated red blood cells the individual corpuscles may not be seen, 
1 Consult Flexner, "On Thrombi Composed of Agglutinated Red Blood Corpuscles," Journal 
of Medical Research, vol. viii., p. 316; also, Pearce, ibid., vol. xii., p. 329; also, Pearce and Winne, 
Am. Jour. Med Sciences, vol. cxxviii. p. 669, 1904, bibl. CHANGES IN THE CIRCULATION OF THE BLOOD 
27 
the whole presenting a hyaline mass. Thus may be formed a variety of 
the so-called hyaline thrombi. Welch1 has suggested the probability 
that under similar conditions leucocytes also may form agglutinative 
thrombi. 
Hyaline Thrombi.-Under a variety of conditions, but especially in 
local and general infections and in intoxications, there is present in the 
capillaries and in the small arteries and veins a homogeneous, translu- 
cent, nearly colorless material, partially or wholly blocking the vessels. 
This hyaline material, whose origin is still in doubt, has in some in- 
stances a staining reaction similar to fibrin. In other cases hyaline 
thrombi are probably special forms of agglutinative thrombi (see above). 
Alterations in Thrombi.-After a certain amount of shrinkage by 
which the fluids are squeezed out and the thrombus becomes denser 
and drier, the changes which occur in it may be either in the direction 
of degeneration and absorption or of organization. The leucocytes, the 
fibrin, and the blood plates may degenerate, forming a granular material 
which may become infiltrated with salts of lime, forming the so-called 
phleboliths, or vein stones. In other cases the thrombi may soften and 
disintegrate. This softening may be simple and the result of fatty or 
other form of tissue degeneration, resulting in a white or reddish or 
brown grumous mass, which may resemble, but is not, pus. Or, in many 
instances, softening probably occurs through the autolytic processes 
(see p. 106), initiated and sustained largely by leucocytes. On the 
other hand, softening of the thrombus may be associated with bacteria 
or other infectious material with general suppuration. In this "puru- 
lent" or "septic" softening of the thrombus the risk is great of a dis- 
tribution of the infectious material through the circulation. Finally, 
the thrombus may be replaced by a new formation of vascular con- 
nective tissue, itself disappearing by autolysis or phagocytosis as the 
new tissue is formed. This is called "organization of the thrombus," 
but in reality the new connective tissue is produced, not from the cells 
of the thrombus itself, but from the cells of the walls of the affected 
trunk, from whose vessels the new blood-vessels of the thrombus also 
arise (compare page 75). In this way the vessel may be completely 
and permanently occluded, or, more rarely, one or several channels may 
be established through the new connective-tissue mass (Fig. 7). 
Effects of Thrombosis.-The consequences of thrombosis vary 
greatly, depending upon the seat, size, and nature of the thrombus. 
They are of two classes: 1, those depending upon the direct disturbance 
of circulation from the occlusion of the lumen of the vessel; and, 2, 
those determined by the detachment of the thrombus or the separation of 
a part of it, and the distribution of these through the circulatory channels 
to various parts of the body. 
1. The occlusion of either arteries or veins may be compensated by 
the establishment of collateral circulation. The partial or total occlu- 
sion of an artery by a thrombus may lead to local anaemia, degenera- 
tion, necrosis, or infarction (see page 29). The obstruction of a vein 
1 Welch, Huxley Lecture, Medical News, October 18th, 1902, p. 731. 28 
CHANGES IN THE CIRCULATION OF THE BLOOD 
may lead to venous congestion and oedema, and to various alterations 
already considered under the heading of Hyperaemia. 
For a further consideration of thrombosis of the heart and separate 
vessels see sections dealing with these organs in Special Pathology. 
2. Whole thrombi or portions of these may be detached and carried 
forward by the blood current, or, as the result of softening and disinte- 
Fig. 7.-Organized Thrombus. 
This shows the vascular connective tissue which has replaced the clot, with five new channels through 
which the circulation is re-established. 
gration, detritus, bacteria, etc., may be set free by unusual move- 
ment, by pressure, or without obvious special force. 
The performances and effects of such detached portions of thrombi 
will be considered in the next section, under embolism.1 
Thrombosis of Lymph-vessels. 
Thrombosis of the lymph-vessels is of occasional occurrence. The 
thrombus consists of fibrin and leucocytes. It may present forms and 
induce changes in the lymph channels analogous with the forms and 
effects of thrombi in the blood-vessels. 
EMBOLISM. 
Embolism is the obstruction of a blood-vessel by the arrest in its 
lumen of some material carried along in the circulating blood. The 
mass causing the stoppage is called an embolus (Fig. 8). This may 
be composed of a great variety of substances. The most common emboli 
are detached portions of thrombi, especially from the heart valves, and 
1 For a thorough and admirable consideration of the subject of thrombosis and embolism, with 
bibliography, consult Welch, Allbutt's ''System of Medicine," vol. vi., pp. 155 et seq. CHANGES IN THE CIRCULATION OF THE BLOOD 
29 
these may have all the variety of structure which thrombi present. 
Masses of bacteria or other animal or vegetable parasites, fragments of the 
heart valves and of tumors, droplets of fat from the medulla of fractured 
bones (Fig. 9), parenchyma cells,1 masses of pigment, bubbles of air, etc., 
may form emboli. Embolism is, in a majority of cases, confined to the 
arteries and to the branches of the portal vein. Emboli after lodgment 
sometimes give rise to thrombosis, which may be very extensive. 
Effects of Embolism - Infarction.- The 
changes which follow the more or less sudden 
and complete cutting off of the arterial blood 
from a part of the body by the lodgment of an 
embolus are so variable, depending upon the 
part of the body affected, the character of its 
vascular arrangement, and the possibilities of 
a collateral blood supply, that a concise com- 
prehensive description is difficult. 
When the arterial blood current is cut off 
from the affected area, this does not at once 
become bloodless, because its vessels still con- 
tain the residual blood and a certain amount 
may enter at least the periphery through ad- 
jacent capillaries and small veins. Then if the 
involved region be not too large and the 
plugged vessels have sufficient anastomoses, 
the establishment of a collateral circulation 
may after a time be effected. On the other 
hand, if the plugged artery does not possess 
anastomosing trunks or is inadequately sup- 
plied with these-that is, belongs to those 
vessels wrhich are called terminal arteries-end 
arteries-the effects are more marked and last- 
ing. There is stasis in the vessels; diapedesis of the red blood cells 
may occur; and while a small amount of blood may enter the periphery 
of the involved region through the capillaries and veins so that the 
vessels here may be markedly congested, the tissues are not sufficiently 
nourished and they suffer varying degrees of degeneration; they may die 
and the whole central region become necrotic. This gradually developing 
process is called infarction, and the portion of involved tissue is called 
an infarct (Fig. 10). The area of infarction corresponding to the region 
supplied by the occluded vessel is usually more or less wedge-shaped. 
Infarcts in which the vessels are distended with blood, with interstitial 
haemorrhage by diapedesis and more or less necrosis of the involved area, 
are called hcemorrhagic infarcts (Fig. 11). 
Fig. 8.-An Embolus Lodged 
at the Point of Division of 
an Artery. 
This is a portion of clot which 
has been detached from a point 
above and swept along the blood 
current. It has increased in 
length by coagulation at its free 
extremities. 
1 The presence of liver-cell emboli in the lung capillaries and in the heart clots after traumatic 
rupture of the liver, and in infectious diseases involving local necroses of the liver, has been described 
by various observers. Emboli believed to be composed largely of placental cells or of cells from the 
bone marrow are also described under various conditions. The facts relating to this subject of paren- 
chyma-cell emboli and its alleged significance may be found summarized by Lubarsch, Fortschritte der 
Medizin, Bd. xi., pp. 805 and 845, 1893; and by Aschoff, Virchow's Archiv, Bd. cxxxiv., p. 11, 1893. 
Consult also Warthin, The Medical News, September 15th, 1900, bibl. 30 
CHANGES IN THE CIRCULATION OF THE BLOOD 
After a time the infarct becomes decolorized by diffusion of the dis- 
solved haemoglobin, inflammatory changes occur in its periphery, the 
blood cells and involved tissues may undergo degeneration and be 
absorbed,1 and finally the seat of the 
infarction may be indicated only by a 
mass of cicatricial tissue, which fre- 
quently contains more or less pigment. 
In another class of cases, instead of 
an excessive distention of the vessels and 
an extravasation of blood in the affected 
region the tissue is simply deprived of 
nourishment and undergoes necrosis. 
The affected area then sooner or later 
becomes lighter in color from the diffu- 
sion of the haemoglobin, and it is then 
called an anaemic or white infarct (Fig. 12). 
Inflammatory changes may occur in its periphery and a new connective- 
tissue capsule form around it, and the dead mass may thus persist for 
some time, or be gradually absorbed and replaced by cicatricial tissue. 
In certain instances it is believed that infarcts may be anaemic from the 
beginning and not, as is apparently usually the case, 
as the result of changes in infarcts which are at first of 
the haemorrhagic type. 
The scope of this book does not permit us to con- 
sider the somewhat complicated and often obscure rea- 
sons why in one case there is haemorrhagic, in another 
white, infarction, as a result of embolus. 
If the embolic material consists of or contains infec- 
tive substances, such as some forms of bacteria, in ad- 
dition to the mechanical effects of simple emboli, we 
may have gangrene, suppuration, formation of abscesses, 
etc., as the result of the local action of the infectious 
material, even though this may be present in very small 
amount. 
The Location of Infarcts.-The organs in which em- 
bolic infarctions most frequently occur are the spleen, 
kidney, brain, lungs; less frequently the heart, retina, 
liver, and small intestines. 
Haemorrhagic infarction is not liable to occur in the 
liver from emboli in the branches of the portal vein, on 
account of the blood supply which may come to the 
affected region through the branches of the hepatic 
artery. On the other hand, embolic abscesses from infectious emboli are 
of not infrequent occurrence here. 
The lung is supplied with blood through the pulmonary and the 
bronchial arteries; and the capillary network of the pulmonary tissue 
Fig. 9.-Fat Emboli in the Blood- 
vessels OF THE LUNG. 
This followed bone fracture. 
Fig. 10.-Infarcts 
of the Spleen. 
1 For a study of the autolytic processes in the absorption of infarcts see Wells, Jour. Med. Res., 
vol. xv., p. 149, 1906. CHANGES IN THE CIRCULATION OF THE BLOOD 
31 
is so abundant that emboli in the pulmonary artery, although this is a 
terminal artery, do not readily lead to infarction in an otherwise healthy 
lung. When, however, the pulmonary circulation is disturbed, as in 
certain forms of heart disease, haemorrhagic infarction may follow em- 
bolism of the pulmonary artery. 
The arteries of the kidney and spleen are typical terminal arteries, 
and infarcts of these organs readily follow embolism. In the kidney 
the infarcts are most commonly anaemic; in the spleen both haemor- 
rhagic and anaemic infarcts are formed. Infarction in the heart may 
follow embolism, but is more commonly the result of thrombosis of 
branches of the coronary artery. Embolism of the cerebral arteries is 
Fig. 11.-Diagram Illustrating the Formation of a Haemorrhagic Infarct. 
The artery, A, plugged by an embolus, E, is a terminal artery, but it has abundant capillary 
anastomoses, so that the territory deprived of blood is not sufficiently nourished and its tissues die; 
but from the abundant capillary anastomoses from the artery B, and from the vein C, a certain amount 
of blood enters the infarct area, which thus becomes haemorrhagic. 
seldom followed by extensive local collateral hyperaemia and haemor- 
rhage, but is more apt to lead to cerebral softening. Haemorrhagic 
infarctions may occur exceptionally in regions not furnished with 
terminal arteries, as in the small intestines. Infarction does not follow 
embolism of single arterial trunks of the arms and legs because of the 
ready establishment of a collateral circulation. 
The Sources of Emboli.-It should be remembered that as a rule 
emboli derived from a vein, and then most commonly detached from a 
venous thrombus, pass to the right side of the heart and are thence 
driven into the pulmonary artery, where, unless most minute, they are 
retained, since they cannot pass the pulmonary capillaries. Emboli 
in the left heart, the aorta, and the arterial system are derived from the 
pulmonary vein, the left heart, the aorta or its branches (Fig. 13). 32 
CHANGES IN THE CIRCULATION OF THE BLOOD 
Paradoxical Embolism.-While as a rule emboli follow the direction 
of the blood current, one does sometimes find in the arterial system 
emboli of considerable size without being able to locate their source in the 
pulmonary vein, the left heart, or the aorta or its larger branches. 
Futhermore, under these circumstances one may discover an obvious 
source in the systemic veins. Since such emboli cannot pass the pulmon- 
ary capillaries they must have passed from the venous to the arterial 
system through an open foramen ovale into the left auricle, thence to be 
driven into the arteries (Fig. 13). This is called paradoxical embolism. 
It is of infrequent occurrence.1 
The artery A is a terminal artery with a few capillary anastomoses with the neighboring artery B, 
so that when the embolus, E, cuts off the blood from the territory supplied by it, the involved region 
becomes anaemic save in the peripheral zone of congestion. This is an anaemic infarct. 
Fig. 12.-Diagram Illustrating the Formation of an Anemic Infarct. 
Retrograde Embolism.-Sometimes an embolus moves in a direction 
opposite to that of the blood current, so that one may find in a small 
vein an embolus obviously derived from a larger vein or from the right 
heart. It has been assumed in explanation of this occurrence that 
under certain conditions in which the venous blood empties itself into 
the right heart with difficulty, as in the case of tricuspid incompetence, 
there might be an actual reversal of the venous current on which an 
embolus could be conveyed. It does not, however, appear that such a 
reflux of the venous blood is possible. Ribbert urges the view that 
while a complete reversal of the current is improbable in a congested 
vein, a pulsation wave may form with each heart-beat which could 
gradually force the embolus toward the periphery along the vessel 
1 For details of unusual forms of embolism consult bibliography in Ziegler's "General Pathology,' 
Warthin's translation of 10th Ed., 1903. CHANGES IN THE CIRCULATION OF THE BLOOD 
33 
wall. This retrograde transportation of an embolus is of rare occurrence 
in the large veins, especially in the inferior vena cava. 
The retrograde transportation of particles of tumor may give rise to 
very puzzling phases of metastasis. 
Fig. 13.-Schematic Illustration of Embolism-after Ribbert. 
The right lung, RL, and the left lung, LL, are connected with the heart through the pulmonary 
artery, PA, PA. The liver, L, and the right and left kidneys, RK, LK, are seen below with the aorta 
A and the vena cava, VC. The right ventricle, RV, and the left ventricle, LV, the right auricle, RA 
and the left auricle, LA, are exposed. From the thrombus T, a small portion, E, is detached and 
carried upward in the venous current through the vena cava to the heart. It turns into the pulmonary 
artery where it may lodge in the larger trunks in the lungs. Owing to its size it cannot pass the capi- 
lary system of the lungs, and hence cannot enter the general circulation. If, however, as is not infre- 
quently the case, an open foramen ovale exists, such an embolus could pass through the septum into 
the left heart, whence it could be sent through the aorta to the viscera, as is shown by the outlined 
embolus. A thrombus in the left heart, say on the mitral valve at M, if detached as is shown in the 
globular mass following the dotted line, may be sent into the aorta and thence into any of the small 
arterial trunks. In the diagram the embolus is lodged in the left kidney. 34 
CHANGES IN THE CIRCULATION OF THE BLOOD 
Fat Embolism.-After fracture of the long bones, fat from the 
marrow may find its way through opened veins into the right heart and 
into the pulmonary capillaries (Fig. 9). It may be found also in the 
capillaries of the kidneys. Fat embolism of the pulmonary capillaries 
may be fatal, but in most cases does not appear to be of great signifi- 
cance. Fat embolism of the lungs is recorded following extensive 
fatty degeneration of the liver in phosphorus poisoning.1 
Emboli of Tumor Cells.-Clusters of tumor cells of considerable 
size may enter the vessels through erosion of their walls and may be 
transported in the blood current as emboli (Fig. 248, p. 401). They may 
lodge in the trunks of large vessels, portal vein, pulmonary artery, etc., 
and in addition to the usual effects of embolism they may grow, forming 
metastatic tumors. 
Air Embolism.-It rarely happens in surgical operations that a large 
quantity of air enters an opened vein and is aspirated to the right side 
of the heart. This may prove fatal. Air bubbles may be found mingled 
with the blood in the right heart, in the large veins leading to the heart, 
and in the pulmonary capillaries. It was formerly believed that this 
was of not infrequent occurrence, and the presence of even small numbers 
of air bubbles in the blood was regarded as of extreme significance. 
The presence of air in the vessels is common in caisson disease (see p. 11). 
In certain cases gas bubbles in the blood are due to infection with a gas- 
forming bacterium, the Bacillus aerogenes capsulatus (see p. 289). 
Experimental Study of Disturbances of the Circulation. 
One may observe many of the local disturbances of the circulation on the mesen- 
tery of the curarized2 frog. A loop of the intestine is drawn out through a lateral 
abdominal incision and laid over the glass window of a Thoma frog-plate (see Fig. 72). 
The part should be kept moist or irrigated with one-half-per-cent, salt solution, 
Under these conditions one may study various phases of hyperaemia and stasis, 
haemorrhage by diapedesis and by slight injuries to the vessels, haemorrhage by rhexis 
and the formation of local thrombi by which it is controlled. By pressure on the 
vessels various disturbances of the circulation, thrombi, etc., can be secured.3 
By drawing forward the tongue of the curarized frog, fastening it in extension on 
the Thoma frog-plate designed for this purpose (Fig. 72), and ligating one of the large 
lateral veins, one can induce interesting phases of passive hyperaemia and transudation. 
Embolism may be studied by the injection into the arteries of small particles- 
tobacco seed in the dog, begonia seed in the rabbit, or poppy seed-suspended in 
salt solution. These may be injected forcibly upward through the crural artery into 
the aorta. Embolism of the abdominal viscera, kidney, spleen, etc., with infarction 
may be thus induced. 
1For a study of fat embolism see Connell, Jour. Am. Med. Assn., vol. xliv., p. 612, 1905; for a 
study of fat emboli of the brain, see Naville and Fromberg, Arch, de Med. exper., 1913, xxv, 405. 
2 The commercial curare is so variable in strength that it is best to make an aqueous solution of 
about 1:1,000 strength and test the effect, using just enough to secure immobility, and no more, since 
serious circulatory disturbances and death of the animal are readily induced with too liberal dosage. 
The solution-at first a few drops-is put beneath the skin in the dorsal lymph sac. It is well to give 
a preliminary dose a few hours before the use of the animal, bringing him partially under the influence 
of the drug, and to complete the effect just before the experiment. Under these conditions the second 
dose may be very small and thus untoward effects upon the circulation may be avoided. 
3 See for a further description of the method of studying the circulation in the living frog, p. 111. CHAPTER III. 
REGRESSIVE TISSUE CHANGES. 
General Considerations. 
There are three phases of activity in the transformations of energy 
which are characteristic of living cells. These are nutrition, reproduc- 
tion, and functional activity. But while these manifestations of energy 
are more or less distinct as properties of living matter, they are closely 
interdependent. It is the suitable balance of these activities fixed by 
prolonged environment which determines what we call health. When 
this balance is disturbed beyond the limits of physiological variation, the 
alterations which result may be manifest, either in the diminution or de- 
struction of tissue or in its increase or new formation. In other words, 
the cells of the body, when placed under conditions which seriously 
interfere with the orderly transformations of energy, may undergo 
alterations from the normal which are regressive on the one hand, or 
progressive on the other. 
We shall in this chapter consider the regressive processes and their 
effects; in the next those which are progressive. 
It is well to remember that the regressive as well as progressive 
changes in the body are not limited to pathological conditions, but form 
a part of the normal processes through which growth is secured and 
function maintained.1 
The maintenance of the normal life and structure of the cell is closely 
dependent upon the conditions under which it is placed. If there is 
lack of sufficient or proper nutriment; if the waste products are not 
properly eliminated; if deleterious chemical substances either coming 
from without or formed by defective metabolism-poisons, toxins, etc. 
-are present; or if harmful physical agencies such as heat, cold, pressure, 
etc., are active; or, finally, if the innervation be defective, both the 
function and the structure of the cell may suffer. 
The functional changes of cells placed under unfavorable conditions 
are very variable and often very subtle owing to their complex and often 
little understood nature, and may be difficult of detection. These 
functional changes may or may not be associated with structural altera- 
tions which are obvious on microscopical observation. Cells may become 
larger than normal through increased functional activity, hypertrophy; 
they may become smaller, atrophy, under a variety of conditions pres- 
ently to be considered. Cells may swell through imbibition of fluid; they 
may be altered in shape from pressure. Finally, they may suffer various 
1 For a resume of the relationship between normal and pathological regressive processes see 
Minot, Middleton Goldsmith Lecture on "The Embryological Basis of Pathology," Science, March 
29th., 1901. 
35 36 
REGRESSIVE TISSUE CHANGES 
changes in internal structure. Various products of their metabolism 
or of degeneration of their cytoplasm may accumulate within them, or 
substances may enter from without-degeneration and infiltration. 
These and other changes due to an unfavorable environment may 
be recovered from if not too extensive. But, on the other hand, if the 
damage be excessive the cell may die and suffer disintegration and 
absorption. This death of the cell, with subsequent physical and 
chemical changes, is called necrosis. 
It frequently happens, however, that the vitality of the cell is not 
at once extinguished, but that the processes of life and necrosis go on 
for a time together, ending in either its recovery or its death. This 
condition is called necrobiosis. 
Not all the cells of the body are equally sensitive to a deleterious 
environment. It is those which are more highly differentiated for the 
performance of special functions, or those which are more frequently 
exposed to harmful influences, which most often suffer. 
Atrophy. 
Atrophy is a diminution in the size of the body, of organs, or of tissue 
elements. It occurs as a physiological process in man as well as in cer- 
tain of the lower animals. Thus in man the thymus and the umbilical 
vessels undergo atrophy at an early period; while in old age, atrophy of 
the sexual organs and of the tissues in general is the usual mark of senil- 
Fig. 14.-Atrophy of Muscle. 
This is atrophy from disuse of the striated muscle. Owing to the muscle pigment which has collected 
in the atrophied fibres this is called "pigment atrophy." 
ity.1 On the other hand, as a pathological process, atrophy may occur 
in connection with disturbances of innervation or nutrition; from disuse 
or from pressure; or from the presence of poisons. Although it is con- 
venient to name these as phases of atrophy, they are not fundamentally 
distinct. In simple atrophy, under whatever conditions it may occur, the 
tissue elements become smaller without marked alterations in structure, 
1 For a study of the changes in the body in development and senility see the monograph of Muhl- 
mann, Wiesbaden, 1900, bibl. REGRESSIVE TISSUE CHANGES 
37 
and may finally disappear altogether. In the majority of cases, how- 
ever, atrophy of cells or other tissue elements is not simple, but is asso- 
ciated with, and often determined by, various phases of degeneration- 
degenerative atrophy. The cytoplasm of atrophic cells is often more 
transparent than normal and may contain an undue proportion of 
pigment. 
An organ which is the seat of even extensive atrophy of some of its 
Fig. 15.-Atrophy and Distortion of the Liver from Tight Lacing-Female. 
The border of the organ is elongated and fibrous; the gall bladder is long and distorted. 
cells is not necessarily diminished in size, but may even be much larger 
than normal. This is the case, for example, in amyloid degenerations of 
the liver. Sometimes the atrophy of parenchyma cells is accompanied 
by a new formation of connective tissue so extensive as to maintain, 
for a time at least, the size of the organ. 
Atrophy may be general or local and it has various phases which we 
shall briefly consider. 38 
REGRESSIVE TISSUE CHANGES 
General Atrophy from Malnutrition affecting the body at large may 
occur as the result of deficient nutriment as in starvation, or a failure to 
assimilate food, and in various acute and chronic diseases. Under these 
conditions fatty and other forms of cell degeneration occur, with loss of 
the general adipose and reduction in size of muscle and other body cells. 
Senile Atrophy.-As the energies of life decline with the advance of 
years, the tissue and organs may undergo gradual and progressive atro- 
phy, but in varying degrees. The muscle cells of the heart are more 
slender, and brown pigment may accumulate within them-brown 
atrophy. The parenchyma cells of the liver, kidney, and generative 
Pressure atrophy from amyloid degeneration of the blood-vessels. 
Fig. 16.-Atrophy of Liver Cells. 
glands and the ganglion cells become smaller and may be more or less 
pigmented. Similarly the bones suffer atrophic changes, becoming 
more brittle, and the skin becomes wrinkled and dry. Senile atrophy 
may be associated with significant sclerotic changes in the blood-vessels 
and with atrophy of the lymph-nodes, spleen, and marrow. 
Atrophy from Suspension of Functional Activity-Atrophy from 
Disuse.-This is well exemplified in disused muscles or bones, as in vari- 
ous forms of paralysis. Voluntary muscles under these circumstances 
become more slender, lose their transverse striations, and become 
fibrillar. Brown pigment derived from the disappearing muscle sub- 
stance may gather in masses in the remaining fibres, and the nuclei of 
the sarcolemma may be increased in number (Fig. 14). The fibres may 
finally disappear and may be replaced by fat or fibrillar connective 
tissue. 
Pressure Atrophy.-This is seen under the ordinary conditions of 
modern life as the result of ill-adapted articles of dress, such as corsets, 
which frequently induce very marked atrophy with distortion of the 
liver (Fig. 15). But within the body itself pressure from a more vigor- 
ously growing tissue may induce atrophy of an adjacent part. Thus, REGRESSIVE TISSUE CHANGES 
39 
tumors, cysts, accumulations of fluids in various cavities, aneurisms, 
degeneration of blood-vessels (Fig. 16), etc., may lead to local atrophy. 
Neurotic Atrophy.-While it is difficult to dissociate the direct tro- 
phic influence of the nerves upon tissues from the accompanying loss of 
function and interference with vascular supply, there appear to be 
cases of atrophy from neurotrophic influences. Atrophy of one side of 
the face in lesions of the trigeminus and in certain cerebral lesions, 
wasting of the associated muscles in destruction of the anterior cornua 
of the spinal cord, are examples. 
Degeneration. 
ALBUMINOUS DEGENERATION (Cloudy Swelling, Parenchymatous 
Degeneration, Acute Degeneration, Granular Degeneration). 
Under a variety of conditions in which there is a disturbance of cell 
metabolism, but especially often in infectious diseases and in intoxica- 
tions when poisonous substances come in contact with the tissues, the 
cells of the body show an accumulation in the cytoplasm of albuminous 
granules, of various sizes and forms. While bacterial toxins are common 
excitants of this change, other vegetable toxins, such as abrin and ricin, 
or mineral poisons, corrosive sublimate, may induce it. This is a type of 
Fig. 17.-Albuminous Degenebation-Kidney. 
The lesion is moderate in degree and is most marked in the largest tubule above. 
cell degeneration which is so often associated with infectious diseases 
and certain phases of inflammation that it is sometimes regarded as a 
part of the inflammatory process. The cells in this condition are 
usually swollen and are more opaque than normal, the nucleus being 
usually somewhat concealed in the granules when these are numerous 
(Fig. 17). The albuminous granules in the cells are soluble in dilute 
acetic acid, but not in ether, being thus distinguished from fat. 40 
REGRESSIVE TISSUE CHANGES 
While all the cells of the body are subject to this phase of proto- 
plasmic degeneration, it is most pronounced and frequent in the paren- 
chyma cells of the liver and kidney, in muscle, in epithelial cells of the 
mucous membranes. These are, it will be seen, cells which have a large 
amount of cytoplasm and in which metabolism is active and the exi- 
gencies of nutrition are imperative. The alterations in the ganglion 
cells of the central nervous system in infectious diseases and in various 
forms of intoxication are somewhat different from those occurring in 
other parenchyma cells and will be described in the section devoted to 
the Brain and Spinal Cord. 
Cells in a condition of albuminous degeneration may return to their 
normal state, they may become fatty, or they may die, become necrotic, 
and disintegrate. 
The liver, kidney, muscle, mucous membranes, etc., when in this con- 
dition, are often swollen and in gross appearance more opaque and gray 
than when normal. 
The exact chemical nature of this degenerative process is obscure 
and will doubtless remain so until we know much more than we now 
do of cell structure and cell metabolism.1 
Technique.-The microscopical study of this lesion is best made in fresh frozen 
sections of the tissue, by the rapid formalin method, page 1028; or in fresh tissue teased 
in one-half-per-cent, salt solution. 
FATTY DEGENERATION AND FATTY INFILTRATION. 
General Considerations. 
It should be remembered that besides the occurrence of fat cells in 
fat tissue and in the interstitial tissue of various organs, the accumulation 
of fat in certain epithelial cells is physiological, as in the functional 
processes of the mammary and sebaceous glands. In the involution 
of the uteYus-also a physiological process-extensive fatty metamor- 
phosis of cell protoplasm occurs. 
It is customary and convenient, in considering the abnormal accu- 
mulation of fat in the tissues, to assume that in one set of cases-fatty 
degeneration-the fat is formed by ajetrograde metamorphosis or degen- 
eration of the proteid elements of protoplasm, a process by which the 
integrity and capacity of the cell are compromised, while in the other- 
fatty infiltration-it may be due to a simple accumulation in the cell of 
fat formed eleswhere-a condition of less significance. 
The validity of this assumption has of late been called in question. 
It involves in large measure the solution of the physiological problem 
whether normally the fat in the body is formed from proteids or from 
carbohydrates. Concerning this, many experiments and much argument 
have been made;2 but it appears not yet to be solved. The traditional 
1 For a study of albuminous degeneration see Albrecht, Verh. Deutsch. Path. Ges., Bd. vi., p. 63, 
1903. 
2 For a critical summary of this question see Taylor, American Journal of the Medical Sciences, 
vol. cxvii., p. 569, 1899. For a study of the role of soluble soaps in formation of fat in cells see Klotz, 
Jour. Exp. Med., vol. vii., p. 670. See also ref. to Albrecht, foot-note above. For a study of myelo- 
genous substances in cells see Albrecht, Verh. Deutsch. Path. Ges., Bd. vi., p. 95, 1903. REGRESSIVE TISSUE CHANGES 
41 
distinction between fatty degeneration and fatty infiltration will there- 
fore be made here, with such modifications and reserve as are fitting in 
view of our lack of knowledge. 
There is apparently a certain amount of fat or closely related sub- 
stances in the cytoplasm of many cells not demonstrable morphologically. 
Similarly there is fat in the blood which may be conveyed to cells. 
Under normal conditions these forms of fat enter into the metabolism of 
the cells and are used up. 
We might perhaps wisely adopt the conception of Ribbert that fatty 
degeneration is a condition in which the involved cells are so damaged 
through various harmful agencies that the fat which they may normally 
contain, but which is invisible in their cytoplasm, or fat taken into the 
cell from without, or fat formed in the cell metabolism, is not properly 
metamorphosed-burned-but accumulates in droplets in the cell 
body. 
Fatty Degeneration. 
In fatty degeneration there is an accumulation of larger and smaller 
droplets of fat in the cell, sometimes so slight as to be scarcely visible, 
sometimes so great as largely to replace the protoplasm, crow'ding the 
nucleus to one side. These strongly refractile fat droplets are not 
changed by dilute acetic acid. They are soluble in ether, and when fresh 
Fig. 18.-Fatty Degeneration-Kidney. 
The fat droplets are stained black by osmic acid. 
are stained black by osmic acid (Fig. 18) or red (Fig. 19) by Sudan III 
or Scharlach R (see technique below). Not infrequently, feathery clus- 
ters of delicate fat crystals are present in the cells. Cells in exces- 
sive fatty degeneration may disintegrate, forming an oily detritus in 
which, especially when much moisture is present, cholesterin crystals 
may form by decomposition of the fat. 
To the naked eye, organs in a condition of marked fatty degeneration 
are usually larger and softer than normal, have a grayish-yellow color or 42 
REGRESSIVE TISSUE CHANGES 
are mottled with yellowish streaks or patches, and the normal markings 
of cut surfaces are more or less obscured. 
Fatty degeneration may be associated with or may follow albuminous 
degeneration and may occur under similar general conditions, as in 
infections, poisoning, etc. It is often associated with the processes of 
necrosis and disintegration in dead cells and dead tissue. It may be 
due to local or general disturbances of nutrition, from a great variety of 
causes-disturbances which either directly affect the life processes of 
Fig. 19.--Fatty Degeneration of Epithelium in the Kidney. 
The fat droplets are stained with Scharlach R. 
the cells themselves or which produce alterations in their nutritive sup- 
ply. In addition to its local occurrence, as a result of local disturbances 
of circulation in the vicinity of inflammations or in tumors, etc., it is 
apt to occur in the liver, heart muscle, and kidney in chronic exhausting 
diseases and in conditions and diseases to which profound anaemia is in- 
cident, in senility, or as the result of the action of certain poisons, such as 
phosphorus and arsenic. 
The function of the cell in fatty degeneration may be greatly impaired, 
as in fatty degeneration of the heart muscle. On the other hand, in the 
liver and kidney, the function of the organ may not apparently suffer even 
with marked degrees of the lesion. The cell may recover if the lesion 
be not too profound. REGRESSIVE TISSUE CHANGES 
43 
Fatty Infiltration. 
This is of common occurrence under normal as well as pathological 
conditions. The fat is believed to originate outside of the cells, accumu- 
lating in them, and inducing a passive atrophy of the cytoplasm. Cells 
in a condition of abnormal fatty infiltration are scarcely to be distin- 
guished morphologically from those involved in fatty degeneration. 
The presence in the cells of large or small droplets of fat, without marks 
of degeneration in the remaining protoplasm, has been regarded as 
distinctive of infiltration. 
In some phases of fatty infiltration, as in the heart (Fig. 20) or the 
pancreas for example, the fat accumulates in the cells of the interstitial 
Fig. 20.-Fatty Infiltration of the Heart. 
The fat cells have accumulated between the muscle cells of the heart, and not within them as 
in fatty degeneration. 
connective tissue in a manner identical with that in which the normal 
panniculus adiposus is formed. The heart muscles or the gland cells are, 
under such conditions, affected secondarily through pressure atrophy 
from the accumulated fat. It should be remembered that fatty infiltra- 
tion and fatty degeneration may occur simultaneously. When fat pro- 
duction or fat storage is largely in excess of fat consumption from either 
local or general causes, the condition is called lipomatosis or liposis.1 
Lipoid Degeneration. In the cortex of the adrenal and in the lutein 
cells of the ovary double refractive granules occur normally. Similar 
1 For a study of lipomatosis with bibl., see Lyon, Arch, of Int. Med., 1910, vi, 10. 44 
REGRESSIVE TISSUE CHANGES 
granules are found in atheroscderotic areas in the vessels, in some of the 
nephritides, in the walls of old abscesses, and in the gall-bladder with 
biliary stasis, also in the so-called adrenal tumors of the kidney, in adeno- 
mata of the adrenal, and in xantho- 
mata of the skin. These granules 
are composed of a combination of 
cholesterin and fatty acid in the 
form of an ester (Fig. 20a).1 
Technique.-Frozen sections should 
be made of fresh tissues, which may then 
be examined in 0.85-per-cent. salt solu- 
tion with crossed Nicols for double re- 
fracting fat; or frozen sections of fresh 
tissue or that hardened in formalin can 
be stained for twenty minutes in a satu- 
rated solution of Sudan III or Scharlach 
R in equal parts of acetone and seventy- 
per-cent. alcohol, washed in seventy- 
per-cent. alcohol, transferred to water, 
and mounted in glycerin or glycerin jelly. 
A saturated aqueous solution of Nile blue sulphate (Griibler) will also stain fat satis- 
factorily. With this stain the neutral fat is red, the nuclei blue, and the fatty acids 
dark blue. The granules which stain a purplish color are lipoids. It is an advantage, 
according to Schmorl, to wash the sections in one-per-cent, acetic acid, and then in 
water, and embed in glycerin or glycerin jelly.2 
Fig. 20a.-Lipoid Globules in Juice Expressed 
from Suprarenal. 
Viewed under crossed Nicols 
GLYCOGEN INFILTRATION. 
Glycogen appears under abnormal conditions in the cells as hyaline, 
mostly globular masses of varying size (Fig. 21). It is soluble in water, 
is stained brownish-red by iodine, 
and does not, like amyloid, as- 
sume a greenish color by further 
addition of sulphuric acid. In 
diabetes it may occur in large 
quantities in the liver cells and 
in the epithelial cells of the 
uriniferous tubules, especially in 
those of Henle's loop, and in 
leucocytes. It may be found in 
fresh pus cells, in the cells of various forms of tumors, and in leucocytes 
in the blood in leukaemia, in chronic diseases of the gastrointestinal tract 
in children, and in various acute and chronic diseases. 
Technique.-If the tissue to be examined for glycogen be fresh, the iodine should 
be used in solution in glycerin (equal parts of Lugol's solution and glycerin), in order 
Fig. 21.-Glycogen Infiltration of 
Epithelial Cells. 
The droplets of glycogen are stained with iodine. 
1 Closely related to these esters, but differing from them by a lack of double refraction, are the so- 
called myelin bodies which appear in tissues undergoing autolysis or decay. They stain with neutral 
red. For a detailed study of certain of these lipoids see Bang, Chemie u. Biochem. der Lipoide. Berg- 
mann, 1911; Kawamura, Cholesterinesterverfettung. 1911. 
2 For method of staining fat-acid crystals see Mallory and Wright's "Path. Technique," 5th edition, 
1913, p. 386. For details of staining fat and lipoid substances see Schmorl, Pathologischen Unter- 
chungsmethoden, 7th edition, 1914, p. 159. REGRESSIVE TISSUE CHANGES 
45 
to avoid its solution. If specimens are to be hardened, this should be done in absolute 
alcohol to avoid the solution of the glycogen. Sections may be stained with picro-acid 
fuchsin (Van Gieson's stain) or with a dilute solution of iodine in alcohol (tincture 
iodine 1 part, absolute alcohol 4 parts), cleared up and studied in oil of origanum. 
SEROUS INFILTRATION OF CELLS (Hydropic Degeneration, Vacuolization). 
Under many pathological conditions, cells, especially those of mucous 
membranes, glands, muscles, tumors, etc., contain one or more larger or 
smaller droplets of clear fluid (Fig. 22). The cell may thus be distended. 
These droplets are usually extra-nuclear and may crowd the nucleus to 
one side of the cell. The nature and source of this accumulated fluid are 
not definitely known. Its transparent appearance in the granular pro- 
toplasm has given rise to the term " vacuole." It may be associated 
with general tissue oedema, with inflammatory and degenerative proc- 
esses, etc. 
Mucous and Colloid Degeneration. 
There is a group of closely related translucent glyco-proteid substan- 
ces which it was formerly thought practicable to distinguish by simple 
chemical tests especially relating to solubility. Among these are the so- 
called mucins and colloid. The simplicity of the earlier distinction has, 
Fig. 22.-Serous Infiltration 
of Epithelial Cells. 
Fig. 23.-Mucous Degeneration of Epithe- 
lial Cells. 
From a cyst-adenoma of the ovary. 
however, not been justified by more modern research, so that the separa- 
tion of mucoid and colloid degeneration along the old lines does not 
express very definite chemical knowledge. It will, however, be con- 
venient, while awaiting light from the chemist, to maintain the old 
distinctions between mucous and colloid degeneration, unstable as are 
the foundations on which they rest. 
Mucous degeneration may occur in cells or in intercellular substance. 
When occurring in cells it consists, under pathological as under normal 
conditions, of the transformation of the protoplasm into a translucent, 
ropy, semi-fluid material, occupying more space than the unaltered pro- 
toplasm and hence causing a swelling of the cells (Fig. 23). The dis- 
tention of cylindrical epithelium by the accumulation of mucin-containing 
MUCOUS DEGENERATION. 46 
REGRESSIVE TISSUE CHANGES 
substances in the outer portion of the cell, with the crowding of the nu- 
cleus and the remnant of the cytoplasm toward the base, often gives the 
cells the shape of a goblet or beaker (Fig. 24). Hence the name "beaker 
cells," often applied to them. This appearance is especially well marked 
when the mucinogenous contents of the cell have been discharged from 
the free end. 
Mucins may collect in small transparent droplets within cells or may 
in the formation of mucous in the epithelium of the small intestine. The mucus is stained with thionin. 
Fig. 24.-" Beaker Cells." 
so distend them as to form a globular body with a scarcely visible rem- 
nant of nucleus or cytoplasm. The cells may be totally destroyed by 
the accumulation of the mucinous material within them. This new- 
formed material contains mucin in solution, which is precipitated by 
acetic acid and by alcohol. It swells up in water and is readily stained 
Fig. 25.-Mucous Degeneration of Fibrous Tissue of Mamma. 
by thionin. It occurs under a variety of conditions, sometimes as an 
abnormal increase of a normal function of cells, as in many catarrhs, 
sometimes as an entirely abnormal transformation. 
In certain cases, as in many tumors, in cartilage, bone, and other 
tissues, the intercellular substance may undergo conversion into mucin- REGRESSIVE TISSUE CHANGES 
47 
containing material, losing almost entirely its original structure (Fig. 
25). The cells in such cases may be affected only secondarily by the 
pressure which the new-formed material exerts upon them. 
Technique.-Tissues should be hardened in Orth's fluid or formalin followed by 
alcohol; the sections are stained with picro-acid fuchsin or with haematoxylin, which 
colors the mucin-containing portions. 
COLLOID DEGENERATION. 
This is very closely allied, both in chemical and morphological char- 
acters, to mucous degeneration, and in many cases there is no definite 
microscopic distinction between them. But colloid material, which is 
normally present in the thyroid, is firmer and more consistent than 
mucinous, does not yield a precipitate on addition of acetic acid or 
alcohol, and its formation is usually confined to cells; not involving- 
intercellular substance, except by an atrophy which its accumulation 
sometimes induces. The cells may contain larger and smaller droplets 
of colloid material, or the latter may nearly or entirely replace the proto- 
plasm and accumulate to such an extent as to cause rupture and destruc- 
tion of the cell. In this way, and by the atrophy of intercellular sub- 
stance which its accumulation causes, cysts may be formed containing 
colloid material and cell detritus. Colloid material accumulates fre- 
quently in the thyroid gland. A material resembling, if not identical 
with, colloid is occasionally seten in the form of homogeneous globules 
in the tubules of kidneys which are the seat of other lesions, in the 
hypophysis, and in various tumors. 
Technique.-Tissues should be hardened in formalin or Orth's fluid, and stained 
with picro-acid fuchsin. 
Hyaline Substances. 
Under a variety of conditions there are deposited in the tissues homo- 
geneous proteid substances whose origin and nature are still obscure. 
Sometimes they are very abundant and seriously interfere with the 
function of the organs in which they occur. But frequently they are 
present in small amount and, with or without association with other 
processes, seem to be of slight importance. While some of these are 
characteristic in appearance and in the conditions under which they 
occur, and give definite gross and micro-chemical reactions, others seem 
at present to have no definite reactions and appearances, except the 
homogeneous character which they all share. 
One of these substances, amyloid, can be definitely differentiated by 
its appearance, color reactions, and the conditions under which it occurs. 
Another, hyaline substance, while less individualized than amyloid, is 
conveniently considered for the present as a definite material. The 
remainder of the homogeneous substances cannot be classified now and 
are probably of diverse origin and composition. 48 
REGRESSIVE TISSUE CHANGES 
HYALINE DEGENERATION. 
This is the transformation of tissues into a transparent, glassy sub- 
stance, much resembling amyloid in its morphological characters (Fig. 
26); but which does not give the micro-chemical reactions of amyloid, 
and appears under different conditions. 
Hyaline substance is resistant to the action of acids, and stains 
readily with acid fuchsin and eosin. It occurs especially in the walls of 
the smaller blood-vessels in various parts of the body, in voluntary 
muscle fibres, and sometimes involves interstitial tissue. It occurs in 
the thyroid, the brain, the reticular tissue of lymph-nodes, and in the 
Fig. 26.-Hyaline Degeneration in the Walls 
of Small Blood-vessels. 
Fig. 27.-Hyaline Degeneration of 
Muscle Cells. 
From a sarcoma. 
Infection of pregnant uterus. 
ovaries; in the membrana propria of the tubules of the kidney and in 
Bowman's capsule; in the walls of aneurisms, in the lesions of diphtheria, 
tuberculosis, and syphilis; in the hyaloid membrane and vessels of the 
eye, and elsewhere. It occurs in the unstriated muscle fibres in infection 
of the uterus during pregnancy (Fig. 27). It is believed that fibrin, 
blood plates, and leucocytes may undergo hyaline degeneration, and in 
the form of so-called hyaline thrombi this substance may block the 
capillaries in many infectious diseases-typhoid fever, pneumonia, 
diphtheria, pyaemia, etc.-and under other conditions (see p. 27). 
Hyaline substance is not uncommon in coarse trabeculae or in masses 
as an apparent modification of fibrin in inflammatory exudates and in 
thrombi. Hyaline casts are common in the kidney tubules.1 
Technique.-Hardening in alcohol, Orth's fluid, or formalin. Staining by picro- 
acid fuchsin or by haematoxylin and eosin. 
AMYLOID DEGENERATION (Waxy or Lardaceous Degeneration). 
This is a process by which the basement substance of various forms 
of connective tissue, and especially the walls of the blood-vessels, become 
1 Consult for bibliography of studies on hyaline degeneration Lubarsch and Ostertag's "Ergebnisse 
der allg. path. Morphologic und Physiologic," etc., Jahrg. i., Abth. i., 1895, p. 210. REGRESSIVE TISSUE CHANGES 
49 
swollen and thickened by their conversion into a translucent, firm, 
glassy, colorless material, albuminous in character. For the micro- 
chemical reactions of amyloid substance see below under Technique. 
This albuminous material may be present in the tissues in such small 
amount as to be recognizable only under the microscope, or it may be so 
abundant as to give a very characteristic appearance to the tissue. 
Parts in which the lesion is marked are usually enlarged, and some organs, 
the liver, for example, may reach a very large size. Affected parts 
contain less blood and feel harder than normal, and have a peculiar 
Fig. 28.-Amyloid Degeneration of Capillary Blood-vessels of a Glomerulus of the Kidney. 
The waxy vessels are stained pink with methyl violet. 
shining and translucent appearance which varies in character, depending 
upon the extent and distribution of the degenerated areas and upon its 
association with other lesions, such as fatty degeneration. It most 
frequently occurs in the smaller arteries and capillaries (Fig. 28), whose 
lumen is encroached upon by the thickening of the walls which the 
process involves. It is usually the media and intermediary layers of 
the intima which are earliest and most extensively affected. The change 
also often occurs in the interstitial connective tissue and membranee 
proprije of organs and in reticular connective tissue. It does not affect 
the parenchyma cells of organs. These, however, frequently undergo 
atrophy as the result of pressure from the swollen, degenerated tissue. 
It is not yet known whether amyloid degeneration is due to a direct 50 
REGRESSIVE TISSUE CHANGES 
transformation of the tissue, or is an infiltration by some abnormal 
material formed elsewhere and brought to it, or is derived from the blood. 
Amyloid degeneration occurs most frequently and abundantly in 
the liver, spleen, kidneys, intestinal canal, and lymph-nodes; but it may 
occur, usually in a less marked degree, in other parts of the body: in 
the larger blood-vessels, in the interstitial tissue of the heart and mucous 
membranes of the air passages, and in the generative organs. It may 
occur locally or appear in various parts of the body at once. It most 
frequently occurs in connection with severe wasting diseases, particu- 
larly in those involving chronic suppuration and ulceration, especially of 
the bones. It is common in tuberculosis, syphilis, and the cachectic con- 
dition induced by malignant tumors, and is occasionally seen in severe 
malarial infection, dysentery, and leukaemia.1 
Technique.-For microscopical examination, the tissue, either fresh or after pres- 
ervation, should be cut into thin sections, and these deeply stained with one-per-cent 
aqueous solution of methyl violet; the sections are washed in water and mounted in 
glycerin. The differentiation between the amyloid and other parts is more distinct if, 
after staining, the specimen be dipped for an instant in HC1 and alcohol 1 : 100, and 
then carefully rinsed, before mounting in glycerin. The degenerated areas are thus 
stained rose-red, while the normal tissue elements have a bluish violet color. In 
some cases, for reasons which we do not know, the amyloid substance does not show 
a well-marked reaction with methyl violet. For the detection of amyloid in fresh 
tissues by the iodine reaction see p. 1012. 
Corpora amylacea are small, spheroidal, 
homogeneous or lamellated bodies (Fig. 29), 
w'hich assume a bluish color on treatment 
with solution of iodine or iodine and sul- 
phuric acid. They are frequently found in 
the acini of the prostate gland, sometimes in 
large numbers; in the ependyma of the 
brain and cord; in the lung and also in 
extravasations of blood and in various 
other situations. They may occur under 
normal as well as pathological conditions, 
and are apparently of little importance. 
They seem to have nothing to do with amyloid degeneration, although 
they somewhat resemble its products. Some of the tube casts of the 
kidney resemble the corpora amylacea chemically.2 
Fig. 29.-Corpora Amylacea. 
From prostate gland. 
There is in this condition a deposition, either in cells or in the inter- 
cellular substance, of larger and smaller granules composed chiefly of 
phosphate and carbonate of calcium (Fig. 30). These particles, when 
CALCAREOUS INFILTRATION. 
1 An extended study of amyloid degeneration may be found in a monograph by Wichmann, 
Ziegler's Beitrage, Bd. xiii., p. 487, 1893. Also for later bibl. Schilder, ibid., Bd., xlvi, p. 602, 1909. 
A later bibliography with a summary of experiments on the production of amyloid degeneration 
in animals will be found in an article by Maximow, Virch. Arch., Bd. cliii., p. 353, 1898. 
2 For a study of the relationship of corpora amylacea to amyloid substances, see Ophuls, Jour. 
Exp. Med., vol. v., p. Ill, 1900, bibl. REGRESSIVE TISSUE CHANGES 
51 
abundant, give hardness, brittleness, and a whitish appearance to the 
affected tissue. Under the microscope they appear dark by transmitted, 
white and glistening by reflected, light. In haematoxylin-stained 
specimens, the tissue about the lime particles and masses is apt to be 
deeply and diffusely colored. Tissues may be nearly completely per- 
meated with salts, or the latter may be scattered in patches through 
them (Fig. 31). Sometimes large lamellated concretions are formed in 
tissues, usually at the seat of some old inflammatory process. Calcium 
salts may be deposited under abnormal conditions either in tissues or in 
the retained secretions and excretions of the body. In pathological 
calcifications they are retained, not in the diffuse state in which they 
Fig. 30.--Calcification of Epithelial Cells of the Kidney. 
This is following sublimate poisoning. Some of the cells are converted into rounded, strongly 
refractile masses of lime salts. In others the lime is in the form of granules within the cells. The 
calcified parts are diffusely stained with haematoxylin. 
exist in bone, but in particles or clumps, although the calcium compounds 
are essentially the same under both the normal and the pathological 
conditions. 
Calcification in tissues usually, if not always, occurs in parts which 
are dead or are in a condition of reduced vitality as a result of some 
antecedent abnormal process, as a rule of an inflammatory nature. 
Fatty degeneration of cells frequently precedes calcification. Among 
the most common and important examples of calcareous degeneration 
may be mentioned those which occur in the valves of the heart in endo- 
carditis and the walls of the blood-vessels in chronic obliterative endar- 
teritis. It occurs in old thrombi, in old tuberculous areas, in old infarcts, 
in long-retained dead foetuses, in cartilage, in ganglion cells in old age 
or after their death from any cause, and under many other conditions. 
Calcification of the epithelium and of casts in the kidney occurs after 
corrosive-sublimate poisoning in man (see p. 421) and may be experi- 52 
REGRESSIVE TISSUE CHANGES 
mentally induced in animals. As examples of calcification of masses 
of secretion and excretion we may mention tonsillar calculi1 in which 
masses of epithelial cells, bacteria, etc., are infiltrated with calcium 
salts. Of similar character are the preputial, bronchial, and intestinal 
calculi, and calculi in the ducts of various glands; and calcification in 
thrombi and other fibrinous structures. 
The calcium salts are derived from the blood and lymph in which 
they are held in solution. The rationale of their deposition in damaged 
Fig. 31.-Calcareous Infiltration (Calcification) of the Kidney. 
Following sublimate poisoning. The calcium salts are deposited chiefly in the necrotic and fatty 
epithelium of the tubules. 
cells and tissues is not yet clear, though much work and discussion have 
centred in the problem. The presence of phosphorus in the affected 
areas; the existence of fatty acids in cells and tissues-since fatty 
degeneration so frequently precedes calcification-with which the cal- 
cium may form insoluble soaps; and proteids capable of uniting with 
calcium, have all been urged as determining factors. We cannot enter 
here upon a discussion of this point.2 
Technique.-The carbonate of lime deposited in the tissues is dissolved by di- 
lute acids with evolution of carbonic-acid gas. This process may be observed under 
the microscope by running five-per-cent, hydrochloric acid under the cover-glass 
upon unstained sections; the gas bubbles are caught as they evolve beneath the cover. 
1 Calculi are masses of solid material of various composition precipitated from the body fluids. 
They will be considered under the separate organs in which they most frequently occur. 
2 Consult WeZZs, "Pathological Calcification," Jour. Med. Research, vol. xiv., 1906, p. 491, bibl. 
Also, for a study of the role of diffusible soaps in the formation of cell fats and in calcareous degeneration 
see Klotz, "Calcareous Degeneration," Jour. Exp. Med., vol. vii., 1905, p. 633, and vol. viii., 1906, p. 
322. REGRESSIVE TISSUE CHANGES 
53 
Pigmentation. 
There is under normal conditions a certain amount of pigment in the 
body-in the rete Malpighi of the skin, in the eye, in muscle, and in fat. 
This pigment is elaborated by the body cells and may vary considerably 
in amount. 
The pigment which is formed under pathological conditions may be 
derived from the blood-hcematogenous; from the bile-hepatogenous', or 
it may be elaborated by various cells after the analogy of the normal 
pigment-metabolic. Finally, pigment maybe introduced into the body 
from without by drugs, in tattooing, or by 
inhalation-extraneous. The pigment in the 
body, of whatever origin, may be in yellow, 
brown, black, or reddish granules, or in 
crystalline form. It is often deposited in 
cells, but may lie free in the intercellular 
substance. It is often transferred from 
place to place in the body.1 
Hematogenous Pigment.-Blood pig- 
ment may form by the decomposition of 
haemoglobin in thrombi, in extravasated or 
in the circulating blood. Under these con- 
ditions the haemoglobin which is loosely 
associated with the plasma of the red blood 
cells readily diffuses, leaving the cells-so- 
called "blood shadows"-pale and almost 
invisible and prone to disintegrate. This 
destruction of blood cells is called hcemolysis. Haemoglobin in solution 
in the body fluids2 undergoes various phases of decomposition which 
we cannot follow in detail here. One of the derivatives or groups of 
derivatives of the haemoglobin is called hcemosiderin. 
Haemosiderin usually appears in the form of brown or black granules 
either in cells or free in the tissues. It is the usual form of blood pig- 
ment resulting from haemolysis. It gives the microchemical reaction for 
iron. For this test for iron in haemosiderin see foot-note below.3 
A further common decomposition product of haemoglobin is hcema- 
tcidin. Haematoidin is identical in chemical composition with the bile 
pigment, bilirubin. It may occur as red rhombic plates or acicular 
crystals or as granules (Fig. 33). It does not contain iron. This is 
Fig. 32.-Pigment Containing 
Ikon within Epithelial Cells of 
the Air Vesicles of the Lungs. 
The iron pigment is colored blue. 
Thisfspecimen is from the lungs of an 
employe in the Subway in New York 
City. 
1 See Askanazy, Cbl. f. Path., Sep. 7th, 1906, p. 642. 
2 See page 456. 
3 To differentiate free iron and certain of the iron-containing pigments of the haemosiderin group- 
sections of the alcohol-hardened tissue are placed for an hour or longer in a two-per-cent aqueous solu- 
tion of ferrocyanide of potassium. Transfer to glycerin containing 0.5 per cent, hydrochloric acid. 
Under these conditions the iron will be stained blue or greenish-blue (Fig. 32). In order to secure 
a reaction for the ferrous as well as the ferric salts, use a mixture of 1 gram each of ferro- and ferricyan, 
ide of potassium in 100 c.c. of water. Transfer to acid glycerin as above. Contrast stains may be 
secured by alum carmine. 
There are, it should be remembered, certain iron compounds-the so-called "masked" iron- 
which are not demonstrable by the ordinary reaction. 
For a resume of the microchemical reactions for iron, with bibl., see Tracy, Jour. Med. Research 
vol. xiv., 1905, p. 1. Also, Mann, "Physiological Histology," 1902, p. 290. 54 
REGRESSIVE TISSUE CHANGES 
the form of blood pigment which after a time is apt to form at the 
seat of old haemorrhages or in old blood-clots, thrombi, etc., where it 
may persist for a long time. 
Red blood corpuscles may be taken up by various forms of phago- 
cytes, and within these cells the decomposition of the haemoglobin may 
lead to their pigmentation. 
Haemolysis may take place in the circulating blood in many forms 
of poisoning, in acute infections, notably in malaria, in pernicious anae- 
mia, in various cachexiae, etc. The haemoglobin thus set free in the 
body fluids may be eliminated through the urine, inducing haemo- 
globinuria; it may be used by the liver in the formation of bile; or it 
Fig. 33.-Hematogenous Pigment. Hematoidin Crystals and Masses Free and within 
Leucocytes. 
may undergo decomposition, and its derivatives may be deposited in 
the cells of various organs and in the tissues as pigment granules. 
A condition called hemochromatosis has been described, in which a 
brown pigment, probably derived from the haemoglobin of the blood, is 
deposited in various tissues of the body. The organs in this condition 
may appear notably pigmented on gross examination. The pigment 
particles which are found in the epithelial cells of glands, especially of 
the liver and pancreas, contain iron; while an iron-free pigment may be 
present in the smooth muscle cells of the gastro-intestinal canal and of 
the blood and lymph vessels, and in connective-tissue cells. This pig- 
mentation is commonly associated with cirrhosis of the liver. Haemo- 
chromatosis may be associated with diabetes mellitus and cirrhosis of 
the liver, together with pigmentation of the skin-"bronze skin." 
The conditions leading to haemochromatosis are still obscure.1 
Hepatogenous Pigment.-Pigmentation of tissues from the bile 
occurs under various conditions. The bile may enter the blood and tis- 
sue fluids in obstruction of the gall ducts by inflammation, tumors, cal- 
culi, etc. In the condition called jaundice or icterus the tissues are 
stained yellowish or yellowish-green by bile pigment. Icterus, it should 
be remembered, may also occur in infectious diseases and in toxaemia, 
under conditions which lead to destruction of red blood cells within the 
vessels. Bile pigment may be deposited in the liver and elsewhere in 
the form of yellow or brown granules. 
1 For a careful study of haemochromatosis, with bibliography, see Opie, Jour. Exp. Med., vol 
v„ p. 279. REGRESSIVE TISSUE CHANGES 
55 
It consists largely of bilirubin, a substance identical with haema- 
toidin, being derived from haemoglobin through the metabolism of the 
liver cells. 
Ochronosis.-Under conditions which are as yet little understood, 
minute, iron-free, gray or black granules of pigment which may be called 
Fig. 34.-Melanotic Pigment in Tumor Cells. 
Metabolic Pigmentation. 
melanotic are deposited especially in cartilage but also in other con- 
nective tissues. Melanuria may accompany this form of tissue pig- 
mentation. This condition has been called ochronosis.1 
Metabolic Pigment.-Pigments called melanins, and probably 
derived from albumins, may be elaborated by various forms of cells. 
Fig. 35.-Pigmentation of Connective-tissue Cells of the Lungs. 
From inhaled coal dust-anthracosis. 
by processes apparently somewhat analogous with those concerned in 
normal pigmentation.2 This is exemplified in melanotic tumors (Fig. 
34), most frequently of the choroid and the skin, and possibly in the 
bronze skin of Addison's disease. 
Pigment whose nature is not very clearly defined may form in the 
smooth muscle tissue of the gastro-intestinal walls, in various cachexiae, 
1 For a study of ochronosis see Pick, Berl. klin. Woch., 1906, pp. 478, 509, 556, 591. 
2 For a study of the nature of skin pigment consult Abel and Davis, Journal of Experimenta 
Medicine, vol. i., p. 361, 1896; also Chittenden and Albro, American Journal of Physiology, vol. ii., p 
291 1899. Also Mann, "Chemistry of the Proteids," 1906, p. 580. 56 
REGRESSIVE TISSUE CHANGES 
in the heart muscle, in the so-called " brown atrophy," and, under certain 
conditions, in the liver. 
Extraneous Pigment.-As examples of pigment introduced into 
the body from without, we may mention the deposition of minute par- 
ticles of silver from the internal use of silver salts-argyria', the coloring 
of the skin and lymph glands from tattooing; and especially the pig- 
mentation of the lungs and bronchial glands from the inhalation of 
coal and other dust-pneumonokoniosis (Fig. 35). This is universally 
present under the conditions of indoor life which modern civilization 
imposes. Such pigment may be brown or black, and is usually in very 
small particles within cells or in the intercellular stroma. 
Necrosis. 
Necrosis is the death of a circumscribed portion of tissue in the 
living body. It may be the result of insufficient nutrition from cutting 
off the blood supply, as by embolism, thrombosis, ligature, pressure, etc., 
or it may depend upon the action of destructive chemical agents, ex- 
treme degrees of temperature, the Roentgen rays and radium. It may 
be due to bacterial toxins or to toxins formed by the animal tissues; 
to nerve lesions leading to trophic disturbances; or to mechanical injury. 
Defective nutrition of the body in various acute and chronic diseases 
disposes the individual to local necrosis when subjected to any of the 
direct agencies just enumerated. The general appearance of dead 
tissue varies greatly. In some cases there is a simple and gradual dis- 
integration and softening of the tissue, resulting in a mass of degenerated 
cells and cell detritus, with more or less fluid and various chemical 
substances arising from decomposition. The softening of the brain in 
embolism is an example of simple necrotic softening-liquefaction 
necrosis. In some cases the dead tissues merely dry and shrivel grad- 
ually and become hard and dark-colored. 
In another class of cases the dead tissues are permeated by fluids 
which may be dark red in color, from the solution of coloring matter 
from the blood, and may contain bacteria which induce putrefaction, 
with the production of gases and various new chemical substances. The 
tissues become swollen and granular, and disintegrate; and finally the 
whole may form a mass of irregular granules, with fat droplets, tyrosin, 
leucin, and various forms of crystals, shreds of the more resistant kinds 
of tissue, and bacteria. 
The death of cells is marked by cessation of function and by certain 
morphological and chemical alterations of the body and the nucleus. 
As a rule the highly specialized cells, such as the functional cells of the 
brain, liver, and kidney, are most vulnerable in the presence of harmful 
conditions. 
There is at first no evident morphological difference between dead 
cells and living cells. But very soon in the former, changes occur. The 
cytoplasm may swell and become homogeneous from imbibition of fluids; 
or, on the other hand, it may become more coarsely granular. The REGRESSIVE TISSUE CHANGES 
57 
nucleus stains less deeply or not at all with haematoxylin or other nuclear 
dyes (Fig. 36), owing to the disappearance of the chromatin which 
seems to dissolve in the tissue juices; this is called karyolysis. Some- 
times, however, the chromatin does not dissolve, or only partially dis- 
The cells in the lower portion of the cut are nearly normal; most of those above are more coarsely 
granular and have failed to take the nuclear stain, while at the top they are disintegrating. 
Fig. 36.-Necrosis of Epithelium in the Kidney. 
appears, the remainder breaking up into irregular, more or less deeply 
staining granules. This is called karyorrhexis. The nuclei of cells 
which are undergoing regressive processes or dying may become smaller 
and denser than normal and stain more deeply; this is called pycnosis. 
A sharp line separates the dead and gangrenous portion of the foot from the living tissues about the 
posterior part and the ankle. 
Fig. 37.-Gangrene of the Foot. 
Presently the cell body may contain fat droplets, or without this it may 
disintegrate. 
Gangrene.-When death of a considerable mass of tissue occurs, and 
this either dries, as is possible on the surface of the body, or is associated 58 
REGRESSIVE TISSUE CHANGES 
with putrefaction in the tissue, the condition is called gangrene. The 
involved part, when on the surface of the body, may dry and become 
hard and brown or black-mummification, or dry gangrene1 (Fig. 37). 
On the other hand it may, when putrefactive bacteria are present, in 
addition to its discoloration, become soft and infiltrated with foul- 
smelling gases-moist gangrene. If the affected part be comparatively 
bloodless, the discoloration, which is largely due to decomposition of the 
blood pigment, may be absent.2 
Focal Necrosis.-Necrosis involving a small circumscribed area of 
tissue, such as is frequent in toxaemia, is called focal necrosis, p. 203. 
Ulceration.-Necrosis with erosion involving the surface of the 
skin or of the mucous or serous membranes is called an ulcer. An ulcer 
may be necrotic in origin, from the cutting off of nutrition in a circum- 
scribed area, as in some forms of gastric ulcer. This may be associated 
with reactive inflammatory processes which tend to promote repair. On 
the other hand, the process may be inflammatory in origin, death of 
tissue following. 
Coagulation Necrosis.-If dead areas of tissue (whether this con- 
dition be due to mechanical injury, to disturbances of nutrition, or to 
the local action of bacterial or other poisons) 
contain the substances necessary for the 
coagulation of their albuminous constitu- 
ents, or if they be bathed with body fluids 
from adjacent parts in which the circula- 
tion is maintained, a characteristic coagu- 
lation of the necrotic elements is apt to 
occur. The composition of the cells of the 
tissue is altered, so that the cell bodies are 
shining and translucent, sometimes altered 
in shape; while the chromatin and finally 
the nuclei of the cell disappear (Fig. 38). 
The white infarctions of the spleen and 
kidneys, the areas of coagulation necrosis 
in tuberculosis, and the pellicle in croupous 
inflammation of the mucous membranes are 
the most common examples of this lesion. 
If, for example, in the spleen, one of the 
small arteries is plugged by an embolus, a 
corresponding portion of the spleen be- 
comes anaemic and appears as a white, 
wedge-shaped mass, sharply defined from 
the surrounding splenic tissue. If such a white infarction has existed 
but a short time, there is hardly any difference between the appearance 
of its anatomical elements and those of the surrounding spleen, except 
that they are differently affected by staining-fluids. If the infarction 
is older, the cells are small and shiny and their nuclei cannot be seen. 
Fig. 38.-Coagulation Necrosis 
in Cells. 
The disappearance of the chromatin 
from the nuclei is indicated by their 
failure to stain, especially marked in 
the upper cells. 
1 For a study of senile gangrene see Falta, Zeitschr. f. Heilkunde, Bd. xx., p. 393, 1899, bibl. 
2 For more detailed studies of gangrene consult works on surgery. REGRESSIVE TISSUE CHANGES 
59 
In croupous inflammations of mucous membranes the epithelial cells 
become shiny, the nuclei disappear, and the shape of the cells is changed 
by the coagulation necrosis, so that a number of them together often look 
like a network of coagulated fibrin. 
Cheesy Degeneration {Caseation).-As commonly used, this term 
embraces the changes in the tissues which we have just considered under 
the more appropriate name of 
coagulation necrosis. But it is 
also applied to that form of degen- 
eration in which, under a variety 
of conditions, the dead tissue ele- 
ments lose their normal structural 
features and become converted into 
an irregularly granular albuminous 
and fatty material (Figs. 39 and 
40), which sometimes tends to dis- 
integrate and soften, sometimes 
dries and becomes dense and firm, 
or may become infiltrated with 
salts of calcium. Thus cheesy de- 
generation may, and very often 
does, occur in tissues which are in 
the condition of coagulation necrosis; but it also occurs in tissues which 
are not the seat of coagulation necrosis, but which, for a variety of 
reasons and in a variety of ways, have lost their vitality. 
The terms "coagulation necrosis" and "cheesy degeneration," as 
commonly used, in part actually cover the same degenerative conditions 
in the tissues. Both are indefinite, and will no doubt remain so until 
we gain a more precise knowledge 
of the conditions under which they 
occur. 
Fat Necrosis.-This is a de- 
generative process most frequent 
in the subperitoneal fat and in and 
about the pancreas, and especially 
associated with lesion of that 
organ. We refer for details to the 
special section, p. 704. 
The Disposal of Necrotic Tissues. 
-Necrotic tissues may be sepa- 
rated from the living body by in- 
flammatory processes and wholly 
cast off, as in gangrene of a limb, or in bone, the dead portion here 
being called a sequestrum. 
Fragments of dead cells and tissues in the living body are in part 
disposed of by leucocytes or other mesoblastic cells which may be 
attracted to them, and may cause their solution by proteolytic enzymes 
Fig. 39.-Coagulation Necrosis. 
In tuberculous tissue. 
Fig. 40.-An Area of Cheesy Degeneration 
(Caseation) in a Miliary Tubercle in the 
Lungs. 60 
REGRESSIVE TISSUE CHANGES 
which are set free or by the incorporation of particles of the dead tissue 
into their bodies where they are destroyed.1 
Furthermore, the absorption of necrotic tissues is in part due to 
proteolytic enzymes furnished by the dead and degenerating cells them- 
selves. The self-destruction of tissues in the ways indicated is called 
autolysis (see p. 106). To what extent the lytic substances through 
which dead tissues are softened may be derived directly from the blood 
plasma is not yet clear. At any rate, through chemotaxis, phagocytosis, 
and autolysis considerable masses of necrotic tissue may be finally re- 
moved.2 Dead bone is dissolved and disposed of by special forms of 
cells called osteoclasts (see p. 103). 
Decent studies relating to the adaptation of the body to various alien 
substances have led to new conceptions of the nature of the processes by 
which the body frees itself of useless or harmful material either devel- 
oped within it or introduced from without. For a fuller consideration 
of these processes see cytolysis, p. 171. 
1 See Phagocytes, p. 98. 
2 Wells, Jour. Med. Res., vol. xv., p. 149, 1906. CHAPTER IV. 
PROGRESSIVE TISSUE CHANGES. 
Hypertrophy and Hyperplasia. 
f Hypertrophy.---Under a variety of conditions, cells, larger parts of 
the body, or organs become larger than normal. The structural change 
to which this enlargement is due may be a simple increase in size of the 
elementary structures of the part, the cells. This is called simple hyper- 
trophy. It is usually associated with some increased functional demand 
upon the cells and an increase in their functional capacity; as, for exam- 
ple, in the hypertrophy of the heart with lesions of the valves, or in the 
hypertrophy of one kidney, which in case of diminution or suspension of 
function in the other assumes the work of both-compensatory hyper- 
trophy.1 
Pathological hypertrophy in response to functional demand-func- 
tional hypertropy-has its physiological prototype in the changes in the 
uterus and in the mammary gland during pregnancy. 
It should be borne in mind that the simple enlargement of a part or 
organ does not necessarily involve the hypertrophy of any of its structural 
elements. Thus there may be an increase of fat in a muscle causing 
its enlargement; waxy degeneration of the liver may determine great 
increase in the size of this organ. It is well to limit one's conception 
of hypertrophy to enlargement of specific structural elements of a part 
with maintenance or increase of functional capacity, and to consider 
other instances of enlargement, such as those just cited, as examples of 
pseudo-hypertrophy. 
Hyperplasia.-In many cases the increase in size of a part or 
organ is due not only, or not at all, to the increase in size of its element- 
ary structures, but to an increase in their number. This increase in 
number of the structural elements of a tissue or organ is called numer- 
ical hypertrophy, or hyperplasia.2 
Hyperplasia of connective tissue is of frequent occurrence in associa- 
tion with atrophy of the parenchyma of various organs, replacing the 
damaged cells as these diminish or disappear. This is called replace- 
ment hyperplasia. 
Hypertrophy and Hyperplasia in Special Organs.-In hypertrophy of 
the heart associated with the increased amount of work which it has to 
do in maintaining the circulation in various forms of valvular lesion, 
1 For bibliography of compensatory hypertrophy see reference to Aschoff, p. 79. 
2 Consult for examples of hyperplasia and hypertrophy the following sections on Regeneration and 
Inflammation. 
61 62 
PROGRESSIVE TISSUE CHANGES 
pulmonary and vascular obstruction, or excessive bodily strain;1 in 
hypertrophy of the unstriated muscle such as may occur in the bladder 
in urethral stricture, calculi, etc., in the stomach in pyloric stenosis, in 
the arteries in chronic diffuse nephritis; as well as in the voluntary- 
muscle hypertrophy from athletic exercises, etc., the individual muscle 
cells and fibers are increased in length and in thickness. 
In hypertrophy of one kidney from the loss of the other or part of 
its own substance by operation or lesion, there is enlargement of the 
epithelium, especially of the convoluted tubules and of the glomerular 
epithelium covering the tuft, the latter being also enlarged. Changes in 
the collecting tubes and in the interstitial tissue are less marked even in 
kidneys which are greatly increased in size. 
Compensatory hypertrophy of the liver following destruction of 
part of the parenchyma seems to be largely due to the new-formed 
iver cells, and to hyperplasia of the interstitial tissue, but the hyper- 
rophy of the old cells occurs. 
Compensatory hypertrophy of the thyroid and adrenals has been 
experimentally induced. Hypertrophy of one testicle occurs after the 
removal of the other, and the same is true of the mammary gland. Com- 
pensatory hypertrophy of the ovaries has not been observed. 
After destructive injury to the spleen its function may be in a 
measure assumed by the bone marrow and lymphatic tissue which 
undergo compensatory hypertrophy. 
In most of these conditions hyperplasia of the interstitial tissue is 
associated with the hypertrophy of the specific parenchyma cells whose 
response to increased functional demands is marked by simple hyper- 
trophy. 
Metaplasia. 
In the development of the body there is a constant and progressive 
differentiation of cells. When development is complete a certain speci- 
ficity exists, marked by functional and structural characters. These 
specific characters in cells are fairly permanent under normal conditions. 
Under a variety of abnormal conditions, however, they may undergo 
modification so that one type of cell or tissue may assume more or 
less completely the characters of another type. But the limitations 
of this change in type are strictly drawn, so that one type can assume 
only the characters of another which is closely related to it. This 
change of one form of closely related tissue into another is called meta- 
plasia. 
Thus, by a gradual change in the cells and stroma of fibrous tissue, 
this may be converted into bone, as mucous tissue may become fat tissue, 
and hyaline cartilage become fibrous. Metaplasia is a process involving 
active changes on the part of the living cells of the tissue, and should be 
clearly distinguished from certain degenerative and infiltrative processes, 
in the course of which one form of connective tissue may assume super- 
1 For conditions of cardiac hypertrophy see p. 550. For a fuller consideration of the phases and 
conditions of hypertrophy see Adami "Principles of Pathology," i, p. 535. PROGRESSIVE TISSUE CHANGES 
63 
ficial resemblances to others of the group, as in calcareous and mucoid 
degeneration. 
The infiltration of the cells of fibrillar connective tissue with fat, 
and the reverse process in which the fat is lost, as in atrophy and emacia- 
tion, are not, strictly speaking, examples of metaplasia. 
While metaplasia is most common among the members of the con- 
nective-tissue group, it sometimes occurs in other tissues. Thus, for 
example, the epithelium of the nose, bronchi, urinary passages, cervix 
uteri, and gall-bladder may under a variety of conditions assume the 
characters of squamous epithelium of the skin type.1 
One should be critical in estimating the value of evidences of meta- 
plasia, which has apparently been assumed to occur more frequently 
than the facts justify. For example, many instances of alleged meta- 
plasia can be equally well accounted for on the assumption of defects 
of development in which a certain portion of tissue has failed to com- 
plete its differentiation, thus remaining in form and in situations which 
simulate the results of metaplasia. Or, cells of the differing types may 
have grown into the region from adjacent parts. 
When differentiation has advanced so that such distinct types of 
tissue have been formed as connective tissue, epithelium, muscle, nerve, 
these do not again merge through metaplasia. There is no evidence 
that mesoblastic tissues can be converted into those of the epiblastic or 
hypoblastic type or vice versa. 
Reversion. 
Under various conditions, but especially when highly differentiated 
cells have been thrown out of function often as the result of inflammatory 
processes, they appear to assume the morphological characters which 
belong to an early stage in their development. This is called reversion, 
reversionary metamorphosis or kataplasia. Thus the flat epithelium of the 
air vesicles of the lungs or the cylindrical epithelium lining the bronchi 
or the stomach may become cuboidal. In the kidney the epithelium of 
the glomeruli and also of the convoluted tubules may become cuboidal. 
So in chronic peritonitis the endothelium may become greatly thickened. 
Muscle fibres and connective-tissue cells may assume for a longer or 
shorter period distinctly embryonic forms. But here, as in metaplasia, 
one should accept the morphological evidence of reversion with due 
reserve, since in many instances the cells in question of the lower type 
may be the results of a reparative process not yet complete, and may 
have been derived from newly-formed cells.2 Furthermore the shape of 
cells in general is so closely dependent upon nutrition, pressure, and 
mutual relationship that even slight departures from these may lead to 
changes in form quite as marked but not of such significance as those in- 
volved in reversion. 
1For references to epithelial metaplasia see Menetrier in Bouchard's "Traite de path, gen.," t. 
iii., pt. 2, p. 784. See also for a discussion of metaplasia Ribbert's "Lehrbuch d. allg. Pathologic," 
2d edition, 1905, p. 323, and "Geschwulstlehre," 1914. Also Adami, "Principles of Pathology, vol. i, 
p. 586. 
2 See Ribbert's "Geschwulstlehre," p. 15, 1914. Also for general review of reversion and growth 
in tissues see Adami, "A. Jacobi Festschrift," 1900, p. 422, and in his Pathology, i p. 810. 64 
PROGRESSIVE TISSUE CHANGES 
Regeneration. 
General Considerations.-It is during the earlier periods of life that 
the new formation of cells in the body is most active. From the fertil- 
ization of the ovum until the tissues and organs have assumed the varied 
forms and functions which the physiological division of labor among the 
cells imposes, cell proliferation and cell adaptation to a changing envi- 
ronment are constant and important features of individual development. 
After this time, under normal conditions, new cell formation is largely 
limited to the replacement of worn-out cells or to the restitution of 
such cells as may be sacrificed in the performance of their physiological 
functions. 
The studies of Bizzozero have shown that, notwithstanding the great diversity in 
the capacity for physiological regeneration among tissues, they may be conveniently 
grouped into three classes, as follows: First, tissues whose cells are capable of multipli- 
cation throughout the life of the individual or for a considerable period after maturity, 
and so lead to a continual regeneration. These are tissues whose cells are labile and 
evanescent. In this class are the parenchyma cells of those glands or structures which 
produce formed elements, such as the spleen, lymph-nodes, bone-marrow, ovary, testi- 
cle. Also the epithelium of the skin with its hair follicles and sebaceous glands, and of 
the mucous membranes of the respiratory, digestive, and genito-urinary organs. Sec- 
ond, tissues whose elements increase by division up to the time of birth, or sometimes 
for a short period thereafter, when evidence of physiological regeneration ceases. 
These are tissues with permanent cells. In this class are the parenchyma cells of those 
glands which secrete fluid material, such as the liver, kidney, pancreas, salivary glands, 
etc. Also members of the connective-tissue group, fibrous tissue, cartilage and bone, 
and the smooth muscle fibres. Third, striated muscle and nerve tissue. In these 
tissues, division by mitosis ceases at an early period and before the tissues have ac- 
quired their special characters. Here extensive regeneration does not occur. 
This grouping of tissues in accordance with their capacity for physiological regen- 
eration, while liable to modification under further research, affords a suggestive guide 
in our studies of regeneration under abnormal conditions. For beyond the regenera- 
tive capacity normally exercised by cells in response to the physiological wear and 
tear of life, they are frequently called upon to make good unusual losses, as the result 
of many forms of injury. 
Regeneration of injured tissues, all new growths, as well as the 
hyperplasias above mentioned, are invariably brought about by prolifer- 
ation or other changes in living cells. Furthermore, just as the cells of 
the adult organism are the offspring of one original cell, the ovum, so 
are all the new cells which appear in the body under abnormal condi- 
tions derived from pre-existing cells by division. 
We shall now briefly summarize the morphological changes which 
cells undergo in division and shall then indicate the degree of regener- 
ative capacity which various forms of tissues possess. 
MODES OF CELL DIVISION. 
The careful and minute study of cells during the act of division, 
which has been recently made, has revealed many most curious phe- 
nomena and has opened a new world of observation nearer to the elemen- 
tary expression of life than has seemed possible in earlier times. It will PROGRESSIVE TISSUE CHANGES 
65 
suffice for our purpose briefly to indicate some of the more striking feat- 
ures of the new cell lore. 
It is well to recall at the outset that recent studies of cells have 
shown that even in their simplest forms they are highly organized, and 
that their different parts have special functions to perform. Thus the 
nucleus presides over the constructive metabolism or assimilative proc- 
ess of the cell and furnishes the physical basis upon which the trans- 
mission of hereditary characters depends. The cytoplasm of the body, 
on the other hand, is concerned in those phases of metabolism which 
result in the liberation of energy in movements of various kinds and in 
the formation of new chemical substances. The centrosome also in 
certain cells, though not apparently in all, appears to play an important 
part in the changes incident to division. 
Two modes of cell division are commonly recognized. First, indirect 
division (mitosis, or karyokinesis); second, direct division (amitosis). 
Indirect (Mitotic) Cell Division. 
This is the most common mode of cell division and is especially char- 
acteristic of embryonic cells and those which are undergoing active de- 
velopment. While it presents great variations, its general features may 
be thus briefly summarized: 
Among the earlier changes which are to be seen in a cell about to 
divide by mitosis are a condensation and an increase in the staining capac- 
ity of the chromatin of the intranuclear network. This chromatin sub- 
stance gathers into a contorted thread or threads, called the spiremes 
(Fig. 41, 2), within the nucleus, whose membrane with the nucleolus 
gradually disappears so that the spireme lies free in the cytoplasm; and 
at the same time with, or preceding, these changes in the nucleus, there 
may be a division of the centrosome when this is present, the segments 
resulting from this division passing to opposite parts of the cell, usually 
outside the limits of the nucleus. Around each of the new centrosomes, 
which stain deeply with haematoxylin or other nuclear dyes, may be a 
clear zone of unstained material, or a series of fine radiating fibrils, or 
both; the whole forming a structure called a polar body (Fig. 41, 2 and 3). 
Now the threads of the spireme break across transversely, forming a 
series of more or less rod-like bodies called chromosomes, which form a 
somewhat flattened cluster or wreath between the polar bodies, lying in a 
plane at a right angle to a line passing between the latter.1 While this 
mass of chromosomes-sometimes called the monaster-has a stellar or 
wreath-like appearance when seen from the side, it is more band-like 
when viewed in profile (Fig. 41, 3 and 4). 
Between the polar bodies and across the monaster there may now be 
stretched a bridge or spindle of delicate fibrils resembling those about the 
centrosome in the polar bodies. 
1 It is believed that every species has a fixed and characteristic number of chromosomes in the 
dividing cells, and that in forms arising by sexual reproduction this number is even. In man the num- 
ber is believed by some to be 16, by others 32. 66 
PROGRESSIVE TISSUE CHANGES 
This fibril-spindle, together with the polar bodies, is called the achro- 
matic figure in distinction to the structure formed from the chromatin, 
which stains with nuclear dyes, and is called the chromatic figure. 
The whole complicated structure composed of both the chromatic 
and achromatic substance constitutes the mitotic figure. 
Now each chromosome splits lengthwise into exactly equal parts. 
These parts separate into groups which pass to the polar bodies at op- 
posite ends of the spindle. This is sometimes called the diaster phase of 
mitosis (Fig. 41, 5 and 6). 
Corresponding to the division of the chromosomes into equal parts, 
the cell body divides, each part containing one of the groups of daugh- 
ter chromosomes or diasters, together with one polar body and a part 
of the achromatic spindle (Fig. 41, 6). Now a new nucleus is formed 
Fig. 41.-Phases of Mitosis. 
1. Resting cell. 2. Spireme phase: the centrosome has divided, the polar body is seen above, 
the nuclear membrane has not yet disappeared. 3. Monaster phase: the polar bodies have arranged 
themselves on either side of the monaster, here seen from the edge. 4. The monaster seen from the 
side. 5 and 6. Diaster phase: the chromosome clusters have separated and the achromatic figure is 
seen. In 6 the segmentation of the cell body has begun. 7. The completion of the nuclear division 
and segmentation of the cell body. 
about the daughter chromosomes which gradually assume the characters 
of the resting intranuclear network (Fig. 41, 7). The achromatic fibrils 
disappear from the new cell, while the centrosome may also disappear or 
may take its place in the cytoplasm beside the new nucleus. 
There are countless variations and details in the minute processes of 
mitotic cell division and much interesting conjecture as to the meaning 
of the various changes in mitosis, which the scope of this work does not 
permit us to consider. But the facts already at hand are of extreme 
significance to the biologist and point toward large fields of research in 
pathology when the normal processes shall have been more clearly and 
exhaustively determined. 
Abnormal phases of mitosis are not infrequent. Thus, the mitotic fig- PROGRESSIVE TISSUE CHANGES 
67 
ures may be asymmetrical, so that the distribution of chromatin sub- 
stance to the daughter cells may be unequal (Fig. 42). There may be 
multipolar mitosis, so that, instead of two, several nuclei may form. Or, 
the new-formed chromosome masses may fail to share in the formation of 
the new nuclei. 
Such abnormal mitoses are 
frequent in certain tumors, and 
they may be experimentally in- 
duced by the application of 
various chemical substances to 
living cells. Too little is known 
about the conditions under which 
abnormal mitoses occur, and too 
little about the nature of the 
impulse to cell division in gen- 
eral, to justify to-day far-reaching conclusions as to the significance of 
these interesting abnormalities in the life of the cell. 
The Significance of Mitosis.-The term mitosis or karyomitosis is 
applied to this indirect mode of cell division, on account of the involve- 
ment of the nuclear threads. It is also sometimes designated as karyo- 
kinesis, from the form changes which these threads undergo. Aside 
from its intrinsic biological interest, a knowledge of mitosis in proliferat- 
ing cells is of importance in pathology, because the recognition of mitotic 
figures often enables us to decide with certainty what particular cells or 
cell groups are involved in the formation of new tissue, The most sig- 
nificant feature, however, of the whole process of mitosis, with all its in- 
tricate variations, appears to be that the chromosomes, during their 
separation into two or more clusters to form the basis of new cells, undergo 
an exact longitudinal division. So that, under normal conditions, no mat- 
ter how unequal the division of the cytoplasm may be, all of the new nuclei 
share alike in the chromatin substance of the parent nucleus. This fact 
appears to be of extreme importance in the recognition of a physical basis 
of inheritance.1 
In both cells the mitosis is asymmetrical, and in 
the cell to the left tripolar. 
Fig. 42.-Abnormal Phases of Mitosis. 
Direct (Amitotic) Cell Division. 
In this, which although relatively rare, appears to be the most simple 
mode of cell division, without those preliminary changes in the nucleus 
which are seen in the mitotic cell division, the nucleus with its membrane 
becomes constricted and finally divides into two or more parts which be- 
come new nuclei. At the same time or following this simple nuclear 
division the cell body divides, and thus two or more cells may form in 
the place of one. If the nuclear division is not followed by that of the 
cell body, multinuclear cells, or "giant cells," may be formed. 
1 See summary by Wilson, Science, Feb. 24, 1905. For a resume of physiology and pathology of 
the nucleus see Adami, Brit. Med. Jour., Dec. 22, 1906, p. 1760. Also Adami "Principles of Pathology," 
vol. i. See also in this connection Boveri, Entstehung Maligner Tumoren, Jena, 1914. 68 
PROGRESSIVE TISSUE CHANGES 
The significance of the difference between the amitotic and the mitotic 
cell division is that, while in the former there is an exactly even division 
of chromatin to the daughter nuclei, the division in the latter is of the 
nuclear mass as a whole. 
Amitotic, as well as mitotic, division occurs in leucocytes, in some 
forms of epithelium, and in pathological new formations. While the 
nature of the process is little understood, there appears to be much 
reason for the belief that, in general, amitotic division is 11 characteristic 
of highly specialized or degenerating cells in which development is ap- 
proaching its end."1 
GENERAL CHARACTERS AND LIMITATIONS OF CELL REGENERATION. 
It should be borne in mind, in studying the regeneration of various 
kinds of cells and tissues, that the acquirement by certain cells of special 
functional powers as the result of the physiological division of labor has 
involved the impairment of some of their more primitive general capac- 
ities, among these that of reproduction. Thus it is that we find in the 
ganglion cells an almost total lack of reproductive capacity; while in 
many of the gland cells this is slight, in others considerable. In some of 
the less highly differentiated cells of the body, on the other hand, as in 
certain forms of epithelium, in blood cells, and in the cells of the con- 
nective tissue, this primitive capacity of protoplasm to form new simi- 
lar cells by division is maintained, and may be evoked by the changed 
conditions which injury or loss involves. 
Although the occurrence of mitosis is the mark by which we espe- 
cially recognize the regenerative process in cells, it should be remembered 
that mitosis or some of its phases may occur in cells, without being fol- 
lowed by those further changes which lead to new cells or new tissues.2 
We may also often recognize new-formed cells and tissues by differ- 
ences in the shape and character of the cells and the arrangement of the 
tissue elements, these often approaching the embryonic type in form as 
well as in character of development. Furthermore, the atypical arrange- 
ment often seen in new-formed cells, both in regard to each other and in 
their association with older tissues, may aid in the identification of the 
formative process. 
Individual cells, even after having undergone marked structural 
changes-as, for example, in albuminous degeneration-or after a cer- 
tain degree of physical injury, may be restored to a normal condition. 
After destructive injury or loss, a full and complete replacement of 
cells and tissues can occur only as the result of a proliferation of cells of 
the same type as those to be restored. Thus a regeneration of epithe- 
ium occurs by proliferation and growth of epithelial cells alone; regen- 
1 For a comprehensive summary of facts and theories concerning the cell, both in higher and lower 
forms of life, consult Wilson's masterly work, "The Cell in Development and Inheritance." 
2 One is often disappointed in seeking for mitotic figures to find so few of them even in rapidly 
growing tissues. This is due to the fact that cell division even when active is not continuous, and 
periods of rest may follow the act of division. See Thoma's "Text-book of General Pathology," English 
Tr , vol. i.,p. 181. For a summary of experimental work on this point see Woglom, Study of Experi- 
mental Cancer, New York, 1913 (bibl.). PROGRESSIVE TISSUE CHANGES 
69 
eration of muscle by muscle cells, etc. In fact, however, in the higher 
types of tissue, after considerable injuries with loss of substance or after 
destructive pathological processes, complete regeneration is not common. 
This, as we have seen, is because the highly specialized cells of the body 
are limited in their capacity for reproduction closely to the domain of 
physiological regeneration. What we ordinarily call healing in exten- 
sive wounds of the more highly specialized tissues is usually a provi- 
sional makeshift repair by means of new-formed connective tissue. 
We have seen that the regenerative capacity in the cells of the human 
body is most marked in the less highly differentiated types of cells, and 
that it is above all connective tissues, blood-vessels, and epithelium 
which most freely and most completely undergo regeneration. These 
are relatively lowly organized tissues and serve for the maintenance or 
protection of more highly specialized tissues, and with them regenera- 
tion may be complete with full restoration of function.1 But although 
the more highly organized tissues in man do not undergo after injury any 
considerable regeneration, they are, when uninjured, capable, under the 
stimulus of increased functional exercise, of compensatory hypertrophy, 
so that the loss to the organism of similar tissue is made good, an ex- 
ample of which is the structural hypertrophy and increased performance 
of one kidney after the removal of the other.2 
The capacity to regenerate lost or injured parts exists to a certain ex- 
tent in all animals but is most marked among the lower forms. Thus if 
an amoeba be cut in two so as to leave one part with the intact nucleus, 
this part lives and the one-celled organism is completely restored. The 
fresh-water hydra, composed of many cells, may reproduce a large por- 
tion of the organism from a small severed fragment. The common earth 
worm can reproduce a severed head or tail. Crabs reproduce a whole leg 
if the severance takes place at a particular joint. Salamanders, snails, 
etc., can reproduce a leg and tail. It is further noteworthy in this connec- 
tion that the larvae of many lower forms, such as reptiles and insects, 
have a much greater capacity for the reproduction of lost parts than the 
same species have when in the adult condition.3 
REGENERATION OF SPECIAL TISSUES. 
Regeneration of the Nerve Tissue.-In the nervous system we find no 
evidence that the ganglion cells are capable of reproduction. Some phases 
of mitosis are occasionally found in them, although they do not appear 
to lead to proliferation. But if the essential parts of the ganglion cells, 
including the nuclei, be intact, a restoration may occur of their central 
as well as their peripheral branches. The fibrous and the neuroglia tis- 
sue of the central nervous system, on the other hand, may increase, and 
1 Consult Morgan, "Regeneration," Columbia University, Biol. Ser., 1901. 
2 For an illuminating discourse on the surplus of functional provision in the body see Meltzer, 
" The Factors of Safety in Animal Structure and Animal Economy," Harvey Lecture, 1907, reprinted in 
Jour. Am. Med. Assn, xlviii, 655, 1907. 
3 For a suggestive study of the laws of growth and changes in cells and tissues during development, 
and their relationship to the nature and cause of old age, see Minot, Harvey Lectures, 1905-1906/ Also 
Pop. Sci. Monthly, Ixxi, 1907. 70 
PROGRESSIVE TISSUE CHANGES 
in this way, even with considerable loss of substance, injuries to the 
brain and cord may undergo a sort of patchwork repair. 
In the peripheral nerves a considerable regeneration of fibres may 
take place after injury, when the corresponding ganglion cells are intact. 
This restoration may be effected in part by fibrous tissue which bridges 
the damaged region and affords guides or channels along which the axis 
cylinders may grow out from the uninjured central segments, finding 
their way to their endings, as in embryonic development they stretch 
into the tissues far from the ganglion cells in which they originate. The 
restitution is possible here because the centre of nutrition and at least a 
limited reparative control in the ganglion cell are intact. 
Further details as to degenerations and regenerations of nerves and 
nerve tracts may be found in the chapter devoted to The Nervous 
System. 
Regeneration of Muscle Tissue.-Regeneration of smooth-muscle tissue 
after injury is slight. Mitosis may occur in the cells and preliminary 
phases of division of the body have been described, but it is doubtful 
whether, except possibly to a very slight extent, new cells are formed. 
Such healing as occurs after wounds and other injuries is largely effected 
by new-formed fibrous tissue. 
A partial regeneration of striated muscle occurs after various forms of 
damage and losses of substance. There may be division by mitosis in 
the sarcolemma nuclei (Fig. 43) associated with the accumulation near 
Fig. 43.-Regeneration of Striated Muscle after Injury. 
The nuclei of the sarcolemma have proliferated and are surroun led by a small amount of non-striated 
protoplasm. 
them of granular protoplasm, which becomes striated, either in situ or 
as independent cells. At the injured end of the muscle fibre a similar 
process may occur, so that these damaged fibres may be in part restored. 
If as the result of the injury some of the nucleated protoplasm escapes 
from the sarcolemma, a similar development of striated cells and cell 
masses may occur. 
It is especially in certain forms of degeneration of the contractile 
substance, after typhoid fever for example, in which the nuclei, the sar- 
colemma, and the general framework of the tissue are uninjured, that 
regeneration of striated muscle fibres is most complete. After injuries 
with considerable destruction of the muscle tissue, regeneration is apt to 
be irregular and incomplete. While there is often much nuclear divi- 
sion and often the formation of large numbers of more or less striated 
and variously shaped cells, these are apt not to develop into useful 
muscle fibres and may disappear by degeneration and absorption or by PROGRESSIVE TISSUE CHANGES 
71 
pressure atrophy. Here, as elsewhere in highly organized tissues, such 
restitution as is possible after considerable injury is achieved by fibrous 
tissue. 
It is interesting to note that such regeneration as does occur in 
striated muscle is not initiated by the highly differentiated contractile 
substance, but by the nuclei and small residual amount of undifferen- 
tiated protoplasm, and that such more or less definitely striated cells as 
are formed are in many respects similar to certain forms of developing 
muscle cells in the embryo. 
Although mitosis and nuclear division have been seen in the muscle 
fibres of the heart after injury, there is no evidence that new muscle can 
be formed. Repair, which is not infrequent, is secured by fibrous tissue. 
Regeneration of Epithelium.-Owing to continuous shedding or to 
functional destruction of epithelium of the skin and mucous membranes 
and certain of their adnexa, physiological regeneration by mitosis is 
common. 
After injuries, also, regeneration of epithelium in these situations oc- 
curs by mitosis and may be extensive and complete. The new epithelium 
always forms from the old, and, when surface losses are to be made good, 
extends inward from the edges across the injured area after a suitable 
substratum has been formed by fibrous tissue and blood-vessels (Fig. 44). 
From a wound of the tongue. At the left is normal epithelium; at the right the thin pellicle of new- 
formed cells is extending over the surface of the wound. 
Fig. 44.-Regeneration of Epithelium. 
The new epithelium is at first atypical in form and arrangement owing 
to the necessity for a gradual adaptation to the sustaining and associated 
tissues. Thus the epithelium, which at first presses forward over a heal- 
ing wound of the skin, may be in the form of an irregular layer of cells 
(see Fig. 45) or of a thin smooth pellicle without the usual variations in 
size and shape by which it is later characterized when the papillae of 
the new cutis are formed and the new cells have adjusted themselves 
to these and to each other.1 In stratified epithelium it is the deeper 
layers from which the new cells chiefly arise. While amitotic division 
has been observed in the restitution of surface epithelium, this occurs 
in the more superficial cells and is believed not to be concerned in the 
regenerative process. 
Regeneration of gland epithelium after injury is of frequent occur- 
1 For a study of the regeneration of mucous membranes see Comil and Carnot, Arch, de med. exp. 
tome xi., p. 413 1899. For repair of bladder mucosa, Lasio, Virch. Arch., Bd. clxxviii., p. 65, 1904. 72 
PROGRESSIVE TISSUE CHANGES 
rence, though this capacity varies considerably in different glands. In 
many cases it appears to be by a proliferation of the epithelium lining 
the smaller excretory ducts that the restitution is accomplished, rather 
than by the more highly differentiated secreting cells. This is of espe- 
cial interest because it affords an excellent example of the rehearsing 
under abnormal conditions and for reparative ends of a developmental 
phase of cell life. 
In the liver very extensive new formation of liver cells may occur 
after experimental removal of a portion of the organ. These new cells 
arising largely from the epithelium of the small gall-ducts do not form 
real liver tissue, however, since in this a definite relationship must exist 
The epithelial cells advancing into and over the superficial portion of the granulation tissue at the 
right are fusiform and irregular in shape. They do not until later assume their usual forms and their 
relationships to one another and to the underlying tissue. 
Fig. 45.-Regeneration of Epithelium. 
between the liver cells and the gall-ducts, the blood-vessels and the 
interstitial tissue. Such a relationship can be secured only under the 
conditions of embryonic development when all the various tissues in- 
volved are being formed together. After large destruction of liver cells 
in certain forms of toxaemia-called acute yellow atrophy of the liver- 
there may be an extensive and successful regeneration because the 
associated tissues are not at the same time destroyed. 
In the thyroid gland new gland tissue may be formed after injury. 
In the kidney the regenerative capacity of the epithelium appears to 
be less marked, though proliferation of the epithelium of the collecting 
tubes may take place and epithelium to a considerable extent may be 
renewed if the blood-vessels and interstitial tissue remain intact.1 
Regeneration of epithelium to a considerable extent may take place 
in the mammary and salivary glands. But here it is the less highly dif- 
i Consult Pearce, Jour Med. Research, vol. xx, p. 53 1909. PROGRESSIVE TISSUE CHANGES 
73 
ferentiated cells of the excretory ducts rather than the secreting epi- 
thelium through which regeneration is secured. In the ovary and 
testicle a slight amount of regenerative capacity may be manifested 
through mitosis and division of epithelium, but its results are insig- 
nificant. The pancreas and spleen show little or no capacity for 
regeneration.1 
In all these cases of partial regeneration it is often difficult to deter- 
mine how much of the increase in parenchyma, which undoubtedly does 
occur, is due to a formation of new gland tissue and how much to a com- 
pensatory hypertrophy of the old. While, therefore, it is true that after 
injuries to the glands a considerable regeneration of epithelium may 
occur, when the loss of substance is extensive it is usually rather by a 
fibrous-tissue repair or by a compensatory hypertrophy or hyperplasia in 
the uninjured portions of the organ than by the new formation of true 
gland tissue that restitution occurs. 
Regeneration of Connective Tissue.-We have seen again and again 
in reviewing pathological regeneration that, in local restoration after 
injury, fibrous tissue plays an important part, either by itself or in asso- 
ciation with various forms of parenchyma. New fibrous tissue readily 
forms in the adult to replace tissue which has been destroyed. It re- 
sults from many kinds of prolonged chemical and mechanical irritants. 
Atrophy of the parenchyma may be followed by interstitial fibrous- 
tissue growth, or new fibrous tissue 
may develop under the influence 
of bacterial and other toxic sub- 
stances, and it frequently forms 
dense capsules about the seat of 
old lesions or around foreign bodies. 
Many forms of compensatory 
fibrous-tissue development will be 
described in the second section of 
this book, such as thickening of 
the walls of blood-vessels, inflam- 
matory adhesions, replacement 
hyperplasia, etc. 
We have now to consider briefly 
the changes involved in the new 
formation of this fibrous tissue. 
Here, as in all other tissues of the 
body, it is the cells alone which take the initiative, the formation of 
intercellular substance being always secondary to the formation of the 
cells and always occurring under their influence. 
New connective-tissue cells may be formed by mitosis (Fig. 46), 
either from older connective-tissue cells, or, as now seems certain, from 
the endothelium of the blood-vessels2 and possibly from the so-called 
Fig. 46.-Mitosis in Granulation Tissue. 
Two of the new-formed connective-tissue cells 
show mitotic figures. Three leucocytes have 
wandered into the new tissue. 
1 For a study of compensatory hypertrophy of hsemolymph-nodes after removal of spleen, see 
Weidenreich, Arch. f. Mik. Anat., 1905, bibl. 
2 See Baumgarten, Arbeiten, Path. Inst. Tubingen, Bd. iv., p. 310. 74 
PROGRESSIVE TISSUE CHANGES 
" plasma cells."1 In either case the cell about to divide shows an increase 
in the size of the body, which becomes more granular; the nucleus divides 
by mitosis, segmentation of the cytoplasm following. This process may 
be repeated so that many cells are derived from one, separated at first by 
a small amount of homogeneous intercellular substance. These cells, 
at first more or less spheroidal in form, may become larger, and polyhedral 
or elongated. Little by little, fine fibrils appear between the cells, some- 
times apparently as extensions of their cytoplasm, sometimes along their 
sides in the homogeneous material in which they lie. Such new con- 
nective-tissue cells concerned in the formation of fibrillar stroma are 
called fibroblasts (Fig. 47). As the fibrous stroma increases in amount 
Fig. 47.-Regeneration of Connective Tissue. 
Showing fibroblasts with a few new-formed intercellular fibrils between them. The walls of the blood- 
vessels are very thin. 
the cells, at first relatively abundant, become elongated and flattened, 
until as the new tissue approaches maturity the more or less dense 
fibrillar stroma preponderates, pressing the cells between its bundles or 
layers into variously shaped plaques, often fusiform or linear in profile. 
In the formation of fibrillar connective tissue from endothelium the 
endothelial cells of thin-walled blood-vessels increase in size, stretch 
slender bud-like extensions into the adjacent tissue, where, after mitotic 
division, they assume a role altogether identical with that of the ordinary 
connective-tissue cell. 
1 Plasma Cells.-It has been held that plasma cells are concerned in the formation of new fibrous 
tissue, but this view has recently been abandoned, and they are now generally believed to be either an 
independent form of free connective-tissue cell or a modified lymphocyte, this modification appearing 
only under certain conditions and stimuli. Plasma cells are round or oval cells (Fig. 48), usually larger 
than the blood or tissue lymphocyte, with an excentric oval nucleus or sometimes two nuclei. The pro- 
toplasm contains a fine basophile granulation, and adjacent to the nucleus there is a clear area which con- 
tains a central corpuscle. Such cells occur normally in the bone marrow, spleen, lymph nodes, and gastro- 
intestinal mucosa, and are found under various pathological conditions, especially in chronic inflamma- 
tion about the cells of neoplasms and in granulation tissue. Their origin and significance are, however, 
as yet under discussion, and the reader is referred to larger monographs for details; for example, Wil- 
liams, Amer. Jour. Med. Sci., 1900, cxix, 702; Schaffer, Die Flasmazellen. Sammlung anatom, u. 
physiol. Vortr. u. Aufatze, Heft 8, 1910; Weidenreich, Blutkbrperchen u, Wanderzellen. Ibid. Heft 
15, 1911; Die Leucocyten u. verwandte Zellformen. Wiesbaden, 1911. PROGRESSIVE TISSUE CHANGES 
75 
The formation of new connective-tissue cells may be large or it may 
be limited to the production of a single pair of cells; the stroma may be 
scanty or abundant, loose or dense; the process is essentially the same, 
namely, the division of cells by mitosis, and the formation by them, or 
under their influence, of more or less fibrillar stroma. This process, it 
will be seen, is practically identical with the formation of fibrous tissue 
in the embryo. 
But here, as elsewhere, the character and extent of new tissue pro- 
duction are largely influenced by the environment, and particularly by 
the nutritive supply, so that the formation of new connective tissue in 
any considerable amount is closely linked to the development of blood- 
vessels. 
Regeneration of Endothelium.-The regeneration of endothelium, 
which seems to be closely related to that of connective tissue, takes place 
readily. The new cells advance over denuded surfaces in a manner 
similar to that in epithelial repair. Whether the new cells always origi- 
nate in the old neighboring endothelium or may be more directly derived 
from fibroblasts is not yet fully determined. 
The Formation of Blood-Vessels.-The formation of blood-vessels in 
post-embryonic life is believed always to start in a budding or sprouting 
Fig. 48.-Developing Blood-vessels in New-formed Tissue Showing Highly Magnified 
Plasma Cells to the Right 
of the endothelial cells of pre-existing capillaries. The sprouts, directed 
outward from the endothelia of the capillaries, consist at first of buds, 
then of slender, conical, or filiform projections of cytoplasmic substance 
(Fig. 48). Now the cytoplasm of the cell from which the sprout springs 
may increase in amount and its nuclei divide by mitosis, so that the base 
of the sprout may consist of a multinuclear mass of cytoplasm or of a 
cluster of new-formed cells. The sprouts may extend for a long distance 
into the surrounding region, whether this be already organized tissue 
in which the vessels are increasing in number or unorganized lifeless 
material like blood-clot, which is to be replaced by new living structures. 
If a similar process be in progress in neighboring vessels, the sprouts may 
unite at their extremities, forming a slender solid protoplasmic bridge 76 
PROGRESSIVE TISSUE CHANGES 
from vessel to vessel. The sprouts now become thickened and gradually 
channelled out at the base by pressure of the blood in the vessel from 
which they spring. The blood enters these lengthening channels, 
forcing its way along them, forming a lumen as it goes. Simultaneously 
with this advance of the lumen, new nuclei are formed by division of the 
old along the sides of the vessel, and the new structure gradually assumes 
a distinctly cellular and vascular character. At length the channel is 
complete; the new vessels have well-defined endothelial walls and 
connective-tissue cells from without, or new connective-tissue cells 
which have been formed about the nuclei of the protoplasmic sprout, 
range themselves outside along the walls. So the new vessel takes its 
place in the vascular system of the part. Thus, in a short time, many 
new blood-vessels may form, furnishing nutritive centres about which 
the organization of tissue proceeds. 
In the new formation of arteries it is believed that the smooth-muscle 
tissue is formed by a growth along the developing vessel from a pre- 
existing artery. 
The Formation of Lymph-Vessels.-The formation of lymph channels 
in granulation tissue takes place in the same way as that of blood- 
vessels, the process being initiated by the formation of buds from the 
endothelium of existing vessels which push their way out into the new 
tissue, gradually acquiring lumina and forming anastomoses with other 
trunks. 
Regeneration of Cartilage and Bone.-New cartilage may form by 
the proliferation either of connective-tissue cells or, to a slight extent, 
of cartilage cells, and the formation about the new cells of the character- 
istic basement substance. It is the connective-tissue cells of the peri- 
chondrium from which especially new cartilage is formed. 
The new formation of bone under pathological conditions is not 
brought about by the bone cells, but by the development, first, from the 
cells of the periosteum or of the marrow, of a cellular connective tissue, 
or from the perichondrium of a form of hyaline cartilage. From these 
tissues, by processes essentially similar to those in the embryonic develop- 
ment, the new bone is formed under the influence of osteoblasts (see 
p. 876). 
The regeneration of bone marrow takes place through the activities 
of the characteristic marrow cells together with those of the blood- 
vessels and cells of the connective tissue and osteoblastic type.1 
Regeneration of Lymph-Nodes.-Regeneration of lymph-nodes may 
take place after partial removal. This appears to be more complete 
in the earlier years of life. After extirpation of lymph-nodes it has been 
shown experimentally that new nodes may form. These Bayer believes 
develop from fat tissue. Further studies are needed in the regeneration 
of lymph-nodes and the relationship of these and lymphatic tissue to 
fat and other forms of connective tissue.2 
1 For studies on the regeneration of bone marrow, see Haasler, Arch. f. klin. Chir., Bd. 1., p. 75 1895, 
and Enderlen, Deutsch. Zeits. f. Chirurg., Bd. lii, p. 293, 1899. 
2 Consult for bibl. of regeneration of lymph-nodes and lymph-vessels, Meyer, Johns Hopkins Hosp. 
Bull., vol. xvii., p. 185, 1906. PROGRESSIVE TISSUE CHANGES 
77 
Regeneration of Fat Tissue.-Fat tissue is formed by the accumula- 
tion of fat droplets in the cells of various types of connective tissue, 
particularly in the young or embryonic forms; but adult connective tissue 
may change into fat tissue by a similar process. The repair of fat tissue 
takes place by the formation of young fibrous tissue, whose cells and 
stroma gradually assume the type of fat tissue. The cells of regenera- 
ting fat tissue are at first more or less spheroidal, and remnants of the 
cytoplasm may be seen as more or less crescentic masses pressed to one 
side by the accumulating fat (Fig. 49). New fat tissue which replaces 
atrophied organs or parts of organs, such as kidney, heart, lymph-nodes, 
etc., is formed in the same way.1 
The new-formed fat cells show a rim of cytoplasm containing the nucleus, which has been crowded 
to the sides of the cells by the accumulating fat. 
Fig. 49.-Regeneration of Fat Tissue. 
Regeneration of Blood.--The formation of leucocytes appears to 
occur chiefly in the masses of lymphoid and myeloid tissue which are so 
widely scattered in the body in the lymph-nodes, in the spleen, and in 
the bone-marrow. The polynuclear leucocytes are formed in the bone- 
marrow, but their development may be completed in the circulating 
blood. Both mitotic and amitotic cell division are to be observed in 
the new formation of leucocytes, but the exact relationship between 
the new cells produced in these tw'O ways, and their respective destinies, 
are not yet very clear. Regeneration of red blood cells seems to occur 
in the bone-marrow and probably in the spleen and hsemolymph-nodes 
through mitotic division of nucleated forms. The latter may, under 
pathological conditions, appear in the vessels in varying numbers (see 
Part II., Chapter I.).2 
TRANSPLANTATION OF TISSUE. 
Transplantation of various types of tissue has been frequently at- 
tempted, and is, on both theoretical and practical grounds, of con- 
siderable interest. Transplantations have been successfully made from 
one part of the individual to another-autoplastic-or from another 
individual of the same species-homoplastic; but not from one species to 
another. 
1 For a study of regeneration, inflammation, etc., in fat tissue see Kraus, Zeits. f. Heilkunde, Bd. 
xxvii., p. 243, 1906. 
2 For a general and extended study upon tissue regeneration see Marchand, Die Wundheilung, Leip- 
zig, 1901. 78 
PROGRESSIVE TISSUE CHANGES 
A variety of general conditions favor successful transfer. The 
tissue to be transplanted must be alive and in good condition; young 
tissues are more readily transferred than old; the site to which the 
transfer is made must be adapted to the growth of the graft. A great 
difference is observed in the success of transplantation of various types 
of tissue. Thus, the epithelium of the skin and various forms of con- 
nective tissue may be, under favorable conditions, readily transplanted, 
and produce new tissue of similar type. Thus, deeply implanted 
epidermal tissue may grow and produce considerable new tissue, especially 
in the form of cysts resembling either simple or complex dermoid cysts. 
Experimental transplantation to another individual of the same species, 
of various gland and other special forms of tissue, such as portions of the 
kidney, liver, sebaceous, salivary and mammary glands, testicles, ovary, 
periosteum, bone, and cartilage, shows that there may be at first, if the 
conditions be favorable, a slight proliferation of the transplanted tissue 
cells. Together with this growth in the better-nourished parts of the 
tissue grafts there is apt to be a more or less extensive necrosis of other 
portions. But the proliferative activities of transplanted gland tissue 
are, as a rule, not permanent; they presently cease and sooner or later 
these tissues, with necrotic portions of the grafts, are absorbed. 
The body seems to react sooner or later to a transplanted organ as to a 
foreign body, and to accomplish its destruction in much the same fashion 
as in the case of invasion by infective agents. 
The many reported instances of successful homoplastic organ trans- 
plantation lack a sufficiently careful anatomical control of the organs so 
transplanted. It is undoubtedly possible to make homoplastic trans- 
plantations of the thyroid;1 the parathyroid, and the ovary; but after a 
shorter or longer period such transplanted tissue undergoes atrophy. 
Transplantation of epidermis for practical purposes has become a 
part of surgery, aiding in the repair of surface losses of skin. The graft 
properly implanted upon the granulating surface becomes closely 
attached by the growth into it of new connective-tissue cells and blood- 
vessels. The old connective tissue of the graft, as well as most of the 
epithelium, especially the superficial layers, usually dies and is cast off 
or absorbed, while new epithelium formed from the remaining cells 
makes its way over the granulating surfaces. 
In transplantations of bone the grafts seem to furnish a nidus into 
which, hand-in-hand with its absorption, new bone grows under the 
influence of osteoblasts of the old periosteum, but does not itself appar- 
ently share in the new production of bone tissue. 
The possibility of successful autoplastic transplantation of organs has 
been shown by Carrel and others.2 In individual cases the results have 
been excellent, but the total number of successes is small and the surgical 
i For study of transplantation of thyroid see Payr, Arch. f. klin. Chir., 1906, Ivxx, 730. 
a Carrel, Trans. Internat. Cong, of Surg., 1914. Payr, Arch. f. klin. Chir., 1900, Ixii; Verhandl. d. 
deutsch. Gesellsch. f. Chir., 1908. For an extremely thorough and conservative study of transplanta- 
tion, with bibliography, see SchSne, Die heteroplastische u. homdomoplastische Transplantation. 
Berlin, 1912. PROGRESSIVE TISSUE CHANGES 
79 
difficulties are enormous; and as the procedure has but little practical 
value it may be regarded simply as a demonstration of the possibilities of 
laboratory surgery. 
The only important form of transplantation is the homoplastic or 
heteroplastic, and certain recent investigations point toward the possibility 
of its ultimate accomplishment. Bashford1 and Da Fano2 some years ago 
showed that the resistance to tumor transplantation was not humoral, but 
was a factor of tissue activity and apparently correlated with the lym- 
phocytic and plasma cell reaction in the neighborhood of the cells of the 
neoplasm. Working along this line, Murphy3 has found that the growth 
of tissues in vitro is inhibited by the presence of growing bone marrow or 
spleen. After interference with the activity of these organs by treatment 
of the animals with Roentgen rays, which are known to be especially 
destructive to lymphoid and marrow tissue, it was found that grafts of 
the Ehrlich mouse sarcoma would grow in irradiated rats for at least 
thirty-two days. Should the results of this experiment be shown to be 
more generally true, they may point the way to the possibility of success- 
ful heteroplastic surgery. 
The Impulse to Cell Regeneration. 
While we can thus summarize the differing capacities of the body-cells for regener- 
ation ; while we know many of the general conditions under which the impulse to cell 
proliferation and growth is manifested; while, further, we have learned something of 
the delicate mechanims through which division is controlled and effected, at the end we 
must acknowledge that we do not know why cells divide. We may say that it is due to a 
chemical or a mechanical stimulus, and it certainly may be associated with both; or 
that increased nutrition favors, while innutrition retards cell multiplication; we may 
cite direct or remote injury, or talk of the inhibition of organic control, disturbed tissue 
equilibrium, diminished pressure, reversion, etc., but when all is said we are forced to 
recur to some unknown factor in the inherited constitution of the cell which determines 
the measure and character of its response to the most varied influences. 
The hypothesis of Ribbert, in accordance with which the capacities of cells to pro- 
liferate and grow, so manifest in embryonic life are held in restraint in the normal adult 
body by a subtle correlation of cells and tissue, is most suggestive in this connection. 
When this mutual relationship is disturbed, as is the case under many of the conditions 
in which regeneration takes place, the cells, in the conception of Ribbert, are freed from 
certain, at least, of their organic restraints. These restraining conditions he calls 
"tissue tension," meaning thereby, however, something more complex and subtle than 
simple physical tension. Thus, free to exert their primitive capacities, formerly held 
in restraint by the environment, we can conceive how cells proliferate and new tissues are 
formed in the regenerative processes without assuming the acquirement of any new 
capacties and without the assumption of vague and special stimuli.4 
1 Bashford, Ztschr. f. Immunitatsforsch., Orig., 1909, 1, 449. 
2 Da Fano, Ztschr. f. Immunitatsforsch., Orig., 1910, v, 1. 
3 Murphy, Jour. Exper. Med., 1913, xvii, 482; ibid., 1914, xix, 513; Jour. Am. Med. Assn., 1914, 
Ixii, 1459. 
4 For a resume of Ribbert's hypothesis and its applications to regeneration, hypertrophy, etc., see 
Ribbert, "Allgemenie Pathologic," 2d Ed., 1905; also references under "Origin of Tumors," p. 351. 
For a criticism of Ribbert's views see Adami's "Pathology," vol i., p. 537, et seq. 
See also, for summary of a new phase of research and interpretation in the nature of the "forma- 
tive stimulus" involved in artificially induced cell division and artificial parthenogenesis, Loeb, " Studies 
in General Physiology," p. 253. For general bibliography of regeneration, compensatory hypertrophy, 
etc., see Aschoff, Lubarsch and Ostertag's Ergebnisse, Jahrg. v. for 1898, p. 22. For a full considera- 
tion of the subjects dealt with in this chapter consult the general pathology "Les Processus Generaux" 
of Chantemesse and Podwyssotsky, 1901. 80 
PROGRESSIVE TISSUE CHANGES 
According to this conception, then, the regenerative processes leading to the forma- 
tion of new cells and tissues are not brought into play by stimuli furnished by injuries- 
the so-called "formative stimuli" of an earlier time. But new cells and tissues form 
as the result of the release of inherent capacities of cells normally held in restraint after 
the developmental period, by their associations as parts of an organism. Thus, when 
conditions of nutrition, pressure, organic association, possibly of protoplasmic con- 
tinuity or of nerve correlation, are disturbed, for example, through trauma, poisons, 
degenerations, prolonged hyperaemia and various other vascular and nutritive cellular 
disturbances, the leash of organic control is loosened, and the primitive capacities of the 
cells are temporarily free to act. But, as we have seen, this resumption of an abeyant 
potency in the ordinary processes of repair is not limitless and, sooner or later, the old 
controlling relationships of organic associations are re-established and the reparative 
activities cease.1 
In a later chapter we shall see, in discussing tumors, how a more complete and last- 
ing emancipation of certain cells, from the restraints imposed by organic association, 
may possibly lead to most significant and baleful consequences in the formation of 
malignant tumors (see p. 350). 
Finally, while we have set forth somewhat at length the conceptions of Ribbert, 
elaborating an original hypothesis of Weigert, there are so many evidences, especially 
clear in lower forms of life, of the direct incitement of cells to overgrowth and prolifera- 
tion by various physical and chemical agencies, under conditions in which the potencies 
of the so-called tissue tension cannot properly be invoked, that the assumption of direct 
external stimuli to regenerative cell activities in many cases seems fully justified. 
The cultivation of tissues outside of the body received its initiative from the exper- 
iments of Harrison, who, in 1907, found that in a hanging drop of sterile, coagulated 
lymph, undifferentiated embryonic tissue of the frog could be kept alive for a long time, 
and that under these conditions growth took place. By the adaptation of this method 
to the tissues of warm-blooded animals, the use of plasma, the warm-stage, and the 
development of various other improvements in the technique, Carrel, Burrows, Lam- 
bert, Hanes, Ebeling, Murphy, and others have made many valuable contributions 
to our knowledge of the biology of cells. In this way the growth of tissues for long 
periods and on a large scale has been observed; and transplantations have been made 
in a long series. In this way, also, tumor tissues of animals may be grown and fragments 
of embryonic heart muscle maintained in pulsation for many weeks.2 
1 For a consideration of the bearing of this hypothesis on compensatory hypertrophy, see Ribbert, 
"Lehrbueh der allg. Pathologic," 1905, p. 315. 
2 For a resume of technique and results of cultures of adult and embrj'onic tissues see Harrison, 
Lambert, and Burrows, Jour. Am. Med. Assn., 1913, lx, 1660-62; Carrel, Jour. Exper. Med., 1912, xv, 
516; ibid., 1913, xviii, 287; and Murphy, ref. p. 79. CHAPTER V. 
INFLAMMATION. 
General Considerations. 
The conception of inflammation was originally a clinical one in which 
the process was marked by special symptoms-redness, heat, swelling, 
pain, and impaired function. This conception was gradually enlarged 
to embrace the new formation of tissue which might be associated with 
or follow these symptoms, or which might be independent of them. 
After the knowledge of the importance of the cell became general it 
was upon the formation and accumulation of cells and other substances 
that attention was especially fixed. Finally, the processes and structural 
alterations embraced in the conception of inflammation became so 
varied and complex that a definition or even a characterization seemed 
not only difficult, but wellnigh impossible. 
It is only within the past decade or two that the processes and lesions 
involved in inflammation have been seriously considered in the light of 
comparative pathology and as biological problems divorced for purposes 
of research from the dominance of traditional clinical conceptions. In 
view of our increased knowledge of the structure of cells and of the im- 
pulses immediate and hereditary which determine their performances, it 
seems possible now to resolve the complex processes and lesions embraced 
in the general notion of inflammation into more simple factors, and to 
arrive, if not at an exact definition, at least at & reasonable conception 
of the relationship of its phenomena to each other, to those of normal 
physiology, and to other phases of disease. 
With this end in view it seems wise at first to rehearse as simply and 
briefly as is practicable some of the more typical of the phenomena and 
lesions which are commonly grouped under the term inflammation. 
While the death of tissue from trauma, and degenerative alterations 
in the tissues in the presence of various forms of poisons are often impor- 
tant factors in the inflammatory processes, we shall not consider them 
separately here, because they are incidental rather than inherent and 
have already been treated in the section on Degenerations and Necrosis. 
But it should be noted that various phases of albuminous degeneration, 
local or general, which are induced by the poisons of the pathogenic 
bacteria, are very often associated with inflammation, and not infre- 
quently modify, or may even determine, its occurrence. 
A comprehensive survey of the conditions under which inflammation 
most frequently takes place shows at once that it is almost always asso- 
ciated with some form of injury. This may be direct trauma, or exces- 
sive heat or cold. It may be poisons of various kinds-from the cruder 
81 82 
INFLAMMATION 
inorganic poisons inducing immediate and gross tissue destruction to the 
subtle toxic substances which result from the metabolism of micro- 
organisms or from the aberrant metabolism or degeneration of the body- 
cells themselves. Dead cells or tissues or foreign substances of many 
kinds within the body are common incitants of the inflammatory processes. 
Let us now look at some of the ways in which the living body re- 
sponds to injury, and first at an injury which is very slight and simple. 
Types of the Inflammatory Reaction of the Body to Injury. 
Injury to Non-vascular Tissue.-If a small clean cut be made in 
living fibrillar connective tissue, not involving blood-vessels, and affecting 
only the cells and fibres in the vicinity of the incision, and if the sides 
of the wound be immediately placed and held together, the resulting 
changes which lead to the complete restitution of the part are compar- 
atively simple. A small quan- 
tity of fluid which oozes from 
the tissue spaces sticks the sides 
of the cut together. Such con- 
nective-tissue cells as have been 
seriously injured, especially if 
the nuclei have suffered, die and 
disintegrate; and these, together 
with such tissue fragments as 
may be present, are removed by 
phagocytes or through autolysis 
and absorption. But cells whose 
nuclei have remained intact, 
whether directly upon the inci- 
sion or in its immediate vicinity, 
become larger and more granu- 
lar, may divide by mitosis, ex- 
tend their bodies or processes 
across the plane of incision, bridging this at intervals with living pro- 
toplasm. Under the influence of these cells, new' intercellular fibres 
are formed, which in a short time bind the sides of the wound firmly 
together (Fig. 50). Thus, with but the slightest amount of tissue 
destruction, and with no involvement of the blood-vessels, a simple 
mechanical injury may be made good. This form of reaction to injury 
of living tissue is known to the surgeons as healing by "first intention." 
The mode of healing does not essentially differ if there be a slight injury 
to the blood-vessels. 
In injury to a non-vascular part, like the cornea, for example, the 
primary reaction to the damage manifested by the fixed connective-tissue 
cells is often complicated by the wandering in of leucocytes from the 
conjunctival blood-vessels in the manner indicated in the next section. 
This participation of distant blood-vessels and leucocytes is, no doubt, 
incited by a reflex stimulation of the nerves of the blood-vessels, and may 
Fig. 50.-Healing of a Wound of the Cornea. 
Without involvement of blood-vessels a few new 
connective-tissue cells have formed along the line of 
slight injury (incision), and the sides of the wound 
are joined by the new cells and fibrils formed by 
them. The epithelium has regenerated over the 
surface. INFLAMMATION 
83 
be fostered under certain conditions by the absorption of injurious sub- 
stances which are carried to the nearest blood-vessels by the lymphatics. 
Thus it is that in injuries to the cornea, a non-vascular part, the lesion 
is often complicated by the secondary participation of the adjacent 
blood-vessels. 
Injury to Vascular Tissue.-Let us now look at the effect on a vascular 
tissue of an injury not immediately destructive. For this purpose the 
mesentery of the bladder of a curarized frog, drawn out upon a suitable 
plate1 upon the stage of the microscope and kept moist by irrigation with 
three-fourths-per-cent. salt solution, affords a succession of most instruc- 
tive pictures. The mechanical disturbance of the organs exposed, 
desiccation, and a variety of other physical and chemical vicissitudes to 
which they are subjected, are sufficiently damaging to incite a complex 
train of responses on the part of the living tissues. 
In studying the circulation of the blood in small vessels under the 
microscope it should be remembered that, while the walls of these vessels 
are made up of living tissue and are capable of responses by movement 
or by structural change to external agencies, whether applied directly or 
through the nerves, they are also elastic pipes through which fluid flows, 
and that both pipes and fluid are subject to the laws of mechanics. 
These mechanical laws are often modified in expression, it is true, by 
the subtle energies which living tissues wield, but, as Thoma more than 
any other has shown, they are not to be ignored by the serious student 
of the living body, either in health or disease. 
In the bladder or mesentery of the frog the arteries and veins with 
their connecting system of capillaries are clearly seen. When the cur- 
rent is rapid the cells of the blood in the arteries and veins are gathered 
into a red axial mass in which the separate cells may not be distinguish- 
able, owing to their crowding and the rapid flow. Outside of this, against 
the walls, is a clear marginal zone in which a leucocyte is occasionally 
visible. If for any reason the rate of flow be considerably diminished, 
the leucocytes, which are specifically lighter than the red cells, gather in 
the marginal zone. If the current become very slow or be arrested, the 
marginal zone disappears and the red and white cells intermingle.2 
Soon after the exposure of the bladder or mesentery the tissues be- 
come hypersemic. The arteries, veins, and capillaries dilate, and the 
blood, encountering less resistance from the walls, flows more rapidly 
through them. This increased rapidity of the blood current does not, 
however, last long, although the vessel still remains dilated. After a 
variable period, owing, it is believed, to changes in the endothelia of 
the vessels, the blood meets with so much resistance that it flows more 
slowly than under normal conditions. Temporary or even permanent 
stasis may occur in some of the vessels, but this is not a constant nor a 
characteristic occurrence. White blood cells-leucocytes-now begin 
to accumulate along the inner walls of the veins and to become fixed 
1 See description of Thoma's frog-plate, p. 111. 
2 This distribution of the blood is almost, if not wholly, mechanical, and may be simulated in glass 
tubes with a fluid in which lifeless particles of different specific gravities are suspended. The particles 
of the lesser specific gravity assume, when the flow is established, the peripheral portion of the stream. 84 
INFLAMMATION 
there, so that after a time the whole inner surface of the veins may be 
more or less thickly sprinkled, and even closely crowded, with adherent 
leucocytes. These may either lie firmly against the endothelium or be 
dragged slowly along by the current of blood sweeping past them. 
Some are dragged by the blood current into pyriform shapes, showing 
that they are adherent at a small point only, and thus they may be 
detached from the wall and rejoin the circulating blood. They may by 
amoeboid movement crawl slowly along the interior of the wall, even 
against the current. In the capillaries, also, a similar comportment 
of the leucocytes may be seen. 
After a time, which varies considerably-in the bladder sometimes 
within an hour after its exposure; in the mesentery usually later-some 
of the leucocytes commence to make their way slowly through the walls 
of the veins and capillaries. At first a little shining knob appears on 
Fig. 51.-Emigration of Leucocytes from the Blood-vessels of the Mesentery of the Frog. 
Some of the leucocytes are clinging to the interior of the vessels; some are passing through the 
walls; some are wandering away through the tissue spaces. There has been diapedesis of a few red 
blood cells. 
the outside of the wall opposite to the cell which is sticking within, and 
this outer portion grows larger as the part still within grows smaller, 
until at length the entire cell is outside of the vessel. The cell now may 
immediately detach itself and wander off in the tissue spaces, or it may 
remain for some time attached to the outside of the wall (Fig. 51). This 
passage of the leucocytes through the walls of the capillaries and veins- 
it does not occur in the arteries-is called emigration. The emigrating 
cells are largely the polynuclear leucocytes, but mononuclear forms- 
lymphocytes-and eosinophiles may also pass out of the vessels. 
The cells pass between the endothelia through the cement substance, 
which apparently is in some way changed in the inflammatory process. 
They may pass through very rapidly, but usually their progress is slow 
and often interrupted, so that cells may be seen motionless for a long 
time in various stages of progress through the walls. A half minute, or INFLAMMATION 
85 
even less, may suffice for their passage, or they may be hours about it. 
Thus, after a variable time, if the conditions have been favorable, the 
tissues immediately around the capillaries and veins, and even those 
somewhat remote from them, may be more or less densely crowded with 
leucocytes, some motionless and in the spheroidal form, others moving 
about through the tissue spaces (Fig. 52). Leucocytes may pass out of 
the tissues on to free surfaces of the inflamed part, or they may wander 
into the lymph-vessels and so re-enter the circulation. 
It is probable that the emigration of the leucocytes is due in part to 
a sort of filtration process with which the pressure of the blood within 
the vessels is concerned, and also to capillary attraction at the point of 
emergence. But the inherent contractility of the cells themselves forms, 
Showing extravasated leucocytes in the vicinity of the blood-vessels, with oedema of the surrounding 
connective tissue. 
Fig. 52.-Exudative Inflammation in the Wall of the Appendix Vermiformis. 
doubtless, a very important factor. That in most cases chemotaxis plays 
a significant part in directing the course of the leucocytes seems to be 
well established, and it is largely to this agency that the gathering of 
leucocytes is due in the vicinity of the deleterious substances which 
incite inflammation. 
In regard to chemotaxis it should be said in brief that the direction 
of locomotion in protoplasm may be determined by chemical substances 
in the vicinity. This is the case not only in the lower forms of life, as in 
certain bacteria and protozoa, but also in such cells of higher organisms 
as have retained a certain independence of locomotion, for example, in 
the leucocytes and certain cells of the connective tissue. To this form of 
response to external agencies the name chemotaxis has been applied. In 
some cases the effect of chemical agents in the environment is not to 
attract, but to repel, protoplasm. This has been called negative chemo- 
taxis. Chemotaxis and certain allied responses to outside influences 86 
INFLAMMATION 
have been found to play an important role in health as well as in some 
forms of disease, and have been the subject of much careful study.1 
If we return now to our observation of the living mesentery it will be 
found that while emigration of leucocytes is going on, the red blood cells, 
although for the most part carried along as usual in the current of the 
veins and through the capillaries, still often find their way in small, and 
sometimes in very large, numbers into the surrounding tissues. They 
are, it is believed, carried passively through the cement substance 
between the endothelia by minute streams of fluid which under these 
conditions are flowing in abnormal quantities through the walls. This 
extravasation of the red blood cells is called diapedesis. It appears to 
follow the emigration of the leucocytes, which seems in some fashion to 
prepare the way for the more mechanical exit of the red cells. 
By this time it will usually be found that the tissue around the vessels 
is somewhat swollen and more succulent than normal, and fluid may be 
poured out on the free surface. The fluid which thus gathers is called 
serum. It is similar to the simple non-inflammatory transudates, 
except that it is richer in proteids and is mixed with cells. This serum 
has passed out of the blood-vessels along with the blood cells, and, as its 
composition differs somewhat from that of blood plasma, it is evident 
that it has undergone a change as it passed. The way in which this 
alteration in the composition of the blood plasma occurs as it passes 
through the walls of the vessels and becomes 
the serum of exudation, we do not under- 
stand. But it is probably due to metabolic 
processes in the endothelial cells by which 
what has been called a "selective filtration" 
is secured. 
The fluid exudate contains fibrinogenous 
substance, and from this, when the condi- 
tions are favorable, fibrin may be formed 
(Fig. 53) by a change similar to that which 
occurs in the coagulation of the blood. The 
leucocytes which wander into the tissue spaces outside the vessels may 
encounter conditions inimical to life, from innutrition or from the pres- 
ence of deleterious substances, and thus these and other cells furnish, 
as they die and disintegrate, the fibrin ferment essential to coagulation. 
Clusters of fibrin fibrils may thus often be seen surrounding dead and 
disintegrating cells (see Fig. 54).2 
If at this time the exposed bladder or mesentery of the frog be 
restored to the abdominal cavity and the animal placed under favorable 
conditions, the reaction of the vessels and cells to the unusual environ- 
ment may, if the injury have not been too severe, gradually subside. 
Fig. 53.-Fibrin in Inflammatory 
Exudate. 
1 For a fuller consideration of chemotaxis, with bibliography, consult Davenport, "Experimental 
Morphology," Part I., p. 32 et seq. For the forms of leucocytes which emigrate under various condi- 
tions see Adler, A. Jacobi's Festschrift, 1900, p. 309. 
2 For a discussion of the relationship of fibrin formation to cells which may furnish a substance 
inducing coagulation see Hauser, Virch. Arch., Bd. cliv., p. 335, 1898; also Arnold, Cbl. f. Path., Bd. 
x., p. 313, 1899. INFLAMMATION 
87 
The circulation is then re-established, the serum is absorbed, the leuco- 
cytes which have not come out upon the surface or died in the tissue 
spaces may re-enter the lymphatics. Fibrin, if this have been formed, 
and red blood cells which have escaped from the circulation are dis- 
posed of under the influence of ferments which leucocytes furnish (see 
p. 105), or may be carried off by the wandering leucocytes; or, as is not 
infrequently the case, blood pigment resulting from the reduction of 
the haemoglobin which leaves the red blood cells by osmosis may remain 
for some time, in situ, as the only mark of an earlier active inflammatory 
process. 
Fig. 54.-Fibbin Forming Around Dead Cells in the Interstices of Tissue. 
Thus in the living animal1 we can learn by direct observation the 
way in which the serum, fibrin, and red and white blood cells get into 
tissues and upon free surfaces in certain forms of injury involving the 
blood-vessels. 
We can see also by this experimental observation just what the 
factors are which induce the so-called "cardinal symptoms" of inflam- 
mation-the redness and heat due to hypersemia; the swelling to accu- 
mulation of exudate; the pain to pressure on the nerves; and the impaired 
function to the disturbances of nutrition to which all of these factors 
contribute. The materials gathering in or upon the tissues under these 
conditions are called exudates, and this phase of inflammation is com- 
monly called exudative inflammation. 
Hand-in-hand with these changes, which are directly associated with 
lesions of the blood-vessels, there occur alterations of the cells of the 
affected part, which are not readily observed in the experimental animal, 
especially of the connective-tissue cells. These may suffer regressive 
changes-albuminous or fatty degeneration or necrosis; or, on the other 
hand, they may undergo progressive changes. The bodies may swell; 
1 Thoma has shown by similar studies on warm-blooded animals that the reaction to injury is in 
them essentially similar to that in the frog. 88 
INFLAMMATION 
mitosis occurs; and they may divide. This may take place in the 
cells of the fibrillar connective tissue and in the endothelium of the 
blood- and lymph-vessels. The new-formed cells may detach themselves 
from their original site and join the leucocytes as wandering cells. If 
there are small islets of lymphoid tissue, such as are widely scattered 
through the body (see p. 481), these may show hyperplasia, and appear 
as clusters of small spheroidal cells with large deeply staining nuclei and 
a small amount of cytoplasm. These clusters of small cells resembling 
lymphocytes are especially noticeable in the vicinity of the lymph 
channels near small blood-vessels. 
Let us now look at the effect upon a living vascular tissue of injury 
inflicted in a different way. 
Injury from Micro-organisms.-Suppose we inject into the ear vein 
of a rabbit a small amount of a pure culture of a well-known and very 
common micro-organism, Streptococcus pyogenes. Little masses of the 
living germ will enter the heart and be driven out again through the 
arteries in whose smaller twiglets or in the capillaries some of them will 
lodge as emboli. Here in the living tissues the bacteria may find good 
nutrient conditions and begin to proliferate, increasing so rapidly in 
number that they may distend 
the vessels in which they lie. If 
after twenty-four hours the ani- 
mal be killed, and one examine 
the organs in which the bacterial 
emboli have caught and grown 
-in the liver, for example-he 
finds small blood-vessels here 
and there distended with bac- 
teria. But the parenchyma and 
interstitial tissue about them 
appear to be intact (Fig. 55). 
If, however, the animal be 
allowed to live longer-say two 
or three days-before the ex- 
amination, the condition of the 
tissue about the growing bacte- 
rial mass in the typical course of 
events shows marked and signi- 
ficant alteration. Immediately 
around the bacteria the nuclei fail to take the nuclear stains (Fig. 56); 
the cytoplasm is unusually granular or fallen into fragments. These are 
the marks of cell death, and from the situation of this area of dead tissue 
about the colony of growing bacteria we may infer-and the inference 
is confirmed by a host of tests and observations-that, in growing, the 
bacteria have set free in the tissue about them some chemical substance 
whose presence is incompatible with the continuance of the life proc- 
esses in the liver cells, which, in fact, has killed them. 
But very soon the tissues near by show a different sort of reaction to 
Fig. 55.-Bacterial Embolus in the Liver. 
The bacteria have grown in a mass within the 
small blood-vessel. The liver cells in the vicinity 
appear unchanged. INFLAMMATION 
89 
this active poison set free upon the spot. Leucocytes gather on the 
borders of the necrotic area and may form a dense ensheathing mass 
about it (Fig. 57). If we look for the origin of these, we find that close 
outside the area of dead tissue and among the gathered leucocytes the 
smaller blood-vessels are dilated, overfilled with blood, and such marks 
of the emigration of leucocytes as a tissue removed from the animal and 
prepared for examination may show are unmistakable. Not infre- 
quently extravasated red blood 
cells and fibrin and a distention 
of the tissue spaces with fluid 
still further characterize the 
process as exudative inflamma- 
tion. 
It was observed in the ex- 
posed mesentery or bladder of 
the frog that the leucocytes, 
once outside the vessels, wan- 
dered off in various directions in 
the tissues, some to the surface, 
some to the lymph-vessels, and 
some far from the veins or 
capillaries from which they 
emerged. Not so here. The 
extravascular leucocytes gather 
close in the border zone of the 
necrotic area or enter it. And 
we may usually see in the outer 
parts of such an area of dead tissue scattered leucocytes which are 
themselves undergoing changes indicating the death of the cell. They 
too have encountered the poison set free by the growing bacteria. 
The changes which have just been described as the result of experi- 
ment in the animal are practically identical with those occurring in man 
as the result of accidental inoculation. 
If the process continue, one may find on later examination that the 
dead-tissue mass has softened through the action of proteolytic enzymes 
developed on the spot (see p. 105), the bacteria are scattered, and the 
whole central portion may be occupied by a grayish or yellowish gru- 
mous or fluid mass of dead cells, cell detritus, albuminous and fatty 
granules, bacteria and leucocytes in various stages of necrosis and 
disintegration. 
Such a localized result of exudative inflammation with death and 
disintegration of tissue is called an abscess; the material which it contains 
is called pus. For a more detailed consideration of suppuration and the 
characters of pus see p. 198.1 
The changes by which, if the animal survive the formation of abscess, 
the active processes are brought to a standstill and repair is effected, we 
Fig. 56.-Bacterial Embolus in the Liver, with 
Necrosis. 
The bacteria are still largely confined to the vessel, 
but a few are outside. There is a zone of necrotic 
liver cells about the growing mass of cocci. 
1For a resume of forms of exudate cells, with bibl., see Helly, Ziegler's Beitr. z. Path. Anat., Bd. 
xxxvii., p. 171, 1905. 90 
INFLAMMATION 
need not now follow. But it concerns us here to appreciate that this is 
a type of one of the most important phases of the inflammatory process; 
a phase in which a poison produced in the body by the metabolism of 
micro-organisms incites a complex train of active and passive tissue 
changes. 
Instead of forming abscesses with softening of the tissue, the pus 
cells and other exudates may be distributed diffusely through the inter- 
stices of the tissues, forming a so-called purulent infiltration. 
Fio. 57.-Necrosis and Suppuration in the Liver from Bacterial Infection-Exudative and 
Necrotic Inflammation. 
The bacteria are scattered in masses, the liver cells about them are necrotic, while leucocytes have 
gathered in large numbers within the necrotic area. With slight further disintegration this mass of 
dead liver tissue and pus cells would form an abscess. 
A narrow canal leading to a focus or area of inflammation is called a 
fistula. 
In our study of illustrative phases of inflammation we now turn to 
the processes by which repair of injured tissues, after more or less involve- 
ment in the inflammatory phenomena, is brought about. 
Resolution in Inflammation.-In many cases of exudative inflamma- 
tion, after the subsidence of the active changes in the blood-vessels, 
the exudates are entirely though often very slowly absorbed, and the 
tissue returns to its normal condition; this is called resolution. 
If many new connective-tissue cells have been formed, these may 
produce fibrils and thus a certain amount of new tissue may develop, NFLAMMATION 
91 
compromising the blood and lymph circulation, so that for a long time 
the site of the inflammation may be swollen and hard. 
Under certain conditions, on the other hand-for example, in the case 
of a wound with loss of substance, or in an acute exudative inflamma- 
tion of a serous membrane in which the surface is deprived of its normal 
mesothelial1 covering, or in the healing of an abscess-a considerable 
amount of new tissue may be produced through the agency of old cells 
or of new cells formed in the inflammatory process. 
We will now consider the way in which repair of a wound or injury 
with loss of tissue is effected. 
The Healing of Wounds. 
The way in which new inflammatory tissues are formed may be best 
understood by following the process of healing in a wound with loss of 
substance-for example, in a wound through the skin or a mucous mem- 
brane into the tissue beneath. At first there may be haemorrhage. 
From a healing abdominal wound. Early stage with very thin-walled blood-vessels, leucocytes, 
and young connective-tissue cells. There are few intercellular fibrils. 
Fig. 58.-Granulation Tissue. 
After this has ceased, the injury to the tissue, the unusual exposure of 
deep-seated parts, the presence of foreign substances, etc., may induce 
the same series of events which we have seen occurring in exudative 
inflammation with production of serum, fibrin, and pus. The blood- 
vessels dilate, the circulation becomes slower, serum transudes, and 
emigration sets in. Certain of the cells and fragments of intercellular 
1 The morphological resemblance of the flat cells covering the surfaces of the great serous cavities- 
peritoneal, pleural, and pericardial-to the endothelium of the blood- and lymph-vessels has led to 
their being also called endothelium. But their genesis as well as certain physiological capacities which 
they still retain, render more fitting the name mesothelium. See reference to Minot in footnote 
on p. 377. 92 
INFLAMMATION 
substance near the seat of injury may die, and in time are cast off or are 
disintegrated or dissolved and absorbed or otherwise disposed of by 
phagocytes (see p. 98). The tissue may become soaked and swollen 
by the transuded serum, and the connective-tissue cells in the vicinity 
may undergo proliferative or degenerative changes. 
Granulation Tissue.-After a variable time, usually on the second or 
third day if all goes well, the surfaces of the wound may be more or less 
covered with tiny red nodules called granulations. These granulations 
contain numerous thin-walled blood-vessels which have sprouted out 
from the old vessels near the seat of injury, and around these a new 
The walls of the blood-vessels are thicker, and intercellular fibrils are forming. 
Fig. 59.-Granulation Tissue from Wound of Skin. 
loose, succulent tissue is formed, largely, it is believed, from proliferation 
of connective-tissue cells. This is called granulation tissue (Fig. 58). 
On the surface of the granulations are usually pus cells in varying 
quantity, or the granulations may be more or less covered with dried 
exudate. The way in which the new blood-vessels form by proto- 
plasmic sprouts from the old, and the manner in which connective 
tissue develops from older connective-tissue cells, have been already 
described in the section on Regeneration. Let it suffice here to say that 
the cells of the granulation tissue are at first mostly small and spheroidal 
or polyhedral, and are usually packed closely together with only a 
small amount of fluid intercellular substance. Presently some of the 
cells become larger and polyhedral, elongated, fusiform, or branched, 
and after a while a delicate, fibrillar intercellular substance makes its 
appearance about them and grows more and more abundant (Fig. 59). 
These larger, variously shaped cells, which appear to be formed out of 
the small spheroidal or indifferent cells of the granulation tissue, are 
usually granular, and the nucleus is generally large and distinct. Some INFLAMMATION 
93 
of these larger cells which seem to be more or less directly concerned in 
the formation of intercellular fibers are called fibroblasts (Fig. 60). 
As the granulation tissue grows, new, small spheroidal cells are 
gathered by proliferation or by continued emigration. Some of these 
participate in the formation of the granulation tissue, while others, not 
finding conditions suitable for their further development, or even for 
their continued existence, die and pass 
off on the surface, together with some 
transuded fluid, as pus. 
The polynuclear leucocytes do not 
apparently share in the formation of 
new tissue. To what extent this new 
tissue is derived from old connective- 
tissue cells and cells of the endothelial 
type-the macrophages of Metchnikoff 
-or how largely it may come from 
emigrated lymphocytes, assuming the 
characters of "plasma cells" (see p. 
74), is not yet certain; but the latter 
class of cells is probably not actively concerned. 
Cicatricial Tissue.-The new tissue gradually becomes more and more 
dense, the intercellular substance more abundant, while the cells decrease 
in number and become flatter and less conspicuous. The epithelium may 
now grow over from the sides, forming by mitosis from the old epithe- 
lium at the edges of the wound (Fig. 61), and finally cover the new 
Fig. 60.-Fibroblasts of New Connective 
Tissue in a Healing Wound. 
There are numerous new-formed intercellular 
fibrils. 
There was loss of substance-muscle, fibrous tissue, and surface epithelium. The lost tissue has 
been replaced by the vascular granulation tissue, which is oldest and most dense in the deeper portion, 
while on the surface is a layer of tissue detritus, pus cells, etc., partly dried and forming a scab over the 
granulations. New epithelium is pressing forward from the old at the edges over the surface of the new- 
formed tissue. 
Fig. 61.-Healing Wound in the Tongue of a Dog. 
vascular tissue. The new tissue, having at last undergone more or less 
shrinkage, with atrophy of the blood-vessels, consists of a dense, firm 
mass composed largely of fibrillar basement substance with a few flat- 
tened cells (Fig. 62); and with this, which is the cicatrix, the healing is 
complete. The cicatricial tissue in its shrinkage, as it becomes more 94 
INFLAMMATION 
fibrillar and denser, often brings about considerable distortion of adjacent 
parts. 
Variations in the Healing Process.-Although in the production of new 
tissue, in connection with or following exudative inflammation, essen- 
tially the same processes are involved in all cases, there are yet very 
marked differences in the degree in 
which the different factors share. 
Thus the vascular and exudative 
phenomena may predominate and 
very large quantities of serum, 
fibrin, or pus collect, while the 
amount of new-formed tissue may 
be insignificant. The production 
of a large amount of exudate, 
particularly of pus cells-suppuration-usually marks the presence of 
micro-organisms whose locally elaborated poisons complicate or retard 
the healing process. 
In other cases the formation of new tissue is the dominant feature, 
and the production of exudates seems to be almost entirely subordinated 
to this end. 
The process of repair which is complicated by exudative inflammation 
Fig. 62.-Cicatricial Tissue from a Healed 
Wound. 
From the inner surface of a granulating ovarian cyst containing pus. The tissue between the 
new capillaries is ill-formed, oedematous, and with few cells, most of which have undergone fatty 
degeneration. 
Fig. 63.-Exuberant Granulations. 
or effected only by the gradual formation of a considerable amount of 
new tissue, is called by surgeons healing by "second intention." 
The distinction between healing by first and second intention, which 
is of practical importance in surgery, is, from the pathological stand- 
point, only a quantitative one; for the restitution of the parts to the 
healthy condition is in both cases brought about by exudation and prolif- 
eration of cells usually under the influence of vascular changes, but in one 
case the latter changes are very slight, in the other more or less extensive. INFLAMMATION 
95 
There is much variation in the formation of granulation tissue. Thus, 
sometimes the body cells respond but feebly to the unusual conditions, 
and neither cell proliferation nor blood-vessel growth is active. On the 
other hand, the development of blood-vessels may be excessive, while 
other tissue formation lags. Under these conditions, loops and tangles 
of thin-walled, contorted new vessels may project from the granulating 
surface, while useful tissue formation remains in abeyance, or the new 
cells undergo fatty or other forms of degeneration (Fig. 63). The result 
of this disproportionate growth of ill-formed blood-vessels is the exuber- 
ant granulations ("proud flesh") which the surgeon frequently removes 
from unhealthy healing surfaces.1 
Fig. 64.-Regeneration of Epithelium over Superficial Wound of Cornea-Rabbit. 
The new epithelium has been formed in excess. 
Cavities formed by abscesses or by necrosis in any part of the body 
may be filled up and their sides drawn together in a cicatrix, by the for- 
mation of a provisional mass of granulation tissue similar in character to 
that which grows in external wounds. So, similarly, cysts may be obliter- 
ated and ulcers partially filled and drawn into cicatricial healing. Large 
free surfaces, like the pleura and the peritoneum, may, through the 
intervention of granulation tissue, pass from the denuded condition 
of an active exudative inflammation, either with or without adhesions, 
into a condition which, though by no means a return to the normal, we 
yet designate as repair. 
The so-called organization of a thrombus in a blood-vessel is brought 
about by processes practically identical with those which have just been 
described in the formation of new tissue in reparative inflammation in 
an external wound. The endothelial cells of the vessels and the con- 
nective-tissue cells in their walls proliferate, new blood-vessels develop 
by sprouts from the already existing smaller vessels in their walls or 
close about them. The new cells and new blood-vessels thus derived 
1 For a special study of granulation tissue see Reinbach, Ziegler's Beitr., Bd. xxx., p. 102, 1901. 96 
INFLAMMATION 
gradually penetrate the clot, forming new connective tissue, which 
replaces step by step the fibrin and blood which are gradually softened 
by autolysis and absorbed or removed by phagocytes. 
The part which the thrombus plays in its so-called organization is 
thus a wholly passive one. It acts only as a temporary supporting 
texture for the development of the new tissue derived from other sources 
which step by step replaces it. 
In the processes of repair by the formation of new tissues, the latter 
are often developed in excess, the overproduction after a time ceasing, 
when the normal condition is restored. Thus, if the epithelium be 
scraped from a small area on the front of the cornea the new epithelium 
which covers the injury is often heaped up in excess (see Fig. 64). 
Hyperplasia and Interstitial Inflammation. 
Hyperplasia of the fibrous interstitial tissue of the internal organs 
and other parts of the body-as, for example, in the liver, kidney, heart, 
nervous system, etc.-is of frequent occurrence and is usually associated 
with changes in the parenchyma. In some cases the formation of fibrous 
tissue clearly follows evident and often acute inflammatory processes 
and bears the same relation to antecedent reaction to injury that the 
cicatrix in a healing wound does to the granulation tissue from which it is 
formed. In other cases it is associated with long-continued hypersemia- 
chronic congestion-of the organ involved. Again, gradual hyperplasia 
of the interstitial tissue takes place by the slow increase of cells and 
stroma, without evidence of an active cell proliferation or marked involve- 
ment of the blood-vessels. Finally, hyperplasia of the interstitial 
tissue may be and probably usually is secondary to damage to or atrophy 
of the parenchyma, as in the spinal cord after degeneration in nerve 
tracts or in the heart after damage to the muscle fibres; in the liver and 
kidney in connection with atrophy of the specific epithelial cells. In 
such cases it is often spoken of as replacement hyperplasia. These forms 
of fibrous-tissue hyperplasia will be considered with more detail in the 
sections dealing with the special lesions of the viscera. They have all 
been usually regarded as marks of inflammation. Some of them unques- 
tionably are so; concerning others, doubt will continue until our knowl- 
edge as to their excitants considerably increases. In the meantime 
the term fibrosis is sometimes applied to the results of fibrous-tissue 
hyperplasia, though this is still most commonly included among the 
inflammatory processes.1 
Those important phases of inflammation which are due to damage 
from special forms of micro-organisms will be considered in detail in the 
chapter of this book devoted to the Infectious Diseases. 
1 For a suggestive and interesting consideration of the relationship between inflammation and 
various forms of "fibrosis" see Adami, Middleton Goldsmith Lectures, Medical Record, March 14th and 
21st and April 4th and 11th, 1896. INFLAMMATION 
97 
Special Phases of Inflammation. 
The several phases of the inflammatory process, which we have now 
considered, are fairly typical of the reaction of the living body to various 
forms and degrees of injury. If we look at them together and seek to 
gather their dominant features, we find that the changes, varied as they 
are in character as well as in degree, are mostly of three kinds: first, 
those involving a greater or less amount of degeneration or necrosis; sec- 
ond, those involving local disturbances of the circulation, as well as 
alterations in the distribution and character of the fluid and cellular 
elements of the blood-exudative changes; and third, regenerative, produc- 
tive, or reparative changes. 
Of these three groups of alterations in inflammation those involving 
the blood-vessels and their contents are, in a clinical sense, most striking 
and characteristic, and to many seem to dominate the inflammatory 
processes. But in fact all are closely associated. The various phases of 
inflammation depend upon the nature and extent of the injury, the 
inherent reactive vigor of the cells, and the character and position of 
the tissue involved. 
Special names have been attached to various forms of the inflamma- 
tory process, descriptive of the feature which from the particular stand- 
point of the observer seems most striking or important. Some of the 
names are descriptive of clinical symptoms, some express the duration 
or character or situation of the lesion, some seek to imply more or less 
well-founded views of the nature of the process. Thus among the forms 
of exudative inflammation, those in which the extravasated serous fluid 
is the most marked feature are often named serous inflammations. If 
fibrin predominate, it is called fibrinous; if associated with much blood 
extravasation, it is termed hamorrhagic. When the agencies are present 
which induce the necessary vascular changes and promote the emigration 
and gathering, and often the destruction, of leucocytes in considerable 
or large numbers, we have a suppurative or purulent inflammation. If 
much tissue death be associated with the process, it is named necrotic 
inflammation. 
Again, if certain mucous membranes or mucous glands be subjected 
to the inciting agencies, they may respond by an overproduction of 
mucus as well as by an increase of death of cells; this is mucous or catar- 
rhal inflammation. In inflammation of the mucous membranes fibrin 
intermingled with other exudate sometimes forms more or less well- 
defined and often tough pellicles or membranes upon the surface. This 
is called pseudo-membranous inflammation. Finally, these various 
forms of exudate may be produced simultaneously, whence arise such 
compound designations as sero-purulent, muco-purulent, etc., inflamma- 
tion. Inflammation with the formation of new tissue is called pro- 
ductive qt reparative. 
Local inflammation, especially when incited by micro-organisms, is 
often associated with systemic infection due to a distribution of the 98 
INFLAMMATION 
inciting agents through the body. This condition will be considered in 
the chapter dealing with the Infectious Diseases (see page 197). 
Inflammation, especially of infective origin, is so frequently asso- 
ciated with degenerative changes in the more highly organized cells- 
the parenchyma cells-of organs that when these are conspicuously 
involved the term parenchymatous inflammation has been used. It is 
better, however, to hold the degenerations apart and consider them as 
associated but not identical with the inflammatory processes. Similarly 
the term interstitial inflammation, though very commonly employed, 
indicates a comparatively rare occurrence. That which is embraced 
under the term is usually an interstitial hyperplasia secondary to damage 
to the parenchyma cells of organs (see p. 96). 
It has seemed wise to many to attempt to draw a sharp distinction 
between those phases of inflammation which involve only the degener- 
ation of tissues or the redistribution of already formed tissue elements- 
serum, fibrin, and blood-and those phases which are productive or 
reparative. But while this attempt aims at the recognition of a biologi- 
cal distinction of fundamental importance, it encounters the great prac- 
tical difficulty that both phases of the reaction of tissues to injury, the 
exudative and the productive, occur together, so that none of the named 
classes of inflammation represent simple and unmixed forms of tissue 
reaction. The important thing is to conceive, as clearly as our knowl- 
edge permits, the nature of the processes which underlie these various 
manifestations of disturbed cell function and their associated tissue 
alterations. Then the names may serve useful temporary ends at least 
without implying too much or concealing too little knowledge. 
The Disposal of Foreign and Dead Substances in the Body- 
Phagocytosis-Autolysis. 
It was stated at the beginning of this chapter that the injuries which 
lead to inflammation are extremely varied. The degree and character 
of the resulting inflammation are closely related to the inciting agents. 
We have already taken as general examples of the inflammatory response 
to injury, one in which there was a simple mechanical damage, and the 
other in which a more extensive and prolonged injury was effected by 
the presence of living bacteria. 
While it is not practicable to classify the various phases of inflam- 
mation according to the character of their incitants it is convenient to 
consider by themselves the effects of animal and of vegetable parasites, 
among the latter especially the bacteria. In subsequent chapters, 
under the headings of Animal Parasites and of Infectious Diseases, we 
shall study the special phases of injury induced by these agents and 
the response which the living cells and tissues of the body make to their 
presence. 
But there are many forms of injury to cells and tissues which, though 
not so extensive and striking as those which we have thus far considered 
in our preliminary survey of inflammation, are yet of great frequency INFLAMMATION 
99 
and importance. One of these we must now consider, namely, the 
presence in the body of foreign substances and of dead portions of the 
body itself. Here again, as in so many instances, we shall come upon 
physiological processes spurred to unusual activity by emergency 
demands upon them. 
The Forms and Origin of Foreign and Dead Substances.-Under the 
conditions of normal life, as the tissues grow and perform their functions, 
worn-out cells die; as bone grows it is absorbed little by little to make 
room for the remodeling and growth of the larger structure; more or 
less constantly, floating matter in the air we breathe gathers in the respi- 
ratory organs. Under all of these conditions the dead cells, the hard bone, 
the foreign particles, are disposed of by certain lowly organized cells, 
leucocytes, lymphocytes, connective-tissue cells, endothelium and 
mesothelium, which are called phagocytes. 
On the other hand, there are many conditions under which foreign 
material abnormal in quantity and character is formed in or enters the 
body and must be disposed of. Thus organic pigments in the form of 
irregular particles or crystals are formed in the body, such as blood and 
bile pigment. Many foreign substances in finely divided form in large 
quantities enter from without, especially in the respired air, such as coal, 
iron,' stone, smoke, and various kinds of organic dust. In various ways 
larger bodies, slivers of wood, particles of metal, bullets, and, in injuries 
or during surgical operations, fragments of clothing, ligatures, sutures, 
fragments of sponge, cotton, gauze, jute, etc., may remain as foreign 
substances doing more or less harm and inciting in various degrees the 
phenomena of inflammation. These, too, the phagocytes dispose of. 
Finally, as the result of the greatest variety of injuries which lead to 
the necrosis of cells and tissues, such as mechanical damage, the action 
of corrosive poisons, excessive heat or cold, disturbances of circulation, 
various toxins, etc., the dead structures themselves become harmful to 
the living tissues about them, which respond in various ways to their 
presence, among others by certain forms of inflammation. 
Let us see how the body cells and tissues comport themselves in the 
presence of alien substances and dead structures. 
Disposal of Foreign Substances.-One of the simplest and most com- 
mon of the phenomena of this class is seen in the disposal of pigment and 
other solid particles, whether introduced from without or formed within 
the body under various abnormal conditions.1 In breathing dusty air, 
whether of badly cleaned dwellings, places of business or assemblage, or 
by those engaged in occupations involving the loading of the air with 
the dust of coal, smoke, iron, stone, tobacco, lint, hair, etc., in the aggre- 
gate large numbers of the dust particles enter the respiratory passages. 
Here sooner or later they are taken up by cells-phagocytes-and if 
the particles are colored they may be seen lying within the cytoplasm 
surrounding, but not within, the nucleus (Fig. 65). These cells may 
be the epithelium of the respiratory passages or of the air chambers of 
1 For a study of the removal of alien substances from the peritoneal cavity see Buxton and Torrey, 
Jour. Med. Res., vol. xv., p. 5, 1906. 100 
INFLAMMATION 
the lungs, or leucocytes which have wandered out upon the surfaces. 
Then a large part of the foreign particles, if these be not too numerous, 
are carried either on the lymph currents or more frequently within cells 
into the lymph channels, along which they make their way to the nearest 
system of lymph-nodes or -nodules or to the smaller areas of lymphatic 
tissue which are widely distributed in the lungs as well as elsewhere in 
the body (see p. 481). In these 
islets of lymphatic tissue or in the 
lymph-nodes of the lung the foreign 
particles both within and without the 
cells are deposited and may remain 
for an indefinite period. 
But the tissues in which they are 
deposited are not indifferent to the 
presence of any considerable accumu- 
lation of these alien substances. 
The connective tissue and endothelial 
cells swell and proliferate and new 
fibrils are formed enclosing the foreign 
material which may lie within the 
cells which brought them or be taken 
up by the new-formed or old connec- 
tive-tissue cells or lie free in the 
interstices of the fibrils. Thus in the 
lymph-nodes and along the lymph 
channels masses of dense fibrous tissue may be formed, shutting in the 
foreign material and compromising in varying degrees, sometimes com- 
pletely destroying, the involved structures (see p. 485). 
Similarly bacteria, which are also foreign bodies, may be taken up by 
phagocytes (Fig. 65) and destroyed within them by agencies presently 
to be considered. 
If a mass of foreign particles be placed beneath the skin, or if at the 
seat of a haemorrhage insoluble blood pigment is formed in considerable 
amount, a similar process may be observed. The pigment is more or 
less taken up by leucocytes or other phagocytic cells which have wan- 
dered in. A certain amount of fluid exudate may collect. New cells are 
formed from the old connective-tissue cells and from endothelium, and 
new fibrillar stroma is formed which becomes dense and assumes the 
character of cicatricial tissue. In these changes the new-formed cells, 
as well as the leucocytes, are capable of moving from place to place, 
that is, may become wandering cells. We have then, in this relatively 
simple response to a small local injury, the presence of fine foreign 
particles, a definite form of inflammation. This is marked, not by the 
phagocytosis, but by the presence of leucocytes and a certain amount of 
fluid exudate, by the formation of new cells, and the production of new 
tissue. 
When the alien material out of place in the living tissue is in the 
form of a loose-textured mass, such as sponge, fabrics, jute, catgut, etc., 
Fig. 65.-Phagocytes. 
The upper cell is epithelial from the lining 
of the air vesicles of the lungs. The pigment 
which it has ingested is coal dust from the 
air. The lower cells are leucocytes. One has 
taken in cocci, the other bacilli. INFLAMMATION 
101 
or is a blood-clot, its interstices become filled with fluid exuded from 
adjacent blood-vessels, with leucocytes which wander in, and with new 
connective-tissue cells derived from the surrounding parts and from 
the endothelium of neighboring lymph-vessels. Slender blood-vessels 
Fig. 66.-Giant Cells. 
The giant cells are at the border of a layer of granulation tissue formed about a mass of dead 
fibrous tissue which is being absorbed. 
form from the old ones near by and penetrate the mass, and new con- 
nective tissue is developed, having the type of granulation tissue at 
first, then becoming denser. If the foreign substances are capable of 
solution, as is the case in the fibrin and cells of a blood-clot or of catgut, 
Fig. 67.-Fragment of Sponge in a Healing Wound.-Three Weeks. 
The sponge trabeculae are not dissolved in the new-formed fibrous tissue, which has completely 
enclosed them. 
proteolytic enzymes1 furnished by the leucocytes or other cells may 
dissolve them; or they become fragmented and the fragments are taken 
up by phagocytic cells. These may be dissolved within these cells or 
may be transported to other parts of the body. Thus in the case of 
1 See Wells p. 103. 102 
INFLAMMATION 
soluble material this may at length be entirely removed and its place 
taken by the new tissue which gradually assumes the character of 
cicatricial tissue. 
If the foreign substance be insoluble or largely so, as in the case of 
bullets, needles, hair, cotton, sponge, etc., the new cells gather about 
the objects; there are often giant cells among them (Fig. 66), and new 
blood-vessels develop among these, leading to the formation of new 
connective tissue which may completely invest them (Fig. 67), forming 
at last a dense connective-tissue capsule. In this condition such foreign 
objects may remain for long periods embedded in the body. If the 
Fig. 68.-Giant Cells and New-formed Fibrous Tissue around a Foreign Body-Cotton Fibre 
This is a so-called "foreign-body tubercle." 
masses of foreign bodies are small, so that the local reaction is limited 
and circumscribed, the new tissue often in a general way resembles a 
tubercle (Fig. 68). Thus these new foreign-body tissue masses are 
sometimes called "foreign-body tubercles." 
Giant Cells.-When foreign objects of considerable size-such as 
hair, cotton fibres, sponges, and various more solid things-get into the 
living body, particularly if these be insoluble, in addition to the leuco- 
cytes and the new connective-tissue cells, there often form close about 
them large multinuclear cells called giant cells (Fig. 69). These are 
sometimes of extraordinary size and may have several score, even 
hundreds, of nuclei. They are apparently formed either by the coales- INFLAMMATION 
103 
cence of new-formed cells derived from the connective-tissue cells or 
from old endothelium, or by the continuous division of the nuclei of a 
cell whose body continues to enlarge without dividing into separate 
cells.1 These giant cells seem to be concerned in the attempt to dis- 
solve the foreign substance and appear to have their prototypes in the 
multinuclear cells called osteoclasts (Fig. 70) whch are concerned in the 
physiological absorption of bone during its development. 
The Disposal of Dead Tissues.-The changes which we have now 
studied, through which alien substances are either removed from the 
body or are rendered relatively harmless by processes which we must 
regard as belonging to inflammation, are similar to those by which the 
body responds to the injury of dead portions of its own tissue. 
From a wound delayed in healing on account of the cotton fibres left in the dressing. 
Fig. 69.-Giant Cells Formed around Foreign Bodies--Cotton Fibres. 
Thus, infarcts resulting from emboli, areas of tissue which have 
become necrotic from poisons or toxins, thrombi or masses of fibrinous 
exudate in the solid tissues or in the great serous cavities, are all virtu- 
ally alien substances, and are harmful in various ways as foreign bodies 
are, and incite similar inflammatory phenomena. They may be in part 
removed by solution through the proteolytic enzymes,2 or by phago- 
cytosis; they may attract leucocytes (Fig. 71); they may lead to the 
proliferation of connective tissue and endothelial cells and of blood- 
vessels which penetrate them and form new tissue which finally replaces 
or encapsulates them. The so-called organization of a thrombus or of a 
pleural or pericardial or peritoneal exudate is not, as we have already seen, 
directly brought about by the aid of the structural or other elements in 
either the thrombus or the exudate. These are passive, except as they 
may aid in their own solution by autolytic substances which they furnish, 
while the new tissue is formed from neighboring cells and vessels. 
Forms of Phagocytes.-There appear to be two most common forms 
of phagocytes in foci of acute exudative inflammations. First, and 
1 Giant cells may be formed from epithelium under certain conditions. For a study of giant cells, 
with bibliography, consult Hektoen, Jour. Exp. Med., vol. iii., p. 21; Fuerst, Ziegler's Beitrage, Bd. 
xxiv., p. 440; and Buxton, "Studies from Department of Pathology, Cornell University," vol. i. 
2 See Wells, Jour. Med. Research, vol. xv., p. 149, 1906, bibl. 104 
INFLAMMATION 
usually the most abundant, are the polymorphonuclear leucocytes- 
the cells containing neutrophile granules which so readily escape from 
injured vessels. The other type of the two more common phagocytic 
cells is usually larger than the polymorphonuclears and has a single, 
Fig. 70.-Osteoclasts Dissolving Bone Lamellae. 
From a case of rarefying osteitis. 
relatively large, rounded or irregular shaped nucleus. These mono- 
nuclear phagocytes of the second type are probably derived from con- 
nective tissue or endothelial and mesothelial cells or from lymphocytes, 
and have been called by Metchnikoff macrophages, while the smaller 
polymorphonuclear phagocytes are called microphages. 
Fig. 71.-Fragments of Necrotic Muscle in Process of Absorption under the Action of 
Phagocytes. 
While the performances of these two types of cells are not fully under- 
stood, it appears that the macrophages are especially concerned in the 
disposal of various proteid and other formed elements which they ingest, 
such as fragments of fibrin and tissue detritus, dead parenchyma cells 
of organs, red and white blood cells, etc. INFLAMMATION 
105 
On the other hand, the polymorphonuclear leucocytes-microphages 
-are drawn to and ingest and destroy various kinds of micro-organisms, 
especially the bacteria.1 
While we have thus far considered certain special cells, leucocytes, 
lymphocytes, and derivations of connective-tissue and endothelial cells, 
as the most common phagocytic cells in inflammation and repair of 
tissues, we should not lose sight of the fact that other types of cells are 
also capable of assuming this role. Thus the epithelium of the mucous 
membranes of the air vesicles of the lungs, of the liver, kidney, and other 
organs, frequently and under the most varied conditions ingest particles 
of foreign material. 
The Mode of Action of Phagocytes.-As to the processes by which the 
phagocytic cells convert into soluble and other forms the substances 
which they ingest there is still some difference of opinion, though the 
so-called intracellular digestion and the autodigestion of tissues have 
been the subject of much painstaking research. 
Recent studies by Opie2 indicate that each of the two types of 
phagocytes above designated is characterized by a distinct proteolytic 
enzyme through which its destruction of organic substances is effected. 
The enzyme of the polymorphonuclear leucocytes is capable of proteo- 
lytic digestion in the presence of a neutral or alkaline reaction, but not 
in an acid medium. This enzyme Opie calls leuco-protease. The larger 
mononuclear cells, on the other hand, the "macrophages" or "macro- 
cytes," which appear to be especially concerned with the ingestion and 
destruction of cellular and other formed elements, contain an enzyme 
active in the presence of a weak acid, but inactive in an alkaline, medium. 
This enzyme is called lympho-protease by Opie. 
Blood serum, according to Opie, inhibits the action of leuco-protease, 
and lympho-protease is not active in an alkaline medium. Hence, the 
living tissues of the body are not digested by the leuco-protease, which is 
active only within the bodies of the microcytes, where it is free from the 
inhibiting action of the serum, while the alkalinity of the blood plasma 
protects the tissues from the action of the lympho-protease. It is 
apparently the action of these proteolytic ferments, present in consider- 
able quantities either within or without the cells or both, in foci of exu- 
dative inflammation, which leads to the softening of tissue which char- 
acterizes abscesses and which, in part at least, brings about the more 
gradual solution of necrotic tissues, fibrin, etc.3 
The action of micro-organisms, especially the bacteria, as incitants 
of inflammation through the injury which they cause, and the ways in 
which the body reacts to and disposes of them, through the action of 
phagocytes or otherwise, will be considered later under the heading of 
Infectious Diseases.4 
1 For a consideration of the ways in which bacteria are destroyed by leucocytes, see pp. 161 and 
178. See also ref. to Buxton and Torrey, foot-note, p. 99. 
2 Opie, Jour. Exper. Medicine, vol. viii., 1906, pp. 410 and 536. 
3 See ref. Wells, p. 103; also ref. to Levene, "Autolysis," p. 107. 
4 For a consideration of Ehrlich's hypothesis as to the way in which bacteria are destroyed in the 
body see p. 176. 106 
INFLAMMATION 
It should be borne in mind, in considering the varied and complex 
performances of phagocytic cells under abnormal conditions, that these 
are only the manifestation in exaggerated form in the presence of emer- 
gencies of physiological capacities of many kinds of cells. To Metchnikoff 
especially we owe our knowledge of the phagocytic powers of cells in 
general. In such lowly organisms as amoeba and in many other cells 
throughout the animal kingdom he has shown that through ingestion and 
intracellular digestion cells not only are nourished but protect them- 
selves against harmful agents and influences.1 
Autolysis.-All the manifestations of cell life are brought about by 
the breaking down or disintegration of chemical substances in the cyto- 
plasm by processes akin to those of combustion. It has long been 
believed that this was exclusively a property of living matter. But it 
has recently become known that dead cells also under certain conditions 
have the power of self-disintegration. This is called autolysis. It 
takes place in the absence of micro-organisms through the action of 
which organic material is decomposed in the commoner processes of 
putrefaction. Thus portions of fresh organs removed from the body 
with the avoidance of bacterial contamination, that is, in a sterile con- 
dition, if immersed in chloroform water, or toluol, or other substances 
which do not cause alterations of the tissue but do prevent the growth 
of micro-organisms, and kept at about body temperature, undergo 
gradual softening. This softening is accompanied by definite struc- 
tural changes in the cells. The nuclear chromatin disintegrates or goes 
into solution; the cytoplasm degenerates, chemical analysis showing 
products of the disintegration of proteid substances. The changes are 
analogous with those taking place in organic material, cells, etc., under 
the influence of the digestive enzymes, pepsin and trypsin, but are due 
not to these but to other enzymes belonging to the cells themselves (see 
p. 105.) 
It appears, for reasons into which we cannot enter here, that the 
proteolytic enzymes active in the autolysis of dead tissues are present in 
the living body and are probably concerned among other things in the 
gradual removal of dead and enfeebled structures as these become 
defective, useless, or harmful. It has been shown that the vigorous, 
living cells, in spite of their autolytic powers, probably maintain their 
integrity through the presence in the body-fluids of substances antago- 
nistic to the autolytic enzymes. Thus it appears that under normal 
conditions a very nice balance exists between the autolytic enzymes 
and antagonistic substances within the body. Under a variety of 
abnormal conditions, such as diseases of the respiratory and circulatory 
systems, phosphorus poisoning, and, as has been shown by Flexner,2 in 
infectious diseases, autolysis may be in a marked degree exalted. 
It is probable that the autolytic substances in the living body are 
important not only in disposing of damaged or dead or harmful tissues, 
1 See Metchnikoff, " Comparative Pathology of Inflammation," English trans., 1893; and " Immu- 
nity in Infective Diseases," 1905. Consult also p. 196. 
2 Flexner, Trans. Assn. Amer. Phys., vol. xviii., p. 359, 1903. INFLAMMATION 
107 
but also in the protection of the body against invading micro-organisms 
through their destruction-see immunity and bacteriolysis, pages 160 
and 173; or by their share in the elaboration of substances which an- 
tagonize the action of their toxins-see antitoxins, page 163.1 
Survey of the Inflammatory Process and its Significance. 
Inflammation a Modification of Physiological Processes. - If now, 
from the vantage-ground which we have won by our study of various 
typical phases of inflammation, we seek to gain an insight into the 
forces which dominate the varied processes, we note at once that from 
first to last the cell and tissue performances in inflammation, however 
exaggerated or perverted, are only the expression of physiological 
capacities which belong to the structures involved. Thus the contrac- 
tions and dilatations of the vessels are paralleled in health. The exuding 
of fluids through their walls occurs by processes akin to those by which 
blood pressure, osmosis, and selective filtration in endothelial cells main- 
tain the initial circulation into and through the tissue spaces. Emigra- 
tion is a physiological process which we find excessive here, because there 
are structural alterations in the walls of the vessels which permit a freer 
exit of the cells, and because there are also present new and active 
chemical agents which, just as in normal conditions though in exagger- 
ated fashion, excite and control the movement and direction of the leuco- 
cytes. The healing processes, complex as they seem to be, are actually 
but a rehearsal under the unusual and often difficult conditions of cell and 
tissue formation, which is characteristic of the normal period of develop- 
ment. Phagocytosis is a factor of the greatest importance in the normal 
as well as in these abnormal performances of the body cells. 
The degenerative phenomena, among which must be reckoned the 
formation of fibrin, are, as we have seen, incidental rather than primary 
factors in inflammation. 
Thus in all the manifold manifestations of abnormal cell performance 
in inflammation we find no new functions, no new cell capacities. 
The Significance of Inflammation.-We are now brought face to face 
with the final question: What does inflammation mean? 
In those phases which involve the repair of wounds and the regener- 
ation of lost tissues it is not difficult to recognize conservative and bene- 
ficial processes. But how is it with those phases of inflammation in 
which the blood-vessels are largely involved and exudates formed- 
serum, fibrin, and pus? Are we to be contented here with a simple 
summary of the phenomena and with the recognition that these are the 
results of exaggerated or physiological cell and tissue performances in 
the face of injury? Or, on the other hand, is there reason for the belief 
that these abnormal manifestations of cell life in the presence of an 
unusual and deleterious environment may, after all, be in the main con- 
1 For an interesting resume of autolysis with bibl. see Levene, Jour. Amer. Med. Assn., vol. xlvi, 
pp. 774 and 866,1906. For a fuller consideration of the subjects dealt with in this chapter consult the 
general pathology, "Les Processus Generaux" of Chant emesse and Podwyssotsky, 1901, or Wells 
" Chemical Pathology," 2d edition, 1914. 108 
INFLAMMATION 
servative in their nature, and, even as normal cell functions do, tend- 
within the limitations of an emergency-to the welfare of the individual? 
The Role of the Exudates.-In the hope of gaining some light upon this 
question let us look a little more closely at the part which the exudates 
play in exudative inflammation; and first at the leucocytes. 
The Leucocytes.-It was through the painstaking and brilliant studies 
of Metchnikoff1 that attention was directed to the importance in this 
connection of comparative studies upon the comportment of lower forms 
of life in response to injury. 
It was found that amoeba, one of the simplest of organisms, when cut 
in two may undergo complete restitution of the part containing the 
nucleus, provided the latter be uninjured. The remaining portion may 
live for a time, but ultimately dies. Furthermore, it was found that 
amoeba and other lowly forms of living beings are capable, by the use of 
their simple digestive processes, of destroying micro-organisms which are 
taken into their interior and which might otherwise damage or kill them. 
Thus it was established that the digestive mechanism may become pro- 
tective in lowly organized cells. 
Rising in the scale of living beings, it is found that in forms in which 
considerable differentiation of some of the cells has taken place, whether 
there be a distinct circulatory apparatus or not, certain other cells are 
left in a more primitive state: these are phagocytic and can ingest or 
otherwise destroy deleterious material. 
When we come to man and other warm-blooded animals, it is upon 
the leucocytes which have retained so many of the capacities of undiffer- 
entiated protoplasm that attention is especially concentrated. It has 
been found, as we have already seen, that the movement of leucocytes 
may be directed toward (sometimes from) chemical substances set free 
in their vicinity. This chemotaxis is frequently manifested in the 
vicinity of dead cells or tissues which are the seat of destructive metab- 
olism. But it is especially in relation to micro-organisms of various 
forms that chemotaxis in the leucocytes is of the highest significance to 
us here. 
Highly virulent micro-organisms may for a time repel the leucocytes, 
probably through negative chemotaxis, but these may later approach. 
On the other hand, leucocytes most often migrate toward bacteria 
which have gained entrance to the body. It has been proven that 
leucocytes, especially the polynuclear neutrophiles, and frequently large 
mononuclear forms, may take into their interior and destroy living 
bacteria. Dead bacteria also, as well as other inert material, they can 
engulf and destroy. 
The Body Fluids.-This capacity of leucocytes and other mesodermal 
cells-endothelia, etc.-to take up living bacteria and kill and digest 
them was persistently and ably urged by Metchnikoff and his pupils as 
the chief protective agency in the body against bacterial incursions, and 
to these observers all the other phenomena of inflammation formerly 
seemed of secondary importance. But it was soon shown that this ex- 
1 Metchnikoff, "Comparative Pathology of Inflammation," Eng. trans., 1893. INFLAMMATION 
109 
treme view is not correct. For it was demonstrated by many observers 
that the body fluids, especially blood serum, are capable of killing 
bacteria with which they come in contact. When, however, this remark- 
able quality of the body fluids was investigated, it was found that it is 
most pronounced under conditions which involve the breaking-down of 
leucocytes or the liberation of the destructive substances into the fluids. 
It was possible now to demonstrate that the leucocytes do, in fact, contain 
a germicidal proteid substance or substances. These substances, which 
appear to be closely associated with or related to nucleinic acid, have 
been called "alexines" or "protective proteids." 1 It has been further 
demonstrated that while the eosinophile cells may move toward bacteria, 
they are not phagocytic, but may set free granules which appear to favor 
the destruction of the germs. 
It thus appears that the earlier view of the almost exclusive impor- 
tance of phagocytosis is not sustained, but that even more than in the 
action of living phagocytes the protective agencies are to be sought in 
the body fluids. But it is also clear that the protective capacities of the 
body fluids are the result of cell activities, as indeed might have been 
inferred in advance of the long line of careful experiments which finally 
led to the demonstration. 
The importance of this protective power of the body cells and body 
fluids is not exhausted with their germicidal action. For not less sig- 
nificant is the role which these may assume in the establishment of other 
phases of immunity to the incursion of micro-organisms. This will be con- 
sidered later in the general survey of the infectious maladies (page 160). 
If now one seek for ways in which the other exudates, serum, and 
fibrin may be useful to the individual, it is obvious that in the dilution 
of locally engendered poisons and in their removal from a vulnerable 
region the fluid may at times be beneficial. Fibrin, too, by closing 
inflammatory foci, through temporary adhesions, or by the sealing of 
absorbent surfaces, may limit the extension of injurious agents, as is so 
frequently the case in local infectious injuries in the peritoneal and 
pleural cavities. That the regeneration and repair of tissue which may 
be associated with or follow the more active phases of inflammation are, 
as a rule, beneficent, is not doubtful. 
There is, of course, another side to the matter. For new cicatricial 
tissues which have formed in the process of repair may be so situated as 
to cause serious impairment of functional performance or even fatal 
strictures. The gathering of leucocytes, too, may be so excessive and 
their proliferation so extreme as to lead to delayed healing or to serious 
exhaustion from suppuration. But notwithstanding these irregularities 
and failures there seems to be good reason for the belief that, on the whole, 
the processes involved in inflammation are conservative, and, within the 
limitations which may be set by the varied and changing conditions of 
injury, tend to maintain the welfare and sustain the life of the individual. 
1 For further consideration of this subject see p. 160. 110 
INFLAMMATION 
CHARACTERIZATION OF THE INFLAMMATORY PROCESS. 
The general conception of inflammation which we have just set forth 
looks beyond the gross manifestations of disordered function and altered 
structure, by which it was originally marked, and beyond the complex 
and varied expressions of aberrant cell activities, with which our later 
science has mostly dealt, to the fundamental qualities of living substance. 
And thus at last, with the heart of the subject in view, a characterization 
of inflammation becomes possible which is suggestive and useful, though 
it may not indeed be final. Perhaps among many such characterizations, 
that of Adami1 is on the whole the most clear and precise, and with him 
we may at present wisely consider inflammation as "the local attempt at 
the repair of injury." The fundamental conception upon which this 
characterization is based is that inflammation is an emergency measure 
incited by injury, in which the body adapts to unusual ends as best it can 
mechanisms and powers normally maintained for other purposes. 
This view of inflammation, however much it may be modified as our 
knowledge grows, recognizes a far-reaching significance in the complex 
processes involved. And while throwing light upon the practical prob- 
lems of the physician, it points the way to a broader conception of other 
abnormal conditions in which also the adaptation of physiological cell 
capacities to new conditions seems to furnish a clew to many manifesta- 
tions of disease as yet but little understood.2 
Now that we have gained a conception of the inflammatory processes 
in general and some suggestions as to their significance, it does not seem 
necessary to enter here upon a detailed description of the variations 
which they present, since these are largely influenced by the character 
of the inciting agents and by the situation in which they act. Such 
details as may fall within the scope of this work are given in the section 
dealing with micro-organisms as inciting factors in disease, and in the 
part dealing with the lesions of special organs.3 
The Experimental Study of Resorption of Foreign Material, Phagocytes, etc., in 
Inflammation. 
Aside from clinical material illustrating the healing of wounds and various phases 
of repair from the lower animals, by very simple operations, to be done with local or 
general anaesthesia, one may obtain many valuable series of demonstrative lesions. 
1 For a fuller consideration of inflammation from the point of view which in general is here adopted, 
one may consult the excellent article on "Inflammation" by Adami in Allbutt's "Systemof Medicine," 
vol. i., p. 54. 
In Thoma's work on "General Pathology," vol. i., is a clear exposition of the various processes 
concerned in inflammation, with a fuller recognition than is commonly accorded to them of the mechani- 
cal factors involved. In both of these works the more important bibliography may be found. 
For bibliography and critical resume of studies on pathological organization, inflammation, etc., 
see Borst, Lubarsch and Ostertag's Ergebnisse, Jahrg. iv., for 1897, p. 461. See also references under 
Regeneration, page 79, and under Tumors, page 351. 
2 Consult, for a clear and comprehensive view of adaptation in pathological processes, Welch, 
Transactions of the Congress of American Physicians, vol. iv., p. 284, 1897. 
3 For a systematic and extensive risum# of inflammatory phenomena, phagocytosis, chemotaxis, 
emigration, diapedesis, protoplasmic poisons and irritants, the nature of exudates, and the general 
physical chemistry of the cell, with extensive bibl., see Heinz, " Handbuch d. exp. Path. u. Pharmakoi.," 
1904, Bd. i. INFLAMMATION 
111 
Phagocytes.-The injection of 1 per cent, agar-such as is used for bacterial 
cultures, which fluidifies at about 40° C. and becomes semisolid on cooling-into the 
anterior chamber of the eye or into the subcutaneous tissue of the rabbit gives most 
instructive pictures of absorption and phagocytosis. Phagocytes of connective-tissue 
origin bring about the solution of the mass and permeate it. If the agar be colored with 
Berlin blue in the form used for blood-vessel-injection masses, the phagocytes may 
become more or less filled with the blue granules as absorption proceeds. In the 
absorption from the anterior chamber in dark-colored rabbits the origin of the 
phagocytes in the iris is revealed by their pigmented character. Giant cells are often 
formed in this process, aiding in the resorption. 
The action of phagocytes in disposing of foreign material in the lungs may be 
seen by making intratracheal injections of a watery emulsion of lampblack or finely 
powdered charcoal in rabbits. The pigment particles will be found both free and 
within epithelial phagocytes in the air vesicles within a few days. The animal should 
be sacrificed and the lungs filled with formalin solution or alcohol through the 
trachea (see p. 1010), after which the tissue is embedded and sectioned. 
Very instructive studies may be made of the disposal of insoluble foreign bodies 
by the implanting of small fragments of cotton, jute, elder pith, etc., beneath the skin, 
and their removal after varying intervals.1 
Practical Study of Exudative Inflammation on the Living Frog. 
In the study of exudative inflammation it is of the highest value to see the phe- 
nomena of emigration, diapedesis, etc., on the living animal. The curarized frog is 
best adapted for this purpose,2 and either the mesentery or the bladder affords much 
clearer pictures than the tongue or the web, which are sometimes recommended. 
The Mesentery.-In a fully curarized frog an incision is made through the skin 
along the abdomen in the axillary line, care being taken to avoid or ligate a large vein 
which usually crosses the line of incision. The abdominal wall is then cut through in 
the same line, and a loop of small intestine drawn out, care being taken to bring out 
only as much as may be necessary to expose over the glass window of Thoma's frog 
plate3 (see Fig. 72) a small area of mesentery. The loop may be fixed by short pins 
passed through the superficial layers of the intestine into strips of cork which are 
crowded in beside the raised glass window. The exposed loop should be irrigated with 
three-fourths-per-cent salt solution which may be made to trickle over the part from a 
reservoir through a glass cannula held by the cannula-holder (see Fig. 72). Peristal- 
tic movements of the intestine sometimes cause the field of observation to shift and 
stasis may occur if the loop be drawn too tightly. But through a little attention to 
adjustment from time to time difficulties may be reduced to a minimum. For long 
observations a cover-glass may be laid upon the loop under which the irrigation 
proceeds. 
In this way observations may be made on arteries, capillaries, and veins, extending 
over several hours. Long focal distance, high-power lenses may be used. 
The Bladder.-The bladder of the frog is a bilobed organ opening into a cloaca 
just within the anus and common to it and the intestine. To expose the bladder an 
incision is made in the axillary line along the lower half of the abdomen, including the 
skin and the abdominal wall. The bladder frequently prolapses at once to a moderate 
extent through this opening. Now a glass cannula is made with a tapering tip with the 
1 For a full exposition of methods of experimental pathology relating to inflammation see Heinz, 
■'Handbuch d. exp. Path. u. Pharmak.," Bd. i., Th. i., p. 255, 1904. 
For many suggestive studies in phagocytosis see M etchnikoff's "Immunity in Infectious Diseases." 
Consult, for the technique of studies on absorption from the peritoneum, Buxton and Torrey, Jour. 
Med. Res., vol. xv., p. 5, 1906. 
2 For the use of curare see p. 34. 
3 Thoma's frog plates are of three forms, adapted for the study of the tongue, the mesentery, and 
the bladder or lung. They are plates of brass covered with hard rubber in which glass windows are 
set so that when put on the stage of the microscope the light passes up through the exposed organ to 
the eye. They are provided with cannula-holders for irrigation with physiological salt solution and 
with pipes for carrying away the waste irrigation fluid. The three forms of plate are shown in Fig. 72. 112 
INFLAMMATION 
The upper plate is adapted to the study of the circulation in the mesentery. The middle plate is for 
the bladder and lung. The lower plate is for the tongue. 
Fig. 72.-Thoma's Frog Plates. INFLAMMATION 
113 
tip for about half an inch bent to an angle of about 45° to the axis of the tube. The 
tube should be large enough to pass the anal orifice with difficulty except at the tip 
and along the bent portion. 
A thread is now passed through the skin just behind the anus, the ends being 
left free. The cannula and a short length of flexible rubber tubing slipped over the 
larger end are filled with three-quarter-per-cent, salt solution, this being retained by 
a clip on the tube. The bent point of the cannula is now inserted into the cloaca and 
its tip carried forward into the base of the bladder and fastened in place by the thread. 
The frog is laid on its back on the Thoma plate adapted to the bladder and lung (Fig. 
72). The rubber tube is attached to a slightly raised flask so that the salt will siphon 
into the bladder under a very low pressure. Now if the clip be released the bladder 
will appear in the opening of the abdomen and will be pressed out as a transparent bag 
by the salt solution over the glass window in the plate. Great care should be taken 
to avoid more distention of the bladder than is necessary to keep it spread over the 
glass, since the circulation is very easily disturbed or interrupted. A cover-glass may 
be laid upon the bladder or held in place over and touching it by an upright attached 
to the plate for this purpose, and irrigation with salt solution started and maintained. 
If the circulation is compromised one should see that the base of the extruded 
portion of bladder is not pressed upon by the abdominal walls; that it is not overfilled 
and is not pressed too much by the cover. By attending to those points in a frog not 
over-curarized one may maintain the circulation for hours. Since the wall of the blad- 
der is very thin, consisting of little else than the almost invisible epithelial lining, a 
membranous connective-tissue wall reinforced here and there by slender bundles of 
smooth muscle cells, and the blood-vessels, one secures in this organ pictures of the 
blood-vessels of incomparable clearness and may study the minutest phases of the 
circulation and its disturbances, emigration, etc. The contraction of the muscle 
bundles brings about occasional shifting of the field, but this is not usually a serious 
drawback to continuous observation even with high-power lenses. 
On the whole, though slightly more difficult to prepare, the bladder is to be pre- 
ferred to the mesentry for studies on the minute phenomena of emigration, diapede- 
sis, hsemorrhage, etc., and it is admirably suited to the study of the local effect of drugs, 
such as adrenalin, on the circulation. 
In neither the mesentery nor the bladder is it necessary to injure the organ further 
than is inevitable in the preliminary operation and exposure, in order to incite the 
inflammatory phenomena in the vessels. In both organs the course of the emigrated 
leucocytes may be followed through the interstices of the tissues after they have left 
the vessels. It is most instructive after the observations on the living animal are 
completed to pith or decapitate the frog, fill the bladder with a fixative such as Orth's 
fluid, in which the organ after ligating is placed, and finally to scrape off the epithe- 
lium, stain with haematoxylin and eosin, and mount pieces of the wall in balsam for 
study. 
The Lung.-The circulation in the lung and various phases of its disturbance may 
be studied on the living frog by the use of the Thoma plate especially adapted for the 
bladder. The preliminary operation is made in the axillary line, the long incision 
reaching forward to the axilla. A cannula tapering to one end so as to pass between 
the folds of the glottis for five or six mm., but not to slip further in, is tied in place by 
a thread through the snout of the curarized animal. A flexible rubber tube over the 
free end of the cannula, which extends a couple of centimetres beyond the snout and is 
controlled by a clip, enables one to blow into the lung and force it out through the 
incision. The inflation should not be excessive and the base of the lung should not be 
constricted. The animal is placed on its back upon the plate with the distended lung 
over the glass window and irrigated in the manner above indicated for the bladder. 
The picture of the circulatory districts of the single-sac lung with the blood shooting 
through the rich capillary network and entering the veins is most interesting and 
important for one who would appreciate the significance of lung lesions involving, as 
most of them do, disturbances of the circulatory mechanism. CHAPTER VI 
ANIMAL PARASITES. 
Protozoa. 
General Characters of the Protozoa.-The protozoa are, with few 
exceptions, unicellular animal organisms of a primitive type, reproducing 
by division, by budding, and by spore formation. Some are very minute, 
others many millimetres in diameter. Some of them seem to lie between 
and to link the two great divisions of living beings somewhat arbitrarily 
established-the animals and the plants. 
While some of the protozoa are relatively simple in structure, others 
are extremely complex. The life cycle, also, of some forms is simple, 
while others, passing through sexual and asexual phases, present at 
different periods the greatest diversity in form and function. 
Some protozoa maintain an independent existence, others are para- 
sitic for men and animals. Among the parasitic forms are important 
groups which require residence in the body of more than one animal 
species for the completion of their life cycle. Many of the protozoa 
possess organs of locomotion, pseudopodia, flagella, and cilia. 
Our knowledge of the protozoa parasitic in man is of recent date, 
but is accumulating with great rapidity especially as regards tropical 
forms. Many forms are so difficult to study and to classify that for 
the moment, in numerous instances, conjecture and a balancing of 
probabilities and analogies are made to do duty in lieu of facts. 
Although not yet proven, it is widely believed that some if not all of 
the exanthemata, yellow fever, and it may be hydrophobia, are probably 
incited by some form of parasitic protozoa. 
Modes of Transmission of Protozoan Parasites.-Some forms of pro- 
tozoa are transmitted by contact, as in certain trypanosomes and the 
syphilis organism; others are ingested with food and drink. 
Congenital transmission of the syphilis organism is of frequent 
occurrence. 
So confident are many observers that small-pox and scarlatina are 
incited by protozoan parasites, presumably by such as in the develop- 
ment of their life cycle form minute spores, that they venture to assume 
that in these diseases, at least, the infective agent may be air-borne in 
floating dust. 
Finally, in many instances, infection takes place through trans- 
mission by intermediate hosts. This is the case in malaria, yellow fever, 
and with certain trypanosomes and sporozoa. In the transmission of 
the malarial organism by the mosquito and in some trypanosomes, 
important phases in the life cycle of the parasite take place in the body 
114 ANIMAL PARASITES 
115 
of the intermediate host. Other insects-ticks, bed-bugs, and leeches- 
act as intermediaries, especially among the lower animals. 
The Effects of Protozoan Parasites upon their host are in many cases 
obvious, in many quite obscure. We shall consider some of these in the 
brief review of species which follows. 
Cultivation of Protozoa.-It has been found practicable to cultivate 
on artificial media, through a few generations at least, some forms of 
protozoa-amoebas, trypanosomes, and the malarial parasite; but the 
knowledge thus far derived from such artificial cultivation is scanty. 
The scope of this book permits only a very limited consideration of the 
most significant forms of protozoa which are related to human pathology.1 
The Classification of Protozoa.-The protozoa are ordinarily separated 
into the following groups: 
A. Plasmodromata 
I. Rhizopoda.-Movement by pseudopodia. 
II. Mastigophora.-Movement by flagella. 
III. Sporozoa.-Motility varied; highly parasitic; propagated by 
spores. 
B. Ciliophorata 
I. Ciliata.-Movement by cilia. 
II. Suctoria.-Without pathogenic importance in man. 
I. Rhizopoda 
The protozoa of this division are usually of simple structure, char- 
acterized by motile organs in the form of pseudopodia. Reproduction is 
by division and by spores. The pathogenic form of this division is 
Entamoeba histolytica. 
Entamoeba histolytica (Amoeba dysenteriae) is of considerable path- 
ologic importance. Councilman and Lafleur2 in 1891 first definitely 
established the significance of this protozoan parasite which they called 
Amoeba dysenteriae, a name now superseded by Entamoeba histolytica of 
Schaudinn. 
It has been repeatedly found in acute and chronic dysentery, most 
frequently in the tropics, in the intestinal contents, at the bottom of the 
intestinal ulcers, and in the secondary abscesses, especially of the liver, 
which may accompany ulcerative colitis. The amoeba is believed 
to be the inciting factor, in some cases, in both the primary ulcerative 
colitis and its complicating abscesses (see page 676). 
This amoeba (Fig. 73) is a spheroidal cell, from five to eight times 
the diameter of a red blood cell, with granular protoplasm and a vesicular 
1 The best presentation of our present knowledge of protozoa is contained in Doflein, Lehrbuch d. 
Protozoenkunde, 3d edition, Jena, 1911, which includes an extensive and well-classified bibliography. 
See also Brumpt, Precis de parasitologie, 2d edition, Paris, 1913; and Neumann und Mayer, Wichtige 
tierische Parasiten und ihrer Ubertrager, Munich, 1914. Calkins, Protozoology, New York, 1909, is a 
readable epitome of the subject; and Park and Williams, Pathogenic Bacteria and Protozoa, 4th edition, 
1910, contains a great deal of fundamental information on pathogenic forms. 
2 John Hopkins Hosp. Rep., ii., 395, 1891. 116 
ANIMAL PARASITES 
nucleus. It often contains larger and smaller vacuoles. Frequently, 
especially when the amoeba is active, a portion of the protoplasm 
appears almost homogeneous-ectosarc-while the rest-endosarc-is 
granular. When moving it assumes various forms, thrusting out and 
withdrawing nearly homogeneous pseudopodia. It may also change its 
shape without progressive movement. It occurs in acute and chronic 
dysentery, frequently in Egypt, occasionally in Russia, India and the 
Philippines, and is often seen in the United States.1 
The parasite is capable of making its way between the epithelial cells 
of the intestinal canal, but the way in which lesions are induced is not 
clear. The organism has been artificially cultivated.2 Animal inocula- 
tions are easily made, especially in young cats, with the production of an 
acute colitis. It is now generally acknowl- 
edged that the Entamoeba tet- 
ragena, described by Viereck, is 
identical with the Entamoeba 
histolytica, though the matter is 
still under discussion.3 
Other species of amoeba have 
been found in the human mouth, 
intestines, and bladder, but are 
apparently not pathogenic. The 
Entamoeba coli is very frequently 
present in health and in intes- 
tinal disorders other than dysen- 
teric.4 There is reason to believe 
that amoebas are acquired 
through drinking water and 
uncooked foods. 
Fig. 73.-Entamceba Histolytica. 
From the intestinal wall near an ulcer in amoebic colitis. 
II. Mastigophora. 
These organisms are of definite or changeable shape, with or without 
a membrane. They are characterized by the possession of one or more 
undulating or vibratile processes or flagella. Some forms seem to be 
closely related to the bacteria. 
Trypanosomes.-Among the flagellated protozoa the trypanosomes 
are of much significance, occurring as free swimming parasites in the 
blood of both cold- and warm-blooded animals-mammals, birds, rep- 
tiles-and in the intestines of certain blood-sucking insects-flies, 
mosquitoes. 
Trypanosomes are elongated, usually pointed, and may have one or 
two flagella and an undulating membrane at the side attached to the 
1 We refer for further details concerning the Entamoeba histolytica to the work of Councilman and 
Lafleur on "Amoebic Dysentery," Johns Hopkins Hospital Reports, vol. ii., p. 395, 1891. For a 
method of differential staining of the Entamoeba histolytica see Mallory, Journal of Experimental 
Medicine, vol. ii., p. 529, 1897. For a resume of Amoebas, cultivation and significance, see Musgrave 
and Clegg, Bureau of Govt. Labt. Dept, of the Interior, Biological Laboratory No. 18, Oct., 1904, and 
Strong on "Amoebic Dysentery," in Osler's "Modern Medicine," vol. i. 
2 See Musgrave and Clegg ref. above. 
3 See Craig, Arch. Int. Med. 1914, xiii, 917. 
4 See Craig, Jour. Infec. Dis., v., 324, 1908. ANIMAL PARASITES 
117 
flagella (Fig. 74). The membrane is often attached in folds or undula- 
tions so that the movement of the parasite in swimming is somewhat 
augur-like. They reproduce by division. 
In many instances the trypanosomes seem to be of no special sig- 
nificance to the host, but in several of the lower animals and in man 
some species are markedly pathogenic. 
Fig. 74.-Trypanosoma Brucei. 
The protozoan parasite of the tsetse-fly disease of Africa. 
Trypanosomes are common in wild rats in all countries. The species 
infesting these animals, Tr. lewisi, can be readily transmitted with the 
blood to a fresh animal by injection and does not appear to interfere with 
the well-being of the rats. A certain immunity to subsequent injections 
seems to be conferred by the presence of these parasites in the blood of 
the rat, from which they usually disappear in two or three months. 
Novy and McNeal first successfully cultivated the Trypanosoma 
lewisi and other forms on nutrient agar containing varying amounts of 
defibrinated or laked rabbit blood. 
Pathogenic Trypanosomes. 
Tsetse-fly Disease.-Among the more important of the trypanosome 
infections we may note Magana or the tsetse-fly disease (Fig. 74). This 118 
ANIMAL PARASITES 
infectious disease of cattle, horses, and mules occurring in Africa, espe- 
cially in Zululand, has long been known and was at one time of great 
economic importance. It is characterized by fever, emaciation, edema, 
etc. 
In 1894 Bruce discovered a trypanosome-Tr. brucei-in the blood 
of the affected animals. He also found that the parasite was conveyed 
to healthy animals through the bite of a tsetse-fly of that country- 
Fig. 75.-Treponema Pallidum. 
Stain by the India ink-method (see p. 278) 
Glossina morsitans-which had shortly before bitten an infected animal. 
The original source of the parasite was found to be the wild animals of 
the region, which did not appear to be affected by it. Man is immune 
to this species of trypanosome. 
Surra.-This disease of horses and cattle, occurring in India, and 
possibly in other tropical countries, has been shown to be due to a 
trypanosome, Tr. evansi, which is conveyed from infected to healthy 
animals by a fly. 
Several other diseases of wild and domestic animals are known to be 
incited by trypanosomes. 
Sleeping Sickness.-The "sleeping sickness" is very common and 
fatal among the negroes of equatorial Africa, assuming in the Congo 
region the character of a veritable pestilence whose victims number 
hundreds of thousands. White men are not exempt. The disease, 
still rapidly extending, is characterized by lethargy, debility, emaciation, 
drowsiness, coma, and death. It is incited by a trypanosome, Tr. 
gambiense, which also is conveyed by a tsetse-fly, Glossina palpalis. 
The lesions noted are congestion of the meninges with fluid exudate and 
enlargement of the lymph-nodes, spleen, and liver.1 
1 For a summary of trypanosomes and diseases incited by them, see Novy, The Harvey Lectures, 
1905-6; Jour. Am. Med. Assn., Jan. 5, 1907, Also Mayer, Kolle and Wassermann, Handbuch, 
2d edition, 1913, vii, 321. For a study of trypanosomiasis with special reference to service in the 
Philippine Islands, see Musgrave and Clegg, Department of Interior, U. S. A., Bureau of Government 
Laboratories, 1903. For a study of chemical therapy, see Terry, Arch. Int., Med., iii., 98, 1909. ANIMAL PARASITES 
119 
Spirochaeta.-Among the spirally curved bacteria it has been cus- 
tomary to recognize a genus called Spirillum, the members of which 
have a rigid spirally curved body, and a genus called Spirochaeta, in which 
the organisms are also spirally curved but are described as flexible. These 
genera have been considered to embrace closely related bacterial forms. 
The discovery by Schaudinn of Spirochaeta, now called Treponema, 
pallidum (Fig. 75), in the lesions of syphilis has given rise to many 
critical studies of spirochetes, and while we cannot enter here into the 
details of the matter, it has finally become probable, if not entirely 
proved, that the spirochetes are protozoa and not bacteria or at least 
that the protozoan characters are predominant in them.1 
The remarkable achievement of Ehrlich in creating, on a carefully 
projected theoretical basis, the synthetical chemical compound of 
arsenic, dioxydiamidoarsenobenzol, popularly 
known as 606, which has a specific destructive 
action on the life not only of the spirochetes of 
syphilis and of relapsing fever, but upon trypano- 
somes as well, would indicate a relationship be- 
tween the spirochetes and the protozoa which tends 
to confirm the evidence from morphology. 
Treponema (Spirochaeta) Pallidum.-This organ- 
ism, now believed to be a protozoan and the incit- 
ing agent in syphilis, is described in connection with 
the lesions of that disease on page 274. 
Spirochaeta Obermeieri.-The protozoan organism inducing relapsing 
fever and Spirochaeta pertenuis of Castellani will be considered among the 
infectious diseases, see page 292. 
The occurrence of spirochetes in tumors is of no pathological signi- 
ficance. 
Leishman-Donovan Bodies.-In some forms of cachexial fever of India associated 
with enlarged spleen and marks of profound toxaemia-the so-called kala-azar; 
dum-dum fever-there have been found in the spleen, blood, etc., peculiar bodies 
now known as the Leishman-Donovan bodies which were believed to belong to the 
trypanosomes and have given rise to much discussion. More recently they have 
been placed in the genus Herpetomonas-an allied form of flagellata or protozoa- 
in which are organisms commonly parasitic in the fly. The organism is believed to 
be transmitted to man through the bite of the bed-bug. For further details, see 
p. 480. 
Trichomonas vaginalis has an oval or pear-shaped body from 0.015 to 0.025 mm. 
long, with a cluster of flagella at one end and an undulating membrane, frequently 
mistaken for cilia, upon the side (Fig. 76). It is of occasional occurrence in vaginal 
exudates. The possibility of mistaking the T. vaginalis for human spermatozoa 
should be borne in mind in medico-legal examinations, although to an observer 
familiar with either structure such a mistake could hardly occur. 
Some forms of Trichomonas have been found in the urine of man, in the intestines, 
and in the sputum.2 
Fig. 76.-Trichomonas 
Vaginalis. 
After Dock. 
1 For a discussion of this subject, see Calkins' "Protozoology," p. 231, 1910; also Amheim, Ztschr. 
f. Hyg. 1914, Ixxvi., 407. 
2 For original studies of Trichomonas with historical summary and bibliography, see Dock, Am. 
Jour. Med. Sc., vol. cxi., p. 1, 1896. 120 
ANIMAL PARASITES 
III. ClLIATA (INFUSIORIA.) 
The infusoria are the most highly differentiated of the protozoa. 
They have numerous motor appendages or cilia, which may persist 
through life or in some forms be replaced 
in the adult stage by suctoria. They re- 
produce chiefly by fission, or budding. 
Among the ciliated infusoria, few if any 
are pathogenic in man. The Balantidium 
coli (Fig. 77) is an ovoidal organism from 
0.06 to 0.1 mm. long; it is a common 
parasite of swine in some regions, and has 
been found a few times in the intestinal 
tract of man under conditions which indi- 
cated its probable pathogenic significance. 
Fig. 77.-Balantidium Coli. 
After Braun. 
IV. Sporozoa. 
The sporozoa are all parasitic, living at some period of their life 
cycle in the cells of their host, and are especially characterized by their 
reproduction through encystment and spore formation and absence of 
definite motile organs. Many forms of the organisms, especially the 
spores, are very minute and difficult of identification. 
The sporozoa are widely distributed, being found as parasites in 
nearly all classes of animals. They may invade the gastro-intestinal 
canal and the kidney and their adnexa, the blood, muscle, connective 
tissue, and skin. While many of them appear to be harmless to their 
host, others may do serious damage by blocking the tissue spaces and 
thus, or in other ways, inducing necrosis, atrophy, or cell death. Some 
forms are wholly intracellular, others remain for only a part of their life 
cycle within single forms of cells, passing then to other cells or to the 
body cavities or to hosts of a different species. The life cycle of many 
forms is extremely complex. On account of their strict parasitism and 
the requirements in some instances of an interchange of hosts, precluding 
the methods of culture applicable to many of the lower organisms, the 
life history of many forms is still unknown or obscure. 
The classification of the Sporozoa is still tentative, but one may con- 
veniently recognize the following orders: 
1. Gregarinx.-These are round or elongated parasites, some of the 
higher forms presenting partitions in the cell with special development 
of one end for attachment. They are parasitic in certain cold-blooded 
animals, especially the invertebrates. The young stages only are in- 
tracellular, mature forms occurring in the body spaces. 
2. The Myxosporidia are parasitic in certain of the invertebrates, 
in fishes and batrachians. Epidemics among silk worms incited by a 
parasite of this class have occasioned serious losses. Many species are 
concerned in diseases of fish, in which they may cause extensive deep 
foci of necrosis and ulceration. ANIMAL PARASITES 
121 
3. Coccidia - Organisms of this order are parasitic in certain of the 
invertebrates, in birds, reptiles, and mammals. They are round or oval, 
usually intracellular parasites having no free motile adult stage. They 
are most frequently found in the epithelium of the intestine and liver. 
One of the most common forms in the mammalia is Coccidium oviforme 
(Fig. 78) which is of frequent occurrence in the 
liver of the rabbit, forming a part of the con- 
tents of yellowish irregular shaped masses, re- 
sembling tumors, or in the form of cysts.1 
The parasites surround themselves with a 
capsule within which elongated sporozites de- 
velop. This encapsulated form may be taken 
up by a new host in which the sporozites are set 
free and enter the epithelial cells in which they 
again become encapsulated. The occurrence of 
Coccidium oviforme has been recorded in the liver, kidney, and heart- 
muscle of man. 
Another smaller form, 
occurring in the intestinal 
epithelium of dogs, cats, and 
rabbits, has been found in 
two cases in a similar situa- 
tion in man. 
4. S ar co sporidia.-In this 
order of the Sporozoa the 
usually elongated slender 
early stage is found in be- 
tween the muscle fibres and 
bundles of vertebrates- 
mouse, hog, and, in a few 
instances, in man. These 
are commonly known as the 
"tubes of Miescher" or "of 
Rainey" (Fig. 78A). Reniform or falciform spores are developed. The 
adult forms are spheroidal or elongated. The life cycle is not well known.2 
5. Hcemosporidia.-These parasites of the blood form a large group 
occurring in the corpuscles or plasma of vertebrates-amphibia, reptiles,3 
birds, and mammals. Some forms are among the most important of the 
protozoan parasites of man. They are of small size; the adult form is 
motile. One stage in the life cycle is passed in the blood of the verte- 
brate host; another in the body of some insect, as an intermediate host. 
Among the mammalian haemosporidia we may mention the haemato- 
zoa of malaria and the haematozoon of Texas fever. 
Malaria.-The characters of the malarial haematozoon, for which the 
Fig. 78.-Coccidium Oviforme. 
This shows the encapsulated 
form of the parasite, with the 
formation of spores. 
Fig. 78A-Sarcocystis muris. 
1 See Tyzzer, Jour. Med Res., vol. vii., p. 235, 1902, bibl. 
2 For a study of the production of sarcosporidia in the mouse see Theobald Smith, Trans. Assn. Am. 
Phys., vol. xvi., p. 576, 1901. 
3 See Langmanri, " Hsemosporidia in American Reptiles and Batrachians," N. Y. Med. Jour., 
January 7, 1899. 122 
ANIMAL PARASITES 
mosquito acts as intermediate host, are described in detail on page 312. 
Texas Fever.-Texas fever (tick fever,) a disease of cattle marked by 
fever, debility, and hsemoglobinuria, occurs in many parts of the world- 
North and South America, Europe, and Africa. The haematozoon in- 
ducing Texas fever was discovered by Theobald Smith and Kilbourne1 
and is now called Piroplasma bigeminum.2 In one stage it is a minute 
pyriform organism occurring often in pairs in the red blood cells of its host. 
Free forms have been found in the blood. While its life cycle has not 
been completely worked out, Smith and Kilbourne showed that a cattle 
tick acting as an intermediate host transmits the parasite through her 
eggs and larvae. It is through these young ticks that fresh cattle be- 
come infected.3 Other species of Piroplasma have been found in the 
dog in various countries; still others in horses and sheep. 
Methods of Study of the Protozoa: 
The protozoa may be studied in the living condition in the fluids in which they are 
found or they may be killed by sublimate solution and stained with iron haematoxylin. 
The movements of the Entamoeba histolytica in the faeces or in the contents of 
abscesses, may be studied on the warm stage. Its morphology may be studied in 
tissue containing it, such as intestinal ulcers, abscesses, etc., which have been hardened 
and stained either with methylene blue or haematoxylin. 
The attempts to obtain pure cultures of certain forms of Amoeba and similar or 
allied forms of protozoa have been partially successful. The method by which Mc- 
Neal and Novy obtained pure culture of trypanosomes, namely, by the use of ordinary 
nutrient agar containing rabbit's blood, is of high promise in related forms of protozoa. 
For details of this method as well as a resume of the cultivation of protozoa, consult 
McNeal and Novy, "Contributions to Medical Research, Vaughan Anniversary 
Volume," 1903, p. 549. 
Among the multicellular parasites, the worms-the flat flukes and 
tape-worms as well as the round worms and a few insects-form the most 
important classes for our consideration. But for the details concerning 
these as well as the other larger parasites we must refer to special 
works on parasitology. 
It may be said in general that the metazoan parasites may be harm- 
ful to the structure or the function of the host, though the damage is 
often very slight,either by their local presence, occluding canals, obstruct- 
ing vessels, inducing local irritation, or structural damage, or by their 
movements about the body; by the appropriation of food belonging to 
the host; or, finally, by the setting free of deleterious metabolic products 
of their own manufacture. 
This toxic action of certain parasites is especially marked by the 
more or less pronounced eosinophilia present in a large proportion of 
patients who are the victims of invasion by parasitic worms.4 
The frequent anaemia associated with the presence of metazoan 
Metazoa. 
1 Smith, Bull. Bur. An. Industry, No. 1, 1893. 
2 Piroplasma and allied genera are now often described under the generic name Babesia, and the 
form here considered is named Babesia bovis. 
3 For a summary of observations on Texas fever (Hsemoglobinuria of Cattle) see Kossel, in Kolle 
and Wassermann's "Handbuch der Mikroorganismen," 1st edition., 1902, Bd. i., p. 841, bibl. 
4 See for a study of the influence of parasites on the host, Ward, Science, vol. xxv., p. 201, 1907; 
consult also Shipley and Fearnsides, Jour. Economic Biology, vol. i., 1906. ANIMAL PARASITES 
123 
parasites and the local injuries inflicted by them, especially of the mucous 
membranes, through which the body is made more vulnerable to second- 
ary bacterial invasion, are all of considerable importance. Some of 
these effects will be referred to in the following brief series of individual 
forms of metazoan parasites. 
Worms. 
These worms are small, flat, tongue-shaped, or leaf-like creatures, 
with an intestine, and a discoiclal structure on the under surface, by 
means of which they attach themselves. There are several genera 
and species found in man. The most common 
genus is Distoma. Of these D. hepaticum is of 
most frequent occurrence (Fig. 79). It is about 
30 mm. long, and usually occurs in the gall- 
ducts and gall-bladder. The embryos are often 
attached to water plants, from eating which the 
infection is believed to occur. D. lanceolatum is 
more slender, pointed at the ends, 8 to 10 mm. long, and has been 
found a few times in the gall-bladder. D. sinense is a slender worm 
about 15 mm. long, and has been found in the bile in considerable 
numbers, particularly in the Chinese. D. hcematobium is a more nearly 
cylindrical worm; the sexes are distinct, the 
male from 12 to 14 mm. long, the female 16 
to 18 mm. long, and the parasite occurs, 
especially in Egyptians, in the portal and 
other abdominal veins. 
TREMATODA (Flukes). 
Fig. 79.-Distoma Hepat- 
icum. 
About natural size. 
CESTODA (Tape Worms). 
These important worms consist, in the 
mature state, of more or less rectangular or 
elongated flat segments, each one represent- 
ing a single individual, arranged in a linear 
series to form a colony. At one end of this, 
called the head, is a variously formed struc- 
ture for the attachment of the colony to its 
host. The neck and head are called the 
scolex, while the segments are called proglot- 
tides. These worms have neither mouth nor 
alimentary canal. They are hermaphrodites, 
the sexes being united in the proglottides. 
The head and neck (scolex) may exist as an 
immature form in various tissues and organs 
where they are encysted, and are often called 
cysticercus. 
Tcenia solium is of infrequent occurrence in man. It may be several 
metres in length, and may be coiled up or stretched out in the small 
intestines. Several worms may be in the gut at one time. The head, 
about the size of a pin's head (Fig. 80), has a projecting proboscis or 
Fig. 80.-Head of Taenia 
Solium. 
X about 40. 124 
ANIMAL PARASITES 
rostellum, around which are arranged a double row of horny booklets. 
Below these are four sucking discs at the sides of the head. The hook- 
lets of the anterior row are larger than those in the posterior row, and 
are from 0.16 to 0.18 mm. long. The proglottides, when fully developed, 
are from 10 to 12 mm. long and from 5 to 6 mm. wide, but those 
nearest the head are much shorter and immature. The eggs of T. 
solium are ovoidal structures, about 0.03 mm. in diameter. The embryo 
of this worm is most commonly seen in the muscles of the pig as an 
encysted scolex, commonly called a "measle." It occasionally occurs 
in man in the muscles, brain, eye, etc., and is called Cysticercus celluloses. 
It is usually about the size of a 
pea, but may be as large as a 
pigeon's egg and surrounded by 
a connective-tissue capsule. 
Infection with the worm oc- 
curs in the human subject from 
the ingestion of insufficiently 
cooked "measly" pork, or, in 
the case of Cysticercus cellulosae, 
from the ingestion of the eggs, 
which may, in a variety of ways 
in uncleanly persons, get into 
the food. 
Tania mediocanellata (T. 
saginata Leuckart).-The head 
of this species is somewhat cu- 
boidal, with neither rostellum 
nor booklets, but with four suck- 
ing discs (Fig. 81). The seg- 
ments are generally broader and 
shorter than in T. solium, and 
the worm is usually larger. In the embryonal form the scolex occurs as the 
Cysticercus tanice mediocanellata in the form of small cysts in the muscles 
of cattle, from the eating of which in the uncooked condition the infec- 
tion occurs. This is the most common tapeworm in the United States. 
Tania echinococcus.-This worm in the mature condition forms a 
short, small colony inhabiting the intestine of the dog. The head is about 
0.3 mm. in diameter and has a double row of booklets around the rostel- 
lum. The proglottides are three or four in number, the last being the 
larger. The entire colony is not more than 4 to 5 mm. in length. The 
significance of this parasite in human pathology depends upon the cysts, 
called hydatids, which it forms, in the immature or cysticercus stage, in 
various parts of the body. Intimate association with dogs favors the 
acquirement of this parasite. When the eggs of the mature worm get 
into the intestinal canal of man they undergo partial development and 
find their way into the tissues and organs, most frequently into the liver. 
Here cysts are formed which become encapsulated by a connective- 
tissue membrane produced by the inflammatory reaction of the organ. 
Fig. 81.-Taenia Mediocanellata. Head and 
Proglottides. 
A, head X about 15. B, mature proglottid, 
showing generative apparatus. C, head and frag- 
ments of immature proglottides, showing gradual 
tapering of the neck. Natural size. ANIMAL PARASITES 
125 
The cyst wall of the parasite is formed of two layers-an outer, finely 
lamellated layer called the cuticula (Fig. 82), and an inner, granular 
layer containing, muscle fibres and blood-vessels called the parenchyma- 
tous layer. Inside of the primary cyst, secondary cysts sometimes form, 
called daughter cysts; and within the latter, tertiary cysts, called grand- 
daughter cysts, may develop. On the inner surface of the cysts, either 
primary, secondary, or tertiary, the scolices or heads of the immature 
worm are formed. These de- 
velop in the walls of the pedicu- 
lated vesicles called brood cap- 
sules. The walls of these vesicles 
have a lamellated cuticula and 
a parenchymatous layer similar 
to those of the primary cysts. 
The scolices, of which there may 
be several in each brood cap- 
sule, are similar to the heads of 
the mature tapeworm. They 
are about 0.3 mm. in diameter, 
having a rostellum surrounded by a double row of booklets and four 
sucking discs (Fig. 83). At the posterior end of the scolex is a 
pedicle by which it is originally attached to the wall of the brood 
capsule. Little, lamellated concretions of lime salts are often present 
in the scolex. The anterior portion of the scolex, the rostellum, 
booklets, and suckers, are often invaginated in the posterior portion. 
The scolices may be free inside of the brood capsules, or, owing to the 
rupture of the latter, they may be free in the cavity of the primary 
cysts. They may die and degenerate, forming a granular mass in which 
the booklets may be embedded, 
or the booklets may be free in 
the brood capsules or in the 
primary cysts. Sterile cysts are 
often found, that is, those in 
which neither brood capsules 
nor scolices are developed. 
The cysts contain, in addi- 
tion to the scolices, a clear, 
gelatinous fluid. This fluid may 
become turbid by admixture 
with disintegrated scolices or 
fragments of the parenchymat- 
ous layer, or it may contain 
fatty detritus, cholesterin crys- 
tals, and particles of lime salts. 
The fluid may be partially absorbed, leaving a thick, grumous material 
within the cysts, which may become calcified or converted into a stony 
mass. When the scolices are not found entire the diagnosis may be 
made by the discovery of the separate booklets (Fig. 84) or fragments of 
Fig. 82.-Cuticula of Echinococcus Cyst. 
Showing lamellated structure. 
Fig. 83.-Scolices of Taenia Echinococcus. 
In one the rostellum is projected; in the others it 
is withdrawn. 126 
ANIMAL PARASITES 
the characteristically lainellated cyst walls. The connective-tissue walls 
of the primary cysts may become fatty, or caseous, or calcified. 
Sometimes the secondary vesicles project outward instead of inward, 
forming a series of cysts outside of the primary one. This variety of 
development is sometimes seen in man, but is more common in the 
domestic animals. It is called Echinococcus scolecipariens or exogena. 
Another variety of echinococcus, 
called E. multilocularis, is almost always 
found in the liver, and appears to be the 
result of incomplete and disturbed de- 
velopment of the embryos or cysts. It 
consists of a congeries of irregular, usually 
small cysts (Fig. 486, p. 739), surrounded 
by broad and narrow bands of connective 
tissue, and sometimes containing gelatin- 
ous fluid and scolices or booklets; but 
the latter structures are commonly absent 
or difficult of detection. The whole is 
often surrounded by a dense connective-tissue capsule which may be 
calcified. The entire mass often presents an alveolar structure and was 
formerly regarded as a tumor-alveolar cancer. The diagnosis may be 
established by the discovery of the booklets or scolices, or fragments of 
the lamellated cuticula. This form of the parasite is rare in America. 
There are four or five other species of taenia, occurring rarely in man. 
Tcenia nana.-This species occurs in the form of small colonies, about 15 mm. in 
length. The rostellum is surrounded by a single row of booklets. It is frequently 
found in the intestinal contents of Italian children, of the inmates of asylums for 
the insane, and of a considerable proportion of the population of some of the South- 
ern States. Tcenia flavopunctata, a species about which little is known, is reported 
twice in America as occurring in the intestine of young children. Tcenia madagascari- 
ensis, also little known and rare, has been seen in two children in Madagascar. 
Tcenia cucumerina.-This species occurs in colonies about 20 cm. long. The head 
is very small and spheriodal, and has four rows of booklets. It is frequent in the 
small intestines of dogs and cats. It occurs occasionally in man. Its scolex inhabits 
the dog louse, and infection may occur in man by the transference of the lice or the 
embryos of the parasite to the mouth, as the result of the filthy habit of kissing dogs 
and cats or permitting the face to be licked by them. 
Bothriocephalus latus.-This, the largest of the human tape worms, has very broad, 
quadrangular proglottides. The head is ovoidal and about 2 mm. long and 1 mm. 
broad. It has no proper sucking discs and no booklets, but by long grooves on either 
side of the head the animal attaches itself to its host. The neck is long and filiform. 
It occurs most frequently in Europe, particularly in the northern provinces. The eggs 
undergo partial development in water, and are taken up by the pike and eel-pout, and 
perhaps by other fresh-water fish, from the ingestion of whose flesh in an imperfectly 
cooked condition the human infection occurs. Two other species of Bothriocephalus 
have been described as of rare occurrence in man: B. cordatus in Greenland and Ice- 
land, and B. cristatus. 
Fig. 84.-Booklets from Scolex of 
Talma Echinococcus. 
NEMATODA (Round Worms). 
These worms are in general cylindrical, elongated, usually pointed 
at the ends, and sometimes filiform. The surface is sometimes smooth, 
sometimes irregularly beset with hairs and papillae, or possesses longi- ANIMAL PARASITES 
127 
tudinal elevated striae or transverse rings; but the body is not segmented. 
There is a mouth at the anterior portion, and a ventral anus near the 
posterior end. The intestine is straight. The sexes are in most forms 
distinct, the male being in general smaller than the female. 
Ascaris lumbricoides.-This is one of the most common of the human 
intestinal parasites, and is of particularly frequent occurrence in chil- 
dren. It is of a light-brownish or reddish color. The female is from 30 
Fig. 85.-Ascaris Lumbricoides. About half natural size. 
A, Male. B, Female. After Peris. 
to 40 cm. long and from 5 to 6 mm. thick. The male is somewhat more 
than half as large (Fig. 85). Both sexes are pointed at the ends, the 
posterior end of the male being curved into a spined hook. The eggs, 
from 0.05 to 0.06 mm. in diameter, are surrounded by an albuminous 
envelope (Fig. 86 A) and are quite resistant to destructive agencies. 
The mode of development and life history of these parasites are not very 
well understood. Their usual seat in man is the small intestine, but they 
may wander into the stomach, and exceptionally get into the mouth, 
nose, bronchi, gall-passages, peritoneal cavity, etc. They may be single 
in the gut or present in great numbers. 
Two other species of ascaris have 
been found in man. A. maritima 
was found in the vomit of a child in 
Greenland, in an immature condi- 
tion. A. mystax, a tolerably com- 
mon form in cats and dogs, has 
been found a few times in man. 
It is smaller than A. lumbricoides. 
Oxyuris xermicularis (Thread- 
worm or Pinworm).-This species 
is very small; the female has a 
pointed tail and is about 1 cm. 
long. The posterior end of the 
male, which is about 4 mm. long, is blunt, and after death somewhat 
curled (Fig. 87). The eggs (Fig. 86 B) are produced in great numbers, 
are oval, and about 0.052 mm. long. This parasite is very common 
in children, and may be present in large numbers in the colon. This 
worm is known to infest only the human subject, and infection doubt- 
less occurs by the ingestion of the eggs, which are widely distributed in a 
variety of ways on many objects, fruits, etc. 
Fig. 86.-Eggs of Nematode Worms. 
A, Eggs of Ascaris lumbricoides, X about 300. 
B, eggs of Oxyuris vermicularis, X about 250. 128 
ANIMAL PARASITES 
Strongylus gigas.-This is a slender red worm, the female being 
sometimes 1 metre long and over 1 cm. in diameter. It has been found 
several times in the pelvis of the kidney in man. It is more common in 
the wolf, fox, horse, seal, and some other animals. 
Strongylus longevaginatus.-The female is about 2.5 cm. long, the 
male, as usual, shorter. It is of a yellowish-white 
color, and has been found once in the lung of a boy in 
Germany. 
Strongylus subtilis.-A very small species (female 
5.6-7 mm. long) has been described by Looss as 
occurring in Egypt in the human intestine. But it is 
believed to be without pathological significance. 
Uncinaria (Hookworm).-There are two forms of 
hookworm, that common in European and other 
countries, Uncinaria duodenalis (Ankylostoma duo- 
denale), Stiles, and the hookworm of the New 
World, Uncinaria americana, Stiles. The latter worm 
is from 7-11 mm. long. The mouth is furnished with 
a chitinous capsule and chitinous claws and teeth. It is found especially 
in the small intestine. The head is burrowed into the mucous mem- 
brane of the host and the animal is nourished by the blood which 
it sucks. Ecchymoses may be produced at the point of attachment 
or even severe haemorrhage. The worms are often present in large 
numbers. The eggs are deposited in the intestine of the host, escaping 
in the foeces. These may develop in a short time outside the body and 
then the parasite can gain access to the host either through the skin or 
by the mouth. 
Hookworm disease, uncinariasis, is widespread, involving in this 
country the Southern States and adjacent islands where it is of serious 
importance on account of anaemia, gastro-enteritis, haemorrhage, and 
general debility, etc., which often mark its presence. It is estimated 
that in some districts 90 per cent, of the inhabitants are affected. 
By proper attention to sanitation in the disposal of excreta, the 
ravages of this parasite could be checked. 
Trichocephalus dispar (Whipworm).-The males and females are of 
nearly equal size, 4 to 5 cm. long. A little less than one-half of the 
body (the posterior portion) is about 1 mm. 
thick, and in the male is rolled into a flat- 
tened spiral, but in the female is but 
slightly bent. The anterior part of the 
body is very slender (Fig. 88) and is em- 
bedded in the mucous membrane of the 
host. The eggs are elongated, oval-shaped, 
about 0.05 mm. long and about one-half as 
wide, with a thick brown capsule. This 
parasite is very common in some countries, especially in France and 
southern Italy. It is commonly found in the caecum, usually in small, 
but sometimes in very large, numbers. It is generally of little patho- 
Fig. 87.-Oxyuris 
Vermicularis. 
A, Female. B, Male. 
Fig. 88.-Trichocephalus Dispar. 
From the skin of the mons veneris. ANIMAL PARASITES 
129 
logical significance, commonly producing no symptoms. Its develop- 
mental history is not well known. 
Trichina spiralis.-The female of this common parasite is, in the 
mature condition, about 3 mm. long, the male from 1 to 1.5 mm. long; 
they are filiform in shape and white in color. The young are born in 
the form of tiny worms about 0.01 mm. in length and somewhat similar 
to the adult in shape. Infection occurs in man from the ingestion of 
insufficiently cooked pork. The muscle of the diseased pig contains 
the embryos of the parasite in an encysted condition. In the stomach 
the capsule of the worm is dissolved and the embryos are set free. They 
very rapidly mature, increasing in size, and the females give birth in 
the small intestine to very large numbers of young. It is estimated that 
a single female may give birth to from 1,300 to 1,500 young. These 
find their way through the mucous membrane and wall of the gut, into 
various parts of the body.1 
Fig. 89.-Trichina Spiralis. 
The parasites are encysted in muscle. In one capsule the parasite has died, and the granular 
material replacing it is calcified. 
The exact course which they take in getting out of the gut is not 
fully established; probably they traverse the tissues in different ways. 
At any rate, they find their way to the voluntary striated muscle tissue, 
which they penetrate, and enter the muscle fibres. Here they cause a 
disintegration of the contractile substance, and coil themselves inside 
of the sarcolemma. In this situation they become encapsulated by 
material in part furnished by themselves, in part by means of the inflam- 
matory reaction which their presence induces in the connective tissue of 
the muscle. The worms are surrounded inside the capsule by granular 
material (Fig. 89). The capsule after a time becomes partially calcified, 
and in this condition may be readily seen by the naked eye as a tiny white 
speck. In this encysted state they may remain inactive but living for 
an indefinite, often for a very long time. Most frequently the cysts 
contain but one embryo, but they may contain from two to four. The 
embryo may die and its remains become calcified. 
1 Herrick and Janeway have found the embryo in the blood, see Arch. Int. Med. iii., 263, 1909. 130 
ANIMAL PARASITES 
The same course of events follows when the muscle trichinae are eaten 
by the pig or a variety of other animals. 
The embryos in the muscle are killed by a temperature of 55° C. and 
by some of the methods of curing pork. 
The embryos may mature and a new generation be born within from 
five to eight days after the ingestion of the diseased meat. 
As the result of the presence of these parasites in the body, if the 
invasion be severe, nutrition may be impaired and catarrhal enteritis, 
broncho-pneumonia, hyperplasia of the mesenteric lymph-nodes, and 
fatty degeneration of the liver may occur. Leucocytosis with a great 
increase in the number of eosinophile cells is common.1 The encapsu- 
lated embryos may be found in enormous numbers in various voluntary 
muscles of the body, but they are most apt to be found, when not very 
abundant, in the muscles of the neck and larynx, in the intercostals and 
the diaphragm. They tend to collect toward the tendinous extremities 
of the muscles. Trichinae also occur in the rat, cat, mouse, and other 
animals. 
Filaria medinesis (Guinea worm).-This is a thread-like worm, the 
female being sometimes as much as 80 cm. long and from 0.5 to 1.7 mm. 
thick. The male, which is rarely found, is much smaller, measuring 
only about 4 cm. in length. It is common in the East, and inhabits 
the subcutaneous connective tissue, in which it often gives rise to ab- 
scesses and ulcers. Eosinophilia is commonly present. The embryos 
live for a time free in fresh water, and are taken up by a species of 
fresh-water crustacean, in whose body they undergo further develop- 
ment, and by the ingestion of which the infection of the human subject 
occurs. 
Filaria sanguinis hominis.-The embryo of this parasite, which 
inhabits the blood and lymph of man, especially in Brazil, Egypt, and 
some parts of the Orient, and occa- 
sionally occurs in this country, is 
about 0.35 mm. long, rounded ante- 
riorly, and pointed at the tail (Fig. 
90). It has about the diameter of a 
red blood cell. It occurs, sometimes 
in great numbers, in the blood dur- 
ing the night time, being as a rule 
absent during the day. It may occur in the urine in connection with 
chyluria and haematuria. The mature female is from 8 to 10 cm. long, 
and has been found inhabiting the lymph-vessels of man, particularly 
in the scrotum and lower extremities. Owing to the obstructions which it 
causes in the lymph circulation, and to the local irritation which its pres- 
ence induces, it sometimes gives rise to lymphangiectasis,2 oedema, ab- 
scesses, and perhaps elephantiasis. Eosinophilia is common. One of 
the embryonic stages of development is believed to take place in the 
body of a species of nocturnal mosquito. Through the bodies of the 
Fig. 90.-Filiaria sanguinis hominis 
-Embryonic Form from the Blood. 
1 See Albert, Am. J. Med. Sci., Aug., 1910. 
2 For a study of filarial lymphatic varix see Opie, Trans. Assn. Am. Phys., vol. xvi., p. 314. ANIMAL PARASITES 
131 
dead mosquitoes, which are liable to fall into the drinking-water, it is 
believed that the spread of the parasite may occur. 
There are several other species of filaria occasionally found in man 
which it is not necessary to enumerate here.1 
Rhabdonema strongyloides.-A small, filiform worm from 1 to 2 mm. 
in length is found, often in enormous numbers, in the intestines, biliary 
and pancreatic ducts of man in Cochin China, Italy, South and Central 
America, giving rise to endemic diarrhoea. It has been thought that there 
are at least two species, which have been described under the generic 
name Aguillula but recent researches by Leuckart have led him to believe 
them to be different developmental stages of the same form, for which he 
suggests the above name. 
Methods of Study of Worms. 
Filaria sanguinis may be preserved by preparing a smear of the blood containing 
it on a slide in the usual way (see p. 316), and staining with methylene blue. 
The larger parasites may be hardened in formalin and studied whole after dehydra- 
tion in alcohol and clearing in oil of cedar or origanum. Or sections may be made after 
embedding, and stained and mounted in the usual way. 
The examination of muscle for trichina is often of great practical importance. For 
this purpose small pieces of fresh muscle are squeezed into a thin sheet between two 
slides, and examined with a low power. A considerable number of bits of muscle 
should be examined, particularly from the above-mentioned favorite situations, be- 
fore excluding them in a suspected case, because they are sometimes present in small 
numbers. A thorough search is of special importance in the examination of pork, 
since, owing to the enormous fertility of the parasites, even a moderate number may 
give rise to a severe infection. 
For the minute examination of the parasite, bits of muscle should be hardened in 
Orth's fluid and alcohol, decalcified if necessary, and, after embedding in celloidin, thin 
sections cut and stained double with hsematoxylin and eosin, and mounted in balsam. 
Bits of muscle may be also teased, the embryos picked out with a needle, and the cysts 
either broken open under a lens with the needle, or squeezed under the cover-glass. 
The embryo worm thus set free may be mounted in a mixture of equal parts of glycerin 
and saturated aqueous picric acid. The adult forms, which may be obtained by feed- 
ing rabbits with uncooked trichinous muscle, and examining after the proper interval, 
may be hardened in Orth's fluid, and mounted in a mixture of equal parts of picric 
acid and glycerin, or in the same mixture which has been lightly tinged with eosin. 
Arthropoda. 
The scope of this work does not permit us to enter in detail into the 
subject of external parasites, which will be found described in treatises 
on diseases of the skin or in the general works on parasites referred to 
below. But, owing to their frequent occurrence and practical impor- 
tance, we may briefly describe two of the more common forms of ar- 
thropods, the "itch insect" and the "louse." 
The common "itch insect"-Sarcoptes hominis {Acarus scabiei)-is 
shaped somewhat like a turtle, with a chitinous covering, and presents 
the general appearance seen in Fig. 91. The female is about 0.45 mm. 
long, the male a little smaller. 
1 See Fulleborn in "Kolle and Wassermann," 2d edition, Bd. viii., p. 185. 132 
ANIMAL PARASITES 
The parasite bores little tunnels in the skin, in which the eggs are 
laid and the young hatched. After a few days these bore fresh channels 
in the skin. For their detection a bit of the superficial layer of the skin 
is snipped out with curved scissors, dehydrated and cleared up with oil 
of cloves, and examined under a low power, when the tunnels and the 
parasites, if present, will be readily visible. 
Fig. 91.-Sarcoptes Hom- 
inis -the "Itch Insect." 
Fig. 92.-Pediculus 
Capitis-the "Head 
Louse." 
Female; back view. After 
Furstenberg. 
The head louse, Pediculus capitis, is from 1 to 2 mm. long, the female 
being slightly the larger. The general appearance of the insect is seen 
in Fig. 92.1 
Male. After Braun. 
These, if small, may be cleared in turpentine and mounted in balsam, or sections 
may be cut after embedding in paraffin. 
Methods of Study of Insects. 
1 Bibliography.-Especially to be recommended for detailed description of human and animal 
parasites is the small work of Brumpt, "Precis de Parasitologic," Paris, 2d edition, 1913. 
Consult also, especially for the forms of eggs and other parts of animal parasites which may be 
found in the excreta, vonJaksch, Wood, or Simon, or other works on clinical microscopy. 
The Reports of the Bureau of Animal Industry of the U. S. Department of Agriculture contain 
many valuable data relating to animal parasites and the diseases of animals in the United States. 
See for a general study of the effects of parasites on their host, Ward, Science, vol. xxv., 201, 1907. CHAPTER VII 
PLANT PARASITES. 
The plant parasites of man belong among the simplest of living 
organisms. Three distinct groups are of frequent occurrence in or upon 
the body. These are: 
1. Bacteria, or fission fungi (Schizomycetes). 
2. Yeasts, or yeast fungi, or sprouting fungi (Blastomycetes). 
3. Moulds, or mould fungi (Hyphomycetes). 
The first group, the bacteria, is of the greatest significance, because 
it contains organisms which are very frequently the excitants of serious 
disease. 
The scope of this work does not permit more than a brief outline of 
the rapidly increasing knowledge of the forms, nature, and performances 
of the bacteria. For details we refer to special treatises on bacteriology.1 
I. Bacteria. 
MORPHOLOGY, PHYSIOLOGY, AND DISTRIBUTION. 
Bacteria are minute unicellular plants devoid of chlorophyll, multi- 
plying by transverse division and in some cases preserving the species 
by the formation of spores. 
The colorless, sometimes granular protoplasm is enclosed by a mem- 
brane, and some forms are surrounded by a transparent capsule. Not 
Fig. 93.-Bacteria with Flagella. 
Fig. 94.-Typical Forms of Bacteria. 
Cocci, Bacilli, and Spirilla. 
infrequently parts of the protoplasm appear less dense than the rest, 
as if from vacuolation, and a few observers have claimed to demonstrate 
in certain forms a nuclear substance. 
Many of the bacteria, especially bacilli and spirilla, less frequently 
the cocci, have hair-like processes called flagella which are apparently 
organs of locomotion (Fig. 93). These may be single or in tufts; may be 
1 Hiss and Zinsser, "Text-book of Bacteriology," 1914; Park and Williams, "Pathogenic Bacteria 
and Protozoa, 1910. 
133 134 
PLANT PARASITES 
at one or both ends or over the general surface. Their number and 
distribution seem sometimes to be characteristic of special forms. (See 
Motility below.) 
Forms of Bacteria.- Bacteria may be grouped in three classes (Fig. 
94). 
1. Spheroidal bacteria.-Cocci or micrococci (singular, coccus,1 micro- 
coccus). 
2. Rod-like bacteria.-Bacilli (singular, bacillus). 
3. Spiral bacteria.-Spirilla (singular, spirillum). 
All straight bacteria which have one axis longer than the other are 
called bacilli, even though the form is oval rather than rod-like. The 
ends of bacilli may be square or rounded, and in stained preparations, in 
some cases, concave. 
While the cocci elongate a little in preparation for fission and in this 
condition present a slight irregularity in the length of their axes, and thus 
resemble bacilli, the complete observation of their life cycle rarely permits 
error in the determination of the primary group to which a given micro- 
organism belongs. 
Variations in Form and Size.-Some bacteria present slight modifica- 
tions of the fundamental form in certain phases of their growth and under 
various chemical and physical conditions. Thus some of the cocci after 
division are slightly flattened on their contiguous sides-biscuit-shaped; 
certain bacilli may bulge slightly in the middle-clostridium forms; others 
may be larger at one end than at the other-racket-shaped; bacilli from 
the same culture may present considerable irregularities in breadth and 
especially in length. The morphology may 
differ somewThat under different growth con- 
ditions. But these slight variations in form 
rarely give rise to serious difficulty in classifi- 
cation. 
Finally, when bacteria are placed under 
conditions unfavorable for the maintenance 
of their life processes, and when they are 
dead, they are often irregularly swollen and 
contorted or may undergo partial disintegra- 
tion, giving rise to what are known as " involution forms." 
While all bacteria are minute2 there is among them considerable 
diversity in size, some being many times larger than others.3 
Certain bacteria, those of the diphtheria group for example, contain 
deeply staining bodies called metachromatic granules the nature of which 
is as yet undetermined. 
Reproduction of Bacteria.-When the bacteria are about to multiply 
by fission they elongate, a dividing septum forms, they become con- 
Fig. 95.-Bacteria with Cap- 
sules. (Pneumococcus.) 
1 Pronounced kok'-us, plural kok'-si. The term micro-organism includes all of these forms of minute 
and lowly plants. They are sometimes spoken of collectively as germs or microbes. 
2 Some forms, those for example inducing the pleuro-pneumonia of cattle, are beyond the present 
resolving power of the microscope-ultramicroscopic. For a review of ultramicroscopic bacteria or 
filterable viruses see Wolbach, Jour. Med. Res., 1912, N. S. xxii., 1. 
3 For convenience of expression microscopists have agreed to let the letter g stand for the word 
micromillimetre, which is one-thousandth part of a millimetre. This unit of measure, equal to about 
one-twenty-five thousandth of an inch, is often called a micron. PLANT PARASITES 
135 
stricted at a right angle to the axis elongation, and finally two inde- 
pendent organisms are produced. The multiplication of bacteria by 
fission may, when the conditions are favorable, occur so rapidly1 as to 
give rise within a few hours to an enormous number of new individuals. 
Aggregations of Bacteria.- 
In many cases, the new individuals 
thus developed fall apart in a form 
identical with that of the parent 
cell. In some species, on the other 
hand, the new-formed individuals 
are prone to cling together with 
greater or less tenacity, thus giving 
rise to growth aggregates which are 
more or less characteristic (Fig. 96). 
Thus among the cocci there are 
those in which a large part of the 
new individuals cling together in 
pairs. These forms are called diplo- 
cocci. In others the pairs cling 
together in longer aggregates or 
chains. Such are called streptococci. 
A similar occurrence in the 
bacilli gives rise to diplobacilli and streptobacilli. Some of the spiral forms 
are due to the close junction end to end of oppositely curved segments. 
Certain cocci divide in two directions at right angles to each other, 
giving rise to four cocci clinging together and lying in the same plane. 
These are called tetrads or merismopedia. 
Finally cocci may divide along three planes at right angles to each 
other, giving rise to cuboidal packets of eight germs or some multiple of 
this-such growth groups are called sarcina2 (Fig. 97). 
Higher Bacteria.-There is a family of fila- 
mentous or branching organisms which are often 
spoken of as polymorphous or higher bacteria, some 
of which may indeed be links between the bacteria 
and higher plant forms. Filamentous bacteria are 
more or less distinctly segmented, and the segments 
may be enclosed in a common sheath. The modes 
of reproduction and a certain specialization of func- 
tion of different parts of the filaments which is 
frequently present indicate affiliations with higher 
forms. By this specialization of function is meant the attachment of the 
threads at one end to the substance on which they grow, and the forma- 
tion at the free ends of structures which appear to be concerned in the 
reproduction. Several groups of these organisms have been named, but 
Fig. 96.-Growth Aggregates of Bacteria. 
1, Diplococcus; 2, streptococcus; 3, meris- 
mopedia; 4, diplobacillus; 5, streptobacilli; 6, 
curved bacteria forming chains. 
Fig. 97.-Sarcina. 
Showing growth aggregates 
in cuboidal masses. 
1 A. Fischer has estimated that the cholera spirillum may undergo complete fission at intervals of 
about twenty minutes so that a single organism might give rise under favorable conditions, could these 
be secured, to 1600 trillions in twenty-four hours. 
2 Bacteria in masses embedded in and held together by a more or less abundant homogeneous 
material which they elaborate are called zodgloea. 136 
PLANT PARASITES 
few of them have as yet been adequately studied. The groups strepto- 
thrix, cladothrix, crenothrix, leptothrix may be named. Among these the 
streptothrix (nocardia) is of the most significance here, since pathogenic 
forms are known.1 The Streptothrix actinomyces, and closely related 
species, and the lesions which they induce, will be described later. 
There are many reasons for the belief that the forms called streptothrix 
and actinomyces are more closely related to the moulds than to the 
bacteria, but the scope of this work does not permit the discussion of the 
subject, particularly difficult as it is on account of the confusion of terms 
and the lack of sufficient knowledge of the life history of the organisms 
involved (see Actinomyces, p. 231). 
Variations in Forms.-Their apparently simple structure and the 
lowly position which bacteria occupy in the scale of living things have 
given rise to the conjecture that marked changes in form within the 
limits of the primary groups, or even changes from one primary group 
to another, may be brought about by alterations in environment, food, 
etc. In the early days of the exact study of bacteria this belief in 
pleomorphism in bacteria found ready currency. But the more exact 
study of separate forms, which the new technique has made possible, 
has led to the general acceptance of the view that variations do not occur 
except within comparatively narrow limits, and that what we are 
accustomed to call species of bacteria maintain their morphological 
characteristics with tenacity under the most varied changes in environ- 
ment, even though these persist through the countless generations which 
may pass within the limits of a single experiment. The physiological 
characters of bacteria are, as we shall presently see, subject to wide and 
significant variation, but, so far as we can now see, 
monomorphism widely, if not exclusively, prevails. 
Spores.-Under a variety of conditions, the limi- 
tations of which are not very well understood, new 
bacteria are produced, and the species is perpetu- 
ated, not by simple division, but by the develop- 
ment of spores. The most common mode of spore 
formation is called endogenous. A small, shining 
mass makes its appearance within the protoplasm 
from which it is formed, grows more and more dis- 
tinct, and finally appears as a sharply defined 
spheroidal or oval, strongly refractile colorless body surrounded by a 
limiting membrane (Fig. 98), which can be separately stained and may 
remain within a cell membrane or may free itself by degeneration of 
the latter. Endogenous spore formation is common in bacilli, rare in 
spirilla and in cocci. The spores appear to be surrounded by a dense 
envelope, and are, as a rule, much more resistant to deleterious agencies, 
such as heat, drying, chemicals, etc., than are the vegetative forms of 
the bacteria themselves. 
Spores, when placed under favorable conditions in the presence of 
Fig. 98.--Bacilli Show- 
ing Spores. 
The bodies of the bacilli 
are stained with methy- 
lene blue, the spores with 
fuchsin. 
1 Some organisms commonly called bacilli-tubercle bacillus for example-may belong in this 
group. PLANT PARASITES 
137 
moisture and nutriment, swell, become less refractile, and develop into 
the usual vegetative form. The actual observation of this transformation 
is, in doubtful cases, the only absolute guarantee of the spore nature of 
these bodies, though staining methods are useful. Another method of 
sporulation-arthrogenous-has been described, but its nature is not well 
understood. 
Motility.-Some bacteria are capable of performing rapid movements, 
others are not; and the same form may be at one time motile and at 
another immotile, depending upon external conditions. Movement is 
largely confined to the rod-like and spiral forms, but has been observed 
in the spheroidal. 
It has been shown that certain of the motile bacteria, when sus- 
pended in fluids, are attracted toward, or repelled from, dissolved chem- 
ical substances. This is called chemotaxis (see p. 85), and it is termed 
positive or negative according as the organisms are attracted or repelled. 
Conditions of Life, Growth, and Multiplication.-The bacteria require 
for their nutrition carbon, hydrogen, oxygen, and nitrogen, and certain 
mineral salts. These they can obtain from proteids and carbohydrates. 
Free oxygen is necessary for the growth and activities of some forms of 
bacteria and not for others. 
Nitrogen may be obtained by some bacteria from inorganic salts of 
ammonia, from nitrites and nitrates. Bacteria grow best as a rule in an 
organic food medium, especially soluble albuminous material which is 
neutral or slightly alkaline. Most of these materials are rendered avail- 
able as food by the action of enzymes-inverting, sugar-splitting, proteo- 
lytic, etc., often given off by the organisms and acting upon the albu- 
minous materials. 
Those bacteria which require free oxygen are called aerobic. Those 
which do not grow in its presence are called anaerobic. But between 
these extremes there are forms which make shift to grow without oxygen 
under favorable conditions, though they make use of it when present; 
others grow in its presence, though flourishing best in its absence: these 
are called facultative aerobes or facultative anaerobes, in distinction from 
those first mentioned, which we call obligate aerobes or anaerobes. 
Bacteria are active only in the presence of moisture. When this and 
other conditions favoring their activity fail they do not necessarily die, 
but some forms may remain, either as spores or as fully developed organ- 
isms, for long periods dry and inert, but capable of resuming their ac- 
tivity whenever they are again restored to favorable conditions. 
Effects of Temperature, Light, etc.-Some bacteria are and some are 
not very sensitive to changes of temperature. At a temperature below 
+ 5° C. they are incapable of marked activity or proliferation. At + 7° C. 
a slow growth has been observed in various species. Many forms may 
remain alive for long periods frozen in ice, while some are not killed by a 
temperature of -250° C. As the temperature is raised their activities 
increase up to a certain point. It may be said in general that they are 
most active at about the temperature of the body, although species differ 
considerably in this respect. In fluids many bacteria are killed by a 138 
PLANT PARASITES 
prolonged exposure to a temperature of from 50° to 70° C. or even less. 
On the other hand, certain species grow at a temperature of from 60° to 
75° C. Such are called thermophilic bacteria. When dry they resist 
much higher temperatures than when moist. All known bacteria, save 
a few very invulnerable spore-forming species, are killed by a short ex- 
posure in the presence of moisture to a temperature of 100° C. The 
spores are, as a rule, more resistant to high temperatures than the bacte- 
ria themselves, some having been exposed, dry, to a temperature of 140° C. 
without destruction of life. Fluids containing the spores of bacteria 
which resist very high temperatures may be sterilized by boiling for a 
short time, then being allowed to stand at ordinary temperatures for 
several hours, and then again boiling; this process being repeated several 
times. In this way, although the spores themselves are not killed by the 
heat, the bacteria into which, if the conditions be favorable, they develop 
during the intervals are killed, so that finally the medium is entirely freed 
from both living spores and adult bacteria. Strong light is in general 
inimical to the life and growth of bacteria, and by direct sunlight many 
forms are readily killed. Various forms of electricity, rapid and contin- 
ued vibration, the action of radium, etc., may kill bacteria. 
Germicides.-Certain chemical agents, when brought into contact 
with bacteria, greatly reduce their activities or destroy their life alto- 
gether; but different species differ greatly in their capacity of resistance 
to these agents. The spores of certain bacteria are exceedingly re- 
sistant, much more so than the bacteria themselves, to the action of 
disinfecting agents. Among the chemical substances commonly used 
as disinfectants may be mentioned formalin, carbolic acid, and espe- 
cially solutions of corrosive sublimate, which is very inimical to the life 
of most bacteria and theii' spores, even in extremely dilute solutions. 
Metabolism of Bacteria.-The metabolism of bacteria may be destruc- 
tive or constructive. Their destructive or catabolic activities find expres- 
sion in the fermentation of carbohydrates and in the cleavage of pro- 
teids and fats. Their constructive or anabolic activities are exemplified 
by their building up of nitrogenous compounds in the soil. We cannot 
here enter into the details of these processes, which must be sought in 
special treatises. 
But it may be said in brief that a large number of complex chemical 
substances are elaborated during the growth of bacteria, their nature 
varying with the species of bacteria and the composition of their nutrient 
material. Some of the chemical compounds set free by the growing 
bacteria are bad-smelling or aromatic; some are inert and harmless sub- 
stances; some are powerful poisons, and may, when they have accumu- 
lated in the fluids where they grow, inhibit activity and growth or even 
destroy the bacteria which have produced them. 
Fermentations and putrefactions are due to the activities of micro- 
organisms, some to bacteria, some to yeasts, some to moulds. Putrefac- 
tion is a form of fermentation in which nitrogenous compounds are de- 
composed by micro-organisms setting free, especially in the absence of 
oxygen, bad-smelling substances. PLANT PARASITES 
139 
Bacteria which induce fermentation are called zymogenic-and each 
species induces fermentation of a particular character in the presence of 
a special substance, as glucose, or members of a certain class of substances 
such as carbohydrates. Some of these fermentations are important in 
the arts; some are concerned in the changes which food products undergo 
under natural or artificial conditions, such as the development of kou- 
myss from milk and the common butyric, lactic, alcoholic, and other 
fermentations. 
The chemical changes which are induced by micro-organisms in the 
process of fermentation are extremely complex and little understood. 
Bacteria may develop, in their metabolic activities, soluble ferments1 
or enzymes of various kinds resembling diastase, pepsin, trypsin, rennet, 
etc. These may remain in the bacterial cell or may be diffused into the 
surrounding media. It is through these enzymes that the fermentations 
and proteid cleavages so characteristic of many phases of bacterial 
metabolism are carried on. 
Many bacteria form pigments as they grow {chromogenic bacteria). 
This pigment may be developed in or upon the germs themselves or may 
be diffused through the surrounding media and may be developed only 
in the presence of light, oxygen, etc. Gas-producing bacteria are called 
aerogenic. Certain species when growing in masses emit a phosphor- 
escent light-photogenic bacteria. 
Bacterial Poisons. 
Ptomains.-Certain basic chemical compounds which are formed by 
the action of bacteria upon various kinds of organic matter are called 
ptomains.2 Some of the ptomains resulting from the breaking up of the 
protein molecule by bacteria in decomposing meat, fish, etc., are poison- 
ous, though not apparently of as much importance as was once believed. 
But ptomains should be distinguished from the true toxins now to be 
considered. 
Toxins.-True bacterial toxins are poisonous substances produced by 
bacteria. They seem to be analogous in nature to enzymes and may be 
given off in artificial culture, as in the infective processes, during the 
metabolic activities of bacteria, like secretory or excretory products. 
The poisonous substances elaborated in the growth of the diphtheria and 
the tetanus bacilli are typical toxins. These toxins are especially 
characterized by their capacity to stimulate the body-cells, when the 
latter are called upon to adapt themselves to their presence, to the forma- 
tion of antibodies (see page 165). 
Endotoxins.-On the other hand certain bacteria which develop toxic 
substances do not set these free as they are formed but store them in or 
build them into the structure of their bodies whence they are freed 
only after the death or disintegration of the bacterial cell through autoly- 
1 See Bayliss, Nature of Enzyme Action, 3d edition, 1914. Also for technique, Wohlgemuth, Grundriss 
der Fermentmethoden, Berlin, 1913. 
2 The terms ptomain and leucomain are falling into disuse as the chemical structure of many of the 
toxic bases is being elucidated. See Barger, The Simpler Natural Bases, New York, 1914. 140 
PLANT PARASITES 
sis or some external agency. Such toxic substances stored in the texture 
of the bacteria are called endotoxins and they do not appear directly to 
stimulate the organism to the formation of antibodies. 
It may be doubted whether the fuller knowledge of the future will 
justify so sharp a distinction between bacterial toxins and endotoxins 
as is at the moment usually made. 
But the distinction is useful at present and of greatest significance in 
forming our conceptions of the nature and phases of immunity. 
The important thing to remember in this connection is that it is 
through the action of these toxins, whether soluble and eliminated during 
the life and functional activities of the bacteria or stored up in their 
bodies to be set free only upon their disruption, that the most striking 
damage is wrought in the organisms when body-cell and bacterial cell 
strive to adapt themselves to one another in the processes of infection 
which we are presently to study. 
It is probable that there is still another group of toxic substances 
derived not directly from the bacteria bi t from the action of certain 
products of bacterial metabolism upon body proteids, so that it may be 
through these secondary toxic albumoses that some of the serious mani- 
festations of infection and intoxication are induced. 
The Role of Bacteria in Nature.-The bacteria play a very important 
role in nature in virtue of their power of feeding upon and decomposing 
dead organic material. A part of the new chemical compounds which 
are thus formed may be used by the bacteria for the purposes of their own 
nutrition and growth, while the rest are set free to serve, sooner or later, 
as food for other forms of plants or animals. In the decompositions 
which are brought about in nature by the bacteria those compounds of 
nitrogen and carbon dioxide are set free which are essential for the nutri- 
tion of the higher plants. 
Without the activities of bacteria, life could not be long maintained 
upon the earth, since the necessary carbon, hydrogen, oxygen, and nitro- 
gen would soon be permanently locked up in unavailable form in organ- 
ized material. Through the action of the various nitrifying bacteria in 
the soil, ammonia is decomposed with the formation of water and nitrous 
acid; nitrous is converted into nitric acid. The so-called denitrifying 
bacteria reduce nitrates to ammonia and to nitrites. In these ways, 
among others, water percolating through the soil may be freed from 
objectionable organic compounds. There are certain soil bacteria which 
aid special groups of plants to fix nitrogen from the surrounding media 
and make it available for the uses of the plant. 
Distribution of Bacteria.-Bacteria are widely distributed in the air, 
in water, and in the superficial layers of the soil, where they may be pres- 
ent in enormous numbers. They are especially abundant among the 
habitations of man, or wherever under favorable conditions of moisture 
and temperature animal or vegetable substances are undergoing decay. 
They cling tenaciously to moist surfaces, but when dried, and especially 
when dried upon comminuted material, they may float in the air as dust. 
In quiet air they gradually settle with other forms of dust on to horizon- PLANT PARASITES 
141 
tai surfaces, and thus in closed, still rooms the bacteria-laden air may in a 
few hours almost wholly free itself of its living contaminations by a proc- 
ess analogous to sedimentation in water. 
This wide-spread transportation of bacteria as dust by moving air, and 
the spontaneous cleansing of the latter by the settlement of the germs, 
are important factors in the sanitary problems which the complex con- 
ditions of modern life present. 
While bacteria may live for long periods in the dried state in dust 
they do not in this condition multiply. But the upper three or four feet 
of the soil forms the great abiding, and when moist, the breeding place 
of the myriads of germs which are concerned in the salutary work of 
food preparation for higher plants. Large numbers of mould spores are 
frequently mingled with the bacteria in dust and soil. 
Surface waters almost always contain bacteria, which may have en- 
tered by aerial dust or from the wash of adjacent soil or from direct 
human or animal contamination. Many bacteria find in water favorable 
conditions of life and flourish on what to other forms would be but scanty 
nutriment. Many pathogenic bacteria may remain alive for consider- 
able periods in water, but they do not usually thrive there. 
The water which in many places lies in hollows of the rocks, bathing 
the deeper layers of the soil or gathered in caverns and recesses beneath, 
is called ground water. This under favorable conditions is almost wholly 
free from micro-organisms; these, through the complex processes of filtra- 
tion, germ metabolism, etc., which go on in the upper soil layers, having, 
together with inorganic contaminations, been largely retained or trans- 
formed as the surface water has slowly sought the lower levels. 
The Relationship of Bacteria to Other Living Beings.-So far as we 
know, with few exceptions, the bacteria whose natural habitat is the soil 
or air or water are not, under usual conditions, harmful to man. On the 
other hand, it is germs from the bodies of men or animals who are the 
victims of infectious disease, gaining access in one way or another to 
these great reservoirs and sources of distribution, which occasionally 
render the bacterial flora of soil and air and water of direct personal 
significance to man. 
It will be seen from what has been said about bacteria and their 
various modes of life that some live in or upon and at the expense of 
other living beings-the hosts-these are parasites. Others which live 
and grow apart from a living host are called saprophytes. In either class 
there are forms which, through the capacity of adapting themselves to 
their environment, can maintain at one time a parasitic, at another a sap- 
rophytic life. Such germs are called, respectively, facultative parasites 
or facultative saprophytes. Those, on the other hand, whose life is strictly 
limited to the parasitic or saprophytic condition are called obligatory 
parasites or saprophytes. 
Not all the bacteria which live in or upon the bodies of men and 
animals are in the stricter sense parasites. The terms messmates and 
commensals have been applied to such organisms as simply live with, but 
do not necessarily derive nutriment from, the host. 142 
PLANT PARASITES 
In some cases parasitic life on the part of the micro-organism may 
contribute to the welfare of the host. This is the case in some bacteria 
which live upon the roots of certain leguminous plants, and to whose 
nutrition they contribute by rendering atmospheric nitrogen directly 
available for the host. This condition of life is called symbiosis. 
Species and Varieties.-As has already been indicated, the morpho- 
logical characters of bacteria are so little subject to permanent variation 
under the widest diversity in the conditions to which they are subject 
that we are justified in the belief in fixed species. But so susceptible to 
external conditions are the functional activities of many species that not 
only is the occurrence of what may be called varieties within specific 
limits frequent under natural conditions, but more or less permanent 
variations may be experimentally produced. 
Modifications of Functional Characters.-Almost all of the functional 
activities of bacteria upon which we rely as descriptive characters may be 
experimentally altered; thus the color-producing capacity may be dimin- 
ished, the peptonizing and fermentative activities lowered, the patho- 
genic powers reduced or exalted, and even the capacity for spore forma- 
tion may be abolished. 
These more or less permanent modifications of function in bacteria 
may be induced by artificial cultivation under adverse conditions of tem- 
perature and nutrition, by the presence of deleterious chemical agents, 
antiseptics, etc., or by association with the body-cells and juices in sus- 
ceptible or insusceptible animals. 
CLASSIFICATION OF BACTERIA. 
The beginning of the systematic study of bacteria by exact and re- 
liable methods is of such recent date, they are so minute, and our present 
optical apparatus reveals so few differential morphological characters, 
and so few, withal, of the many existing forms have as yet been studied 
that a satisfactory classification or nomenclature of the bacteria is not yet 
possible. 
Outside of the limit of the primary classes above described and based 
upon the form, position of flagella, and motility, we are obliged to use for 
the purposes of identification and description the results of physiological 
activities which the special forms of bacteria display when placed under 
diverse and usually entirely artificial conditions of food, temperature, and 
general environment, It is evident from this condition of affairs that 
what in our attempts at classifications we are wont to call genera and 
species, are not such in the strict sense in which these terms are used in 
other domains of biology. That which corresponds to the generic name 
in the more exact vocabularies is in ours usually the growth form which 
indicates the primary class to which the germ belongs, as coccus, bacillus, 
or spirillum, or some growth modification of this, as diplococcus, strep- 
tococcus, streptobacillus, and the like. To this is usually appended a 
more or less distinctive specific name, which ordinarily indicates some 
noteworthy physiological capacity of the germ, such as its peptonizing PLANT PARASITES 
143 
power, the pigment which it elaborates, some prominent chemical reac- 
tion which it initiates, some marked effect upon an artificial culture 
medium, its disease-producing power in men or animals, or some fact 
about its habitat, or the situation in which it was found. All of these and 
other heterogeneous characteristics, largely functional, which may be 
developed under natural or artificial conditions, constitute data in the 
life history of germs upon which the classification and nomenclature of 
bacteria are at present based. 
Notwithstanding the value of this principle of grouping and nomen- 
clature, its inadequacy even for temporary use is becoming painfully 
evident as research proceeds, partly because of the large variations to 
which physiological activities are liable, and partly because we cannot 
always sharply distinguish between races, varieties, and species. 
Methods of Morphological Study of Bacteria. 
The simplest mode of studying bacteria is to examine them either in the fluids in 
which they grow or in one-half-per-cent, salt solution. For the study of many of the 
phenomena of life this method is important. 
This may be accomplished by the examination of a thin layer of the fluid under a 
cover-slip, in the usual way; or a small drop may be placed on the cover-slip and this 
inverted on a hollow slide so that the observation is made in the hanging drop. A 
streak of vaselin painted around the edge of the cover will prevent evaporation of the 
fluid. 
Staining.-By far the most important aid in the morphological study of the bac- 
teria is derived from the use of staining agents. Most of the bacteria are stained more 
or less readily by one or more of the basic anilin dyes. The ease with which they are 
colored varies considerably in different species and with the different dyes. The tissue 
elements, and a variety of other materials with which the bacteria may be associated, 
also stain more or less readily at the same time; but most of these part with their color 
more readily than do the bacteria on being treated with alcohol or dilute acids. It is 
thus possible to obtain a differentiation in color between bacteria and other structures. 
The bacteria, moreover, differ among themselves in respect to the tenacity with which 
they hold their stain in the presence of decolorizing agents, and upon this fact is based 
one of the important methods of distinguishing between different species. 
The anilin dyes more commonly employed for bacteria staining are fuchsin, gen- 
tian violet, and methylene blue. A saturated alcoholic solution of these dyes should 
be kept in tightly stoppered bottles, and from these the more dilute solutions required 
for staining may be prepared. For ordinary purposes one part of alcoholic solution 
of fuchsin or methylene blue, added to twenty parts of water, will give a staining 
solution of suitable strength. 
Special stains and modes of staining, such as are necessary for some forms of bac- 
teria-the tubercle bacillus, for example-will be described under the appropriate 
headings. 
To Stain Bacteria in Fluids.-A small drop of the fluid is placed on a clean cover- 
glass, spread a little with a needle, and dried by gentle heat. The cover-glass is now 
held with the forceps, specimen side up, and passed moderately rapidly three times 
through the flame of an alcohol lamp or Bunsen burner. The material on the cover 
should not be burned. This heating not only fixes the contents of the fluid firmly on 
to the glass so that it will not easily soak off, but renders insoluble any albuminous 
materials which may be mixed with the bacteria, and which might otherwise interfere 
with subsequent examinations by forming granular precipitates. 
A drop of the aqueous staining fluid is now put on to the dried specimen on the 
cover-glass, and if this be held in the forceps and tilted slightly up and down a few 
times so as to bring fresh portions of the staining fluid into contact with the bacteria, 144 
PLANT PARASITES 
the staining will usually be completed in two or three minutes. The stain is now 
washed off with a jet of water from the wash bottle, and the specimen is either mounted 
in a drop of water for temporary study, or the washing w'ater is drained off and, after 
drying in the air, it is mounted directly in balsam. It is well to use balsam which has 
been softened, when this is necessary, with oil of cedar or xylol rather than with 
chloroform, since this is apt to decolorize the bacteria. Solid cultures of bacteria 
should be mixed with a little w'ater and spread on the cover-glass before drying and 
staining. 
Gram's method (see below) is often useful and in some cases almost indispensable 
for the differential staining of bacteria.1 
To Stain Bacteria in Tissues.-1The tissues should be well hardened in alcohol. 
Thin sections are placed in the above-described aqueous coloring solutions, where they 
may remain from five to fifteen minutes. In some cases a much longer staining is nec- 
essary. Gentle warming (40° to 50° C.) will hasten the staining. The entire tissue as 
well as the bacteria is in this way deeply colored. The sections are rinsed with dis- 
tilled water and then placed in alcohol. This, with varying degrees of rapidity with 
different stains and tissues, gradually extracts the color from the tissue, most slowly 
from the nuclei. The time required and the exact degree of decolorization to be sought 
for must be learned by experience in different cases. Sometimes five, sometimes 
thirty minutes are required, sometimes only a few seconds. It is often necessary, and 
the decolorizing of the tissue is thereby hastened, to add a few drops of acetic acid to 
the alcohol. When acetic acid is used it should be finally thoroughly washed out by 
alcohol. The specimens are now cleared up by oil of origanum and mounted in 
balsam. In specimens prepared in the above way, the nuclei of cells usually retain to 
some extent a color similar to that of the bacteria, but their size and shape serve for 
the differentiation. 
Gram's Method.-This is a much more generally useful method of staining bacteria 
in the tissues than that just given, although not in all cases applicable. The sections 
are stained for from two to four minutes in anilin-gentian-violet solution, prepared by 
adding 1 c.c. anilin oil to 10 c.c. distilled water, shaking thoroughly, and filtering 
off the excess of anilin oil through a moistened paper filter. To the clear filtrate, satu- 
rated alcoholic solution of gentian violet is added, in the proportion of about 1 of the 
dye to 10 of the anilin solution. 
From the staining solution the sections are transferred to a solution of iodine in 
potassium iodide and water (I 1.0-KI 2.0-H2O 300.0), remaining from one to three 
minutes, when they are transferred to strong alcohol; this should be changed two or 
three times so as to dehydrate the specimen, which at the same time will lose much of 
its color. The section is cleared in oil of origanum to which a little eosin has been 
added, and mounted in balsam. In specimens prepared in this way the bacteria and 
some of the nuclei are violet, the remainder of the tissue is red. 
In this as in other methods of staining bacteria in tissue the section is liable to 
shrivel and curl. This may in many cases be avoided by fixing the sections on to the 
cover-slip with albumen fixative (see p. 1034) before the staining begins, carrying 
cover-glass as well as section through the subsequent processes. Since some bacteria 
are decolorized by Gram's method it is not applicable to the staining of all organisms 
in tissues. It is often a valuable aid in the differentiation and identification of species 
with similar morphology-and in some instances, as in the staining of gonorrhoeal pus, 
has an especial diagnostic value (see p. 222). 
Weigert's Modification of Gram's Method.-1The sections are laid for half an hour in 
the anilin-gentian-violet solution prepared as above, then rinsed off in three-quarter- 
per-cent. salt solution and spread on a slide. They are now dried with blotting-paper 
and covered for two minutes with the iodine solution. The iodine solution is now 
washed off in the water, the section dried with blotting-paper, and decoloriz ed with 
anilin oil of a mixture of 2 parts of anilin oil and 1 part of xylol, several times renewed. 
Finally the sections are cleared in xylol and mounted in balsam. 
In many cases it is well to accomplish a double staining by a preliminary contrast 
stain. Thus, before the use of Weigert's modification of Gram's stain the sections may 
1 For the methods of staining spores see special works on bacteriology. PLANT PARASITES 
145 
be put for half an hour in a solution of picro-carmin, then rinsed in water and stained 
as above. By this modification of Gram's method, fibrin is deeply stained. 
Loffler's alkaline-methylene-blue solution is a very valuable and powerful stain for 
bacteria, either in fluids or in tissues. 
It consists of- 
Saturated alcoholic solution of methylene blue, 30 parts 
Aqueous solution of caustic potash 1 : 10,000, 100 parts 
For staining bacteria in tissues the stain is allowed to act for a few minutes. The 
section is then put for a few seconds in one-half-per-cent, acetic acid, then rinsed in 
water, and the superfluous color removed from the tissue by repeated rinsing in alco- 
hol, which at the same time dehydrates it. Then it is cleared with oil of cedar and 
mounted in balsam. Care should be taken not to remove too much color with the 
alcohol. 
It should always be borne in mind in staining the bacteria that great exactness is 
not usually necessary either in the strength of the coloring solutions or in the time of 
exposure of the bacteria to them. We are seeking for certain effects-namely, the 
staining of the germs-and this depends not only upon the quality and strength of the 
dye, the time of exposure, etc., but also upon the nature of the bacterial species and its 
conditions at the time the staining is undertaken. Thus it not infrequently happens 
that bacteria which will stain readily and deeply with a given solution when they are 
in a condition of active growth, may be scarcely at all colored if they have been dead 
or inactive for a long time, although their outward shape appears to be unchanged. 
So it should be remembered that, while there is little difficulty in most cases in staining 
the bacteria, the operation is not one of mere routine, but requires intelligent attention 
to the particular conditions of the species in hand. 
For the recognition and study of bacteria the best optical apparatus is requisite. 
An homogeneous immersion lens (at least one-twelfth) and the Abbe condenser are 
indispensable for ordinary work. 
For a consideration of the methods of Artificial Cultivation of Bacteria, we refer 
to special works on Bacteriology, ref. p. 319. 
Artificial Cultivation of Bacteria. 
Collection of Material for Bacterial Cultures. 
Material obtained from the human body which is to be subjected to bacterial ex- 
amination should be collected with every precaution against accidental contamination. 
A convenient mode of collection and transportation of small quantities of fluid or 
semi-fluid material, such as exudates, discharges, etc., for purposes of bacterial exami- 
Fig. 99.-Sterilized Cotton Swab in a Sterilized Tube, for Collecting Fluids Containing 
Bacteria. 
nation is to twist a small wad of absorbent cotton on to the end of an iron or steel wire 
about five inches long, put this, swab end foremost, into the tube (Fig. 99), plug the 
mouth with cotton, and sterilize the whole in a dry oven for an hour at 160° C. 
Several of these cotton swabs may be prepared at once and kept on hand. The 
swab, carefully removed and saturated with the material to be examined, is at once 
returned to the tube; this is plugged, and may be thus safely transported.1 
1 For further suggestions for the collection and examination of specimens for micro-organisms, and 
for references to studies on the bacteria of the human body, see pp. 150 and 151. Consult for details 
of species, general works on bacteria, especially Kolle and Wassermann's "Mikroorganismen," 2d edition, 
1912-13. 146 
PLANT PARASITES 
IL Yeasts. 
These micro-organisms-larger than bacteria and mostly saprophytes 
-consist of oval or spheroidal cells with granular protoplasm and a thin 
membrane. They multiply by sprouts or buds from the parent cell 
(Fig. 100). The new individuals may separate from the old, or may 
cling to them so that chain-like combinations may 
occur. They sometimes form endogenous spores, 
known as ascospores. Some species develop bright 
colors in their growth. 
There are many forms of yeasts which are con- 
cerned in various phases of fermentation. Some of 
these, alcoholic fermentation for example, are of great 
economic importance.1 Certain forms of yeasts flourish 
in the stomach during digestive disorders and in the bladder in diabetes 
without inciting lesions. Various yeasts have been proven to be patho- 
genic in lower animals and in man. 
Blastomycotic dermatitis2 (Oidiomycosis) is a localized inflammation, 
papular and pustular in character, leading to warty outgrowths, to the 
Fig. 100.-Yeast- 
Saccharomyces. 
From skin lesions, showing giant cells containing the oidium with mast cells and eosinophile cells 
in the adjacent tissue just beneath the epithelium. 
Fig. 101.-Oidiomycosis Cutis-Blastomycotic dermatitis. 
formation of abscesses beneath the skin, and to ulcers. Deeper parts, 
such as bone, may be involved. Hyperplasia of epithelium and develop- 
ment of granulation tissue beneath with the formation of giant cells 
1 For a consideration of the relationship of micro-organisms to various forms of fermentation, with 
bibh, consult J orgenson, "Micro-organisms and Fermentation," Eng. Transl. 1900. 
2 Gilchrist, Johns Hopkins Hospital Reports, vol. i., p. 269, 1896. For a resume of pathogenic 
blastomycetes with experiments and bibliography, see Foulerton, Journal of Pathology and Bacteriol- 
ogy, vol. vi., p. 37, 1900; and Sternberg, Ziegl. Beitr., Bd. xxxii., 1902, p. 1; also Ricketts, " Blastomy- 
cosis of Skin," Jour. Med. Res., vol. vi., 1901, p. 377; also Otis and Evans, Jour. Am. Med. Assn., vol. 
xli., p. 1075, 1903; also Bassoe, Jour. Inf. Dis., vol. iii., p. 91, 1906; Irons and Graham, ibid,., p. 666, 
1906, and Stober, Arch. Int. Med. 1914, xiii., 509. PLANT PARASITES 
147 
(Fig. 101), mast cells, and eosinophilic cells may be associated with the 
local growth of the blastomycetes and the formation of abscesses, the 
latter often intra-epithelial. The local lesion may extend to the involve- 
ment of large areas of skin and subcutaneous tissue. 
The organism-Oidium-is present in the involved tissues as a rounded 
double contoured body (Fig. 102), varying in diameter from 10 to 20/z. 
It sometimes buds and contains various rounded refractile or granular 
structures. These organisms may be enclosed in a homogeneous jelly- 
like mass. They are readily cultivated in 
artificial media and can be successfully inoc- 
ulated into animals, such as the guinea-pig. 
Generalization of the blastomycotic in- 
fection may take place and be fatal. In 
the systemic disease the lungs, spleen, and 
kidneys are especially involved in the 
formation of abscesses and local tissue 
hyperplasia containing the organism. 
There seem to be several forms of blasto- 
mycetes among the pathogenies already 
described, but their classification is unsatis- 
factory. 
Thrush.-A micro-organism frequently 
found growing in the mouth and fauces 
and oesophagus of children, in the form of 
a whitish pellicle, is the so-called Oidium 
albicans, which consists of branching, jointed threads and spores which 
penetrate between the epithelial cells. This fungus may assume 
considerable importance, when in very feeble children it blocks the 
oesophagus, or when, as is rarely the case, from the surface of ulcers it 
penetrates the blood-vessels and gives rise to visceral metastasis. It is 
grouped with the yeasts, and the disease with which it is associated is 
to be regarded as an oidiomycosis. 
Fig. 102.-Oidium from a Case 
of Oidiomycosis Cutis (Blastomy- 
cotic dermatitis). 
III. Moulds. 
The moulds are considerably more complex in structure than either 
the bacteria or the yeasts. Some of the forms are very common and 
universally known. In general, it may be said that the moulds consist 
of a series of delicate, translucent, branching jointed threads-mycelium 
-usually giving rise to hyphce, from which, either directly or in more 
complex forms through the intervention of a special structure, the sporan- 
gium, the spores are developed (Fig. 103). The moulds which are apt to 
occur in the human body may be of the former, more simple, or of the 
latter, more complex, type.1 Among the simpler forms of moulds which 
occur in the body may be mentioned the Achorion Schonleinii, Microspo- 
1 See Renon, "Etude sur 1'aspergillose chez les animaux et chez 1'homme," Paris, 1897; also Leo- 
pold and Levi, Gaz. des Hopitaux, June 26th, 1897, bibl.; also Pierson and Ravenel, University Med Mag. 
August, 1900; also Sayer, "Pneumonomykosis aspergillina," Jena, 1900. 148 
PLANT PARASITES 
ron furfur, Trichophyton tonsurans. There is a close morphological 
resemblance between these forms. 
The Favus Fungus (Achorion Schonleinii), is formed of a much-branch- 
ing mycelium from which the spores 
are directly developed (Fig. 104). 
It grows readily on artificial cul- 
ture media, such as nutrient agar 
and gelatin, at the temperature of 
the body. This fungus is most apt 
to grow upon the hairy part of the 
head, where it forms small surface 
crusts and grows into the shafts 
and root sheaths of the hair, excit- 
ing inflammation in the adjacent 
tissue. 
Ring Worm (Tinea circinata; 
Herpes tonsurans).-The inciting 
agents of this readily communi- 
cable disease are several species of 
Trichophyton tonsurans which de- 
velops in the form of a moderately 
branching mycelium, forming com- 
paratively few spores. It grows 
in the skin, either about or apart from the hairs, or in the nails, induc- 
ing the lesions of various phases of ring worm which differ considerably, 
depending upon the particular structures involved. At body tempera- 
ture it grows readily on artificial culture 
media, differing markedly in appearance 
from Achorion. 
Pityriasis versicolor.-Microsporon fur- 
fur, the mould fungus causing pityriasis 
versicolor, is more prone than the Achorion 
to the development of many spores, but 
otherwise considerably resembles it mor- 
phologically. It has not yet been culti- 
vated on artificial media. By its infiltra- 
tion of the epidermis, especially of the 
body and upper extremities, it causes 
larger and smaller yellowish or brownish 
patches. 
The Higher Moulds.-The more com- 
plex types of moulds are only occasion- 
ally dwellers in the human body and appear to be but rarely the cause 
of disease, passing, rather, a saprophytic existence on dead material in 
parts of the body which are in communication with the air. Thus they 
may be found growing on accumulations in the external auditory canal, 
in dead tissue in the lungs, on walls of cavities, dilated bronchi, etc. 
Many cases have been reported, however, in which the moulds, especially 
Fig. 103.-Aspergillus Glaucus. 
Showing mycelium, from which arise the spore- 
bearing structures, the sporangia borne upon the 
hyphse. 
Fig. 104.-Achorion Schonleinii- 
Favus. 
From a culture. PLANT PARASITES 
149 
aspergillus, have been the apparent excitants of serious lesions in men 
and animals.1 
Sporotrichosis.-An interesting group of fungi inciting lesions in man 
was discovered by Schenck2 in 1898, was later studied by Hektoen and 
Perkins,3 and has recently been more fully described by de Beurmann and 
Gougerot.4 The disease induced by these parasites had usually been con- 
fused with syphilis or tuberculosis until examination of sections and isola- 
tion of moulds from the lesions showed that they were due to a group of 
organisms differing slightly from each other in their cultural and mor- 
phological peculiarities. These organisms have been named for their 
discoverers, Sporotrichum Schencki, Sporotrichum Beurmanni, Sporo- 
trichum Jeanselmei, and Sporotrichum Gougeroti. The lesions which 
they induce are chronic, often ulcerating granulomata. Large abscesses 
with secondary lymphangitis may occur, and the bones and synovia are 
occasionally involved. Cases of pyelonephritis, of generalized infection, 
and of bronchopneumonia due to the fungus have been described. Three 
deaths are on record. The clinical diagnosis is not difficult to one who is 
familiar with the disease, but it is usually necessary to make sections or 
cultures from the lesions. In sections the characteristic oval spores may 
be found, either free or in connection with the mycelium or in phagocytic 
tissue cells. The yeast grows abundantly at room temperatures on 
Sabouraud's medium, which is composed of water, 1,000 g.; peptone, 10 g.; 
glucose, 40 g.; agar, 18 g. When the mould is removed from the medium 
and examined it is found to be composed of a branching mycelium with 
oval or pear-shaped spores attached in continuity or forming lobulated 
masses at the ends of the mycelial threads. 
Methods of Studying Yeasts and Moulds. 
The yeast organisms are in general stained and cultivated by the same methods as 
those used in studying the bacteria. By treating unstained sections of tissue contain- 
ing them with a solution of caustic potash the organisms may often be readily demon- 
strated. 
The higher moulds may be simply teased and studied in glycerin or in glycerin and 
water. They may be stained with alkaline-methylene-blue solution (Loffler's solution, 
see p. 145). When spores have formed in considerable numbers on the more complex 
forms of moulds, these are not easily wetted by the usual staining fluids, because the 
air clings so closely among the spore masses. In a mixture of four parts of alcohol and 
one of aqueous solution of ammonia they are instantly wetted, and may then, with or 
without staining, be teased and mounted in glycerin. In studying the moulds in the 
above-described skin diseases it is well, when crust-like masses are to be teased apart, 
to allow them first to soak for a few minutes in a five-per-cent, solution of caustic 
potash. In this solution they may be studied, or they may be teased and mounted in 
glycerin for preservation. Most of the more common moulds'are readily grown on 
the ordinary culture media. 
1 For resume and bibliography of relationship of yeasts and moulds to human diseases consult 
Ricker, Lubarsch and Ostertag's "Ergebnisse der allg. Aetiologie der Menschen- u. Thierkrankheiten," 
Abth. i., 1896, p. 892. See also Hektoen, Journal of Experimental Medicine, vol. v., p. 77, 1900; Plaut in 
" Kolle and Wassermann's Handbuch," 2d edition. Bd. v., p. 1; Buscke, ibid., p. 155; Gougerot, 
ibid., p. 211. 
2 Schenck, Bull. Johns Hopkins Hosp., 1898, ix. 286. 
3 Hektoen and Perkins, Jour. Exper. Med., 1900, v., 77. 
4 de Beurmann and Gougerot, TraitS des sporotrichoses, Paris, 1912. See also Hamburger, Jour. 
Am. Med. Assn. 1912, lix, 1590; and Taylor, ibid., 1913, lx, 1142. CHAPTER VIII. 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE-INFECTION 
AND IMMUNITY. 
THE PRESENCE OF BACTERIA AND OTHER MICRO-ORGANISMS IN THE 
BODY: ITS PROTECTIVE MECHANISM. 
The Presence of Bacteria.-Bacteria are invariably present in greater 
or less numbers in the mouth, nose, upper air passages, gastro-intestinal 
and genito-urinary tracts of men and animals.1 Into these places they 
are more or less constantly brought by the respired air,2 by food and 
drink, and in other ways. They are always abundant upon the skin and 
about the hairs, and the sweat and sebaceous glands. But common and 
often abundant as are these germs upon the external and internal surfaces 
of the body, they do not often pass through the healthy mucous or cuta- 
neous surfaces,3 so that under normal conditions the tissues, the viscera, 
and the circulating fluids are practically sterile.4 
Except for certain pathogenic forms which may, under unsanitary 
conditions, have been set free and transported from men or animals 
suffering from infectious disease, the bacteria upon the cutaneous or 
mucous surfaces of the body are for the most part harmless; while cer- 
tain intestinal forms may even be useful in promoting digestion. 
The Safeguards of the Body.-The body is guarded in various 
ways from the incursions of pathogenic and other bacteria, which may be 
commonly present or only occasionally lodged upon its surfaces. Among 
the protective agencies of the body may be mentioned the firm, dense 
skin which while intact protects the interior from the entrance of almost 
all known micro-organisms; the epithelial investment of the mucous mem- 
branes in several places swept by cilia; the protected situation of most of 
the mucous surfaces, the germicidal qualities of some of the secretions, 
such as the saliva, gastric juice, mucus, etc.5 
1 For a summary of facts concerning the bacterial flora of the body surfaces consult Welch, " Surgi- 
cal Bacteriology," "System of Surgery by American Authors," Dennis. See also Ford, "The Bacteri- 
ology of Healthy Organs," Trans. Assoc. Amer. Phys., vol. xv., p. 389, 1900, bibl.; also, " Bacteria in 
Healthy Bodies and their Portals of Entry," Setter, Zeits. f. Hygiene, etc., Bd. liv., p. 363, 1906. 
2 For a resume of micro-organisms in the air see Gott st ein, Lubarsch and Ostertag's " Ergebnisse," 
Jahrgang iv., pp. 87 et seq., 1897; also Firth, "Studies from the Department of Pathology," Col. Phys, 
and Surg., Columbia University, vol. vii.; also Chapin, Air as a Vehicle of Infection, Jour. Am. Med. 
Assn., 1914, Ixii., 423. 
3 It should be remembered that the gastro-intestinal canal, the lungs, and other viscera which are 
in communication with the exterior, although within the limits of the body, still form, strictly speaking, 
its outside, in distinction from the intimate recesses of the tissues in which the life processes go on. 
4 See p. 151. 
6 For a resume of the protective action of the skin, mucous membranes, etc., see Metchnikoff, 
"Immunity in Infective Diseases," Trans., 1905. 
See for summary of protective agencies of the lungs, p. 600. For a study of the action of saliva on 
bacteria see Clairmont, Wiener klin. Wochenschr., Nov. 22d, 1906, bibl. For bactericidal action of 
mucus see Arloing, Jour, de Phys, et de Path. g6n. 1902, iv., 291, bibl. 
150 THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
151 
The Portals of Entry.-But notwithstanding the safeguards of 
the body against the access of micro-organisms, these do frequently enter; 
this may occur in severe injuries to the skin or mucous membranes or 
through very slight and unnoticed abrasions or other solutions of con- 
tinuity. Entrance may be gained to the tissues through the minute ducts 
of the sebaceous or sweat glands; from the mouth, tonsils, gastro-intes- 
tinal canal,1 and the respiratory passages and surfaces, either with or 
without obvious injuries to the investing epithelia. The role of insects 
in the conveyance of infectious agents is of great importance.2 Micro- 
organisms may enter the body during intrauterine life.3 
There is abundant evidence that even in health, through the pharynx, 
tonsils, and intestines, a small number of bacteria frequently enter 
the recesses of the body, but are safely disposed of through the 
protective mechanism presently to be considered. So that while we 
may, as above stated, consider the interior of the healthy body as 
practically sterile, it is still possible by careful and discreet searching 
to discover here and there bacterial detritus and bacteria on their way 
to destruction.4 
The Protective Mechanism.-When in one way or another bacteria 
or other germs have entered the tissues, they may encounter a series of 
obstacles to their spread or continuance as well as to their proliferation 
there, even should the general nutritive conditions be favorable. In the 
first place the lymph-nodes filter out of the tissue fluids micro-organisms 
which have entered them, holding them back from the general circula- 
tion or destroying them.5 The power of certain of the body fluids and of 
living cells-phagocytes-under favorable conditions to kill and dispose 
of germs, is of great importance and will be referred to again.6 The elimi- 
nation of micro-organisms from the body through its secretions,7 such as 
urine, bile, milk, sweat, saliva, etc., is a matter of great significance, but 
one upon which the scope of this book does not permit us to enter.8 
1 For bibliography concerning the permeability of the gastro-intestinal canal for bacteria refer to 
p. 681. 
2 Nuttall, Johns Hopkins Hospital Reports, vol. viii., p. 1, 1900. For a resume with bibl. of the 
transmission of infective material by flies and other insects see Chapin, Sources and Modes of Infection, 
2d edition, New York, 1912; also Graham-Smith, Flies in Relation to Disease, Cambridge, 1913; 
for study of economic loss by insects see Howard, U. S. Dep. Agricult. Bureau of Entomology, Bull. 
78, 1909. 
3 For a resume of studies on the congenital transmission of infectious agents see Wassermann and 
Keysser in Kolle and Wassermann 2d edition, Bd. i., p. 659, bibl.; also, Balantyne's " Antenatal Pathol- 
ogy," 1902 and Lynch, Johns Hopkins Hospital Bull., x., 283, 1902. 
4 Adami on "Latent Infection and Subinfection," etc., Jour. Am. Med. Assn. 1899, Dec. 16 and 23; 
and Brit. Med. Jour., 1914, p. 177.; also Wrzosek, Virch. Arch., Bd. 178, p. 82, 1904; see also for an experi- 
mental study of the disappearance of bacteria from the blood, Schwarz, Zeits f. Heilkunde, Abth. f. 
Path. Anat., Bd. xxvi., p. 295, 1905. 
6 Manfredi, Virch. Arch., Bd. civ., p. 335, 1899, for a study of the germicidal and other action of 
lymph-nodes; also Bezant on and Labbe, Arch, de med. experimentale et d'anat. path., t. x., p. 389, 
1898. 
6 For studies of the capacity of the living body to dispose of bacteria when these are injected into 
the blood, see Werigo, Ann. Inst. Pasteur, t. viii., 1894, also Bail, Arch f. Hygiene, Bd. lii., p. 272, 
1905; see also Buxton and Torrey, Jour. Med. Res., vol. xv., p. 5, 1906. 
7 Consult Sherrington, "Experiments on the Escape of Bacteria with Secretions," Journal of 
Pathology and Bacteriology, vol. i., p. 258, 1893; Biedl and Kraus, Arch. f. exp. Path., Bd. xxxvii., p. 1, 
1895, bibl.; Hintze and Lubarsch, "Ergebnisse der allg. Aetiologie der Menschen- und Thierkrank- 
heiten," 1896, p. 287. For study of disappearance of bacteria from the body, see Pawlowsky, Zeits. f. 
Hygiene and Infect. Krankheiten, Bd. xxxiii., p. 261; see also ref. to Asch, p. 755. 
8 For a suggestive summary of the various factors which are or may be concerned in the protection 
of the body against the invasion and action of micro-organisms, see Meltzer, "Physiological Methods 152 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
ACTION OF BACTERIA AND THEIR PRODUCTS IN THE BODY. 
The Bacteria.-When bacteria do enter and grow in the body, the cells 
and tissues near them may show very marked alterations, due to their in- 
fluence. The cells may be swollen, or their nuclei may disappear, and the 
protoplasm may be converted into hyaline material or into a mass of 
transparent or coarsely granular particles, or may completely disintegrate. 
The intercellular substance near the bacteria may also soften and disin- 
tegrate. In a word, the tissue in their immediate vicinity is often 
found in a condition of necrosis of one kind or another. The walls of 
blood-vessels near which they lie may be damaged and the blood which 
these carry may form thrombi. The bacteria may themselves enter the 
vessels and proliferate in the blood; they may be swept away as emboli 
to remote parts of the body (Fig. 56, p. 89), and establish new foci of 
bacterial proliferation and tissue necrosis-septicaemia. 
Some bacteria, instead of inducing a simple necrosis, incite at the 
same time, as we have already seen, a more or less intense inflammation 
(Fig. 57, p. 90). This inflammation may be of a simple productive 
form, similar in its effects to that incited by the presence of any irri- 
tating foreign body; or it may be active, progressive, and exudative in 
character; or the bacteria may determine, in some way as yet unknown 
to us, very peculiar and characteristic inflammatory changes, which result 
in the formation of new tissues of various kinds (see Tuberculosis). 
Some forms of bacteria find in the blood, others in the tissue spaces and 
lymph-vessels, the conditions most favorable for their proliferation. 
Bacterial Poisons.-But the presence of micro-organisms themselves 
is not indispensable for the incitement of either local or general pathologi- 
cal processes. These may be induced by various chemical products 
eliminated or stored up in their protoplasm by the metabolism of the 
germs. These deleterious bacterial products may, as we have already 
seen, be those alkaloidal substances called poisonous ptomains, or toxins, 
or they may be albuminoid substances-toxalbumins or toxalbumoses. 
Stored up in the protoplasm of the germs themselves, this poisonous 
material has been called bacterio-protein and endotoxin. 
It seems probable that the toxic effects of some bacteria may be due 
not to their immediate product but to the action of bacterial enzymes, 
whose action upon certain body proteids results in the development of 
the toxic albumoses which are the active damaging factors.1 
of Protection of the Body against Bacteria," Trans, of the Congress of Am. Phys, and Surg., vol. v., p. 
12, 1900; see also ref. to Wassermann above. 
See also for the importance of a lesion in animal tissues for the lodgment and multiplication of 
bacteria within it, Cheesman and Meltzer, Jour. Exp. Med., vol. iii., p. 533; and Brewer on unilateral 
infection of the kidney following injury, Surgery, Gynecology, and Obstetrics, vol. ii., p. 485, 1906; 
also on the significance of granulation tissue in wound infection, Afanassieff, Ziegler's Beitrage, Bd. 
xxii., p. 11, 1897; also Cobbett and Melsome, Centr Ibl. f. Path., Bd. ix., p. 827, 1898, bibl.; also Jurgelu- 
nas, Ziegler's Beitrage, Bd. xxix., p. 92, 1901, bibl. For the role of the spleen in infection and intoxi- 
cation see Courmont and Duffau, Arch, de Med. exp., May, 1898, p. 431, and Nicolas and Beau, Jour, 
de phys. et path, gen., t. iii., 1901, p. 68. 
1 Much of the literature on this subject has been brought together by Vaughan and Novy, ''Cellu- 
lar Toxins," See also Vaughan, Protein Split Products in Relation to Immunity and Disease, New 
York, 1913. The general chemical relationship of bacterial products to other organic compounds 
is set forth in Halliburton's ''Text-book of Chemical Physiology and Pathology;" see also Oppenheimer 
on ''Bacterial Poisons" in Kolle and Wassermann's "Handbuch der Mikroorganismen," Bd. i., p. 344. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
153 
Aggressins.-It has been found by Bail that when one injects into animals steril- 
ized exudates induced by the action of various pathogenic micro-organisms-tuber- 
cle, typhoid, and dysentery bacilli, pneumococcus, staphylococcus, etc.-together with 
sublethal doses of cultures of the organisms themselves, the death of the animal is 
brought about much sooner than when the bacteria alone are introduced. Bail, as 
the result of many experiments, assumes that under these conditions the exudate con- 
tains substances which foster the deleterious effects of the living organisms by inter- 
fering in some way with the protective agencies of the body. These hypothetical 
substances he has called aggressins, and he believes them to be formed by the bacteria 
as they grow in the body.1 This aggressin theory has not found general acceptance 
and much experimental data has been brought forward to controvert it.2 
Intoxication-Toxaemia.-Some of the poisons act locally at or near 
the seat of their manufacture by the growing germs. Others gain access 
to the body at large and are widely distributed, inducing what may be 
called the phenomena of septic intoxication-toxcemia. 
The phenomena of septic intoxication may be induced by the prod- 
ucts of bacterial growth outside of the body when these in considerable 
quantity are in any way taken into it. This is true not only of poisons 
elaborated outside the body by pathogenic bacteria, but also of many 
forms of bacteria usually harmless. Thus are caused many forms of 
food poisoning which simulate but are not actually infectious diseases, 
because there is no development within the body of the disease-inciting 
germs. 
Similar local and general effects may be induced in the body by other 
poisons than those of bacterial origin. Ricin and abrin, for example, 
well-known vegetable poisons, and the venom of scorpions and of certain 
snakes are closely similar in their action to the toxins which the bacteria 
form either within or without the body. 
It should be remembered in this connection that effects closely resem- 
bling those due to bacterial or allied poison may be induced by toxic 
agents developed within the body as a result of defective elimination or 
faulty cell metabolism-auto-intoxication ( see p. 426). 
Thus the deleterious effects of pathogenic bacteria upon the body are 
but in small measure simply mechanical. Local necrosis3 and inflam- 
mation, albuminous degeneration of cells, leucocytosis and other altera- 
tions of the blood, fever, structural lesions and functional disturbances 
in the nervous system, irregularities in the circulatory and respiratory 
mechanisms, haemolysis and agglutination of the red blood cells and 
thrombosis,4 etc., may follow the distribution in the body of bacterial 
toxins.5 
PROOFS OF THE INFECTIVE NATURE OF BACTERIA FOUND IN THE BODY. 
It will be seen, from what has now been said of the bacteria, that in 
different parts of the system in health, and in a large number of abnor- 
1 For a discussion of the so-called aggressins see Bail and Weil, Cbl. f. Bak., Ab th. I., Orig. Bd. 
xlii., pp. 51, 139, 241, 335, 437, and 443, 1906. 
2 See Sauerbeck, Arch. f. Hyg., Ivi., 1907. 
3 See Flexner, "The Pathology of Toxalbumin Intoxication," Johns Hopkins Hospital Reports 
vol. vi., p. 259, 1897. 
4 For bacterial haemolysins see Pribram, Kolle and Wassermann, "Handb. d. path. Mik." 2d edition, 
913, ii, 1328. 
6 On the theory of bacterial infection see Radziewsky, Zeits. f. Hygiene, Bd. xxxvii., p. 1. 154 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
mal conditions, various forms of bacteria occur; but it is quite evident 
that the significance which we must attach to their mere presence varies 
greatly. In a large number of cases, especially when on parts exposed 
to the air or in the gastro-intestinal canal, they are evidently of no more 
importance than so much inorganic dust. When, however, special 
forms of bacteria are uniformly present in connection with well-defined 
diseases, or in their lesions, and especially if these largely preponderate, 
the conjecture is certainly justified that the micro-organisms may have 
something to do with their incitement. Yet in all such cases we have to 
consider the possibility that it is the abnormal state of the body or the 
character of a lesion, brought about perhaps in other ways, which 
affords conditions suitable for the growth of this form of bacteria, and 
that these may consequently be present in considerable numbers, while 
in the absence of such conditions they would be unable to develop. 
Even the constant presence in the body, in certain diseases, of bacteria 
which evidently produce well-marked local effects, either inflammatory 
or degenerative, does not absolutely prove their etiological relationship 
to the disease, although it renders it in a high degree probable. 
It is desirable in every case in which the evidence of the etiological 
relationship of a specific micro-organism to a disease is to be set forth, 
that we should be able to demonstrate the constant presence in the body 
of the special form of micro-organism during some period of the disease, 
obtain this by culture in a pure condition unmixed with any other living 
thing or with any chemical substance not belonging to it, and finally, by 
the introduction of the purified organisms into a healthy animal, be able 
to induce the disease in some definite form. When all this is done, and 
not before, can we assert that the evidence establishing the causative 
relationship between a given form of bacteria and any special infectious 
disease, is entirely at our command. 
But the fulfilment of these strict logical requirements is very difficult 
in many cases, and in some, apparently, almost if not quite impossible; 
for we must remember, in the first place, that the lower animals, upon 
which alone, for the most part, inoculation experiments are practicable, 
are apparently not subject to certain important diseases of man; and, 
second, that they present among themselves the most marked differ- 
ences in the degree and manner in which they are affected by inocula- 
tion with pathogenic bacteria. Desirable as is the complete fulfilment 
of the above requirements in every case, it must be admitted that a rea- 
sonable certainty regarding the bacterial origin of a given disease may 
sometimes be arrived at without positive results from the inoculation 
of the bacteria associated with its lesions. The agglutination test and 
the tests for specific lytic substances or opsonins applied under proper 
conditions may afford valuable evidence of the nature of an infection 
(see pp. 186 and 193). 
The complete demonstration which is desirable has as yet been fur- 
nished in but a moderate number of diseases. In many others, however, 
enough has been done in the way of study and experimentation to render 
it altogether certain that they are infectious and to establish beyond THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
155 
reasonable doubt the identity of the micro-organism or micro-organisms 
involved. 
CONDITIONS INFLUENCING THE OCCURRENCE OF INFECTIOUS DISEASES. 
Conditions of the Body.-It has been learned as a result of a great 
deal of observation and experiment, that although certain diseases are 
always associated with the presence and growth in the body of particular 
species of micro-organisms, there are still various other accessory factors 
which have an important bearing upon the inception and course of the 
diseases. Thus, while the presence in the body of a particular species of 
micro-organism is the most significant and fundamental of the determin- 
ing agencies in the infectious diseases, the numbers in which they are 
present-i.e., the size of the dose-and the varying virulence which the 
same species under different conditions possesses, as well as the varying 
capacity of resistance to the incursions of the germs which the body-cells 
at different times and under differing conditions exhibit, are all factors 
of the greatest moment. 
Malnutrition, mental or physical overwork, injuries, bad hygienic 
surroundings, the abuse of alcohol and other forms of intemperance, as 
well as many other conditions which lead to deterioration in the general 
health, are often decisive factors in determining the intensity or even 
the occurrence of the diseases due to bacterial incitement. It is thus 
clear that the action of a given germ in the living body depends only in 
part upon its intrinsic capacities-which in themselves are very variable 
-but also and in marked degree upon the capacities, also variable, 
which exist at the moment in the body-cells among which the lot of the 
germs is cast. 
It should be always borne in mind that the human body is a great 
aggregate of groups of co-ordinated cells which, under normal conditions, 
all act in harmony for the maintenance of the life and functions of the 
individual. The cells and cell communities in health not only do this, 
but they have the power of resisting and to a certain extent overcoming 
various deleterious agencies to which the body is more or less constantly 
liable. 
What we call hereditary or acquired predisposition to an infectious 
disease, such as tuberculosis for example, is simply a lack of the usual 
capacity of the cells of the body-whether through a structural or physi- 
ological fault we do not yet know-to cope with-that is successfully to 
adapt themselves to-the destructive tendencies of the living micro- 
organisms when once these gain a foothold in the body. 
Conditions of the Micro-organisms.-On the other hand, the varying 
potencies of the bacterial species concerned in a given infection, which 
are linked especially to their toxins, and the influence of environment 
upon these, exalting or reducing them, as the germs adapt themselves to 
antagonistic or to congenial hosts; the origin of the strains and the 
numbers involved-these are all factors in virulence of supreme impor- 
tance, but our space does not permit us to consider them further here. 
We thus see that, in studying the conditions under which infectious 156 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
diseases occur, the work is by no means complete when the bacterial 
species which incites the disease has been discovered, but that then the 
more obscure determining and influencing age/rcies must be worked out 
in each case.1 
Infection and Immunity. 
Infectious diseases are those which are incited by the entrance into the 
body and proliferation there of pathogenic micro-organisms. Infection 
is the act or process by which such diseases are incited. The process of 
infection is "the interaction between the organism and the micro- 
organism." 
In the more exact usage of the words "infectious" and "infection" 
which our new knowledge demands, it is customary and convenient to 
limit the term "micro-organism" to the fungi-bacteria, yeasts, and 
moulds-and to the protozoa representing the animal kingdom, exclud- 
ing altogether the entozoa and other animal parasites.2 
The modern conception of infection implies the presence in the body 
of the living micro-organisms themselves; that is, of something capable 
of multiplication, or at least of reproduction and development, and not 
alone of the poisons which they may and usually do produce. It is 
customary to look upon the effects of the absorbed poison which micro- 
organisms furnish as intoxications, whether these poisons be formed 
inside the body in infectious diseases arid in other conditions, or outside 
of it and subsequently introduced. That condition in which there is 
evidence of wide distribution of pathogenic micro-organisms and their 
products in the blood is called septicemia (see p. 203). 
It is evident from what has been said that infectious disease cannot 
exist without the presence in the body of micro-organisms. But, on the 
other hand, micro-organisms can and do frequently exist in the body 
without the incitement of infectious disease. Whether a micro-organ- 
ism be pathogenic or not depends upon the variable susceptibilities of 
the host as well as upon its own-also variable-nature and qualities. 
No micro-organism is intrinsically pathogenic; the very conception 
implies a relationship. This obvious fact is overlooked by those who see 
in the micro-organisms alone the essential specific features of infectious 
diseases; who would classify these diseases exclusively by the nature of 
their excitants, and who look upon the latter as the true "causes" of 
the phenomena through which disease is manifested (see p. 5). 
INFECTIOUS DISEASE AND THE NATURE OF INFECTION. 
INCUBATION PERIOD. 
It is characteristic of infection that a certain time elapses between 
the entrance of the infective agent and the manifestation of symptoms 
1 For a resume of the nature and conditions of infection, see Wassermann and Keysser, Kolle and 
Wassermann's " Handbuch der Mikroorganismen," 2d ed., 1912, Bd. i., 555, bibl.; for a study of the 
general reaction of the body in infection see Blumenthal, 1st ed. Bd. i., p. 326. 
2 With this somewhat arbitrary limitation, neither trichinosis nor scabies, for example, would be 
considered an infectious disease, although they are often, for the lack of a distinctive word, thus desig- 
nated. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
157 
or the development of lesions. This interval is called the "incubation 
period" of the infection and varies with different infective organisms. 
This incubation period is that time during which the micro-organisms 
are increasing sufficiently in number or virulence in the body to induce 
symptoms and lesions or are passing through developmental cycles 
marking their adaptation to the environment furnished by the host. 
FORMS OF INFECTION. 
Mixed or Concurrent Infection.-It should be borne in mind that the 
body which is already the seat of an infectious disease is usually espe- 
cially susceptible to the action of other pathogenic germs, should these 
once gain entrance; and also that the lesions which are associated with 
many of the infectious maladies afford portals of entry through the skin 
or mucous membranes to other micro-organisms, against the entrance of 
which the healthy body opposes most efficient barriers. In fact, we now 
know that the action of two or more pathogenic micro-organisms in the 
body at the same time is of very frequent occurrence, many of the 
so-called complications of the infectious diseases being due to secondary 
infection with a new germ species. Numerous examples of this "mixed" 
or, better, "concurrent," infection are noticed in other parts of this 
book.1 
Many important facts have been revealed by the study of bacterial 
association in cultures as well as in infectious diseases of men and ani- 
mals which cannot here be considered.2 It may be said in general that 
in animals as in man concurrent infection with a second micro-organism 
increases the gravity of the original situation. On the other hand, cer- 
tain experiments seem to indicate that sometimes the concurrent action 
of a second germ-streptococcus, for example, with the anthrax bacillus 
-may render a virulent organism comparatively innocuous. But the 
conditions of the experiments are in either case so complex that the full 
significance of many curious phenomena is not yet apparent. 
Congenital Infection.-Infection of the foetus through such lesions of 
the placenta as permit of the passage of pathogenic micro-organisms from 
the blood of the mother to that of the child is of occasional, but not 
frequent, occurrence. While the barriers against such transmissions are, 
under normal conditions, effective, disturbance in the placental circula- 
tion, lesions of the vessel walls or of the tissues and covering of the 
chorionic villi favor it. But infection may occur without demonstrable 
evidence of such lesions. Thus foetal infection is known to have occurred 
in various phases of suppurative inflammation, in tuberculosis, typhoid 
fever, anthrax, syphilis, the exanthematous fevers, etc. There is con- 
siderable evidence that rarely the tubercle bacillus may be transmitted 
1 For bibliography of mixed infection see Bernheim and Gruber, Lubarsch and Ostertag's "Ergeb- 
nisse," Jahrg. 2, for 1895, p. 1; also Wassermann and Keysser, in Kolle and Wassermann's "Handbuch 
der Mikro-organismen," 2d ed., 1912, Bd. i, 632. 
2 Consult Th. Smith, Trans. Assn. Am. Phys., vol. ix., p. 85, 1894; also Moore, "Pathology and 
Differential Diagnosis of Infectious Diseases of Animals," 1906. 158 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
from mother to offspring, and remaining for a time inactive may later 
induce the characteristic lesions.1 
Terminal Infection.-The victims of chronic disease of the heart, 
blood-vessels, kidneys, liver, etc., are particularly susceptible to the 
incursions of pathogenic micro-organisms and to infectious diseases of 
one kind or another. Such persons, with or without definite lesions, 
are in fact liable finally to succumb to the complicating disease. The 
phrase "terminal infection" has been applied by Osler and others to 
this concurrence of diseases of such different nature, in which the chance 
infection of a vulnerable organism is so apt to prove fatal.2 
Great care is, however, necessary in determining the significance of 
the various forms of bacteria which may be present in the body after 
death. Not only may bacteria develop to a considerable extent in the 
body during the hours which precede death when the natural protective 
agencies are halting or abeyant, but this may occur without such a 
reaction on the part of the body cells as is necessary to constitute an 
actual infection. Furthermore, multiplication and distribution of bac- 
teria in the body after death is of frequent occurrence and must in every 
case be taken account of in weighing the evidence for terminal infection. 
COMMUNICABILITY OF INFECTIOUS DISEASES. 
It is important in practical dealings with the infectious diseases to 
consider them in the light of the relative liability of transmission of the 
actually known or assumed micro-organisms from diseased to healthy 
individuals.3 
In the first place, it should be borne in mind that the lower animals 
are insusceptible to the ravages of some of the micro-organisms which 
readily incite infectious disease in man. Thus the lower animals are, 
so far as we know, naturally immune to syphilis. To certain diseases of 
the lower animals, on the other hand, man is not subject. But to certain 
other infectious diseases, tuberculosis for example, both men and lower 
animals are susceptible, and both are, in fact, under the prevailing con- 
ditions of modern life, frequent victims. 
So far as the liability to the transmission of the infectious agents from 
man to man is concerned, there is a very marked and significant differ- 
ence between the infectious diseases. It is common usage to speak of the 
transmission or communication of disease, as if disease were a self-exist- 
ent thing. This usage fosters much loose thinking. What we call dis- 
ease is a process involving a departure from, failure in, or perversion 
of normal physiological action, either in the material constitution or in 
the functional integrity of the living organism. When, therefore, we 
speak of the transmission or communication of disease, what we really 
mean is not that the disease, but the agent capable under suitable con- 
ditions of inciting the disease, is transmitted or communicated. If we 
1For bibliography and summary of foetal infection see Lubarsch, "Ergebnisse der allg. Aetiologie 
der Menschen- und Thierkrankheiten," Jahrg. i., p. 427, 1895; also Fischl, in Grancher, Comby, and 
Marfan's "Traite des Maladies de 1'Enfance," t. i., p. 454, bibl. 
2 For a study of this class of cases see Flexner, Trans. Assn. Am. Phys., vol. xi., p. 229, 1896. 
3 See Chapin, Sources and Modes of Infection, 2d edition, New York, 1912. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
159 
hold this obvious implication in mind, it is useful to group the infectious 
diseases of man into two great primary classes: 1st, Those which under 
the usual conditions of life are not readily communicable. 2d, Those 
which under the usual conditions of life are readily communicable. 
But while, for convenience, we may speak of non-communicable and 
communicable infectious diseases, we should remember that these two 
classes merge into each other, and that in fact the agents of infection 
may at least artificially in all cases be conveyed from one individual to 
another. It is only when the conveyance under natural conditions occurs 
in a round-about way, or through intermediary agencies, such as the 
mosquito for example, in malaria or yellow fever, that one may advis- 
edly speak of non-communicable infectious diseases. 
Among the communicable infectious diseases there exists the widest 
difference in the liability to transmission under ordinary circumstances. 
Thus the infectious agents in measles are given off from the body under 
such conditions as render possible and frequent their direct transmission 
to another individual without the obvious contacts of person or discharges 
with which the conveyance of infective agents is associated in most of the 
communicable diseases. In syphilis, tetanus, and rabies, on the other 
hand, transmission of the infectious material is rare or impossible without 
a direct inoculation. 
Between these extremes the widest diversity exists in the liability to 
transmission of the infectious agents of the diseases of this class. In 
fact the liability to infection on the part of a healthy individual in the 
presence of a victim of infectious disease is largely dependent upon the 
intelligent care which is exercised in the disposition of the material con- 
taining the pathogenic micro-organism, usually secretions or excretions, 
which in one way or another the infected body sets free. 
So that while it may be useful to arrange the communicable infectious 
diseases in groups, or in such serial order as may indicate the degree of 
communicability of each under the ordinary conditions of life, it should 
always be borne in mind that this classification is not fundamental as is 
that by which the infectious diseases as a whole are set apart from other 
diseases, but is closely dependent upon the sanitary conditions under 
which each case may be placed. Thus tuberculosis, or diphtheria, or 
pneumonia may be high on the list as readily communicable if the 
patient be housed in a crowded tenement with ignorant or careless attend- 
ants, while if subjected to the intelligent ministry of sanitary science 
these diseases may be accounted as relatively slightly communicable.1 
Communicable infectious diseases sometimes affect a considerable 
number of persons in a community. This constitutes an epidemic, and 
the term epidemic disease is used. So also if an infection is constantly 
present in a certain locality it is said to be endemic. The term pandemic 
is used to indicate the involvement of persons all over a large territory 
in a particular infectious disease. 
1 Before the knowledge of pathogenic micro-organisms had become precise, readily communicable 
diseases were called contagious in a rather loose and ill-defined way, and the unknown excitant was 
called the contagium. The word "contagious" is still used, in various senses, to the detriment of 
science and should be replaced by the word "communicable" as above indicated. 160 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
IMMUNITY. 
Nature and Forms of Immunity. 
We have seen that an infectious disease is one incited by the entrance 
into the body and proliferation there of pathogenic micro-organisms, and 
that infection is the act or process by which such a disease is incited. 
The fact that all animals are not equally susceptible to the ravages of 
pathogenic micro-organisms, and that in man an individual and often a 
changing predisposition or invulnerability to the incursions of these 
organisms exists; the further observation that one attack of an infectious 
disease often protects the victim for a longer or shorter time against a 
recurrence; finally, the fact that recovery is ever possible when once 
self-multiplying disease-producing germs have obtained a foothold in the 
body-all these facts and observations are of such singular import and 
interest that, especially of late years, there has been much study on 
the nature of the agencies which the body brings into play in establish- 
ing immunity in the face of microbic invasion, and in coping with the 
various deleterious factors at work when once a foothold is obtained. 
The scope of this book does not permit us to enter in detail into this most 
fascinating and important field. We can give only a brief summary of 
some of the more important features. 
Immunity is insusceptibility, or capacity for resistance on the part of 
the body to disease or, in the more limited sense, to infection or intoxication 
or their effects. 
If we recall the ways in which bacteria damage the organism, it will 
be evident that immunity may be due to the fact that the micro-organ- 
isms in question simply do not proliferate in the body, failing, even 
should they gain entrance, to find the necessary conditions.1 On the 
other hand, though the conditions be in general favorable, substances 
may exist or be formed in the body which destroy the invading germs. 
In other words these may at once or soon be disposed of by germicidal 
substances, either in cells or in solution in the body fluids. 
Or, the toxic substances which micro-organisms set free, as in the 
process of their nutrition they decompose organic ingredients of the tis- 
sues or body fluids, may be rendered inert by further decomposition or 
combination with substances present or formed in the tissue fluids. Or, 
furthermore, the cells which are susceptible to the presence of the toxins 
may become less vulnerable by adaptation to the deleterious effects of 
the latter. Thus by a total unsuitability of the tissues or of the general 
conditions to bacterial growth; by destruction of the invading germs; 
by neutralization or destruction of toxins; or, finally, by a capacity of 
resistance or tolerance won through adaptation to a new and intrinsically 
harmful environment, we may conceive of conditions which in a measure 
account for the known phenomena of immunity. 
1 For a most suggestive and valuable paper on the adaptation of pathogenic bacteria to different 
species of animals see Theobald Smith, Philadelphia Medical Journal, May 5th, 1900. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
161 
Immunity from an infectious disease may be natural or hereditary.1 
The absolute or relative insusceptibility of turtles and fishes for 
tetanus, of rats for anthrax, and of the lower animals for syphilis and 
for scarlatina, are examples of hereditary or natural immunity which we 
need not further consider here. Immunity is variable and rarely abso- 
lute, and is subject to individual, as well as racial, variation. 
On the other hand, immunity may be acquired. Acquired immunity 
may be secured by an attack of the disease from which the individual 
has recovered-natural immunization. Or, immunity may be acquired 
by the introduction into the body of some material which gradually 
diminishes susceptibility without inducing distinct disease-artificial 
immunization. Acquired immunity may be transmitted from parent to 
offspring. 
Fig. 105.-Phagocytes. 
In fluid from the peritoneal cavity of an immunized guinea-pig a few hours after the introduction 
of the bacilli of typhoid fever. Degenerative changes are seen in many of the bacteria within the cells. 
Most of the infectious diseases appear to confer a certain degree of 
insusceptibility to subsequent attacks of the same disease, though this 
may be partial and temporary. But the exanthemata afford the most 
striking examples of acquired immunity after an attack of infectious 
disease. 
Let us now look more closely at some of the ways in which the body 
may thus protect itself from the consequences of infection. 
It is well known that bacteria artificially introduced into the blood 
of animals may, after a short time, wholly disappear from the circulating 
fluid, and be found in large numbers in leucocytes and other cells. We 
have already seen in the study of inflammation (see p. 98) that cer- 
tain cells of the body are capable of taking up not only various kinds of 
alien substances, but also micro-organisms which enter the tissues, into 
their cytoplasm (Fig. 65 p. 100) and may there kill and destroy them 
(Fig. 105). This mode of destruction of micro-organisms, largely by 
leucocytes, but also by other mesodermal cells, which when thus engaged 
are called phagocytes (see p. 99), plays a most important part in the 
establishment of immunity. On the other hand, certain ingredients 
of the body fluids, formerly called alexins or " defensive proteids," 
acting outside of cells, have been shown to possess marked germicidal 
1For a study of the theories of natural immunity see Muller, "Infection u. Immunitat," 1912. 
For a study with bibl. of the protective processes in natural immunity, see Kisskalt, Zeits. f. Hyg. u. 
Infkr., Bd. xlv., p. 1, and ibid., xlvii., p. 243, 1904. For a study of inherited immunity see Kleine and 
Mollers, Zeits. f. Hygiene, etc., Bd. lv., p. 179, 1906. 162 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
powers. While thus it might appear that two fairly distinct agencies 
are of importance in enabling the body to resist the incursions of path- 
ogenic germs-cellular or "phagocytic," and what may be called "hu- 
moral" or chemical-it is obvious that ultimately whatever destructive 
power the body possesses toward micro-organisms must be due, directly 
or indirectly, to cell activities. This phase of immunity has been char- 
acterized as anti-microbic, anti-bacterial, or bacteriolytic immunity, 
because it is a mode of protection in which bacteria are destroyed or 
their growth in the body is limited or prevented. 
Not less important is another phase of immunity-antitoxic immunity 
-by which the body protects itself against the toxic substances through 
which, in many instances, the most serious manifestations of infection 
occur. 
These two forms of immunity-antitoxic and anti-bacterial or bac- 
teriolytic-will be considered in detail in a following section. 
Furthermore, the microbic toxins which are set free by the micro- 
organisms, like other poisons, may be eliminated together with the waste 
products of body metabolism through the kidneys, skin, etc. 
Artificial Immunization. 
General Methods and Principles of Artificial Immunization.-It was 
not possible to gain a clear conception of the factors entering into the 
complex problems of immunity until animal experimentation had 
revealed a host of significant facts bearing directly upon questions which 
for a long time had seemed insoluble. It has been found as the result 
of experimental researches that artificial immunity can be secured by 
gradually rendering the body tolerant to the presence of the infective 
or toxic agencies without actually inciting the characteristic specific 
disease. 
I. In one class of procedures artificial immunity is secured directly or 
indirectly through the action in the body of bacteria or other microbes or 
microbic poisons whose virulence has been in one way or another reduced 
but not rendered altogether inert; or by the action on relatively insusceptible 
animals of microbes or microbic poisons of unimpaired virulence. Im- 
munity induced in this way as the result of direct adaptation of the body 
cells to the new conditions is called active immunity. 
1. Active immunity to particular forms of infectious disease may be conferred by 
inoculation with cultures of the germ inciting the infection whose virulence has been artifi- 
cially reduced-attenuated cultures. This reduction of virulence may be accomplished 
in various ways: by cultivation at temperatures above their optimum; by successive 
inoculations into insusceptible animals; by prolonged artificial cultivation in the pres- 
ence of oxygen; by exposure to certain inorganic chemical substances, as the diphtheria 
bacillus to trichlorid of iodine, anthrax to bichromate of potash, etc.; by exposure of 
cultures to organic extracts or products of animal or vegetable cell metabolism; by 
drying (hydrophobia), or by exposure to sunlight; by killing the germs by heat, using 
for injection emulsions of their dead bodies containing the so-called endotoxin; and 
in other ways. 
With the virulence of the micro-organisms reduced in varying degrees in one or 
other of the ways just mentioned, the gradual habituation of the bodies of animals to THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
163 
the presence of pathogenic germs may be pursued until cultures of full virulence are 
tolerated.1 
2. Active immunity may be conferred by the injection, in gradually increasing 
doses, of the metabolic products of bacterial growth, either with or without the dead 
bodies of the germs themselves-the bacilli of typhoid fever, for example. The pri- 
mary virulence of these usually toxic products of microbic growth may be in various 
ways diminished, by heating, by mixing with organic extracts such as that of the thy- 
mus gland, or with an inorganic chemical substance such as trichlorid of iodine, or by 
small doses of the already prepared antitoxin-see below. 
3. Active immunity may be secured in some cases by the inoculation of animals, 
which are but moderately susceptible to the species employed, with small but increas- 
ing quantities of germs having unimpaired virulence. Under these conditions the 
animal becomes less and less responsive to the germ, until finally it may display no 
reaction after a quantity of the virulent culture which at first would have been in- 
evitably fatal. 
Immunization in man by the direct use of dead bacteria or bacterial poisons or of 
virus of diminished virulence has been largely practised in typhoid fever, cholera, and 
hydrophobia. 
In active immunity the protective material is elaborated by the 
immunized individual, the process requires considerable time, and the 
effect lasts for a considerable period. 
II. In a second class of procedures artificial immunity is secured by the 
direct mingling of the body fluids from an individual already immunized in 
some of the above ways, with those of the individual to be protected. Im- 
munity secured in this way, in which the immunizing substance used has 
been elaborated by another individual, is called passive immunity. 
1. Extracts of various organs and tissues of animals suffering from infectious dis- 
ease rendered germ-free and injected into healthy animals, have been found in some 
cases to confer a certain degree of immunity. 
2. The blood serum of animals naturally immune to a particular infectious disease 
has been found, on injection into those which are susceptible to the same disease, to 
impart in some cases a certain degree of insusceptibility. 
3. The blood serum, finally, of animals which have been rendered in one way or 
another artificially immune to certain diseases, if introduced under proper conditions 
into another susceptible animal, has been found not only to confer a temporary immu- 
nity, but, if administered to an already stricken individual, to aid him in the most 
marked and efficient way to overcome the deleterious agencies at work. 
The use of blood serum of artificially immunized animals for this purpose is of far 
greater practical importance than either of the methods 1 or 2. 
In passive immunity the protective material is furnished ready made, 
the effect is secured at once and is temporary. 
Antitoxic Immunity. 
It appears from a study of the results of artificial immunization, as 
well as of the immunity which is involved in the natural recovery from 
infectious disease, that one of the ways in which immunity is secured is 
1 On the contrary the virulence of a particular strain of pathogenic bacteria may be exalted by a 
series of "passages" through a susceptible animal. When the infection from inoculation has developed 
in the first animal, cultures derived from it are used to infect a second, and so on through a series of 
"passages." 
In this way, it is assumed, the self-protective adaptations of the bacteria are made evident in the 
increasing potency of the toxins which they produce, the toxins being one of the important factors in 
virulence. 164 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
by the formation of substances in the body fluids which in some way 
neutralize or suspend the action of toxins-antitoxic immunity. 
Thus in diphtheria and tetanus the antitoxic substances are largely 
developed, while in many other infectious diseases, such as cholera and 
typhoid fever, it appears to be, in part at least, through the bacterio- 
lytic substances that protection is secured. While in many instances 
both of these types of protective substances may be formed during im- 
munization, one or the other is usually preponderant.1 
The antitoxic substances are most closely related to the globulins, 
but beyond this their chemical nature has not been definitely ascertained.2 
The effect of antitoxin in the blood in rendering harmless the toxic 
substances which they form apparently is accomplished, not by the 
destruction of the toxins, but by a chemical union of toxin with anti- 
toxin, whereby the former is deprived of its capacity to injure cells. 
The knowledge of this antitoxic immunizing action of specially 
endowed blood serum has been most fully developed in diphtheria and 
tetanus. 
During the growth of the diphtheria bacillus in nutrient broth a 
toxic substance is developed which mingles with the broth. This is 
called diphtheria toxin, and subcutaneous injections of this toxin in 
animals-guinea-pigs, for example-prove fatal, in appropriate dosage, 
with symptoms and lesions similar to those caused by inoculation with 
the living germ. It has been found that by repeated injections of the 
diphtheria toxin in susceptible animals, at first with small, then with 
gradually increasing, doses, the animal may at length become so insus- 
ceptible to the action of the poison that many times the usually fatal 
dose is borne without sensible reaction. Similar immunity can be con- 
ferred in certain animals by the use of the living cultures of the diphtheria 
bacillus either fully virulent or with reduced virulence (see p. 163), 
administered at first in small doses which are gradually increased. 
In whichever way immunity be conferred, it has been found that the 
blood of the artificially immunized animal contains a substance, or sub- 
stances, called diphtheria antitoxin, which, on being introduced with the 
blood serum into other susceptible animals, may not only confer a 
quickly established immunity-passive immunity-but, without destroy- 
ing the diphtheria germ, may protect against its toxic effects when 
the disease is already under way. Thus, through the artificial immuniza- 
tion of horses and the hypodermatic use of the serum of their blood in 
man, the so-called "serum therapy" has assumed a very important and 
beneficent role in the prevention and treatment of diphtheria.3 
1 The damage or destruction of bacteria by anti-bacterial, batericidal, or bacteriolytic substances 
naturally limits or prevents the formation of toxic materials by the micro-organisms, although the 
cells of the body may be very susceptible to the action of these. So that the absence of evidence of the 
establishment of antitoxic immunity in an infectious disease may mean, not that the body is incapable 
of this, but only that no opportunity is offered for its development. 
2 See Hiss and Atkinson, Journal of Experimental Medicine, vol. v., p. 47, 1900. 
3 The antitoxic value or power of each specimen of antitoxic serum is experimentally determined 
by finding the amount of the serum required to protect the test animal against the action of a definite 
amount of toxin of known strength. Various standards have been adopted, the value of the serum being 
expressed in terms of the " antitoxin unit." For example, in the determination of antitoxin value made 
use of by the Department of Health of the City of New York, an antitoxin unit is the amount of anti- 
toxic serum required to protect a guinea-pig weighing 250 grammes from death, when one hundred times THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
165 
Results similar to those obtained in the study of diphtheria antitoxin 
have been realized in the investigations of tetanus. But the practical 
value of the tetanus antitoxin as a therapeutic agent is less obvious. It 
has been shown, further, that antitoxic sera may be developed in the body 
during immunization to snake venom, the poison of the spider and 
scorpion, vegetable poisons, such as ricin and abrin, and to other 
albuminous animal and vegetable materials. Thus, also, through 
experimental adaptation, the living body-cells may elaborate and set 
free into the serum substances which suspend the action of ferments, 
like rennet, pancreatin, fibrin ferment, etc. 
Not all toxic substances, however, are capable of inciting the living 
body to the formation of antitoxic substances; nor are these apparently 
formed in such considerable amount in most of the infectious diseases, 
as is the case in diphtheria and tetanus. 
The action of these antitoxic substances is, within certain limits, 
specific; that is, the antitoxin of diphtheria protects against diphtheria, 
that of tetanus against tetanus, etc.1 
EHRLICH'S "SIDE-CHAIN" HYPOTHESIS. 
We have seen that a most remarkable series of facts is developed by our studies of 
infectious diseases illuminated by the results of animal experimentation. When the 
living body is invaded by a certain toxic complex organic material, not always of mi- 
crobic origin, the body adapts itself to the new conditions by the elaboration of sub- 
stances which protect it from the action of that poison. Each new protective sub- 
stance is effective against the particular poison which induced its formation. Not 
only this, but if the blood serum containing these new protective substances be trans- 
ferred to another individual they protect him also-passive immunity-against the 
special poison which called them forth in the body of the first. 
How are we to conceive of this wonderful adaptive power of the living body under 
conditions which seem to be wholly new in the life of the individual; a power which 
at first appears to transcend the known capacities of the body-cells? 
This singular capacity of the body-cells to develop in emergencies apparently new 
substances has naturally given rise to much study and to many speculations and hy- 
potheses. The scope of this book does not permit even of enumeration of these. But 
it is necessary to bring forward at least in outline the so-called " side-chain" hypothesis 
of Ehrlich by which he strove to account for the phenomena of antitoxic immunity as 
exemplified with especial clearness in diphtheria and tetanus. Without his hypothesis 
we are to-day still practically at sea in our views of the nature of antitoxic immunity, 
while this remarkable capacity of the body to manufacture the greatest variety of 
potent specific antidotes to the most subtle and virulent poisons becomes, for the first 
time, comprehensible in the light of this ingenious conception. It is now several years 
since Ehrlich's hypothesis was enunciated, and, whatever may be its merit as a direct 
contribution to science, there can be no doubt that it has been, in a remarkable degree, 
an inspiration to the most fruitful research. It is practically impossible to follow the 
recent work on immunity without a knowledge of this hypothesis and familiarity with 
the nomenclature to which it has given rise. 
the fatal dose of diphtheria toxin is mixed with the serum and the mixture injected subcutaneously into 
the animal. The usual dose for human administration may contain from three hundred to six thou- 
sand units. 
1 For a detailed consideration of the specificity of infectious agents see Kolle in Kolle and Wasser- 
mann's "Handbuch der Mikroorganismen," Bd. i., p. 288. 
The monograph by Citron, " Die Methoden der Immunodiagnostik und Immunotherapie," 1910, 
contains many facts of practical importance in the application of theories of immunity; while Kraus 
and Levaditi's "Handbuch der Technik und Methodik der Immunitatsforschung," I Enganz., 1911, 
furnishes a most valuable survey of the entire subject from the point of view of method. 
For a summary of the results of serum therapy see Park, Harvey Lectures, 1905-06. 166 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
In order to comprehend the hypothesis of Ehrlich regarding the origin and nature 
of antitoxin, it is necessary for us to form with him a clear conception of cell 
assimilation. 
We conceive of the cell as a mechanism for the storage of energy derived from 
without and for its release under definite conditions. This storage of energy is possible 
through the assimilation and building up by the cell of complex molecular combina- 
tions. These, owing to their instability, are readily stored into less complex and 
more stable combinations with the release of the stored-up energy. Thus is the life of 
the cell manifested. 
This broad conception of the cell is a purely intellectual one, however, for the de- 
tails of cell metabolism still elude the keenest scrutiny of the chemist. He cannot 
formulate protoplasm nor express its chemical changes by proportionate symbols. 
Now, accepting this condition of affairs as for the moment inevitable, Ehrlich 
seeks to express his view of the character of the cell's performances in general terms, 
disregarding its morphological peculiarities, somewhat as follows: We may conceive of 
the cell as consisting of a central group of very complex molecular combinations which 
maintains the characteristics and special capacities of the cell as an organism under all 
Fig. 106.-Diagram Illustrating the Action of Receptors in the Nutrition of the Cell. 
A, Portion of cell body; a, food molecule; b, c, d, receptors. 
the vicissitudes of its existence. Associated with this central organic group are many 
and various subsidiary atom-complexes which by means of their unsatisfied affinities 
bring the central group into relationship with food material through those chemical 
combinations which in living protoplasm characterize assimilation. 
These unsatisfied affinities by which assimilable material is fixed or united to the 
cell have been called "side chains," a term adopted from the chemist. Not to press 
too closely, however, the analogy between the chemical processes in lifeless substances 
and assimilation in living matter, these affinities or "side chains" of protoplasm are 
now commonly called receptors. 
^If we seek to illustrate Ehrlich's conception we shall be obliged to use graphic 
figures of extreme crudity. If the arc of a circle in Figure 106 represents a portion of 
the periphery of a cell, we may indicate the side chains or affinities or receptors by 
projections whose special shape shall indicate their special capacity to combine with 
any substance coming in contact with them under favorable conditions. Suppose in 
this figure we let a represent a nutrient molecule which is capable of combining with THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
167 
the receptor b, belonging to the cell A. Through its union with b, and only through 
this, is it capable of entering into the metabolism of the cell. This molecule a cannot 
unite with the receptor c or d, but only with such receptors-to use the crude expression 
which our illustration requires--as it fits. Through the receptors c and d other 
forms of food molecules may enter into the metabolism of the cell. 
Thus it is in Ehrlich's conception, which after all is only a graphic way of illustrat- 
ing the preliminary phases of assimilation by living protoplasm, that the cell is capable 
of selecting, or "fixing," out of the host of various substances with which it comes in 
contact, just those and only those to which its receptors bear a definite chemical 
relationship. 
The same thing is true of toxic as of nutrient substances. In order to be toxic to 
the cell they must enter into chemical combination with a suitable receptor of the 
cell. Then only can they lead to the forms of damage which we 
are here considering.1 
As the result of many studies on the nature and effects of 
toxins, Ehrlich is led to believe that the toxin molecule con- 
sists of two forms of affinities: one through which the chemical 
union with the cell is effected-called the haptophorous group; 
and the other-called the toxophorous group-by which the 
damage to the cell is brought about when once the toxin mole- 
cule is anchored to it.2 
This conception may be illustrated as in Figure 107, in which 
the toxophorous group a of the toxin molecule can be effective 
in damaging the cell only when united to the latter by the 
haptophorous group b. 
Having now conceived of the living cell as consisting of a 
central essential complex molecular group, brought into rela- 
tionship with its food materials by means of a great number of 
the most varied receptors, through which, under normal conditions, assimilation is 
secured, let us see what may happen if toxins come in contact with living cells which 
are furnished with receptors capable of uniting with them. 
The union of the toxin molecule with the living cell being effected, the cell is more 
or less damaged. If the damage be sufficient, the cell dies. But suppose the damage 
to be but slight, as may be the case in artificial immunization or in early stages of an 
infection. The cell is at least deprived of the useful offices of the receptor to which 
the toxin molecule is now united. This is in itself a loss to the cell, and through the 
regenerative impulses common to all living cells it proceeds to regenerate the lost parts, 
which in this case are the receptors. But as more receptors are thrown out of function 
by the continued action of the toxin, the necessity for compensation continues. 
Now it is a fact long known to pathologists, and especially emphasized by Weigert, 
that the regenerative impulse is apt to be in excess of the obvious requirements and 
leads to overproduction of new cells, tissues, chemical substances, etc. This is what 
now happens to the cells, some of whose receptors have been rendered useless by com- 
bination with the toxin. New receptors are formed, more than the cell requires; so 
numerous may these become that many are at last cast off into the blood. Here is the 
point at last. These receptors or substances, normal and useful to the body, but now 
formed in excess through over-compensation, and set free from the cells into the body fluids, 
are the antitoxin. 
Fig. 107.-Diagram 
Illustrating Sup- 
posed Character of 
the Toxin Molecule. 
ajToxophorous group; 
&,Jhaptophorous group. 
1 It is evident, from what has been said about the conditions under which substances can be toxic, 
that the natural immunity of one animal to a given agent which is toxic in another may be simply due 
to the fact that the cells of the former have no receptors with which this agent can unite, or, if this 
union does take place, that the cell is not thereby damaged. This consideration has an important bear- 
ing upon our conception of natural immunity. 
This so-called "fixing" or "binding" of toxin to tissues may be demonstrated by mixing some of 
the potent tetanus toxin with fresh brain tissue of the horse or guinea-pig, whereupon the mixture, if 
made in suitable proportions, becomes innocuous. 
2 Ehrlich was led to this belief in the complex nature of the toxin molecule through the curious 
fact that diphtheria toxin may under a variety of conditions lose its toxicity, but still retain its capacity 
of neutralizing antitoxin and also of uniting with cells, and thus inducing the formation of antitoxin 
in the animal body. Such toxin molecules deprived of the toxophorous group are called toxoids. 168 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
For, set free in the body-fluids, these superfluous receptors still retain their com- 
bining power for the free toxin molecules, which, also, are in solution in the body-fluids, 
and unite with them. This union having been effected, the toxin molecules are no 
longer a menace to the cell, because the affinities are now satisfied through which they 
joined the receptors while these were still a part of the cell, and in this way became 
harmful. This now inert combination of toxin molecules and detached receptors is 
physiologically indifferent stuff, and may be removed from the body by the usual 
processes of excretion. 
But the antitoxin which has not united with toxin in the body of the animal 
which produced it is still available on the transference of the serum to another in- 
Fig. 108.-Diagram Illustrating the Formation and Action of Antitoxin in Accordance 
with Ehrlich's "Side-Chain" Hypothesis. 
A, Portion of cell-body; b, receptors combined with cell protoplasm; c, receptors separated from 
cell; a, toxin molecules; y, free receptors-antitoxin. 
dividual whose blood contains diphtheria toxin, and who may thus secure passive 
immunity. 
If we have recourse again to the graphic method, the hyperproduction of recep- 
tors by the damaged cell, their separation, and their action as antitoxin, may be indi- 
cated, as in Figure 108. Let A represent a portion of a cell-body. The toxic molecule 
a, uniting with the receptors b, leads through the injury to the cell, as well as by its 
deprivation of the normal use of b, to the production, and at length to the overproduc- 
tion, of new receptors of the same kind. These superfluous receptors c are now set free 
into the body fluids,1 where, as at x, they may freely unite with the toxin molecules, 
forming harmless compounds and preventing further access of the toxin to the, cell, 
1 These receptors of various kinds, cast off into the body fluids under the most diverse conditions, 
Ehrlich has called "haptines." THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
169 
where alone the damage can be done. Or, when free, as at y, the receptors may be 
transferred in the serum, becoming effective as antitoxin in another individual. 
It is well to note that so long as the receptor maintains its connection with the cell 
it is not antitoxin, but an element of vulnerability to the cell. It is only when the 
receptor has been set free from the cell that it is antitoxin. 
The antitoxin substance which neutralizes the action of the toxin molecule of diph- 
theria is not effective for the poison of tetanus, for example, simply because it does not 
combine with the molecule of tetanus toxin. It is specific for diphtheria, because it 
was the diphtheria toxin which excited its overproduction through a chemical union 
identical in character, whether this union takes place while the receptor is a part of the 
cell, in which case the toxin becomes harmful, or when the receptor is detached from 
the cell, in which case the combination is harmless. 
In the light of this hypothesis the specific character of the antitoxic substances 
appears to be but the result of adaptation to unusual conditions of cell capacities 
evolved and fostered for the every-day maintenance of life. The specific relationship 
between the toxin and the antitoxin is not developed during immunization, but 
existed beforehand as a necessary condition of toxic action. 
This hypothesis not only accounts for the formation, protective action, and speci- 
ficity of antitoxin, but reveals, also, a special significance in the incubation period, dur- 
ing which the conservative forces are mustering. We can realize, furthermore, in the 
light of this hypothesis, how it is that the protection secured in active immunization is 
less immediate and also why it is more prolonged than in the passive, since in the latter 
the available antitoxin is limited to the dosage and is not replenished as in active 
immunity by the continued cell activities of the affected individual himself. 
The conception of Ehrlich as to the nature of antitoxin is that of the chemist, and 
carries over to the performances of protoplasm the presumptions upon which chemical 
reactions in general are conceived and formulated. But this is not an easy matter, 
since our knowledge of the ultimate phases of protoplasmic metabolism is very incom- 
plete. The physiological chemist presents to us as his final achievement in analysis an 
extremely elaborate complex which he calls the proteid molecule. This he does not 
yet venture to formulate. Thus it is that when we attempt to illustrate in graphic 
fashion our conception of the performances of proteid molecules, either in normal metab- 
olism or in poisoning, we are forced to use the crudest of symbols. The use of such 
symbols is not without hazard, for these toxins and these receptors are, in truth, not 
histological structures, but molecular groups; they are not alone upon the surfaces, but 
through all the mass, of the protoplasm. They do not "break" off from the cell, but 
are set free as are other chemical substances which result from molecular transfor- 
mations. Thus, if one cannot at last translate these uncouth symbols into the nice 
conceptions of the chemist, they will prove but stumbling-blocks. 
There has been much discussion of Ehrlich's hypothesis, and it has withstood many 
assaults, mostly inspired by misconceptions of the fundamental claims. The scope of 
this book does not permit us to consider the many and ingenious experiments by which 
this view of antitoxic immunity has been sustained, nor is it practicable now to call 
attention to many of the phenomena not yet accounted for or seemingly inconsistent 
with the interpretations here set forth. 
It is a working hypothesis which no doubt indicates but crudely the nature of the 
subtle processes concerned, as must indeed be the case while our knowledge of the 
phases of energy which sway and determine life is still very meagre; but it has already 
inspired much fruitful research which is an important feature of working hypotheses 
in whatever field, and whatever their ultimate fate. 
Bactericidal or Antibacterial Immunity (Bacteriolytic Immunity.) 
General Considerations.-An extended series of studies on artificial 
immunization has shown, as we have seen, that in relatively few instances, 
notably in diphtheria and tetanus, whose inciting bacteria set free in 
cultures, as in the body, soluble toxins of great potency, is the protection 
secured by the formation of antitoxic substances. Nevertheless, when 170 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
in some of the ways detailed above (p. 162) an animal has been grad- 
ually adapted to cultures of pathogenic bacteria either living or dead, 
or to their products, it has been found that the body fluids contain pro- 
tective substances. The protective action in these instances in some 
cases has been shown to be associated with the induction of morpho- 
logical changes in bacteria which indicate their damage or destruction- 
bacteriolysis. Active immunization in man with the dead bodies of 
their respective bacteria has been widely practised in typhoid fever, 
Asiatic cholera, and plague, with apparently favorable results, while the 
use of the serum of immunized animals, in these and certain other dis- 
eases, has not been thus far very encouraging in conferring passive 
immunity. 
While, therefore, the data at hand in those artificial immunizations 
which are not antitoxic, point to the bactericidal and bacteriolytic action 
of substances developed in the body as the important, if not the domi- 
nant protective factors, there may be many other processes contributing 
to the same end, which are as yet not clearly defined. Thus, there may 
be increased phagocytosis; vulnerable body-cells may become less suscep- 
tible, the growth of bacteria may be inhibited though they be not 
destroyed, etc. But these possibilities cannot be discussed here. 
Furthermore, it should not be forgotten that the antitoxic action of 
protective sera may often be associated with those agents which directly 
damage the infecting organism. 
As regards the destruction of bacteria in the body, we have seen that 
this may take place directly through the action of phagocytes or by the 
action of the body fluids. But the details and exact nature of this de- 
structive process have been extremely difficult of study, owing to their 
complexity and the minuteness of the micro-organisms. Quite recently, 
however, a series of remarkable studies in a related field have led to a 
clearer conception of the ways in which bacteria and many other alien 
organic substances are destroyed in the body, under ordinary circum- 
stances as well as under the special conditions which infection involves. 
"Pfeiffer Phenomenon."-Several years ago, Pfeiffer1 showed that 
the blood serum of a guinea-pig, artificially immunized against the 
cholera vibrio, was capable, under certain conditions, not only of immobil- 
izing and killing cholera germs in a short time, but also of causing their 
disintegration and destruction. This significant capacity of immune 
serum was, after a long series of experiments, finally found to be due to 
two distinct substances. One of these appears to be formed in the body, 
as the result of the gradual adaptation of the animal to the cholera 
microbe, and was called the immune substance. The other seemed to 
be normally present in the serum of the warm-blooded animals, and to 
be identical with the substance which had long been regarded as in 
itself germicidal, and which had been called by Buchner alexin. It was 
presently found that lysis of the cholera microbe occurred only when 
these two substances act together, neither of them when separate having 
lytic power. If the two substances, the immune substance and the alexin, 
1 Zeits. f. Hygiene, Bd. xvii, p. 355, 1894. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
171 
lytic when together, are heated to 56° C., the lytic capacity is lost. But 
if a small amount of fresh blood serum containing alexin be now added, 
the lytic power is at once restored. These curious facts, set forth in 
part by Pfeiffer and further developed by Bordet and Metchnikoff, 
obviously have a significant bearing upon our conception of the proc- 
esses by which those phases of immunity are secured, in which the 
destruction of micro-organisms plays an important part. 
But the study of the effects of lytic sera upon bacteria is one of great 
technical difficulty, so that it is only since an important series of obser- 
vations were made upon the lytic action of the body fluids on other and 
more easily studied forms of cells that our conception of the nature of 
bacteriolysis has become at all clear. 
It is therefore necessary for us to look briefly at a new line of research 
bearing upon bacteriolytic immunity which has already led to most sig- 
nificant results and opened biological fields of great scope and complexity. 
CYTOLYTIC SUBSTANCES-CYTOLYSIS. 
Haemolysins-Haemotoxins.-It has been known for some time that 
the blood serum of one animal species, when injected into the vessels of 
another, may do serious damage and even kill the latter through a rapid 
separation of the haemoglobin from the red blood corpuscles. This 
dangerous effect brought to a speedy end attempts which were at one 
time made to sustain the ebbing forces of life by the transfusion of alien 
blood. But the significance of this so-called "laking" of the blood by 
mixture with alien sera was overlooked. 
Bordet, however, was recently led to inquire whether if the animal 
body be capable of adapting itself to toxic substances and to bacteria in 
such a way as to neutralize the effects of toxins and to destroy bacteria 
as had been shown by earlier experiments, it may not respond similarly 
to the introduction of other foreign substances such as alien red blood 
cells, for example. 
The blood serum of the guinea-pig is not normally lytic for the red 
blood cells of the rabbit; that is, it does not cause the separation of the 
haemoglobin from the stromata, with a partial destruction of the latter.1 
Now Bordet injected a few cubic centimetres of the whipped blood of 
the rabbit, containing the serum and red blood cells, into the subcutane- 
ous tissue or peritoneal cavity of normal guinea-pigs. This operation, 
which does not markedly interfere with the well-being of guinea-pigs, 
was repeated five or six times with intervals of a few days. When now 
blood was drawn from the treated pig, allowed to clot, and the clear 
serum secured, it was found to have become markedly lytic for rabbit 
corpuscles. A very small proportion, mixed with rabbit's blood diluted 
with physiological salt solution, in a short time brought the haemoglobin 
into a clear ruby solution in which the stromata or "ghosts" of the 
corpuscles floated as a pale and scarcely visible cloud. This process is 
1 While the serum of the guinea-pig is not normally lytic for the corpuscles of the rabbit, the serum 
of the rabbit is lytic for the corpuscles of the guinea-pig. Similarly, normal rabbit serum is not lytic 
for the beef corpuscles, but beef serum is lytic for the corpuscles of rabbits and guinea-pigs. 172 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
called haemolysis; serum possessing this capacity is called haemolytic or 
hcemotoxic serum. 
This adaptation of one animal to the red blood cells of another species 
may be accomplished without difficulty with a great variety of animals. 
But a most remarkable thing about this newly acquired lytic capacity 
of the serum is that it is limited to the red corpuscles of the species of 
animal whose blood was used for the injection-in Bordet's experiment 
to the corpuscles of the rabbit. Red blood cells of the dog, cat, sheep, 
bovines, fowl, etc., are no more affected by this serum of a guinea-pig 
which has been adapted to the blood of the rabbit than they were before. 
In other words, the adaptation to foreign corpuscles is specific. 
The statement that this adaptation to alien blood is specific-that is 
to say, that the serum becomes active only for the corpuscles of the 
species injected-should be so qualified as to recognize the curious fact 
that a slight degree of lysis may often be induced in corpuscles of species 
of animals very closely related to those from which the injected blood is 
derived. For example, if a rabbit be adapted to human blood by intra- 
peritoneal injections, the serum of this rabbit, now strongly lytic for the 
corpuscles of man, may be slightly lytic for the corpuscles of monkeys. 
Similarly, serum artificially lytic for the red cells of goats may be slightly 
lytic for those of sheep, but not for the corpuscles of cats, dogs, man, 
etc. See for technique of haemolysis tests p. 194. 
This form of test, delicate beyond anything hitherto known in physi- 
ological chemistry, may thus prove of value in defining the relationships 
and limitations of animal species.1 
This preliminary observation of Bordet was followed by a series of 
studies upon artificial haemolysis, the results of which we can only briefly 
summarize. In the first place, to what is this remarkable acquired lytic 
capacity of the serum due? Bordet heated for half an hour to 56° C. 
some of the lytic serum secured by adapting the guinea-pig through 
subcutaneous injections to the red blood cells of the rabbit. He found 
that it had completely lost its new lytic powrer. Such serum is said to be 
inactivated. But wThen he now added to this inert serum a little fresh 
blood serum from a normal guinea-pig, which is not in itself lytic (see 
p. 171), the original dissolving powrer of the heated serum for rabbit 
corpuscles was at once restored-reactivated. The inference from this 
experiment is obvious. The dissolving capacity of this artificially lytic 
serum is due to two distinct substances. One of these, that one which 
results from the adaptation of the animal to the alien blood, is stable 
at 56° C.; the other, which is present in normal serum, is rendered inert 
at 56° C.; that is, it is very labile. These twro substances were named 
early and have been often renamed. For the present we may speak of 
the stable substance resulting from the adaptation to the alien blood 
as the immune substance or immune body, and of the other, more sensi- 
tive to heat present in normal serum and not increased in the processes 
of immunization, as alexin, a name which was long ago applied by 
Buchner to a substance or substances in normal serum, to which its 
1 For further data on this subject see Nuttall, " Blood Immunity and Blood Relationship," 1904. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
173 
germicidal capacity, first clearly demonstrated by Nuttall, was attributed. 
But this alexin is now called complement for reasons given on page 177.1 
There now followed a series of important studies by Ehrlich and his 
associates which throw still further light upon these curious lytic agents. 
Separation of Alexin and Immune Substance.-We have seen that in 
order to secure the immune substance free from the alexin one has only 
to heat the lytic serum to 56° C. for half an hour, when the alexin is 
destroyed. If one wishes to secure the alexin apart from the immune 
substance he makes use of a very curious property of the latter; namely, 
its capacity of uniting with the cellular element under whose influence it 
was elaborated. For example, if one places a small portion of the serum 
of a rabbit which has been adapted to beef blood in contact with beef 
corpuscles at a low temperature2 for a few hours, he will find that the 
immune substance has formed so stable a combination with the cor- 
puscles that on their separation from the fluid by centrifugation in the 
cold, none of the immune substance, but all of the alexin, will be left in 
the fluid. 
That the corpuscles under these conditions actually contain the 
immune substance is readily shown by carefully washing them in salt 
solution and centrifuging them again in the cold and finally adding to them 
a little normal serum-containing alexin, but no immune substance- 
whereupon the lysis will at once take place, as shown by the red color of 
the fluid. This union of the immune substance with corpuscles, called 
"fixation" of the immune substance, is specific, occurring only with the 
corpuscles of the animal species used in the adaptation. 
Many other points of extreme interest and significance have been 
revealed in these studies on artificial haemolysis which the scope of this 
book does not permit us to touch upon. 
Multiplicity of Immune Substances and Alexins.-The question of a 
multiplicity of immune substances and of alexins has been brought for- 
ward, and it seems probable, especially from the researches of Ehrlich, 
that in adaptation of each animal species to a single form of cell several 
immune bodies may be developed. It is possible, though not yet proven, 
that more than one alexin may be normally present in the blood serum 
of each animal species, and that a single immune body may be capable 
of uniting with several forms of alexin.3 
Bacteriolysis.-It is evident that this artificial haemolysis, secured by 
the adaptation of one species of animal to the red blood cells of another, is 
quite analogous to the process by which immunity is secured against 
pathogenic bacteria-those of cholera, for example, whose most obvious 
poisonous elements are endotoxins-and which is called bacteriolysis. 
Both are specific examples of the general process called cytolysis, meaning 
cell destruction. But this reaction of hsemolysis is not only one of 
1 It has been found that the haemolytic capacity of the normal blood serum, which in many animals, 
as we have seen, is very marked for the corpuscles of alien blood, is also due to two substances which 
in character and action are similar to those which have been so carefully studied in the lytic sera of 
artificially adapted animals. 
2 It is necessary to reduce the temperature in this experiment in order to inhibit the action of the 
lytic agencies. 
It has been shown that lecithin may act as alexin-complement-in this form of cell destruction. 174 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
extraordinary delicacy, but is easily observed under conditions quite 
within our control, and permitting such elaborations and variations as 
involve great technical difficulties when we are directly engaged with 
the phenomena of bacteriolysis. 
Thus these studies of haemolysis have a practical significance in their 
bearing upon our conceptions of bacteriolytic immunity quite apart from 
the interesting general biological field into which they have led the way.1 
Special Cytolysins-Cytotoxins.-The development of cytolytic capac- 
ities in the blood serum of the living animal as the result of adaptation 
to bacteria and to alien red blood cells being known, it was natural to 
extend the method to other cells. Thus it has been claimed that in the 
adaptation of one animal to the spermatozoa of another species by 
intraperitoneal injections, a serum is obtained which quickly brings to 
an end the movements of fresh spermatozoa of the species used-spermo- 
lytic serum. 
Similarly, specific leucolytic sera have been described as procured by 
intraperitoneal injections of emulsions of lymph-nodes, spleen, and bone 
marrow. Such leucolytic sera may not only destroy the leucocytes 
outside of the body, but they are extremely toxic when introduced into 
the living species from which the tissues originated. The effects of these 
leucolytic-leucotoxic-sera in the body are most pronounced in the 
blood-forming organs. Here, as the studies of Flexner2 show, a very 
significant impulse to new cell formation may be associated with the 
action of the leucotoxic sera. 
Emulsions of kidney cells of one species injected into the peritoneum 
of another have led to the development of nephrolytic serum; that is, 
serum which on injection into the body of an animal of the same species 
as that furnishing the kidney cells induces noteworthy degenerative 
changes in the kidney. Thus, also, hepatolytic, pancreolytic, thyreolytic, 
neurolytic, and other analogous cytolytic substances have been described. 
But the earlier view of the specificity of toxic (lytic) substances devel- 
oped by the injection of various body-cells-somatogenic cytotoxins 
-has been materially modified by later studies. Thus it has been found 
that in many of the earlier experiments red blood cells were injected 
with the special cells of liver, kidney, etc., and the hsemagglutinative 
sera induced thrombi which led to local necroses, confusing the results. 
Furthermore, it has been found by Pearce and others that even blood- 
free organ cells are capable of inducing haemotoxins as well as the specific 
toxins. It appears, therefore, that specificity is not so much a matter 
of cell morphology as of molecular structure; that is, of receptors. 
Thus Pearce found that the sera secured by the injection of washed 
liver, kidney, pancreas, and adrenal cells, all agglutinate and haemolyze 
red blood cells; that some of them have no effect upon organs for which 
they were formerly believed to have a specific affinity; and, finally, that 
only the so-called nephrotoxin has a distinctly injurious effect upon the 
1 For technic of haemolysis experiments and the adaptation of animals to alien substances see 
pp. 194 and 195. 
2 Flexner, Univ, of Penn. Med. Bull., vol. xv., 1902, p. 287; also Bunting, ibid., vol. xvi., 1903, 
p. 200. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
175 
organ by the injection of which the alleged specific serum was derived. 
Pancreas and adrenal serum Pearce found to be devoid of special action 
in these organs, while the lesions of hepatotoxin are doubtful and may 
be produced by other sera.1 
So far as they have been studied, the nature of the active agents in 
these various cytolytic sera and their mode of action are analogous with 
those in haemolytic sera. Here, as there, the action is due to two groups 
of substances: one, the "immune body," stable and increased by the 
adaptive process; the other, the alexin, occurring normally in the body, 
not increased in adaptation, and readily destroyed or rendered inactive 
by heat. 
All of these last-mentioned forms of cytolytic sera require more 
extended study before far-reaching conclusions should be drawn from 
them. But it is now evident that the different functional types of cells 
in one animal are capable in the adaptation to the economy of another 
of inciting more or less definitely specific responses, as shown by the 
various types of cytolytic sera which are formed. 
When one musters all the possible combinations in this form of adap- 
tation and considers the probability that multiple immune bodies may 
develop in each instance, and that these, furthermore, may correspond to 
multiple alexins, the complexity of artificial cytolysis becomes evident. 
Antigens.-We have seen that the introduction into the living organ- 
ism of alien proteid substances of many kinds, derived from animals or 
plants, some of them poisonous, many of them not, incites the formation 
of so-called antibodies of divers sorts. It has been found convenient to 
call these "antibody producers," or "antibody incitors," antigens.2 
Anticytolysins.-But now still another phase of this subject demands 
a word. These cytolytic or, as some prefer to call them, cytotoxic sera, 
when introduced into the living bodies of the species from which the cells 
inciting their formation are derived, act as toxins to which the organism 
responds, each after its kind, by the development of antitoxic substances. 
These are called anticytolysins or anticytotoxins. 
Let us look at an illustration of this interesting point. The blood 
serum of the normal guinea-pig has, as we have seen, no lytic action on 
the red blood cells of the rabbit, but after the adaptation of the guinea- 
pig to the blood of the rabbit by repeated intraperitoneal injections, the 
guinea-pig serum is strongly lytic for the rabbit corpuscles in test-tubes 
outside the body. But this lytic serum is not less toxic when introduced 
into the body of the rabbit. Under these conditions the rabbit produces 
an antitoxin, an antihaemolytic substance, which is in solution in his 
serum. If a little of this antihaemolytic serum be mixed with some of 
the lytic serum from the adapted guinea-pig, it will be found, on the 
addition of rabbit corpuscles, that the lytic serum has lost its power, just 
as diphtheria toxin loses its harmful properties on mixture with diph- 
theria antitoxin. Thus may be formed a great variety of specific " anti- 
1 For further details on this subject see Pearce, Univ, of Penn. Med. Bull., xvi., p. 217, 1903; Jour. 
Med. Res., xii., p. 1, 1904; Jour. Exp. Med., viii., 1906. 
2 For a study of the locus of antibody formation see Gay and Rusk, Trans. 15th Internat. Cong. 
Hygiene and Demography, 1913, ii., 328. 176 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
bodies"-anticytolysins-from sera which are normally lytic or have 
become so through experimental adaptations. 
Isolysins and Autolysins.-In view of the remarkable results of the 
adaptation of the body to alien cells from different animal species which 
we have reviewed, it was natural to ask how an animal would respond to 
the introduction into the recesses of his body of cells-red blood corpus- 
cles, for example-from another individual of the same species. It was 
found, in fact, that under these circumstances lytic substances are 
sometimes, though not uniformly, developed. The possibility of the 
formation of isolytic substances was thus established. But if this be 
possible, why, it was asked, may not autolytic substances be formed by 
the adaptation of an animal to his own cells experimentally displaced? 
Such substances have, however, not been found under the experimental 
conditions thus far observed.1 
Still it is well known (see p. 98) that cells and tissues worn out 
from use, or dead as the result of injury, inflammatory exudates, etc., 
are constantly removed from the living body by processes apparently 
analogous to, if not identical with, those which can be experimentally 
evoked. So that autolysis in some form seems to be an important 
factor in the maintenance of the integrity of the body (see p. 106). Just 
what the agencies are under which normal living tissue cells are pro- 
tected from the action of autocytolytic substances is not yet clear. 
But the multiplicity of known " antibodies" justifies the conjecture 
that such substances-anticytolytic-may be constantly formed and 
act as safeguards to living and useful cells (see p. 191). 
The Application of Ehrlich's Hypothesis to Cytolysis.-If we now turn to the 
various hypotheses which have been advanced to account for the formation and 
action of these cytolytic substances, we find that an elaboration of Ehrlich's views as 
applied to antitoxin is here a source of great illumination. It is evident at once, how- 
ever, that the matter is not so simple as in the case of antitoxin, because we have here 
two substances at work, the immune body and the alexin. Neither the immune body 
nor the alexin alone induces cytolysis. They must act together. 
The phenomena are, in the main, accounted for if we assume that it is the alexin 
which, when the necessary conditions are fulfilled, exert the destructive action upon 
the bacterial or animal cell. But the alexin cannot enter under ordinary conditions 
into direct chemical combination with the cell receptors. The union is effected only 
by the intervention of the substance which is increased in amount in the process 
of adaptation; namely, the immune body. 
A long series of experiments has led to the belief that the immune body has two 
free atom complexes which enable it to form chemical unions. Through one of these 
atom complexes it unites with the cell or bacterium to be destroyed; through the other 
it is joined to the alexin. Then, and not until then, is the alexin so linked to the cell 
that its toxic or destructive action upon the cell occurs. 
This conception may be illustrated, as in the case of antitoxin, by crude figures. 
Here it should be remembered we are illustrating, not the production of the cyto- 
lytic substances, which we shall speak of later, but the action of them upon the cells 
to be destroyed. 
Let a--Fig. 109, A-be the cell which is to be destroyed, with one of its receptors 
indicated at d. Let b represent the immune body with one atom complex e capable of 
uni ting with the cell receptor d, and with another f capable of uniting with the alexin 
1 Some observations are recorded in which, after profuse internal haemorrhage, hsematuria has 
developed, indicating the possibility of autohaemolysis under special conditions. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
177 
c through g. Now the alexin which appears to be the effective agent in the destruction 
cannot unite directly with the cell receptor. When, however, it becomes linked to the 
cell by means of the immune body, b, its destructive capacity can come into play. 
In a similar way one may indicate the action of anticytolytic substances which may 
be effective through union either with the alexin or with the immune body, as shown 
in Figure 109, B and C. In B the " antibody " h prevents the linking of the alexin c to the 
immune body b by itself uniting with the former. It then acts as an anti-alexin. In 
C the antibody "i" prevents the linking of the immune body b to the cell receptor d, 
and hence acts as an anti-immune body. We shall see in a moment why at present the 
substance here spoken of as anti-alexin is usually called the anticomplement. 
The experimental evidence that the anticytolytic substances may be thus due to 
the formation of adaptive substances of two classes, anti-immune substances and anti- 
complements, cannot be entered upon here. 
Fig. 109.-Diagram Illustrating Cytolysis in Accordance with Ehrlich's Hypothesis. 
A-a, Cell; b, immune substance (amboceptor): c, alexin (complement); d, cell receptor; e, atom 
complex of the amboceptor capable of uniting with the receptor, d; f, atom complex of the amboceptor 
capable of uniting with the haptophorous group, g, of the complement, c. 
B-a, Cell; b, immune substance (amboceptor); c, alexin (complement); d, cell receptor; h, anti- 
alexin (anticomplement). 
C-a, Cell; b, immune substance (amboceptor); c, alexin (complement); d, cell receptor; i, anti- 
immune substance (anti-amboceptor). 
In view of the rationale of cy to lysis, as just set forth, we may consider the immune 
substance to be an intermediary between the alexin and the cell to be destroyed; or, on 
the other hand, we may consider the alexin as the complement to the immune sub- 
stance, since only through their union is the toxic action possible. 
In fact, following Ehrlich, one sometimes speaks of the immune body as the inter- 
mediary body, or intermediary substance; but since it is furnished with two combining 
affinities, it is now usually called the amboceptor. Furthermore, since the experimental 
analysis of the lytic process by the new technique has shown that the germicidal and 
destructive action of blood serum, formerly supposed to be due to a single substance 
called alexin, is really due to the combined action of two substances, the use of the 
word alexin for one of them is misleading and has now been largely given up. The 178 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
substance present in the serum of both normal and adapted animals through which 
lysis is effected when it is linked to the cell by the amboceptor is called the complement. 
Other names have been applied to these hypothetical complexes or substances which 
we cannot consider here.1 
This, then, is the rationale in accordance with Ehrlich's hypothesis of the action of 
these cytolytic or cytotoxic substances, either existing naturally, as they do in some 
animals, or being called forth in larger quantities in the process of adaptation to the 
cells which they destroy. This view has been most fully tested upon hsemolytic sera, 
since here the reaction is most easily studied. But so far as one can see, it applies as 
well to the phenomena of bacteriolysis, whose direct study is much more difficult. It 
should, however, be borne in mind that the erythrocytes are very delicate and very 
peculiarly constituted cells, and it is possible that inferences drawn from haemolysis 
are not applicable without qualification to other and less vulnerable cell types. 
The origin of the amboceptors of these cytotoxic substances is accounted for in the 
same way as in the case of antitoxin. The alien cells or substances which are intro- 
duced into the animal, and to which it proceeds to adapt itself, lead, through union 
with such body-cell receptors as may be fitted to them, to the overproduction of these 
special complex receptors. These are presently cast off as superfluous to the body-cell 
producing them, and are then free as amboceptors in the body fluids. 
As in the case of antitoxin formation, it is probable that the cell receptors which 
are thus increased are normally concerned in cell assimilation, and it is not unlikely 
that their complex character may have some relationship with the complexities of the 
"giant" protein molecules, which must suffer initial changes before becoming fit 
for assimilation. At any rate this hypothesis assumes that in the process of adapta- 
tion either to toxic substances or to foreign cells or other protein material, the body 
develops no new capacities, but only an exaggeration of those already existing. 
As to the exact source of the amboceptors in artificially immunized animals we 
cannot yet speak with certainty. 
The Action of Phagocytes in Cytolysis.-It was inevitable that the 
remarkable studies just summarized on cytolytic sera should have led 
to a clearer conception of the manner in which phagocytes destroy bac- 
teria and other organic substances. It is no longer permissible to hold 
as distinct and unrelated processes the action of phagocytes and the 
action of the body fluids in the destruction of foreign substances in the 
body. 
Metchnikoff, the learned and able advocate of the importance of 
phagocytosis in the protection of the body against micro-organisms, now 
recognizes the importance of the adaptive substances, some of which may 
be largely increased in amount in the processes of immunization. More 
strenuously than other observers, however, he insists upon the phago- 
cytic cells, especially the leucocytes, as the originators of the substances 
concerned in cytolysis, and holds that under ordinary conditions it is 
only within these cells that these substances are effective. In artificially 
1 It was natural in the early studies on bacteriolysis, which were incidental to researches on im- 
munity, that the new substance which was found in the serum as the result of the immunizing process 
should be called the immune substance or immune body. It was natural also, although less appropriate, 
to apply the same term, "immune substances," to the analogous substances which appeared in the 
serum as the result of the injection in the same fashion of cells and other materials which were not infec- 
tious, not disease-producing, and against which, therefore, the body is not, in the old sense, immunized. 
But these new uses of the word are, I think, unfortunate because the word "immunity" has come 
to have a special and useful significance in relation to infection, intoxication, and other conditions of 
natural or acquired tolerance to obviously and seriously harmful agents. The process in both instances 
is, indeed, one of adaptation, and the newly acquired capacities of the serum are due to substances 
resulting from this adaptation. They arise from a functional modification of parts of the body, and 
hence may be appropriately called adaptive substances. It seems to the writer that it would be better 
to consider immunization as a special phase of adaptation, and so limit the application of the word that 
it shall still connote infection and intoxication in the traditional sense. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
179 
immunized animals, however, the intermediary substances, it is conceded 
by Metchnikoff, may be set free from the cells which produce them and 
mingle with the body fluids. The complement, on the other hand, 
which he, in common with others of the French school, calls cytase, in 
recognition of its ferment-like characters, Metchnikoff does not believe 
to be set free in the body fluids except through some damage to the 
leucocytes in which it is formed. Such a damage, for example, as 
befalls the leucocytes in the clotting of the blood; for in this process it 
is assumed that the setting free of the fibrin ferment involves the destruc- 
tion-phagolysis-leucolysis-of the leucocytes. 
The views advanced by Bordet and others of the French school 
regarding the union of the amboceptors with the cells to be destroyed 
are less precise than those of Ehrlich. Both, however, recognize the 
importance of an association of the amboceptor as a condition for the 
effective action of the complement (cytase). It is for this reason that 
the amboceptor is called by Bordet, Metchnikoff, and others, the sensi- 
bilizing substance (substance sensibilisatrice) or the fixative (fixateur). 
Finally, a long and ingenious series of experiments has led Metchni- 
koff and his associates to believe that there are two forms of cytase, one 
called macrocytase, formed by the macrocytes (large lymphocytes 
derived from the spleen, lymph-nodes, and certain endothelial and 
connective-tissue cells) and concerned in the destruction of animal cells, 
such as red blood cells, leucocytes, spermatozoa, various parenchyma 
cells, etc.; and microcytase, derived from the microcytes (polymorpho- 
nuclear leucocytes), which is active in the destruction of bacteria (see 
p. 104). 
The greatest diversity of view concerning the cytolytic process 
between Metchnikoff and his followers and the observers of the Ehrlich 
school relates to the question whether the complement (cytase) does or 
does not exist free in the blood plasma, for upon the answer to this 
question depends largely our belief as to the relative significance of 
intra- and extracellular cytolysis. This is one of the points concerning 
which more data are urgently needed. But even now the views of 
Metchnikoff are not inconsistent with the hypothesis of Ehrlich. 
There is reason to believe that bacteria are destroyed within phago- 
cytes by the action of enzymes1 in a manner analogous, at least, with 
that of their destruction in the bacteriolytic fluids which we have just 
considered. But just how these intracellular processes are fostered by 
protective sera is not clear. 
AGGLUTINATIVE SUBSTANCES. 
Agglutinins.-But there are important adaptive resources of the 
living body when called upon to deal with foreign material of special 
character introduced in unusual ways into its recesses in addition to 
those just considered. 
The phenomenon of agglutination has been widely known for several 
1 See Opie, ref. p. 105. 180 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
years, especially on account of its practical application in diagnosis. 
The general fact is that as an individual adapts himself-that is, becomes 
immunized-to a special bacterium or its toxic products, either in the 
course of an infectious disease or as the result of artificial processes, 
his serum, if placed under suitable conditions in contact with cultures of 
this special micro-organism, may speedily immobilize the organism if it 
be motile, and, whether motile or not, lead to its clumping into irregular 
masses. This reaction has been used, not only as a clinical test of 
special infections,1 but also as a means of differentiating species or 
varieties of bacteria. 
Group Agglutination.-But the serum of an animal adapted to a particular 
bacterial species sometimes has the power of agglutinating closely related organisms, 
such, for example, as members of the colon-typhoid group. 
However, the organism used for adaptation-the so-called "homologous" organ- 
ism-usually agglutinates in so much greater dilutions than do the other organisms of 
this group-the heterologous organisms-that with due care, in spite of the group 
agglutination, the test is useful. 
Recent studies have emphasized the fact that agglutination is a 
much more general phenomenon than has been commonly supposed, and 
is by no means limited to the sera of animals immunized against bacteria 
and bacterial products. 
For example, in the adaptation of one animal to the red blood cells 
of another species, the serum of the adapted animal may become not only 
lytic but agglutinative also for the corpuscles used for the injections. 
This is true not only in adaptation to red blood corpuscles but to other 
cells as well. We have, then, to add agglutinative substances or agglu- 
tinins to the list of those which are developed in the body in this form of 
adaptation. (See Table, p. 188.) These also, within the limits already 
set forth, are specific. 
Just as the specific red blood cells are capable of "fixing" the immune 
substance in lytic serum, so also the agglutinating substance may be 
"fixed" and removed from serum by placing in contact with the serum 
some of the corpuscles of the particular animal species or some of the 
bacteria under whose influence the agglutinative substances were formed. 
While agglutinative substances are developed in the process of 
immunization, they are not, so far as we know, directly protective, though 
by the grouping of micro-organisms the action of phagocytes may be 
favored. The virulence of pathogenic bacteria is not reduced by agglutin- 
ation. 
The agglutinative seem to differ in many ways from the lytic sub- 
stances. Thus their activities are not suspended by a temperature of 
56° C. They become inert, however, at a higher temperature-70° to 
78° C.-and their agglutinating capacity is not restored by the addition 
of normal serum. It is inferred from this fact that the receptors con- 
cerned in agglutination are of simpler character than those through 
which lysis is secured. 
1 For the general demonstrative test for agglutinin see p. 193. For details of special applications of 
the agglutination test see Wood's "Chemical and Microscopical Diagnosis," or other works on clinical 
pathology. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
181 
The normal blood serum of some animals contains substances which 
are agglutinative for the red cells of other species. Thus, normal beef 
serum is agglutinative for the corpuscles of the cat and rabbit. This 
capacity of the normal serum sometimes is, sometimes is not, associated 
with marked lytic capacity. 
The mode of action of these so-called agglutinins is not yet very 
clearly understood, but a great many interesting facts have been devel- 
oped in the studies on the general phenomena of agglutination which we 
cannot mention here. 
The specific character of the agglutination reaction has led to its 
use in determining the nature of many infections, the serum of the 
infected individual being used with cultures of known micro-organisms. 
On the other hand, the test is often useful in determining the specific 
character of closely related micro-organisms and their variations.1 
PRECIPITATING SUBSTANCES. 
Precipitins.-There is still another way in which the body reveals 
adaptive alterations in the presence of foreign proteid substances. If 
a few cubic centimetres of the blood-serum or exudate containing globulin 
from one animal be injected into the subcutaneous tissue or peritoneal 
cavity of another species in repeated doses, it is found that, on adding a 
little of the blood serum of the adapted animal to a dilution of the fluid 
injected, a precipitate is formed. This reaction is also specific, save 
that in some instances body fluids from closely related species, such as 
man and monkey, fowl and pigeon, sheep and goat, horse and ass, dog 
and fox, may both afford a precipitate. But this precipitate is invari- 
ably much more marked in the fluid used for adaptation than in the 
similar fluid from the related species. 
This reaction is extremely delicate, it having been possible to recog- 
nize human blood in a dilution of 1:50,000. 
By the use of this test Nuttall, who has made very extensive observa- 
tions, has been able to demonstrate in a most striking fashion phylo- 
genetic relationships between animal species and groups of species, both 
warm and cold-blooded, which have an important bearing upon classi- 
fication.2 
The Precipitin Test in Forensic Medicine.-The use of this precipitation test 
has been urged in forsenic medicine to reinforce the present unsatisfactory methods of 
distinguishing between human and other blood. For if one have a rabbit or other 
animal artificially adapted to human blood from which fresh serum can be secured 
(even the dissolved dried serum will answer), he has only to dissolve in a little salt solu- 
tion a suspected blood clot, and, mixing the two, observe the result. If, under suitable 
conditions of dilution, cloudiness develops within a short time or if a precipitate be 
formed, it is claimed that the suspected material could have been derived from no 
other animal than man. Since, however, it has been found that the blood not only of 
monkeys but of some other of the lower animals may give slight precipitates under 
these conditions, and since other human fluids containing albuminous substances, such 
1 See for agglutination tests in classification Park, Jour. Inf. Dis., Suppl. No. 2, Feb., 1906, p. 1. 
2 See Nuttall, " Blood Immunity and Blood Relationship," 1904. 182 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
as saliva, pus, inflammatory exudates, etc., may also give precipitates, it is evident 
that the result of this test should be interpreted with great caution.1 See technique 
of precipitin test, p. 194. 
The white of a hen's egg, injected into the peritoneum of a rabbit, after 
a time gives rise to substances in the rabbit's serum which induce a 
precipitate in fresh solution of hen's egg albumen. No precipitate is 
produced by this serum in albumen solutions from the blood of the 
mammalia, and only a slight precipitate is formed in the egg albumen of 
related fowls, such as the duck, for example. 
It has been stated that by the adaptation of the living animal to 
extracts of muscle tissue from another species, precipitating substances 
may be formed in the serum which are specific for the muscle used in the 
injection. 
Milk of one animal thus introduced into the body of another gives 
rise to a substance in the adapted animal which causes a precipitate in 
the diluted milk used for injection, but not in the milk of another species, 
save sometimes in slight degree in milk from closely allied animals. 
This reaction is also applicable to plant albumens. Thus, if an ani- 
mal be adapted to a given species of bacteria, its blood-serum, on being 
added to the clear filtrate of the pure culture, throws down a precipitate 
which is in some instances light, in others voluminous. This reaction is 
again specific, except within the group limits of related species. Thus, 
as Norris has shown,2 precipitating substances which are developed by 
the adaptation of the rabbit to the typhoid bacillus induce a slight pre- 
cipitate in the culture filtrate of the colon bacillus, but not in the filtrate 
of B. prodigiosus, for example. 
Numerous experiments have shown that other vegetable albumens call 
forth specific adaptive precipitins. 
This precipitation test is so delicate that it appears possible not only 
to distinguish the albumens from different animal and vegetable species, 
but to differentiate also some at least of the various albuminous sub- 
stances in the individual. 
Anti-precipitin.-Finally, it is worthy of note that it has been possi- 
ble, by the adaptation of a fresh animal of the appropriate species to 
these precipitating sera, to obtain "antibodies"; in the case of milk 
adaptation, for example, by the use of the so-called lacto-serum, to 
secure an antilacto-serum capable, when added to the test fluids, of 
preventing the formation of the specific precipitate. 
Nature of Precipitin.-A great deal of most careful research has been 
devoted to the nature of the precipitating substances which the scope 
of this book does not permit us to touch upon. But it should be said 
that in their resistance to heat and in other ways the precipitating sub- 
1 For a study of the precipitation test for blood, bibliography, see Graham-Smith, Jour, of Hygiene, 
vol. iii., pp. 258 and 354; also Ewing and Strauss, Med. News, Nov. 7th and Nov. 14th, 1903, 
bibl.; also Robin, N. Y. Med. Jour, and Phila. Med. Jour., March 5th and 12th, 1904; also Nuttall's 
book, ref. above, p. 181. For the suggestion of a new method of differentiating bloods by a haemolysis 
test see Neisser and Sachs, Berl. klin. Wochensch., 1905, p. 1388. For special details of the most re- 
cent methods, see Uhlenhuth and Weidanz, Praktische Anleitung zur Ausfuhrung des biologischen 
Eiweissdifferenzierungsverfahrens, 1909; and Leers, Die forensische Blutuntersuchung, 1910. 
2 Norris, Jour, of Infect. Dis., vol. i., p. 463, 1904. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
183 
stances appear to be more closely related to agglutinating than to lytic 
substances. It has been shown that the specific serum precipitates are 
capable of fixing complement and removing it from solutions as immune 
substances may be fixed and removed-red blood cells for example- 
by the specific elements which incite their formation, see p. 172.1 
The Adaptive Bodies not Permanent.-The effects of foreign cells and 
their derivatives upon whatever body cells produce the lytic, agglutin- 
ating, and precipitating substances are apparently not lasting, since if 
the injections be suspended they gradually disappear from the serum. 
The time of their disappearance, however, like that of appearance, is 
not regularly the same, even in the same animal. 
OPSONIC SUBSTANCES-OPSONINS. 
The importance of phagocytosis among the agencies protective 
against micro-organisms has been for some time fully recognized and 
many facts are known about their ingestion and intracellular destruction. 
But the exact processes by which this is secured and the effects of natural 
and artificial immunization upon phagocytosis are still obscure. It 
has been assumed that the protective substances in the plasma of immu- 
nized individuals stimulate the phagocytes to the ingestion and destruction 
of micro-organisms, and so-called stimulins have been the subject of 
much discourse. It has been claimed that through the germicidal 
power of the serum, bacteria are killed and are then, more readily than 
when living, engulfed by phagocytes. But the existence of stimulins 
has not been demonstrated, and it is now well known that living as well 
as dead germs are ingested and destroyed by phagocytes. It has been 
assumed by many that the promotion of phagocytosis by immune sera 
is due to a sensitizing substance (substance sensibilisatrice) which by 
action on either the leucocytes or the bacteria changes a negative 
chemotaxis into a positive. 
In 1904 Wright and Douglas,2 by the use of methods suggested by 
Leishman,3 discovered in normal human serum, and in larger amounts in 
the serum of persons who had been immunized to certain micro-organ- 
isms, substances which when placed in contact with the specific bacteria 
are capable, without inducing appreciable morphological changes, of 
so modifying them that they are more readily taken up by polymor- 
phonuclear leucocytes than are the bacteria which have not been sub- 
ject to this preliminary treatment (see Fig. 110). These substances 
Wright and Douglas called opsonins^ Those opsonins tested by these 
observers were found to be rendered inert by heating for half an hour at 
60° C.; but later studies of others have shown that some opsonins- 
the opsonin of immune sera, for example-are more thermostable, 
resisting temperatures above 70° C. It was shown by suitable experi- 
1 See Gay, Centrbl. f. Bak., Bd. xxxix., p. 603, 1905. This capacity of precipitates to fix comple- 
ment has an important bearing on the accuracy of the Wassermann and Noguchi tests, p. 278. 
2 Wright and Douglas, Proc. Royal Soc., 1903, vol. Ixxii., p. 357; also iMd.,1904, vol. Ixxiii., p., 128. 
3 Leishman, Brit. Med. Jour., 1902, vol. i., p. 73. 
4 From the Latin opsono, I prepare food for. 184 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
ments that opsonins do not act upon the phagocytic cells, but only upon 
the bacteria. 
Many studies of the serum of normal and immunized men and animals 
have been made by others since the announcement of Wright and 
Douglas. They are in general confirmatory and many new and interest- 
ing facts have been discovered relating to these protective substances 
-opsonins-present in the serum of normal individuals and markedly 
increased in the serum of those who have undergone natural or artificial 
immunization to special forms of bacteria.1 
Neufeld and Rimpau2 found in the serum of artificially immunized 
animals, substances acting, not upon the phagocytic cells, but upon the 
bacteria in such ways as to promote their ingestion. These substances 
Fig. 110.-Phagocytes, Showing the Effect of Opsonic Substances in Preparing Bacteria 
for Ingestion by Leucocytes. 
In the cell to the left the staphylococci were placed in contact with normal serum; in the cell to 
the right the cocci had been in contact with the serum of an animal artificially immunized to the micro- 
organism. The cocci thus sensitized by the opsonic substances in the serum of the immunized animal 
have been taken up much more abundantly than those not thus prepared. 
Neufeld and Rimpau called bacteriotropic in distinction to bacteriolytic 
substances sometimes formed in immunization, but they are apparently 
identical with opsonins. 
It has been shown by Hektoen and Ruediger3 that the opsonins in 
serum and plasma resemble toxins in that they apparently have toxoph- 
orous and haptophorous molecular groups (see p. 167), by which, on 
the one hand, they secure union with the bacteria, and, on the other, 
effect changes in these organisms which render them susceptible to 
phagocytosis. 
The opsonic substances occurring normally or developing in immune 
serum are not alone capable of preparing bacteria for cell ingestion, but 
other formed elements as well, red blood cells, for example.4 Sub- 
stances opsonic for red blood cells have been called haem-opsonins or 
erythrocyto-opsonins, in distinction to the bacterio-opsonins. The relation- 
ship of opsonins to other immune substances-amboceptors and agglu- 
1 The substance or substances which Wright and Douglas called opsonins had apparently been 
previously described by Metchnikoff as fixateurs, of which there seem to be two forms, bacteriolytic and 
phagocytic; see Lohlein, Ann. Inst. Pasteur, t. xx., p. 939, 1906. 
2 Neu eld and Rimpau, Deut. med. Wochenschr., 1904, p. 1458; also Zeits. f. Hyg. u. Infkr., Bd. 
li„ p. 283, 1905. 
3 Hektoen, Jour. Inf. Dis., vol. iii., p. 721, 1906. 
4 Neufeld and Topfer, Centbl. f. Bakt., Abth. I., Orig. Bd. xxxviii., p. 456, 1905. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
185 
tinins-formed in. similar adaptive processes is not yet clear, but they 
appear to be distinct. 
Phagocytosis of red blood corpuscles by endothelial and other cells 
in the lymph-nodes, bone marrow, spleen, etc., is common in various in- 
fections, notably in typhoid fever (see p. 239), as well as in toxic and 
anaemic conditions. 
Hektoen1 has found that normal serum may contain opsonins for 
heterologous as well as homologous erythrocytes, and that the adapta- 
tion of animals to alien blood commonly gives rise to the accumulation 
of haemo-psonins in the blood. He has shown, furthermore, that leuco- 
cytes in varying degrees may be phagocytic for opsonized red blood cells. 
An interesting example of spontaneous phagocytosis by leucocytes has 
been noted occurring after direct transfusion in a case of pernicious 
anaemia.2 
Opsonins of immune sera appear to be specific, each uniting only with 
the formed elements under whose influence the special adaptation is 
secured. In this union-called "fixation" of the opsonin-the formed 
elements-bacteria or red blood cells-are said to be sensitized, and 
from a serum containing several specific opsonins each can in turn be 
removed by fixation to its special cells and the separation of these by 
centrifugalization, just as specific amboceptors may be separated from 
haemolytic or bacteriolytic sera. (See p. 172.) 
The nature of the alterations which bacteria and other cells undergo 
by their union with opsonins is not understood. The bacteria are not 
killed or their capacity for growth diminished by it. The opsonins of 
immune sera of the lower animals sensitize bacteria and erythrocytes 
to human leucocytes, and vice versa. Thus the leucocytes of animals 
as well as those of man may be used in the determination of the presence 
of opsonins in sera. 
It is clear that opsonic action is of the highest importance in promot- 
ing phagocytosis. It is also evident from the numerous studies which 
have been made on the subject that in many instances this mode of de- 
struction of bacteria by phagocytes is often effective under conditions 
in which extracellular bacteriolysis does not suffice for the protection of 
the infected individual. 
The mere fact of phagocytosis, however, is not evidence of success- 
ful protection, since the ingested bacteria may destroy the phagocyte at 
once, may possibly gain in its interior by adaptation an exalted viru- 
lence, or may be transported to various parts of the body. 
The virulence of bacteria has an important bearing upon the effect- 
iveness of phagocytosis. It has been found that bacteria of high viru- 
lence are much less susceptible to phagocytosis than are the less virulent 
strains of the same species, both in normal and in immune sera. It 
would appear that virulent bacteria may be protected from phagocytosis 
both by their insusceptibility to opsonification and their capacity to 
produce substances harmful to the phagocytes. 
1 Hektoen, Jour. Inf. Dis., vol. iii., p. 434, 1906. 
2 Hopkins, Arch. Int. Med., 1910, vi., 270. 186 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
In the light of the new knowledge of opsonins and their relations to 
phagocytosis, the occurrence of leucocytosis in various infections becomes 
of special significance. For if either a local or general leucocytosis be 
fostered hand in hand with the effective production of opsonins, the 
conditions would appear to be most favorable for the control of the 
infectious processes. 
Clinical Significance of Opsonins.-The determination of changes in 
the opsonic power of the blood serum is claimed by Wright and his fol- 
lowers to be of great practical importance as a guide to the administration 
of immunizing substances in the treatment of certain forms of infection. 
For a rise in the opsonic content marks, in accordance with this view, the 
successful development of those protective substances in the body which, 
by uniting with the bacteria, favor phagocytosis. If, on the other hand, 
after the administration of immunizing substances, the opsonic power 
falls, as is sometimes the case, and continues low, the indication is for a 
reduction or suspension of the dosage. 
Remarkable curative results are recorded as the result of the admin- 
istration of sterilized and standardized suspensions of the dead bodies 
of Staphylococcus pyogenes aureus in furunculosis and carbuncle, and 
of the tubercle bacillus in tuberculosis, especially in its local phases, 
as well as in other infections. But for success in these or other forms of 
artificial active immunization with the dead bodies of specific micro- 
organisms, great stress is laid by Wright on the control of the treatment 
by the constant observation of the opsonins. The dead bodies of cultures 
used in this way are called by Wright and his followers "vaccines."1 
Fig. 111. -Glass Capsule for Drawing a Small Amount of Blood from the Finger Tip. 
As suggested by Wright. 
Opsonic Power and its Determination.-Studies of the effects of opsonins upon 
bacteria as marked by phagocytosis are readily made outside the body. The 
simplest form of observation may be made by mixing equal parts of defibrinated blood 
and a suspension of a bacterial culture in 0.85-per-cent. solution of sodium chlorid, 
keeping this for fifteen to twenty minutes at 37° C., staining smears made upon a 
slide, and then determining the average number of bacteria found in the polymorpho- 
nuclear leucocytes. Since, however, under these conditions, the leucocytes are too 
few to obtain readily the averages of a large number, it has been found desirable for 
most purposes to concentrate the leucocytes by the centrifuge. The blood is diluted 
as it is drawn with a solution of sodium citrate 1.0 per cent, in 0.85-per-cent. solution 
1 This use of the word vaccine is not altogether to be commended, since the analogy between these 
substances and those used in the traditional vaccination for smallpox is not close. For a summary 
of the methods of preparing vaccine, see Hiss and Zinseer, "Text-book of Bacteriology," 2d edition, 
1914. For an interpretation of present-day uses of vaccines see Theobald Smith, Jour. Am. Med Assn., 
1913, lx., 1591. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
187 
of sodium chlorid. This prevents coagulation, and the performances of living 
leucocytes are not interfered with. This dilution can be effected by drawing blood 
from the finger tip into small glass capsules (Fig. Ill) containing the sodium-citrate 
solution. This blood dilution may now be centrifugalized, and the leucocytes, 
which take a place above the red cells, may be drawn off by a pipette, washed with 
salt solution, and centrifugalized twice to remove the citrate, and then mixed with 
the bacterial suspensions and with the serum to be tested. This mixture is incubated 
for fifteen to twenty minutes; the smears are stained by the Jenner method (see 
p. 468). 
In comparative studies it is necessary to free the leucocytes from their own serum 
by repeated washing in salt solution with centrifugalization, before testing their phago- 
cytic power with bacteria exposed to an heterologous serum. Such washed leucocytes 
are found to be incapable of ingesting many forms of bacteria. 
The determination of the opsonic power of sera in routine practice, following 
largely the suggestion of Wright, may be briefly outlined as follows. 
This capacity of the serum is tested and measured by mixing three substances: 
1. Washed living leucocytes from man, one volume. 
2. A uniform suspension of a culture of the selected micro-organisms, one volume. 
3. The serum whose opsonic power is to be tested, one volume. 
These three substances are mixed in capillary tubes and kept for fifteen to twenty 
minutes at 37° C. A portion of the mixture is then smeared upon the slide and stained 
by the Jenner method1 which stains both the phagocytes and the bacteria. Now 
under the microscope one examines the leucocytes as they come into the field, and 
counts the number of bacteria which each leucocyte has ingested. At least forty of 
these leucocytes should be examined. The average number of bacteria in the leuco- 
cytes obtained by dividing the whole number of bacteria found by the number of 
leucocytes examined, gives what is called the phagocytic count.2 
Opsonic Index.--If the phagocytic count obtained with the use of the serum of 
normal man be considered as the unit, the proportion which the phagocytic count of 
the special serum bears to the unit is called the opsonic index. 
Thus, if the average number of bacteria ingested by the leucocytes after exposure 
to normal serum is 5, and if the average number ingested by the phagocytes after ex- 
posure to the special serum to be tested should be 4, then, reducing the figures to the 
basis of unity for the normal serum, the opsonic index would be 0.8. 
The significance of the opsonic index in the treatment of infections and the value 
and mode of action of the bacterial "vaccines" are still sub judice. Many factors in 
the life and performances of the individual seem to modify the opsonic index; the 
variation in the number of bacteria ingested by phagocytes is so great that the validity 
of averages in determining the opsonic index must in each case be carefully judged. 
Variabilities in the characters of the leucocytes have not yet been fully investigated, so 
that altogether, while great theoretical and practical interest attaches to the bacterio- 
tropic substances called opsonins, it remains for further and much more extended ob- 
servation to determine their real significance3 and the practical value of the so-called 
"vaccines" in various infections. Finally, the importance of the opsonic index as a 
guide to immunization by "vaccines" has not yet been established. 
1 See p. 468. 
2 For the determination of the phagocyte count in opsonized tubercle bacilli the following procedure 
is recommended by Ross: 
1. Fix smears of opsonized bacteria and leucocytes in a saturated aqueous solution of corrosive 
sublimate for one-half minute. 
2. Rinse quickly in water. 
3. Stain with Ziehl's carbolic fuchsin, heating the slide until the fluid barely steams (boiling 
injures the leucocytes). 
4. Rinse quickly in water. 
5. Decolorize quickly-a few seconds-in 2.5-per-cent. sulphuric acid. 
6. Wash in five-per-cent, glacial acetic acid for one minute or less. 
Counterstaining may be effected in the following solution: methylene blue, 0.5 gramme; sodium 
carbonate, 0.5 gramme; water, 100 c.c. Stain about one-half minute. Rinse in water. 
3 For an excellent summary of phagocytosis and opsonins see Hektoen, Jour. Amer. Med. Assn., 
vol. xlvi., p. 1407, 1906. For bibl. and summary of opsonins see Potter, Ditman, and Bradley, Jour. 
Amer. Med. Assn., vol. xlvii., pp. 1722 and 1793, 1906. Also see Wright, Studies on Immunization, 
1909. 188 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
In his studies upon opsonins Wright1 has devised many delicate and clever tech- 
nical procedures for collecting, measuring, standardizing, and mixing the various ele- 
ments involved in the reactions, with which the worker in this field should make him- 
self familiar.2 Furthermore, much practice is required and many sources of possible 
error must be learned before one can be certain that his results are to be relied upon. 
Although we have considered separately the development in the body 
of cytolytic, agglutinating, precipitating, and opsonic substances, it 
should be remembered that these may be and often are formed together 
in the same animal. 
Table (After Aschoff) Showing Various Forms of Adaptation Products 
with their Relationships and Synonyms. 
A 
Antitoxins, 
Antiferments, 
Complement: 
Alexin, 
Addiment, 
Cytase. 
Amboceptor: 
Immune body, 
I n t e rmediary 
body, 
Substance Sen- 
sibilisatrice, 
Fixateur, 
Praparator, 
Copula, 
Desmon. 
The body-cells 
in adapta- 
tion to alien 
substances 
of protoplas- 
mic origin 
may e 1 a b - 
orate 
Haemolysins, 
B a c t e r i oly sins- 
bacteriocidal sub- 
stances. 
Special Cytotoxins: 
Spermatoxin, 
Nephrotoxin, 
Hepatotoxin, etc. 
Cytolysins, 
(Cytotoxins), 
Formed of 
two 
substances. 
Agglutinins, 
Precipitins, 
Opsonins"!-Fixateur? 
B 
Anticytotoxins, 
Anticomplements, 
Antiamboceptors (anti- 
immune bodies). 
Antiagglutinins, 
Antiprecipitins. 
The "antibodies" 
Cytotoxins, 
Agglutinins, 
Precipitins, 
may lead to the for- 
mation of 
" anti-antibodies." 
LEUCOCYTE EXTRACT. 
We have seen that the phagocytes, particularly the polymorpho- 
nuclears are possessed of very subtle, and in the aggregate very powerful, 
capacities for bacterial cell destruction both in their interior, and through 
the substances which they may furnish to the body fluids. 
It is apparent that, in the complex series of adaptations to one 
another in infection of the body cells on the one hand and the micro- 
organisms on the other, the balance must often be very nice in this 
muster of opposing forces. 
Hiss has proposed,3 therefore, that the overtaxed or threatened phago- 
cytes might be aided in an emergency if an extract of cells of their own 
1 Wright, A. E., Technique of the Teat and Capillary Tube, London, 1912. 
2 For general technique of opsonic work see Welker, Jour. Med. Res., xix., p. 237, 1908. 
3 Hiss, Jour. Med. Res., xiv., 3, 1908. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
189 
kind in diffusible form such as might be secured by a sterile emulsion 
of dead cells were introduced into the body. 
He has pre'pared such extracts and they have been administered 
both to men and to animals in divers infections with marked benefit in 
a large proportion of cases. Cases of cerebrospinal meningitis, lobar 
pneumonia, staphylococcus and streptococcus infection have been thus 
treated and in experimental animals the infective processes induced by 
the pyogenic bacteria, meningococcus, typhoid and dysentery bacilli, and 
others has been markedly modified. 
Preparation of Leucocyte Extracts.-The exudates containing a large proportion 
of leucocytes are secured from rabbits by intrapleural injection of sterilized aleuronat 
(see p. 195). After twenty-four hours the copious exudate is withdrawn, the cells 
separated by the centrifuge. These cells are extracted with sterile distilled water 
and after careful control as to the freedom from bacteria of the final emulsion, this 
is introduced beneath the skin.1 
DIVERSION OF COMPLEMENT. 
It has been shown that the relative proportions of amboceptors and complements 
present in bacteriolysis is not a matter of indifference. 
Thus if one add increasing amounts of amboceptors, in the form of immune serum, 
to fixed volumes of bacterial emulsion and complement, i.e., normal serum, it is found 
that, on the addition of a small amount of amboceptor, i.e., immune serum, complete 
bacteriolysis may be secured. But if a greater amount of amboceptor be added than 
is necessary to secure complete lysis, the latter may fail to occur. 
From such experiments it has been assumed, probably incorrectly however, that 
when in such mixtures amboceptors are present in considerable excess, while some 
of the amboceptors combine with complement, other free amboceptors may unite 
with the receptors of the bacterial cells more readily than the combination group of 
complement-amboceptor will do, and in this way the union of complement-ambocep- 
tor and cell receptor necessary for effective lysis is prevented. This has been called 
diversion or deviation of the complement. The phenomenon is much more probably 
due to the binding of the complement by other substances present in the mixture, 
and not to a union of the cell receptors with the excess of amboceptor. 
FIXATION OF COMPLEMENT. 
We have seen when considering haemolysis (page 172), that when haemolytic serum 
which contains amboceptors is heated to destroy its complement, the amboceptor, if 
placed in contact with the species of red blood cells to which it has been adapted, 
unites with them. Such blood cells are said to be "sensitized," because if now a 
small amount of complement in the form of fresh normal serum, "activating serum," 
be added, haemolysis takes place. 
Similarly when heated bacteriolytic amboceptor in the form of an immune serum 
is added to its homologous bacteria-antigens-the latter are sensitized and are thus 
capable of absorbing and using up complement if fresh normal serum be added. 
This delicate haemolytic reaction several years ago was made the basis of an 
ingenious method of testing for the presence of immune body by Bordet and Gengou.2 
The Bordet-Gengou test has been characterized as the method of fixation of comple- 
ment for reasons which will be made clear through an example, as follows. 
If one take bacteriolytic amboceptor in the form of, say, heated typhoid immune 
1 For a study of bactericidal substances in leucocyte extracts, see Zinsser, Jour. Med. Res., xxii.. 
397, 1910. 
2 Bordet and Gengou, Ann. de 1'Inst. Pasteur, 1901. 190 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
serum and add to this, first, an emulsion of typhoid bacilli and, second, complement in 
the form of fresh normal serum, and allow these to stand for five hours, it is evident 
from what we have seen above that the complement, if this has been added in proper 
proportion, will have been all absorbed in the bacteriolytic reaction between itself, 
the amboceptor, and the typhoid bacilli. So that if we now add sensitized red blood 
cells, i.e., heated haemolytic serum and red blood cells, no haemolysis will take place 
because the complement necessary for this was previously absorbed, that is "fixed," 
in the bacteriolytic reaction. 
That this is actually the case may be shown by replacing in the above experiment 
the heated typhoid immune serum by heated normal serum. In this case on the 
addition of the sensitized red blood cells haemolysis occurs. 
This method assumes that in the activating serum the haemolytic and bacteriolytic 
complement are identical at least in their combining capacities. 
This "fixation of complement" has been brought more recently into practical use 
in testing for immune bodies in diagnosis (see Wassermann reaction), as well as in the 
determination of bacterial species and in the differentiation of proteins. 
ALLERGY AND ANAPHYLAXIS. 
Under the general term "allergy" are classed a number of complex phenomena 
of immunity, the name signifying an altered reactive quality of the body or the 
individual tissues. This changed reactivity may be due to previous disease or to 
the administration of foreign substances, as the injection of drugs or of horse serum, 
or to the occurrence of a disease like tuberculosis, which renders the body unusually 
susceptible to products of the tubercle bacillus. The altered reactivity of the body 
may express itself in three forms: 1, as an alteration in the speed of the reaction; 2, 
as an alteration in the amount of the reaction; and, 3, as an alteration in the quality of 
the reaction. Those substances which are capable of altering the reactive power of the 
organism are called allergins, which is a broader term than the word antigen, the 
latter being employed to designate those highly specific generators of immunity present 
in the proteins giving rise to antibody formation when placed in contact with the body 
cells. The term anaphylaxis is now being limited to that form of allergy due to the 
sensitizing of the body cells with some form of protein. The other form of allergy is 
due to substances which do not act as antigens but are, as a rule, well characterized 
chemical substances, as, for example, salvarsan, which sensitizes the tissue so that 
frequent doses may cause very severe reactions, or morphine, which acts less powerfully 
with each dose owing to the fact that the body cells ultimately develop a capacity 
to oxidize this alkaloid with greater activity than when administration is first begun. 
The toxins of bacteria, such as the diphtheria and tubercle bacilli, may induce the 
production of antitoxins which neutralize the toxins or may sensitize the cells so that 
a second dose of the toxin may cause the death of the animal with symptoms of the 
disease which the particular toxin in question has the power to produce; for instance, 
a second dose of tetanus toxin may kill an animal with all the symptoms of tetanus. 
It is believed that the mechanism of death under these conditions is different from that 
which occurs in true anaphylaxis due to the introduction of a foreign protein into the 
circulation. If a dilute solution of tuberculin is dropped into the conjunctival sac of a 
person suffering from tuberculosis, a violent inflammatory reaction occurs which is 
allergic in nature. The classic example of true anaphylaxis in that which follows the 
spaced injection of foreign protein. If, for example, a guinea-pig is inoculated with a 
small quantity of horse serum and then seven to eleven days afterward a second in- 
jection is given, the animal ofteh dies in a few minutes with symptoms of dyspnoea, 
convulsions, involuntary defecation and urination, and fall of temperature. If the 
animal does not die it is immune and does not react to further injections of the same 
serum. If the second injection is made within a few days after the first no anaphylactic 
symptoms are produced nor can they ever afterward be produced by large or small 
doses. This anaphylactic condition can be transferred by injection into other animals 
of blood from an animal potentially anaphylactic. The condition may also be 
transmitted from mother to child, irrespective of whether the mother was rendered THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
191 
hy persuscept ible before or after the beginning of pregnancy; it is not, however, trans- 
mitted in the milk. 
Numerous theories have been proposed to explain this phenomenon, von 
Pirquet and Schick1 thought that the reaction was a simple one between antigen and 
antibody, with the setting free of a product whose action on the remnants of the antigen 
still circulating in the blood caused the disturbance. Wolff-Eisner2 thought that the 
first injection produced a ferment from the cells, capable of splitting the foreign protein 
injected, and that when this protein was injected a second time it was split rapidly, one 
of the split products being toxic. This view has received a good deal of support from 
the work of Vaughan.3 According to this theory the reaction takes place in the blood. 
Gay and Southard4 suggest that a portion of the protein introduced in the first in- 
jection is assimilated by the cells, but that a fraction which is not digestible remains in 
the circulation and renders the tissue cells abnornally sensitive to reinjections of the 
same form of protein. The toxic nonassimilable substance they call anaphylactin. 
Besredka5 holds that the antigen and the substance producing anaphylaxis are different. 
The sensitizing protein contains an active element which gives rise in the injected 
animal to a specific antibody. This antibody circulates in the blood and is stored in 
the cells of the central nervous system. On a second injection a reaction takes place 
between the specific antibody and a third substance present in the protein, which acts 
upon the nerve cells and gives rise to the symptoms. Doerr and Russ6 regard ana- 
phylactic shock as an intercellular precipitin reaction.7 Weil8 holds that anaphylaxis 
is due to a reaction between specific antibodies present in the cells and the introduced 
antigen. When passive sensitization is produced by the introduction of the blood of 
an anaphylactic animal, the body cells of the recipient absorb the introduced anti- 
bodies from the blood and thus the cells become anaphylactically sensitive. This 
takes a certain time, usually twenty-four hours, at the end of which the animal can 
be killed by a single dose of antigen, because it has in its circulation an insufficient 
amount of antibody to protect the cells from the toxic effects of the introduced antigen 
or its split products. Weil thinks that an immunized animal is potentially anaphyl- 
actic, but is protected by the immune bodies in the circulation, and that the difference 
between immunity and anaphylaxis lies solely in the fact that in the former the anti- 
bodies predominate in the serum, while in the latter they predominate in the cells, 
the cells being thus left unprotected. 
This limited sketch of a few of the views on anaphylaxis is necessarily incomplete 
since it is impossible in a work of this sort to do more than refer the student to larger 
treatises. Many of the observed phenomena do not fit any of the hypotheses. For 
instance, it is not clear why anaphylaxis should be prevented by placing the animal 
under the influence of chloral hydrate,9 while morphine does not have this effect. 
Auer and Lewis,10 having shown that the rapid death is due to asphyxiation induced 
by tetanic contraction of the smooth muscles of the bronchioles, have been able to show 
also that atropine will prevent anaphylactic death. It must be remembered, also, 
that typical anaphylaxis to sera is seen chiefly in the guinea-pig. Other animals 
react quite differently to horse serum and may not be sensitive, though highly sensitive 
to other proteins. It is evident that our knowledge of this subject is still imperfect in 
spite of the enormous amount of investigation which has been carried out in the last 
five years. 
1 von Pirquet and Schick, Wien. klin. Wchnschr., 1903; and Die Serumkrankheit, Vienna, 1905. 
2 Wolff-Eisner, Centralbl. f. Bakteriol., 1904, xxxvii., 350, 566, and 684; and Berl. klin. Wchnschr., 
1904, xli., 1105, 1131, and 1156. 
3 Vaughan, Protein Split Products in Relation to Immunity and Disease, New York, 1913. For an 
attempt to use the demonstration of these ferments in specific diagnosis see Abderhatden, Abwehrfer- 
mente, 4th edition, Berlin, 1914. 
4 Gay and Southard, Jour. Med. Research, 1907, N. S. xi., 143. 
6 Besredka, Ann. de 1'Inst. Pasteur, 1907, xxi., 384. 
6 Doerr and Russ, Ztschr. f. Immunitatsforsch., Orig., 1909, iii., 101. 
7 For an extensive review of the facts leading to the humoral theory of anaphylaxis see Friedemann, 
Jahresb. f. Immunitatsforsch., 1911, Abt. I, vi., 31; Ztschr. f. Immunitatsforsch., Orig., 1909, ii., 591; 
and Rosenau and Anderson, Harvey Lectures, New York, 1908-9. For the views of Richet, who did 
much of the pioneer work on this subject, see his recent monograph, L'anaphylaxie, Paris, 1912. 
8 Weil, Jour. Med. Research, 1913, N. S., xxii., 497. 
9 Banzhaf and Famulener, Jour. Infect. Dis., 1910, vii, 577. 
10 Auer and Lewis, Jour. Exper. Med., 1910, xii., 151. 192 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
The Bearing of the New Studies on Serum Therapy.-We have seen in an earlier 
section that the use of the blood serum of animals immunized against pathogenic 
micro-organisms for protective purposes in man has been of practical value in but few 
instances, and these mainly in cases in which the protective action was antitoxic. 
Protective sera for pneumonia and typhoid, streptococcus septicaemia, plague, tuber- 
culosis, cholera, and many other infectious diseases whose chief toxic incitors seem to 
be endotoxins have been persistently tested and found to be for the most part of 
doubtful value in man. 
But in the light of the new knowledge of cytolytic sera, and the conditions under 
which these may be effective, the promise of serum therapy, so long limited to anti- 
toxic immunity, seems now to be more encouraging. 
It is possible that the reason why the serum of an animal immunized against a 
given pathogenic micro-organism is not protective is that neither this serum nor the 
body fluids of the individual into whom it is injected for protective ends contain suffi- 
cient or suitable complements. 
We have seen in our review of haemolysis that haemolytic serum heated to 56° C. 
loses its lytic power owing to the destruction of the very labile complements. We have 
seen, further, that this power is restored by the addition of a little fresh serum from a 
normal animal; that is, serum containing complement. Now it has been found that 
this "reactivation" of the serum, as it is called, can often be brought about by the 
sera of various animals. Thus, for example, the serum of the guinea-pig adapted to 
the erythrocytes of the rabbit is lytic for these cells of the rabbit. If such serum be 
heated to 56° C. it is no longer lytic, the activities of the complement are destroyed; 
but the serum can be reactivated by a little fresh serum, not only from a normal rabbit, 
but from the goat and the rat. The serum of many other animals, however, is ineffec- 
tive under these conditions. The reason for this, of course, in accordance with 
Ehrlich's hypothesis, is that the complements of the reactivating sera have combining 
capacity with the special amboceptors, and so can become effective, while in other 
sera, the linking of the complement to the red cells through the amboceptors being 
impossible, there can be no restoration of the lytic action. 
It is not difficult to secure immune substances (amboceptors) by the adaptation of 
animals to various kinds of pathogenic bacteria. These may be formed in such abun- 
dance as to be out of proportion to the complements. But unless these immune sub- 
stances, when injected into the body for protective purposes, either carry with them or 
find in the new environment an abundance and appropriate forms of complements, they 
are not wholly available in destroying bacteria. One of the great problems of the 
immediate future, then, so far as serum therapy is concerned, seems to be to secure 
suitable complements to act with immune substances if the former do not exist in the 
human fluids, or to reinforce these substances from the sera of suitable animals if the 
human stock be scanty. There is, however, much ground for believing that in order 
to be most effective the complements with which we may seek to reinforce the potency 
of bacteriolytic sera in man should come from species closely allied to him. 
If the securing of an appropriate complement is thus of such importance in the 
attempt to prepare bacteriolytic sera for therapeutic purposes, the maintenance of 
sufficient complements in the human body must be of the utmost significance in its 
intrinsic protective mechanism against infection. That this consideration is not 
without support in fact is shown by the studies of Abbott, Longcope, and others,1 who 
have found that after the continuous administration of alcohol and in various chronic 
as well as acute diseases, the amount of complement in the blood may be notably 
reduced. We have thus a definite contribution to our knowledge of one of those fac- 
tors in predisposition to infection which, in a general way, are so fully recognized, but 
which are, for the most part, but ill-defined and little understood. 
But the securing of effective bactericidal and bacteriolytic agents wmuld not 
in itself be a satisfactory solution of this urgent problem in serum therapy. One can 
readily conceive that complete success in this respect might be an added source of 
danger to the victim of infection. For in case of those bacteria whose harmful effects 
in the body seem to arise largely through the setting free of endotoxins it is probable 
For a study of this subject see Longcope, Jour, of Hygiene, vol. iii., 1903, p. 28. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
193 
that if these were not at once and properly combined or otherwise cared for the 
wholesale destruction of the bacteria might prove a curse and not a blessing. 
The Specific Character of Artificial Immunization.-It is not yet possible to say 
in many cases to what extent the immunization effected in any of the various ways 
indicated above is specific. In some cases it appears to be so. That is to say, the pro- 
tection which is afforded, for example, by an attack of diphtheria or by the gradually 
increased administration of the diphtheria toxin, or by the use of the immunizing serum, 
is limited to this particular disease, and is not to be secured, at least in such marked 
degree, by the use of other bacteria or bacterial products. In some instances, on the 
other hand, immunization against one micro-organism or its toxins, or against special 
toxic substances, affords protection against infection or intoxication by entirely 
different agents. Thus animals may be immunized against anthrax by inoculation 
with bacillus pyocyaneus. 
It should be borne in mind, however much importance we may attach to the forma- 
tion and action of the antitoxic substances, that these are not necessarily always present 
either in natural or acquired immunity to bacteria or their toxins. Tolerance to bac- 
terial toxins may be established, as may tolerance to other kinds of poisons, without the 
intervention of antitoxic or other chemical agents. 
The Complexity of the Proceeses Involved in Immunization.-It thus appears 
that while we know a great deal about the ability of the living body to protect itself 
against the incursions of micro-organisms and the ravages of their poisons; while a field 
is opened for the study of artificial immunization which is of the highest promise, both 
for the advancement of science and for practical benefit to the victims of infectious 
disease; while illuminating and far-reaching hypotheses are current which account for 
many of the complex phenomena, we are yet very far from comprehending manf of 
the details of the processes by which immunization is secured. 
We do not know why the cells of certain animals or why different kinds of cells in the 
same animal are more susceptible than others to the presence of particular poisons; 
why, for example, the rabbit is less susceptible than man to morphine; why strychnine 
should affect the nerves while curare acts upon the muscles; why the common fowl 
should be extremely insusceptible to the tetanus toxin so powerful in many other ani- 
mals. We are even ignorant as yet in most cases of either the chemical or structural 
changes in cells by which the deleterious action of poisons is effected. This is indeed 
not surprising when we reflect that the processes which are involved are of the most 
subtle and complex nature and that our knowledge of cell metabolism even under nor- 
mal conditions is most crude and fragmentary, consisting largely in rather gross deter- 
minations of end-products and leaving out of the account the numberless molecular 
transformations and combinations through which the life processes of the cell are car- 
ried on. 
The living body-cell is very nicely adapted to its normal environment; the living 
bacterium is almost equally sensitive to the conditions under which its metabolism 
takes place. Thus it is that, when these subtle organisms react upon each other, we are 
wholly unable with our present knowledge to follow the steps by which the more gross 
manifestations of disturbance which we call disease are reached. 
But there seems to be abundant ground for the belief that the protective agencies 
which are evoked in both natural and artificial immunization are simply those which 
the body makes use of in its normal metabolism, exaggerated and diverted to different 
ends, it is true, in the face of emergencies and the establishment of new cell environ- 
ments, but giving evidence of the birth of no new physiological capacities.1 
1 The hypothesis of Ehrlich, which so closely correlates the action of toxins with the assimilation 
of nutrient stuff, has led to new conceptions of the details of the relationship of foods transformed by 
the preliminary digestive process to the material which is finally placed at the disposal of the cells. It 
seems not unlikely that through the action of the cell receptors the food material which arrives in the 
body fluids may not only be adapted to the specific uses of the cells, but that by the formation of count- 
less varieties of substances analogous to the so-called "antibodies" of immunization, the cells are pro- 
tected against equally various toxic substances. If this be true, the hope seems justified that, follow- 
ing the lines of research suggested by this new technique we may be able ultimately to understand 
more clearly the details of the so-called internal secretion and those disturbances of chemical adjust- 
ment which give rise to many important phases of auto-intoxication. 194 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
Technique. 
Fok Micro-organisms.-The serum to be tested is mixed in the proportion of 
1 c.c. to 9 c.c. with 0,8-per-cent. sodium-chloride solution, making a dilution of 1 : 10, 
and cleared from red corpuscles, if necessary, by filtration. From this solution various 
dilutions are prepared in a diminishing series, 1 : 20, 1 : 50, 1 : 100, etc. These solu- 
tions may be put into slender test-tubes, and to each is added an approximately equal 
quantity of a suspension in a 0.8-per-cent. NaCl solution of a twenty-four-hour-old 
agar culture of the micro-organism to be tested. 
To secure these suspensions add 5 to 10 c.c. of the salt solution to the culture, dis- 
tribute with a platinum needle, allow the larger lumps of culture to settle, and pipette 
off the turbid supernatant portion. This suspension of the culture in 0.8-per-cent. 
salt solution is now mixed with the diluted serum to obtain the requisite proportions. 
Thus, 1 c.c. of the 1 : 10 serum mixed with 1 c.c. of the suspension gives a 1 : 20 dilu- 
tion; 1 c.c. of the 1 : 10 serum with 2 c.c. of the suspension, a 1: 30 dilution. These 
suspensions of the culture in the series of tubes of diluted serum are now kept for from 
one to twenty-four hours at 37° C. The clumps of bacteria when agglutination has 
taken place may be seen by a hand glass. The clumps oftentimes sink in the tube and 
the fluid becomes clear. Microscopic study of agglutination is made by mixing the 
diluted serum and the bacterial emulsion on a cover-glass which is then inverted on a 
hollow glass slide and sealed with vaseline. For special and for diagnostic purposes 
more exact methods are required, for which see works on bacteriology or on clinical 
diagnosis.1 
For Blood Cells.-A demonstration of the agglutinability of red blood cells 
may be made by adding to a 5-per-cent. dilution of defibrinated blood in 0.85-per-cent. 
salt solution, a small quantity of an aqueous emulsion of ricin. The blood cells soon 
clump and settle, leaving the fluid clear and colorless. 
Agglutination Tests. 
Precipitin Test. 
While the precipitin or so-called biological test for human blood has been sug- 
gested and used in medico-legal cases of importance, its limitations are not yet fully 
determined and one should not enter upon its practical applications in cases of im- 
portance without large experience of the method and the possibilities of error. 2 
For demonstrative purposes, however, the technique is simple. A fragment of 
blood clot to be tested as to its human origin is dissolved in a small quantity of 0.5- 
per-cent. salt solution and passed through filter paper to secure a clear fluid. To this 
solution in a test-tube is added about twice the quantity of the serum of a rabbit or 
guinea-pig which has been injected with successive doses of human serum. This 
adaptive serum should have been tested with a known human serum to insure its 
reliability. Control tubes should be made containing mixtures of the several ingredi- 
ents used without the clot solution to be tested. The tubes are now all kept for one 
hour at 37° C., when if the suspected clot is of human blood the tube which contains 
it will show a precipitate while the controls will remain clear. The charatceristic 
precipitate should soon settle in the tubes, leaving the fluid clear. 
In comparative observations on haemolysis it is convenient to make a 5-per-cent. 
dilution of defibrinated blood with salt solution 0.85-per-cent. One may use narrow 
test-tubes, 5 mm. in diameter, putting into a series of these 1 c.c. of the diluted blood, 
adding to each the serum or other haemolytic agent to be tested, and filling up with 
salt solution to, say, 2 or 2.5 c.c. The tubes are shaken and placed for an hour at 37° 
C., then in an icebox. A control tube of the blood in simple isotonic salt solution 
0.85-per-cent. should accompany each series. 
Haemolysis Tests. 
1 Hiss and Zinsser, "Text-book of Bacteriology, "1910, or Wood, "Chemical and Microscopical 
Diagnosis," 1909. 
2For technical and other details of the precipitin test, see Uhlenhuth and Weidanz, Praktische 
Anleitung zur Ausfiihrung des biologischen Eiweissdifferenzierungsverfahrens, 1909; Leers,- Die 
forensische Blutuntersuchung, 1910. THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
195 
Following the suggestion of Wright, tests for haemolysis may be made in capillary 
tubes, each long tube containing several tests or dilutions by the intervention of a 
bubble of air between each segment of the mixed test fluid and diluted blood. 
To Secure Sterile Inflammatory Exudate Containing Leucocytes and other Living cells. 
It has been found that the injection of wheat gluten into the pleural cavity of 
rabbits or dogs induces an exudative inflammation, the exudate usually containing, at 
the end of twenty-four hours, many living leucocytes. Leucocytes secured in this way 
have been largely used in determining the chemical character of their cytoplasm, as 
well as for experiments on phagocytosis. The most convenient preparation is the 
so-called aleuronat, a mealy food preparation. A convenient method is to inject into 
the pleural cavity 10 c.c. of a suspension of aleuronat in starch water (aleuronat 5 
grammes; starch, 1.5 grammes; water, 100 c.c.). The exudate may be removed with 
a capillary pipette if small quantities only are required, or the animal may be sacri- 
ficed if larger quantities of the exudate are necessary. 
Polymorphonuclear leucocytes may also be secured in considerable quantity by 
the injection of 10 grammes of sterile bouillon into the peritoneum of the rabbit. The 
exudate is removed at the end of twenty-four hours. 
To secure an exudate containing a preponderance of mononuclear cells one may 
inject into the peritoneum of the rabbit a solution containing 1 mm. of pilocarpin, the 
exudate to be removed at the end of twenty-four hours. 
If the serum of rabbits adapted by successive injections into the peritoneum to the 
blood of guinea-pigs be injected into the peritoneal cavity of guinea-pigs, after a time 
the peritoneal fluid as well as the spleen and other blood-forming organs are found to 
contain various cells which have ingested the erythrocytes. The peritoneal fluid may 
be secured for examination at various intervals by a capillary tube inserted into the 
peritoneal cavity. 
Hsemophagocytosis in vitro may be studied by procedures similar to those em- 
ployed in the study of bacteriophagocytosis. (See opsonins, p. 186.) The serum of 
an animal adapted to alien blood, if lytic, is deprived of this power by destroying the 
haemolytic complement by heating for half an hour at 60° C. A small portion, say, 
0.1 c.c. of this serum, is now mixed with an equal quantity of a 5-per-cent. suspension 
of washed red blood cells in 0.85-per-cent. salt solution. To this is added a small 
quantity of living leucocytes of man or of the guinea-pig or dog secured from citrated 
blood or, in animals, from fresh aleuronat exudates (see above), and the mixtures kept 
for an hour at 37° C. Smears are then made and stained with the Jenner or other 
double stain.1 
The Study of Haemophagocytosis. 
To Collect Small Samples of Serum for Agglutinative, Precipitin, or Haemolysis Tests. 
The suggestions of Wright are most helpful in the technique of serum collection 
in small quantities. The finger is constricted by the handkerchief or a bandage, not 
tightly enough to stop the blood flow, but enough to induce marked congestion; and 
the puncture is made by a needle or a fine-pointed glass. The drop of blood as it 
exudes is drawn into a small capsule of the form shown in Fig. Ill, held so that it will 
act as a siphon. When partly filled, the ends are sealed, first the larger end, then as 
the air here cools, the blood will be drawn back from the capillary end, when this is 
closed. The tube is set slightly aslant for clotting, after which the serum may be 
secured in capillary pipettes by breaking off the larger end of the capsule after scratch- 
ing it with a file. 
The Method of Adaptation of Animals to Alien Substances. 
The adaptation, or immunization, as it is called, of animals to various alien sub- 
stances, sera, red blood cells, etc., in order to secure lytic agglutinating and precipitat- 
ing substances, is readily accomplished. For general demonstration purposes the 
rabbit is well suited. A simple and effective method is by intraperitoneal injection. 
1 See Hektoen, Jour. Inf. Dis., vol. iii., p. 434, 1906, and also Jour. Amer. Med. Assoc., vol. xlvi., p. 
1407, 1906. 196 
THE RELATIONS OF MICRO-ORGANISMS TO DISEASE 
The lower left abdominal region is shaved and disinfected with lysol. The skin is 
punctured with a scalpel and the slightly blunted needle of the syringe is introduced, 
care being taken not to puncture the intestine. Five c.c. of whipped blood or serum, 
warmed to body temperature, may be injected. On the withdrawal of the needle the 
part is dried and the opening is sealed with tincture of benzoin. There is apparently 
no discomfort to the animal in this procedure. The weight of the animal may fall 
slightly after the injection, but unless this is considerable the dose may be repeated at 
intervals of from five to seven days, until five or six injections have been given. The 
dosage in the later periods may be increased, even doubled, if the animal is in good 
condition. After the first three or four injections a small amount of serum may be 
secured for testing by opening one of the ear veins after cleansing the part. The blood 
may be drawn directly into a Wright capsule (see above), where it is allowed to clot, 
and the serum secured. If the animal is to be sacrificed to obtain a large quantity 
of the immune sera it may be bled into sterilized receptacles by a glass cannula tied 
into the carotid artery. 
The above is only a rough and general description of the method of securing adap- 
tive sera for general purposes of demonstration. For exact work one must carefully 
select animals, regulate and control dosage, etc. For details and many interesting 
data consult Nuttall, " Blood Immunity and Blood Relationship," 1904. 
Bibliography of Recent Studies on Immunity. 
For an early admirable resume of immunity, consult article by Weigert, Lubarsch 
and Ostertag's" Ergebnisse" for 1897, p. 107; for a good later summary see "Infec- 
tion and Immunity" by Muller, 1912, also Rickett's "Infection, Immunity, and Serum 
Therapy," 1906. Consult also Metchnikoff, "Immunity in Infectious Diseases," 
Transl., 1905, in which much lore is gathered and many ingenious points of view of the 
author are set forth. Kolle and Wassermann's " Handbuch der Mikroorganismen" 
2d edition, 1912-13, contains excellent summaries of various phases of immunity; as 
does also in more compact form the " Experimentelle Bakteriologie" of Kolle and Hetsch, 
3d edition, 1911. Many valuable reviews are contained in the Jahresbericht fiir 
Immunitatsforchung, Stuttgart. See also Kraus and Levaditi, Technik u. Methodik 
d. Immunitatsforschung; Much, Immunitatswissenschaft, 1914, and Pfeiffer, 
Eiweissanaphylaxie, 1911. 
The records of the recent researches just summarized in cytolysis and the applica- 
tion of Ehrlich's "side-chain" hypothesis are widely scattered through the German, 
French, and English technical periodicals. The most important of the studies of 
Ehrlich and his associates in this field are collected in the " Gesammelte Arbeiten zur 
Immunitatsforschung," Ehrlich, English Transl. by Bolduan, 1907, see also Bordet, 
Studies in Immunity, translated by Gay, 1909. 
The summary of Aschoff (" Seitenkettentheorie and ihre Anwendung auf die 
kiinstliche Immunizierungsprozesse," Zeitsch. f. allg. Physiol., Bd. i., Heft 3, 1902) 
is most complete and contains a full bibliography. The monograph of v. Dungern 
("Die Antikorper," 1903) contains much valuable material. 
In English, the Huxley Lecture by Welch ("Recent Studies of Immunity," 
Medical News, October 18th, 1902) is admirable, and deals with especial fulness with 
toxins and their relationship to various important pathological processes. 
Ritchie's discussion of the subject (Jour. Hygiene, vol. ii., Nos. 2, 3, and 4, 1902) 
treats in a clear and philosophical fashion the facts and hypothesis involved. 
See also Nuttall's book, "Blood Immunity and Blood Relationship," 1904; 
Bolduan's "Immune Sera," 1907, and Hektoen's "Resume of Immunity," 1905. 
For study of Transmission of Immunity to offspring see Theobald Smith, Jour. 
Med. Res. xvi., p. 359, 1907. 
Hiss and Zinsser, "Text-book of Bacteriology," 2d edition, 1914, contains an ad- 
mirable summary of immunity and the immunizing processes framed from the stand- 
point of modern biology. See also Zinsser, Infection and Resistance, New York, 
1914. 
For a study of the local specific therapy of infections see Flexner, Jour. Am. Med. 
Assn., 1913, Ixi, 447, 1872. CHAPTER IX. 
THE INFECTIOUS DISEASES. 
General Considerations. 
In the study of the infectious diseases it is especially important to 
bear in mind that the abnormal processes through which the disturbances 
incited by micro-organisms are manifested are processes of the body-cells 
and not processes of the micro-organisms. The micro-organisms do, 
indeed, incite the train of phenomena by which the disease is mani- 
fested, and the nature or "species" of the micro-organism may largely 
influence the character of the phenomena, but the stored-up energy 
which is released in this manifestation is body-cell energy and not that 
of microbic metabolism. The microbes are excitants of disease, but 
the disease is a performance of the body-cells. If these obvious con- 
siderations be held in view, it will be convenient, in considering certain 
of the infectious diseases, to use the familiar and much abused term 
"specific" as indicative of those phases of abnormal body-cell per- 
formance which are apt to occur in characteristic ways in response to 
special forms of microbic stimulus. Thus the poisonous substances 
which the tubercle bacillus builds up out of the organic material upon 
which it feeds are in part such as exert a peculiar influence upon con- 
nective-tissue cells, leading to their proliferation and the temporary 
formation of new tissue-the tubercle. This, together with associated 
action of the same or other metabolic products of the living bacillus, 
forms a group of lesions and disturbances which is characteristic of the 
action of the tubercle bacillus in the body. In this sense tuberculosis 
is a "specific" disease. On the other hand, the poisons eliminated by 
the tubercle bacillus may incite responses on the part of the body-cells 
which are practically identical with those which many other toxic sub- 
stances, both of bacterial and of other origin induce-fever, degeneration, 
etc. These manifestations of the action of the tubercle bacillus upon the 
living body-cells are not "specific." 
In our study of the individual infectious diseases we shall encounter 
many examples of this variety in the effects which pathogenic bacteria 
induce-the more characteristic, on the one hand, and, on the other, the 
more general responses which the body-cells make to deleterious agents. 
Classification of the Infectious Diseases.-It is common to group dis- 
eases either from the clinical or the morphological or the etiological 
standpoint. But a complete rational classification of disease is not at 
present possible, because in very few diseases have we even an approxi- 
mately complete knowledge of the symptoms, the excitants, or the 
morphology of the lesions. 
197 198 
THE INFECTIOUS DISEASES 
In the infectious diseases as we now define them, the excitant is 
definite and in many cases known, but a classification based upon the 
character of the excitants alone would be, as Martius has urged, a classi- 
fication of the micro-organisms and not a classification of the diseases. 
If every micro-organism capable of exciting disease always met in the 
body a similar response, the matter would be comparatively simple. 
But the fact that the responses of the body-cells to bacterial invasion are 
exceedingly varied, and that dissimilar organisms may evoke similar 
responses, renders a simple etiological classification even of the infectious 
diseases unsatisfactory, if not impracticable. Thus it is that it is con- 
venient to consider the infectious diseases in part together, in part in 
connection with the special organs in which their more common and 
characteristic lesions are manifested. Such a classification of the in- 
fectious diseases as is here made is based in part upon similarity of 
lesions, in part upon the relationships of the micro-organisms concerned, 
and may wisely be regarded only as a convenient form of catalogue. 
Groups of Bacterial Disease-Excitants.-One of the interesting results 
of the later studies of bacteria and their associations with the infec- 
tious diseases is the discovery that many micro-organisms which have 
been proved to be excitants of disease in men or in lower animals are 
closely related to forms which are not pathogenic. So that we now 
recognize many bacterial groups which we are wont to characterize 
by the name of the pathogenic representative. Thus there are staphy- 
lococcus and streptococcus groups of closely similar organisms, most 
of them harmless to man. There is the colon-bacillus group, embrac- 
ing many closely related forms difficult to identify. The tubercle-bacil- 
lus group, the diphtheria-bacillus group, the actinomyces or strepto- 
thrix group, are other examples of this relationship. The more these 
related forms are studied, the more evident it becomes that in very 
slight physiological variations may lie the difference between patho- 
genic and non-pathogenic forms, and that equally slight variations in 
the susceptibility of the host may be of corresponding significance. 
In the arrangement and associations of the infectious diseases con- 
sidered in this section, the existence of these bacterial groups will be 
frequently recognized. 
SUPPURATIVE AND ALLIED FORMS OF INFLAMMATION. 
We have seen in an earlier part of this book that in various kinds of 
injury in the living tissue there may be a series of responses on the 
part of the body-cells which constitute or give rise to the phenomena and 
lesions of inflammation. One of these forms of tissue response to in- 
jury is called suppuration or suppurative inflammation. 
We have seen that the characteristic feature of suppurative inflam- 
mation is the collection at or near the seat of injury of leucocytes, mostly 
of the polymorphonuclear type. These leucocytes, attracted through 
chemotaxis, emigrate from the smaller vessels and gather in the tissues. 
Here through their phagocytic powers they may directly or indirectly de- THE INFECTIOUS DISEASES 
199 
stroy living micro-organisms; by lytic substances which they elaborate 
they may soften and remove dead tissues (see p. 103); or they may 
themselves succumb to the action of poisons or other local conditions 
inimical to their life. While, to a limited extent, a suppurative inflam- 
mation can be incited by chemical agents, such as ammonia, turpentine, 
etc., in most cases it is incited and sustained by micro-organisms or by 
poisons which these micro-organisms set free as the result of their own 
metabolism or by the decomposition of substances in the tissues or the 
tissue fluids. 
Before considering in detail the characteristics of the various forms 
of micro-organisms which may act as excitants of suppurative inflam- 
mation, it is necessary for us to survey the various phases which this 
process presents under different conditions. 
Phases of Suppurative Inflammation.-In the first place while the 
emigration, proliferation, and gathering of leucocytes are the most char- 
acteristic features in this form of inflammation, these are always associ- 
ated with the accumulation of more or less fluid transudate from the 
blood-vessels and often with the formation of fibrin. These, the leu- 
cocytes, the serum, and the fibrin, constitute the exudate. Further- 
more, associated with the accumulation of the exudate there may be 
albuminous degeneration and necrosis of cells and tissue of the affected 
part or of the formed elements of the exudate itself. Finally, a pro- 
liferation of the fixed cells of the affected region, connective-tissue 
cells, endothelium, etc., frequently accompanies the exudative phases 
of inflammation and may dominate the processes when regeneration 
and repair are under way (see p. 73). 
Although the processes involved are essentially the same, it has been 
found convenient to attach special names to various topographic forms 
of suppurative inflammation, the differences depending largely upon the 
origin, situation, extent, and complications of the primary lesion, some- 
what, however, upon the qualities, fixed or variable, of the infecting 
micro-organism. Thus a suppurative inflammation involving the serous 
surfaces and resulting in the accumulation of a purulent exudate in the 
serous cavities, such as the pleural and the pericardial, is called em- 
pyema. An exudative inflammation of the mucous membranes with a 
marked emigration of leucocytes from the vessels of the submucosa is 
called a purulent catarrh or blennorrhcea. 
Pustules are superficial collections of purulent exudate in the skin. 
Furuncle.-A furuncle is an acute, circumscribed, suppurative, and 
necrotic inflammation of the skin, the necrosis commonly involving a 
central plug or core. Furuncles are usually incited by Staphylococcus 
pyogenes aureus, rarely by Streptococcus pyogenes. They are common 
on the neck, back, buttocks, perineum, and axilla. Diabetes, marasmus, 
and obscure nutritional disturbances, often associated with worry and 
overwork, seem to predispose to this form of infection. The invasion 
of the staphylococcus is usually through the sebaceous glands and hair 
follicles. Furuncles may be experimentally induced by rubbing cul- 
tures of staphylococcus over the intact skin. 200 
THE INFECTIOUS DISEASES 
From the seat of infection the inflammation extends outward and 
n depth to a varying extent. The tissue becomes hard from infiltra- 
tion of the tissue interstices with fluid and leucocytes, by the swelling 
of the stroma and connective-tissue cells (Fig. 112). The vessels are 
congested and the central portions become more or less necrotic, with 
gradual liquefaction of the tissue and the development of pus. Lym- 
phangitis and hyperplasia of the associated lymph-nodes may accompany 
furuncles. 
Carbuncle.-If the infection of several contiguous hair follicles, 
either immediately or in rapid succession, takes place, so that several 
centres of necrosis, with surrounding areas of exudative inflammation, 
On the left the connective-tissue cells are swollen and proliferated and the lymph-spaces are dis- 
tended with fluid. Nearer the centre of the boil the connective-tissue spaces are infiltrated with pus 
and the fibrils of the stroma swollen. 
Fig. 112.-Section of a Boil-Furuncle. Showing the Red and Swollen Area. 
merge, the resulting lesion is called carbuncle. The process is essentially 
similar to that involved in furuncle, but usually more severe and ex- 
tensive. Carbuncle is common on the neck, back, and face. 
A diffuse infiltration of the. subcutaneous or deep fibrous tissue, 
muscle tendon, periosteum, or of the interstitial tissue of the viscera, 
with exudate, is called phlegmon. If in this phlegmonous inflammation 
there be much serous fluid associated with the cell accumulation, as is 
commonly the case in the earlier stages of the process, the condition is 
often named purulent oedema. When, on the other hand, there is a 
more or less circumscribed collection of purulent exudate in the depth 
of the tissues or organs, associated with necrosis and fluidification of 
the tissues involved, it is customary to call the result of the process an 
abscess. 
In some cases of exudative inflammation, particularly those in- 
volving the serous surfaces, the exudates often occur together in the 
most variable proportions; they are formed under the influence of 
the same agents, and frequently an exudate at first simply serous in 
character becomes fibrinous or purulent or both together. THE INFECTIOUS DISEASES 
201 
Pus and Pus Cells.-It will thus be seen that the exudate which is 
formed in suppurative inflammation varies considerably in its composi- 
tion and structure. Primarily, pus consists of an albuminous fluid 
containing leucocytes, some mononuclears, most of them polymor- 
phonuclears (Fig. 113). While the exu- 
date is in the tissue and the conditions 
are favorable, these cells may be alive 
and without structural abnormalities. 
But often, and especially in accumula- 
tions, they present various phases of de- 
generations-albuminous or fatty-or of 
necrosis and disintegration. It is on ac- 
count of their relative frequency and 
abundance in purulent exudates that the 
leucocytes are regarded par excellence as 
pus cells. But other cells, as we have 
seen, may be present in .pus; thus in in- 
flammation of the serous membranes, such 
as the peritoneum, pleura, etc., the exfoliated and proliferated meso- 
thelial cells may furnish no small part of the cellular content of the 
exudate. Red blood cells, detached and young connective-tissue cells 
formed from the old and capable of emigration, and endothelial cells 
may be present in considerable num- 
ber. In inflammation of the mucous 
membranes, also, the epithelial cells, 
either new-formed or simply exfoliated, 
may be abundant. Furthermore, pus 
may contain a variety of chemical sub- 
stances and formed elements depend- 
ing upon the place of its formation or 
accumulation. Thus mucus, fibrin, 
cell and tissue detritus, fat, and micro- 
organisms may be intermingled with 
the pus cells. 
Ulcers-in whatever way originat- 
ing (see p. 58)-may be the seat of 
suppuration, the exudate passing off 
upon the free surfaces. 
The bacteria which are found in the 
various phases of suppurative inflam- 
mation may lie free in the interstices of 
the tissue with the exudate, or they 
may be in part within the cells which 
have gathered about them (Fig. 114). 
Both within and without the cells the bacteria may present those 
structural alterations which denote their death and degeneration in 
the struggle for existence to which the two forms of living beings, the 
microbes and the body-cells, are subjected under the conditions which 
Fig. 113.-Pus Cells in Suppurative 
Inflammation. 
Some of the cells show the marks of 
necrosis and disintegration with frag- 
mentation of the nuclei, etc. 
Fig. 114.-Staphylococcus Pyogenes 
Aureus, in and Among the Pus Cells, 
from an Abscess of the Kidney. 202 
THE INFECTIOUS DISEASES 
mark infection. The local and systemic reaction, on the other hand, 
and the cell necrosis which so frequently follows the growth of microbes 
in the body are expressions of an unfavorable environment to which the 
body-cells as individuals and the body as a composite organism are sub- 
jected, and to which they may successfully react or under unfavorable 
conditions may succumb.1 
In the softening of tissue involved in the development of abscesses, 
as well as in the removal of exudates by absorption it is probable that 
the solution of the formed elements of the tissues is accomplished by 
the development of lytic-autolytic-substances (see p. 106).2 
Fig. 115.-Focal Necrosis in the Liver in Pneumonia. 
Showing the local effect of a toxin circulating in the blood in toxaemia. 
Toxaemia.-While the various forms of exudative inflammation are 
more or less circumscribed, the soluble toxins which are formed at the 
seat of local bacterial growth may, without the dispersion of the germs 
themselves, be diffused through the blood and the other fluids of the 
body, giving rise to the symptoms and lesions of toxaemia-fever (see 
p. 440) and various other forms of functional disturbance, albuminous 
degeneration of the viscera, focal necroses, petechial haemorrhages, haemo- 
lysis,3 thrombosis, leucocytosis, chromatolysis of the ganglion cells, etc. 
Of these alterations in the body, which are of frequent occurrence in 
many forms of toxaemia, whether induced by bacterial or other kinds of 
1 For an exhaustive review of suppurative inflammation from the modern standpoint, with bibli- 
ography, consult Janowski, Ziegler's " Beitrage zur path. Anatomie," etc., Bd. xv., p. 128, 1894. 
2 For a fuller reference to removal of exudates by autolysis see p. 106. 
3 For a summary of facts relating to the haemolytic power of various species of bacteria see Pribram, 
foot-note, p. 206. THE INFECTIOUS DISEASES 
203 
poisons,1 the only ones which demand special notice here are the focal 
necroses. These usually small, often sharply circumscribed areas of 
dead tissue2 may be present in any of the viscera, but are often most 
abundant and conspicuous in the liver (Fig. 115). They vary con- 
siderably in appearance, depending upon the stage of the tissue in- 
volvement. The cells in the affected area may be swollen, the cyto- 
plasm more transparent than normal, while the nuclei may remain 
unstained with the usual dyes or show various phases of fragmentation 
or disintegration; or they may disappear altogether. Again, the cells 
in the involved areas may become more coarsely granular than is nor- 
mal, may undergo a change similar to that seen in coagulation necrosis, 
and with destruction of the nucleus may form deeply staining, irregular 
clumps or masses, or may disintegrate. 
Associated with or following these changes there may be a gathering 
of leucocytes about and within these necrotic areas, so that the foci 
may present the appearance of little abscesses or masses of lymphoid 
tissue. Finally, these necrotic areas may undergo repair and be re- 
placed by small, spheroidal, young connective-tissue cells, granulation 
tissue, or finally by small masses of cicatricial tissue.3 
Septicaemia and Pyaemia.-Bacteria as well as their toxins may be 
distributed from a local portal of entry or an infected region throughout 
the body, not only inciting general functional and structural changes, 
but, when the bacteria lodge in various situations, giving rise by new 
local proliferation to fresh foci of inflammation. 
It is customary to designate a pathological condition in which 
bacteria as well as their toxins are distributed through the body by the 
blood- and lymph-channels, as septicaemia.1 When fresh suppurative 
foci develop as the result of this distribution, the condition is called 
pycemia. 
The terms septicaemia and pycemia are survivals of a nomenclature 
adapted to the period before the nature of the excitants of infectious 
disease was definitely known. The manifestations of septicaemia were 
then attributed to the presence of putrid material in the blood. Pycemia 
expressed the belief that the lesions characterizing this condition were 
due to the presence of pus in the blood. The term bactericemia is some- 
times and more correctly used to indicate the presence of bacteria in the 
blood, but the old words with their new implications and limitations are 
still commonly employed.5 
1 See for effects of abrin and ricin intoxication, Flexner, Journal of Exp. Med., vol. ii., p. 197, 
1897; also Muller, Ziegler's " Beitrage," Bd. xxvii., p. 331, 1900, bibl. 
2 It seems probable that this marked localization of the action of a soluble poison in the tissue 
fluids may be due to some local vulnerability or susceptibility induced, perhaps, by limited vascular 
disturbance or by nutritional defects otherwise induced. In some instances local necrotic foci may be 
due to agglutinative thrombi (see p. 26). 
3 For a comprehensive study of focal necrosis and other associated lesions in certain forms of toxae- 
mia consult the excellent study of Flexner, "The Pathology of Toxalbumin Intoxication," Johns 
Hopkins Hospital Reports, vol. vi., p. 259, 1897, bibl. 
4 The mere presence of a moderate or even of a large number of bacteria in the blood does not of 
itself indicate septicaemia, since the protective mechanism of the body suffices, under usual conditions, 
for the disposal of such an invasion. See ref. to Subinfection, foot-note, p. 151, and to Schwarz, foot- 
note, p. 151. 
6 It has long been known that persons who have received injuries or wounds may suffer from con- 
stitutional symptoms, among the most marked of which may be fever, and develop local or disseminated 204 
THE INFECTIOUS DISEASES 
The term pyaemia, as will be seen, indicates a clinical and anatomical 
phase of septicaemia. 
The new foci of suppuration in pyaemia are called metastatic ab- 
scesses, and in distribution these may bear an obvious relationship to 
the seat of the primary lesion. Thus, in suppurative processes in the 
intestinal tract, metastatic abscesses are liable to occur in the liver. 
From suppurations in the skin, bones, muscles, etc., infectious emboli 
may be transmitted to the lungs and lead to infarction and abscess; 
or, passing these organs, the germs may induce multiple abscesses in 
the kidneys and in other viscera. 
It should be remembered that the point of introduction into the 
body of the offending germs may be wholly concealed and not associated 
Fig. 116.-Micrococci in Masses in the Fibrinous Exudation of Pyemic Pleurisy. 
with any form of demonstrable external lesion. This is often called 
crypto-genetic pyemia or septico-pyaemia. 
After death from septicsemia and pysemia there is a considerable 
variety in the post-mortem appearances. 
There are cases in which there are no recognizable gross lesions. 
There are cases characterized by early post-mortem decompositions; 
post-mortem staining of the tissues; congestion of the lungs, stomach, 
intestines, and kidneys; extravasations of blood in the serous mem- 
branes; swelling of the solitary and agminated lymph-nodules in the 
small intestine; swelling of the spleen and albuminous degeneration of 
the liver and kidneys; chromatolysis of the ganglion cells of the brain 
and cord. 
There may be localized inflammations. The joints and the tissue 
about them, the pleura, the pericardium, the endocardium, the perito- 
esions. To designate the condition of these patients the terms pyaemia, septicaemia, septico-pyaemia, 
pyo-septiccemia, ichorcemia, inflammatory fever, surgical fever, traumatic fever, suppurative fever, puerperal 
fever, and purulent infection have been used. THE INFECTIOUS DISEASES 
205 
neum, the pia mater, and the connective tissue in different parts of 
the body may be inflamed. These local inflammations are usually puru- 
lent, except in the serous membranes, where the principal inflammatory 
product may be fibrin (Fig. 116). The veins in the neighborhood of the 
wound may contain softened, purulent thrombi, without infarctions in 
the viscera, while there may be inflammation of the joints and serous 
membranes. On the other hand, with the venous thrombosis there may 
be infarctions and abscesses in the viscera; local inflammations of the 
joints and serous membranes may be present or absent. While thrombi 
are often formed in the veins near the wound, they may be situated in 
veins at a distance, and sometimes, although infarctions and abscesses 
be present, no thrombus can be discovered. The veins may be distended 
by the thrombi or contain only small coagula. The different kinds of 
thrombi, and the varieties of emboli and infarctions which they produce, 
are described in the section on Thrombosis, p. 24. Leucocytosis usually 
accompanies pyaemia and septicaemia as well as the suppurative process 
with which they are associated. Studies of the blood in various forms 
of septicaemia are numerous and instructive, but we cannot consider them 
here.1 
Various lines of research on minute changes in cells which bacterial 
and other poisons may induce, justify the expectation that more and 
more we shall be able to associate characteristic groups of symptoms in 
toxaemia and septicaemia for which there is now no morphological basis, 
with well-defined cell alterations. Among the most striking of the 
toxic cell lesions thus far studied in septicaemia and bacterial toxaemia 
are those involving the cytoplasm of the ganglion cells (see Nervous 
System). 
THE PYOGENIC BACTERIA. 
While many species of microbes are capable under favorable condi- 
tions of inciting suppuration and other forms of 
exudative inflammation and may, when they or 
their toxins are disseminated in the body, give rise 
to toxaemia, septicaemia, and pyaemia, there are 
two forms which, on account of their early dis- 
covery and their relative frequency, are commonly 
considered as par excellence "pyogenic" bacteria. 
These, which are called Staphylococcus and Strepto- 
coccus, we shall consider first. 
Fig. 117.-Staph ylo- 
coccusPyogenes 
Aureus. 
From a beef-tea culture. 
Characters of Staphylococcus Pyogenes. 
The Staphylococcus pyogenes aureus (Micrococcus pyogenes aureus) (Fig. 117) is a 
relatively small coccus, the individuals varying, however, considerably in size (0.4 to 
1.2 ,h in diameter). In its growth it does not show a characteristic grouping, but 
grows in irregular masses and heaps (the somewhat crude resemblance, when studied 
under a cover-glass, to a bunch of grapes gave rise to the generic name); sometimes, 
1 Consult White, Jour, of Exp. Med., vol. iv., p. 425, 1899; also Adami, Jour, of the Am. Med. Assn., 
Dec. 16th and 23d, 1899. Both have bibliography. See also Kolle and Wassermann, " Mikroorganis- 
men." 206 
THE INFECTIOUS DISEASES 
however, pairs and groups of four or short rows of the cocci are seen. The germ is 
readily stained by the anilin dyes, and does not lose its color in Gram's method of 
staining. It does not show spontaneous movement, and, like other spheroidal forms, 
does not appear to develop spores. It is quite tenacious of vitality, surviving long 
drying and degrees of heat and cold and an exposure to chemical bactericides to which 
many pathogenic germs readily succumb. It grows well at ordinary room tempera- 
ture in such artificial culture media as nutrient-gelatin, agar, beef-tea, and milk, and 
on potatoes, forming somewhat voluminous masses of culture. It rapidly fluidifies 
gelatin through the formation of a ferment, it coagulates milk, and in the various 
media develops a yellowish white or a deep golden yellow color, whence its specific 
name, aureus, and its common name, "golden coccus." Its color-producing capacity 
is subject to wide variation. Staphylococcus pyogenes aureus1 forms in old cultures a 
haemolytic substance which may be demonstrated in plate cultures mixed with red 
blood cells (Fig. 121) or in tubes containing the washed corpuscles to which filtrates of 
old bouillon cultures have been added. 
Fig. 118.-Infective Embolus of Staphylococcus Pyogenes Aureus in the Kidney. 
Rabbit - Experimental. 
Effects of Staphylococcus Pyogenes in the Body.-The virulence of 
cultures of Staphylococcus pyogenes obtained from different sources 
varies considerably, but, in general, suppuration is not readily induced 
in the lower animals by its subcutaneous injection. Liability to sup- 
puration is greatly increased by mechanical or chemical injury to the 
tissues with which the germ is brought in contact. Injection of a viru- 
lent culture into the ear vein of the rabbit is usually followed by multi- 
1 For a study of the bacterial haemolysins see Pribram, Kolle and Wassermann, " Mikroorganismen " 
2d edition, 1913, ii., 1328. THE INFECTIOUS DISEASES 
207 
pie abscesses in the kidneys and muscles, by suppuration of joints, etc. 
(Fig. 118). 
In man this coccus grows readily and rapidly, and may induce necro- 
sis and exudative inflammation, especially the suppurative phases (Fig. 
119). The lesions which it induces are apt to be circumscribed, but it 
may induce septicaemia and pyaemia. It may induce pustules, boils, 
and abscesses, and various suppurative inflammations of the visceral 
and serous membranes, joints, bones, endocardium, etc. These effects 
may be induced by the staphylococcus alone or by it in association 
with other species of germs. It is frequenty lassociated with Strepto- 
coccus pyogenes. 
Fig. 119.-Masses of Micrococci in a Blood-vessel of the Kidney, Inducing a Small Abscess. 
From a case of pyaemia. Around the dilated and partially necrotic blood-vessel in which the bacteria 
lie is an area of necrotic tissue and a small-celled infiltration or zone or pus. 
Staphylococcus pyogenes aureus incites these changes in the body 
in virtue of certain toxins or toxalbumins which are produced as the 
result of its metabolism, and which are either at once set free or stored 
up in the body of the germs-endotoxins-until their release by dis- 
integration after the death of the germs. The special power of the 
staphylococcus to cause the gathering of leucocytes is apparently due 
to the marked chemotaxic powers of some of the protein substances in 
its protoplasm. In its growth in the body staphylococcus may lead to 
the development of haemolytic, agglutinative, leucocidal, leucolytic, and 
opsonic substances. 
Portals of Entry.-It may enter the body through wounds, small or 
large, of the skin or mucous membranes, through sweat and sebaceous 
glands and hair follicles, and sometimes through uninjured surfaces. 208 
THE INFECTIOUS DISEASES 
In many cases its mode of access is not evident.1 While usually this germ 
dies in the body, it may remain for a long time alive. 
Sources.-It is widespread in inhabited regions, especially in towns, 
being frequently found on the surface of the body, and in the saliva, par- 
ticularly of those with acute or chronic catarrh of the upper air pas- 
sages. As the result of the filthy habit of indiscriminate public spitting 
and unguarded sneezing, it is common in the dust of hospitals, houses, 
towns, public conveyances, and places of public assembly.2 It is prob- 
able, however, that the larger part of the acute staphylococcus infections 
are incited by organisms derived directly or indirectly from others 
already infected. 
Susceptibility.-In man there may be a susceptibility to Staphy- 
lococcus pyogenes associated with a general disease, diabetes for example. 
On the other hand, local susceptibility in man is of frequent occurrence. 
In the so-called furunculosis and in carbuncle, local areas of inflamma- 
tion may develop and persist for long periods, fresh foci developing 
as the older ones heal. In some instances this local vulnerability is 
apparently associated with minor local injuries, such as the friction of 
garments at the back of the neck or pressure and friction in the gluteal 
regions. Sometimes, however, the local vulnerability appears to arise 
from disturbances in the sebaceous and sweat glands and hair folli- 
cles, leading to stagnation of secretions in which the bacteria long per- 
sisting on the surface find lodgment and conditions favorable to their 
development. 
The studies of Wright have indicated that in cases of carbuncle and furunculosis 
the opsonic index3 for the special strain of staphylococcus concerned may be low, and, 
further, that the raising of this by the injection of emulsions of the dead bodies of these 
organisms-vaccines of Wright-may lead to a rapid immunization of the individual, 
marked by a rise in the opsonic index of his serum and the speedy decline of the local 
inflammatory reaction. 
Other Forms of Staphylococcus. 
Not all the yellow staphylococci found in dust and on the person are pathogenic- 
These may be indistinguishable from the infective forms by the usual culture methods- 
They may, however, be differentiated not only by their innocuousness to animals, 
but in their failure to develop in these either agglutinative or leucolytic substances. 
Staphylococcus pyogenes albus.-This appears to be a variety of the Staphylo- 
coccus pyogenes which does not develop the yellow color in cultures. It is of frequent 
occurrence both in connection with the aureus and alone. Its action on the body is 
similar, but it has seemed to many observers to be in general less virulent. 
Staphylococcus epidermidis albus.-This coccus has been described by Welch as of 
frequent occurrence in the epidermis, and, although of rather feeble pyogenic power, 
yet seems frequently to cause small stitch-abscesses and moderate suppuration along 
drainage tubes. Welch regards it as possibly a variety of Staphylococcus pyogenes 
albus. 
Other forms of staphylococcus have been described-S. salivarius pyogenes, S 
cereus albus and flavus-but they are apparently of little pathological significance.4 
1 For a resume of the r61e of S. pyogenes aureus in the skin disease, with bibl., see White, Bost. 
Med. and Surg. Jour., vol. cxli., p. 235, 1899. 
2 For bibilography of S. pyogenes aureus consult article by Neisser in Kolle and Wassermann's 
"Handbuch der Mikroorganismen," 2d edition, 1912, Bd. iv., 355. 
3 See p. 187. 
4Forastudy in differentiation between pathogenic and saprophytic staphjdocoeci see Geisse, 
Ztschr, f. Hygiene, etc., 1913, Ixxvi., 282. THE INFECTIOUS DISEASES 
209 
Characters of the Streptococcus Pyogenes. 
The Streptococcus pyogenes (Micrococcus pyogenes) is distinguished morphologi- 
cally from the cocci just described by the marked tendency which the individuals 
exhibit, when growing, to hang together in longer or shorter chains (Fig. 120). It is, 
ike the Staphylococcus pyogenes, immobile, and stains easily in the same way. By 
a special method Hiss has demonstrated a capsule on streptococci.1 
It grows readily, but more slowly than Staphylococcus pyogenes, on the ordinary 
culture media. It does not fluidify gelatin, on which it grows as small, inconspicuous, 
grayish white colonies. On the surface of agar plates kept in the thermostat at 37° C. 
for twenty-four hours, the small grayish colonies 
usually show, under the microscope, loops and 
fringes of the chain-like cocci extending off from the 
borders. The growth on potatoes is inconspicuous. 
In nutrient broth it usually forms delicate, flocculent 
masses, which cling to the sides of the tubes, leaving 
the fluid clear. Occasionally the masses of strepto- 
cocci are dense and compact. Not infrequently 
the growth is diffused through the nutrient broth, 
rendering it turbid. When in vigorous growth it 
coagulates milk and develops slight haemolytic power.2 
Under the term streptococcus are included 
several closely related forms: the Streptococcus 
longus or pyogenes, which is the organism first 
described as a streptococcus, and the inciting agent in erysipelas; the Streptococcus 
viridans, which has been isolated most often from cases of endocarditis, but also from 
cases of other infections, and has for its chief characteristic the power to cause haemolysis; 
the Streptococcus mucosus or capsulatus, which occurs in a certain number of cases of 
pneumonia and quite frequently in cases of middle-ear disease, and has but little 
haemolytic power though resembling the pneumococcus in its great pathogenicity 
for white mice.3 
Fig. 120.-Streptococcus 
Pyogenes. 
From a broth culture. 
Effects of Streptococcus Pyogenes in the Body.-Streptococci which 
give evidence of little virulence in animal inoculation are very common 
in the mouths of healthy persons. The significance of these germs in 
healthy mouths is not yet clear. 
The results of animal inoculation with the Streptococcus pyogenes 
are in general similar to those with the Staphylococcus pyogenes aureus. 
The streptococcus is very frequently associated with the staphyloccocus 
both in its distribution outside the body, in healthy persons, and in 
disease. In general it may be said that the streptococcus incites those 
forms of suppuration and fibrino-purulent inflammation which tend to 
spread both locally and through metastasis. 
Streptococcus pyogenes has been found either alone or in association 
with staphylococcus in a large number of suppurative and other in- 
flammatory processes in various parts of the body; the condition in some 
cases receiving special names, in others not. Thus, in boils and car- 
buncles, in abscesses and phlegmons, in herpes, impetigo, and panaritium, 
1 Hiss, Science, March 7th, 1902, p. 367; Jour. Exper. Med., 1901-05, vi., 317. 
2For haemolysis of streptococcus see Schlesinger, Zeit. f. Hyg., 1903, xliv., 428. 
3 For a recent study in differentiation of streptococci see Hopkins, Jour. Infect. Dis., 1914, xv. (July.) 210 
THE INFECTIOUS DISEASES 
in phlebitis and lymphangitis, in erysipelas, in suppurative inflamma- 
tion of various mucous and serous membranes, especially of the throat 
and the gastro-intestinal canal, and of the bones and joints, in some 
forms of bronchitis and pneumonia, in puerperal and other forms of 
septicaemia, in the pustules of smallpox, one or other or both of these 
germs are frequently concerned.1 
One of the most important features of the relationship of Streptococ- 
cus pyogenes to man is the frequency with which it enters as a concur- 
The streptococcus was cultivated in a culture medium-gelatin-with which red blood cells were 
mixed. Around each colony the color has left the red blood cells and is diffused through the plate. 
Fig. 121.-Haemolysis by Streptococcus Pyogenes. 
rent pathogenic agent in already established infectious diseases due to 
other forms of micro-organisms. Thus, some of the most serious com- 
plications to which the victims of scarlatina, diphtheria, typhoid fever, 
and pulmonary tuberculosis are liable are due to the action of the strep- 
tococcus in the body rendered unusually vulnerable by the existence of 
another form of infection. 
The serum of individuals adapted (immunized) to streptococci may 
agglutinate the homologous micro-organisms.2 
Streptococci, which upon their isolation from the body in suppurative 
or other infectious processes are very virulent, usually, and sometimes 
1 Anaerobic streptococci have been found by various observers in abscesses and other forms of 
suppuration of which they are apparently the excitants. 
2 For a study of agglutination of streptococci see Moser and v. Pirquet, Centrbl. f. Bak., Abth. I., 
Bd. xxxiv., 1903, pp. 560 and 714; also Neufeld, Zeitsch. f. Hyg. u. Infkr., Bd. xliv., 1903, p. 161; also, 
Weaver, Jour, of Inf. Dis., vol. i., 1904, p. 91. THE INFECTIOUS DISEASES 
211 
very quickly, partially or wholly lose this virulence under artificial 
cultivation. On the other hand, cultures of streptococci which have 
largely lost virulence under artificial cultivation, or whose initial viru- 
lence was slight, may experience a great exaltation of virulence by a 
long succession of inoculations from animal to animal.1 
In streptococcus infections haemolytic, agglutinating, and opsonic 
substances may be formed in the body. 
Artificial Immunity.-The metabolic products formed by virulent 
streptococci growing in nutrient broth have been found to induce in an- 
imals the symptoms of toxaemia. The results of preliminary experiments 
on immunization with these toxic products, and the dead and living 
bodies of the germs and the use of the blood serum of the immune 
animal for therapeutic purposes, are complex, and along the present 
lines of work apparently not very promising. 
SEPTIC SORE THROAT. 
There have been known for some time in England, and recently have 
occurred in several localities in the United States, serious epidemics of 
inflammation of the throat and tonsils associated with particular milk 
supplies. The milk apparently is contaminated by a streptococcus from 
the inflamed udder of cows or from the throats of the milk handlers. 
This organism closely resembles Streptococcus pyogenes and has been 
called Streptococcus epidemic us.2 
ERYSIPELAS. 
Erysipelas is a diffuse inflammation of the skin and subcutaneous 
tissue which tends to spread, and is characterized locally by swelling of 
the tissue and a bright red color of the integument. It is usually accom- 
panied by constitutional disturbances, the most marked of which is 
fever. The morphological changes at the seat of lesion, as we see them 
after death, vary considerably in different cases and in different stages 
of the disease. The redness of the skin usually disappears after death. 
But the tissues may be swollen by the accumulation of serous fluid. 
This fluid may be nearly transparent, or turbid from admixture with 
pus cells (Fig. 122). Pus cells may infiltrate the tissues either sparsely 
or in dense masses. Fibrin may be present, abscesses may form. Some- 
times vesicles or scabs are found on the surface, or the affected region 
may become gangrenous. Aside from the local lesions, there may be 
toxsemia marked by petechise in the serous membranes, swelling of the 
spleen, focal necroses, and albuminous degeneration in the kidneys and 
liver. 
1 For bibliography of streptococcus consult the article by v. Lingelsheim, in Kolle and Wasser- 
mann's "Handbuch der Mikroorganismen," Bd. iv., p. 453, 2d edition; for a study of the action of the 
toxin on various parts of the body see Ho men and others, Ziegler's " Beitrage," Bd. xxv., 1899. 
2 For a summary of such epidemics and a study of the streptococcus see North, Jour. Infect. Dis., 
1914, xiv., 124. 212 
THE INFECTIOUS DISEASES 
The most common excitant of erysipelas is Streptococcus pyogenes.1 
This organism may be present in large numbers in the lymph-vessels, 
especially in the borders of the inflamed region. The reasons for the 
clinical peculiarities of this phase of inflammation are not yet very clear. 
INFECTIOUS PSEUDO-MEMBRANOUS INFLAMMATION OF MUCOUS MEM- 
BRANES. (Pseudo-Diphtheria; Diphtheroid Angina; Membranous Angina.) 
Under a variety of conditions, as during scarlatina and measles, 
whooping-cough, typhoid fever, etc., or entirely apart from any compli- 
cating disorder, an acute exudative inflammation of the mucous mem- 
Fig. 122.--Erysipelas of the Skin. 
Showing streptococci in the lymph-spaces. 
branes, especially of the upper air passages, occurs, which is associated 
with and is apparently induced by the growth of Streptococcus pyog- 
enes.2 There may be mu,ch or little fibrinous exudate; there may in 
early stages, or even throughout, be none at all. The pellicle when formed 
may be loose or adherent, sharply circumscribed or tending to spread. 
The submucous tissue may show little change, or may be congested and 
cedematous, or may be the seat of suppurative inflammation (see Fig. 123), 
necrosis, or gangrene. The process may be confined to the tonsils. 
While under these varying conditions the inflammatory process is usually 
a local one and runs its course with or without the symptoms of septicae- 
mia, occasionally the streptococcus which enters the blood may induce 
the lesions of pyaemia. On the other hand, it may by aspiration gain 
access to the lungs and induce varying phases of complicating broncho- 
pneumonia. The Staphylococcus pyogenes is not infrequently associated 
with the streptococcus in these lesions, but is not apparently of primary 
significance. 
Simulating very closely, as it does in many cases, both the local and 
1 In the early days of modern bacteriology the "chain" coccus which was discovered in the exu- 
date of erysipelas was thought to bear a peculiar relationship to this clinical form of phlegmonous inflam- 
mation and was called by Fehleisen Streptococcus erysipelatis, but it has now been definitely identified 
with the S. pyogenes. 
2 Prudden, Med. Record, 1891; Baginsky, D. Med. Zeits., 1900. THE INFECTIOUS DISEASES 
213 
general phenomena of diphtheria, this disorder has formerly been con- 
founded with it, and has only recently been recognized as a distinct 
phase of disease. It is now most frequently called pseudo-diphtheria. 
It seems in part to cover the condition formerly known as croup, in part 
those cases formerly thought to be mild diphtheria. In many phases of 
acute angina, and in many cases of follicular tonsillitis, streptococci 
a b c 
Fig. 123.-Pseudo-Membranous Inflammation of Trachea. 
In this case there is purulent infiltration of the mucosa and submucosa, and of portions of the 
mucous glands, a, False membrane; b, portion of intact epithelium; c, infiltration of the mucosa with 
fibrin; d, portion of mucous gland infiltrated with pus. 
have been found in large numbers. Other bacteria, either alone or in 
association with the pyogenic cocci, may be excitants of pseudo-mem- 
branous as well as simple angina. 
OTHER BACTERIA WHICH ARE FREQUENT EXCITANTS OF SUPPURATION. 
While the Staphylococcus pyogenes and Streptococcus pyogenes are 
the most common excitants of local suppuration with and without 
toxaemia and septicaemia, such conditions, as we have seen, are not in- 
frequently due to other micro-organisms. Among these we may men- 
tion here as the more common and important:-Diplococcus pneumoniae, 
the gonococcus, Micrococcus tetragenus, Bacillus pyocyaneus, the colon 
and the typhoid bacillus, the bacillus of glanders, the tubercle bacillus, 
the pneumo-bacillus of Freidlander, the diplococcus of cerebrospinal 
meningitis, Bacillus pyogenes fcetidus, and Actinomyces with its related 
forms. 
In some of these organisms the pyogenic qualities in their relation- 
ships to human infections are most conspicuous; in others, the reaction 
of the body to their presence is such as to justify a special name. The 214 
THE INFECTIOUS DISEASES 
latter is particularly noteworthy in the case of the pneumococcus, the 
gonococcus, glanders, typhoid, and tubercle bacilli, diplococcus menin- 
gitidis, and actinomyces. 
Many other micro-organisms may be excitants of suppurative inflam- 
mation in man as well as in the lower animals under experimental 
conditions, but this exceptional reaction of living tissues does not fall 
within the scope of this work, which deals primarily with such tissue 
reactions as may occur under the usual conditions of life. 
The Bacillus Coli Communis and the Colon Group. 
The Bacillus coli communis is an organism so commonly present in the 
intestines under normal conditions as to be usually called the " colon 
bacillus." It is motile, facultative, aerobic, asporogenous, considerably 
resembling in general form the typhoid bacillus (see p. 235). It grows 
readily in artificial cultures and does not fluidify gelatin. It has been 
repeatedly found under such conditions in connection with suppurative 
processes as to justify the belief that it is often their excitant. 
It has been found in various forms of peritoneal suppuration, both 
with and without such lesions of the intestine as would obviously permit 
of its egress; in appendicitis; in suppuration about the gall-ducts; in 
haemorrhagic pancreatitis; in inflammatory processes in the genito- 
urinary apparatus; frequently in the bladder, in the pericardium and 
pleura, and it is believed to be concerned in certain types of diarrhoea. 
It is often concerned in terminal infections. 
Local infection with this organism is often associated with serious 
toxaemia and septicaemia. Intravascular injections of virulent cultures 
in rabbits are usually followed by symptoms and lesions of septicaemia. 
Introduced subcutaneously and intraperitoneally, it may excite local 
suppuration or sero-fibrinous inflammation, often haemorrhagic in char- 
acter, terminating fatally.1 
It is not possible to indicate very definitely all the conditions under 
which the colon bacillus, an ordinarily harmless intestinal saprophyte, 
may gain access to the tissues and become actively pathogenic. Whether 
it is special strains of the bacillus coming in from without which are 
pathogenic, or whether the ordinary forms assume virulent capacities 
under unknown conditions, we cannot tell to-day. It appears in any 
event that very slight damage to the mucous membrane of the intes- 
tinal tract which may permit the exit of the germs, or the existence of 
damaged tissues elsewhere in the body-in the kidney, ureter, perito- 
neum, etc., for example-favor infection with this organism. To what 
extent a reduction in efficiency of the protective fluids of the body 
may determine infection we cannot say with certainty. Shortly after 
death the colon bacillus may pass from the intestine into the tissues. 
The possibility of this post-mortem invasion should be borne in mind 
1 For details concerning B. coli, see Conradi and Bierast, Kolle and Wassermann's "Handbuch der 
Mikroorganismen," 2d edition, 1913, vi., 483. THE INFECTIOUS DISEASES 
215 
in cultures from the dead body, since it may readily and doubtless 
often has given rise to errors in diagnosis. 
The Colon Group.-There are so many organisms so closely resembling 
the colon bacillus in their morphological and biological characters 
that it has been found convenient to consider them as possible variations 
of one form and to speak of them collectively as the "colon group." 
The differentiation between the individual members of this group and 
between these and the typhoid bacillus has presented many difficulties 
to bacteriologists and given rise to much technical finesse. It is now 
possible to differentiate between members of the colon group and the 
typhoid bacillus and to separate them in cultures (see ref. to Hiss, p. 246.) 
The Bacillus Pyocyaneus. 
The occurrence of brilliant greenish or bluish pus in superficial wounds 
has been noted for over a century, although the organism causing it was 
unknown until its isolation by Gessard in 1882. The organism was not 
regarded as possessing any special pathogenic qualities until 1898 when 
Charrin published a study of the disease induced by its growth, under the 
name " La maladie pyocyanique." His observations were confirmed by 
Schimmelbusch, and since that time the Bacillus pyocyaneus has been 
recognized as a widespread organism occurring in air, dust, water, and the 
intestinal contents of man and animals, and regularly infesting the skin of 
the human body, especially the axillary and inguinal folds. It is also 
found saprophytically in the external auditory meatus. Its occurrence 
has been noted in purulent otitis media, in acute throat infections, in 
endocarditis and pericarditis, in inflammations of the urinary tract, in 
meningitis, in bronchopneumonia, and in gastrointestinal disturbances in 
infants and adults. A moderate number of cases of general infection with 
isolation of the organism from the circulating blood have been reported. 
It is frequently found in the blood post-mortem, but its presence is then 
considered to be due to a terminal invasion from the intestinal tract and 
not to a true infection. The infection by the organism of superficial wound 
especially abdominal incisions for the drainage of appendical abscesses 
is frequent; as a rule, however, it merely delays the healing process and 
does not seem to play a more active part. In closed cavities, on the 
contrary, it is highly pathogenic. Among the more marked lesions which 
are usually present in cases of pyocyaneus infection are albuminous 
degeneration of the viscera, focal necroses, hyperplasia of the lymph-nodes, 
haemorrhages, and especially superficial, circumscribed, or diffuse necrosis 
and ulceration in the intestinal mucous membrane. The most striking 
characteristic is the haemorrhagic nature of the lesions. 
Characters of the Organism. 
The Bacillus pyocyaneus is a slender rod, is motile, and is negative to Gram. 
It grows readily on artificial media, liquefies gelatine, and ultimately forms pig- 
ment. It is highly pathogenic for rabbits and guinea-pigs.1 
1 For further details see Foss, Der Bacillus pyocyaneus im Ohr., Berlin, 1908; and Heller and Lepore, 
Kolle u. Wassermann, Handbuch, 2d edition, 1913, v., 1185. 216 
THE INFECTIOUS DISEASES 
Bacillus Mucosus Capsulatus {Friedlander Bacillus'). 
In a small proportion of cases of lobar and lobular pneumonia, and 
in a few cases of exudative inflammation of the pleura, pericardium, 
meninges, nose, throat, and middle ear, this short encapsulated bacillus 
has been found. It is sometimes found alone, but in pneumonia is often 
associated either with the pneumococcus or with the pyogenic cocci. It 
has been found in the nasal secretion and mouths of healthy persons. 
While belonging definitely among the bacilli, it so frequently occurs in 
the form of very short rods or ovals or short chains that it was formerly 
thought to belong among the cocci. It is readily cultivated on artificial 
media and is slightly pathogenic for certain animals. 
It seems highly probable, rather than proven, that it may be at least 
partially responsible for the lesions with which it is infrequently asso- 
ciated in man. This germ was formerly believed to be of great impor- 
tance in connection with acute lobar pneumonia, and for a time was 
generally spoken of as the pneumococcus of Friedlander. It is now 
known not to be a coccus, and is certainly of subordinate, though occasion- 
ally serious, importance in inducing inflammation of the lungs.1 
Micrococcus Tetragenus. 
This organism has been many times found about the mouth and 
respiratory tract, especially in connection with suppurative processors 
tuberculous cavities, etc. It has been found also in metastatic abscesses. 
While not very virulent it is apparently an occasional excitant, eithe, 
alone or with other organisms, of suppuration.2 
Characters of the Organism. 
It is a coccus about 1 M in diameter, usually occurring in groups of four. These 
tetrad groups may be encapsulated. It stains by Gram's method, and is readily 
cultivated on artificial media. It forms a dense whitish growth on gelatin, which it 
does not fluidify. Septicsemic lesions with local suppuration may be induced in guinea- 
pigs by subcutaneous injection with cultures. 
The Proteus Group of Bacilli. 
This is a large and in the economy of nature an important group of 
bacilli much concerned with the putrefactive processes. 
Characters of the Group. 
The bacilli of this group may be aerobes or facultative anaerobes. They are of 
medium size, asporogenous, and while staining readily with ordinary dyes are apt to 
be decolorized by the Gram method. While the organisms of this group are bacilli, 
they often present considerable variation in form as they grow, sometimes being very 
1 Howard, Philadelphia Medical Journal, vol. i., p. 336, 1898; Stuhlern, Cbl. f. Bak., Abt. I., Orig. 
Bd. xxxvi., p. 493, 1904; Perkins, Jour. Infec. Dis., vol. i., p. 241, 1904. 
2 For resume of the significance of M. tetragenus and for bibliography consult Lartigau, Phila. 
Med. Jour., Apr. 22d, 1899. THE INFECTIOUS DISEASES 
217 
short so as to resemble cocci, sometimes forming threads which may be so bent as to 
suggest spirals. Their growth on solid media is especially characterized by the ten- 
dency to send runners from the central growth out into the surrounding media, thus 
establishing secondary growth centres. They are particularly sensitive to environ- 
ment, so that physiological as well as morphological variations are frequent. It is for 
these reasons that the name Proteus has been given to the group and to various 
species. The limitations of the named species are, however, in many cases quite ill 
defined. 
One of the most common forms has been called Proteus vulgaris. 
While this bacillus is very widespread, it is only occasionally the exci- 
tant of pathological processes in man, and then almost always in concur- 
rence with other organisms, usually the pyogenic cocci. Under these 
conditions a suppurative inflammation with foul exudate is apt to de- 
velop. Thus it has been found in purulent peritonitis and endometritis, 
in pleurisy and in phlegmonous inflammation in various parts of the 
body. Although this bacillus is not apt to grow in the human body, 
except in association with other micro-organisms which may damage 
the tissues or in tissues already vulnerable from injury, it may in the 
bladder independently incite an exudative inflammation. In animals, 
subcutaneous injection of the pure culture in considerable quantity 
may lead to abscess, while the soluble products of broth culture may 
induce toxaemia. 
Several other forms of Proteus, as well as closely related species, 
have been found in human lesions for the most part suppurative and 
necrotic in character, and these, in some cases, have been conclusively 
shown to be the excitants of the pathological processes, but the scope 
of this work does not permit further details. 
OTHER PYOGENIC BACTERIA. 
Among the other bacteria which commonly induce local suppuration, 
with or without toxaemia and septicaemia, some are of frequent occur- 
rence as excitants of such well-marked and more or less characteristic 
forms of disease as have long been recognized clinically and have re- 
ceived special names, such as pneumonia, gonorrhoea, cerebro-spinal menin- 
gitis, etc. The tubercle bacillus may also induce suppurative inflam- 
mation. These will be in part considered in the section dealing with 
the organs in which their more characteristic lesions are manifested. 
ACUTE LOBAR PNEUMONIA AND OTHER INFECTIOUS DISEASES INDUCED BY 
. THE DIPLOCOCCUS PNEUMONIAE (Pneumococcus Lanceolatus). 
Diplococcus pneumoniae is sometimes spoken of as the "pneumo- 
coccus of Frankel," because its significance and life history in connection 
with acute lobar pneumonia were first demonstrated by him.1 It is 
commonly called simply the "pneumococcus." 
1 It was discovered by Sternberg in saliva, and its pathogenic power demonstrated some years be- 
fore its full significance in connection with pneumonia was understood. 218 
THE INFECTIOUS DISEASES 
Characters of the Diplococcus Pneumoniae. 
During their development these germs are distinctly spheroidal; but in their ma- 
ture condition they are apt to become slightly elongated or oval and are often a little 
broader at one end than at the other, assuming a lanceolate form. They are very 
apt to occur in pairs, and frequently are seen in short chains, rarely in long chains. 
Very frequently, when growing in the living animals, the pneumococcus is surrounded 
by a distinct, homogeneous capsule of varying thickness (see Fig. 124). Except in 
certain media capsule development is not readily seen in artificial cultures. The 
coccus itself is readily stained by the anilin dyes and retains the stain by Gram's 
method; the capsule is not easily demonstrated except by special staining 
methods.1 
The pneumococcus has no spontaneous movement and grows but feebly at ordi- 
nary room temperature. It grows much better at blood heat, forming on the surface 
of blood-serum or on very slightly alkaline glycerin-agar 
plates faint grayish, dewdrop like, inconspicuous colonies, 
somewhat similar to those of Streptococcus pyogenes, but 
usually more delicate. In beef-tea it forms at body tempera- 
ture a delicate shimmering turbidity and a faint whitish 
sediment. As a rule, the cultures are prone to lose soon 
their virulence and to die off early, but the virulence may 
be maintained by successive inoculations in the rabbit. 
The pneumococcus may remain viable and virulent for 
many days when dried in sputum but in the form of small 
particles such as are distributed in coughing and sneezing it 
remains alive, as Wood2 has shown, for from one to one and 
a half hours. In direct sun-light it may die in a few 
moments. 
The serum of persons suffering from acute lobar pneu- 
monia, as well as the serum of lower animals artificially 
immunized to the Diplococcus pneumoniae, induces agglu- 
tination of the organism in broth cultures. Wadsworth has shown that by the use 
of centrifugated cultures of the organism, the reaction of agglutination can be ob- 
tained in much greater dilution than by the usual method.3 Precipitins are also 
found in immune sera. 
Cultures which have been reduced in virulence, so as not to cause early death by 
septicaemia, may, when introduced into the trachea of rabbits, induce circumscribed 
pneumonic lesions, especially if these animals are made vulnerable by cold or by other 
agencies which impair the integrity of the blood or other tissues. Wadsworth has 
shown that by partially immunizing rabbits to the pneumococcus, so that they do not 
speedily die from septicaemia, and then introducing the virulent organism into the 
lungs through the trachea, diffuse pneumonic lessons comparable to the lobar pneu- 
monias of man may be induced.4 Lesions of lobar pneumonia are readily induced in 
the dog by intratracheal injections of the pneumococcus. Different animal species 
vary in vulnerability to the pneumococcus. 
This germ is the incitant of typical lobar pneumonia in man, and in a 
large proportion, if not in all, cases it is present in the blood.5 It induces 
locally in the lungs an acute exudative inflammation associated with an 
enormous and rapid multiplication of the germ and a toxaemia due to the 
distribution of soluble toxic products through the blood. 
Fig. 124. - Diplococcus 
Pneumoniae. - P n e u m o- 
coccus. 
Showing the stained cap- 
sules. 
1 See Wadsworth, Jour. Inf. Dis., vol. iii., p. 610, 1906. 
2 Wood, Jour. Exp. Med., vii., 592, 1905. 
3 For details of this method see Wadsworth, Jour. Med. Research, vol. x., p. 228, 1903. 
4 See references to experimental pneumonia, p. 614. 
6 See Rosenow, Jour. Inf. Dis., vol. i., p. 280, 1904; also Dochez, Jour. Exper. Med., 1912, xvi., 680. THE INFECTIOUS DISEASES 
219 
For a more detailed description of these lesions of pneumonia, and an 
account of other bacteria which may be present, see page 603. 
In addition to its more common effect in inducing lobar pneumonia, 
the pneumococcus is frequently the excitant of exudative inflammation 
in other parts of the body, either in connection with or without a primary 
lobar pneumonia. Thus it has been repeatedly found in pleuritis, 
otitis, meningitis, empyema, pericarditis, endocarditis, and in perit- 
onitis. It has been found in abscesses of the viscera and in exudative 
inflammation of the joints. It may induce pseudomembranous inflam- 
mation of the mucous membranes. Leucocytosis usually accompanies 
infection with the pneumococcus. 
Sources of Pneumococcus.-The pneumococcus has been found in 
the mouths of a large proportion of healthy persons examined. The 
forms present in the mouths of healthy persons are apparently usually 
less virulent than the strains concerned in the incitement of pneumonia.1 
It is thrown off in the sputum in lobar pneumonia, and no doubt from 
this source to a certain extent in the dried condition, as dust, but more 
often in the droplets of sputum ejected in the coughing of pneumonics 
or in the fine spray formed in sneezing,2 furnishes the infectious agent 
which in favoring conditions of the body lights up the inflammatory 
process in the lungs.3 
Toxic Products of the Pneumococcus.-Although clinically pneumonia 
bears many marks of toxaemia, investigators have not thus far succeeded 
in finding evidence that, either in artificial cultures or in the infected body, 
very potent soluble toxins are given off through the metabolic activities 
of the pneumococcus. There is evidence, on the other hand, that the 
toxic effects may be induced by endotoxins which are set free when in the 
course of the disease the organisms die and suffer lysis.4 
The Crisis in Pneumonia.-The dramatic character of the crisis in 
many cases of pneumonia has led to much conjecture as to the changes 
in the body fluids or the bacteria which may occur at this time. There 
appears to be no marked development of bactericidal power of the serum 
alone; antitoxic substances are not demonstrable. It has been con- 
jectured that the new lore of the opsonins might throw light upon the 
role of phagocytes. But in spite of much research no very decisive 
data have as yet been elicited. 
While the crisis in pneumonia is a striking feature in its symptomatol- 
ogy it is only an accentuation of phenomena which occur in recovery from 
all infections. In pneumonia, as in other infections, two phases of the 
bacterial action are to be recognized: first, the capacity to proliferate in 
1 For a consideration of the pneumococcus of the mouth in healthy persons, and for a study of 
varieties or strains of pneumococci, see studies carried on under the auspices of the Medical Commission 
for the Investigation of Acute Respiratory Diseases of the Department of Health of the City of New 
York, by Park and Williams: Collins: Longcope and Fox: Norris and Pappenheimer: Duval and Lewis: 
Buerger: Hiss: and Longcope: Jour. Exp. Med., vol. vii., pp. 401-626,1905; also Eyre and Leathern, Jour, 
of Path., vol. ii., p. 246, 1906. 
2 See Wood, Jour. Exp. Med., vol. vii., p. 592, 1905. 
3 For study of communicability see ref. Edsall and Ghriskey, p. 606. For a study of disinfection of 
the mouth and of sputum, see Wadsworth, Jour. Inf. Dis., iii., 1906. 
4 See Cole, Jour. Exper. Med., 1912, xvi., 644. 220 
THE INFECTIOUS DISEASES 
the host, and, second, the potency of the toxic substances elaborated and 
set free in the body during the disease. Thus far in most of the experi- 
mental and critical studies of pneumonia the reactions of the cells of the 
host resulting in the production of protective substances have received 
chief attention. Many believe with Neufeld that bacteriotropic or 
opsonic substances play an important role. Others, as Romer, think 
that the chief factors in recovery from pneumonic infection are bactericidal 
substances of unknown nature in the serum. But it is not definitely 
known at present what the substances are upon which recovery depends.1 
Although both of these agencies may be important, the capacity for 
growth of the pneumococcus in the body, and the mechanism for the 
neutralization of the poisons developed in infection are also important, 
and the consideration of both classes of factors is necessary in an adequate 
survey of pneumonia. 
For in this as in every other infection, the reaction of the micro organ- 
ism as well as that of the host is decisive in the destruction of the invasive 
germs, as in the neutralization of the poisons, whether these are derived 
from the bodies of the bacteria, or in ways apparently more subtle because 
less clearly understood.2 
Serum Therapy in Pneumonia.-Cole and Dochez and Gillespie have found as 
the result of a series of immunizing and agglutination tests, made at the Hospital 
of the Rockefeller Institute, that the pneumococci present in a series of cases of 
lobar pneumonia treated there, differed in biological and to a certain extent in 
morphological characters, so that they could be classified in groups. Furthermore, 
they have shown that the effectiveness in man of curative sera secured by the use 
of these groups or strains of pneumococci in the horse, is closely dependent upon 
the choice of an homologous serum; that is, of a serum prepared through the reaction 
of the horse to pneumococci of the particular strain which the examination of the 
patient discloses.3 
Staining Reactions.-For staining the pneumococcus with its capsule the following 
method of Hiss4 gives good results. Mix the exudate or culture containing the 
organism on the cover-glass with a drop of blood-serum spread thin, dry and fix by 
heat. Add a few drops of the following stain: Five- or ten-per-cent, solution of 
gentian violet (5 c.c. saturated alcoholic solution of gentian violet plus 95 c.c. distilled 
water). Heat gently until steam rises. Wash off the stain with a twenty-per-cent, 
solution of cupric sulphate. Dry and mount in balsam. 
If the material containing the organisms already contain serum, the preliminary 
mixing with this is unnecessary. Pneumococci in sputum, which without the addition 
of serum are often stained, with it not infrequently give better results. 
The method of Welch6 gives good results, but annoying precipitates often form. 
After drying and fixing the specimen upon the cover-glass in the usual way, it is 
treated with glacial acetic acid, which is at once drained off and replaced by anilin- 
gentian-violet solution (p. 144), this being drained off and renewed several times until 
1 See Cole, Harvey Lecture, Arch. Int. Med. 1914, xiv., 56; also Hektoen, Jour. Amer. Med. 
Assn. 1914, Ixii., 254, bibl.; and Dochez, Jour. Exper. Med. 1912, xvi., 665. 
2 For studies on pneumococcus infection and the mechanism of recovery see Wadsworth, Jour. Med. 
Res., 1912, xvi, 54 and 78, bibl. 
3 For details of these studies, as yet incomplete, see Dochez and Gillepsie, Jour. Am. Med. Assn. 
1913, Ixi, 727, also Cole, ref. above. 
4 See on methods of staining encapsulated pneumococci Hiss, Jour. Exp. Med., vol. vi., p. 317, 
1901-5; also Wadsworth, Jour. Inf. Dis., vol. iii., p. 610, 1906. 
• 6 Welch, Johns Hopkins Hospital Bulletin, vol. in., p. 128, 1892. THE INFECTIOUS DISEASES 
221 
the acetic acid is displaced. The specimen is now washed with a two-per-cent, solu- 
tion of sodium chlorid, in which it may be covered and studied. The pneumococcus 
may be stained in sections by Weigert's modification of Gram's method with prelim- 
inary contrast stain (see p. 144). By this method the fibrin in pneumonic exudate 
is also stained.1 
Streptococcus Mucosus Capsulatus. 
In pneumonic and other exudates and in the normal throat one occasionally finds 
a capsulated organism growing in short chains and forming about the colonies a mass 
of mucus-like material. It is virulent for mice, less so for rabbits. After growth 
through several generations on artificial culture media it loses its capacity for forming 
the mucous material and its virulence diminishes. This organism is regarded by 
some as a variety of the pneumococcus, by others as a streptococcus (see p. 209).2 
GONORRHOEA AND OTHER INFLAMMATORY LESIONS INDUCED BY THE 
MICROCOCCUS GONORRHCEtE (Gonococcus). 
The Micrococcus gonorrhoea (gonococcus) is most commonly found in 
the exudate of gonorrhoeal inflammation of the mucous membranes, 
especially of the urethra. It may be free or enclosed in leucocytes or 
other cells (Fig. 125), within or between the epithelial cells. The 
organism may be distributed from 
the seat of primary lesion, giving 
rise to gonorrhoeal arthritis, to ma- 
lignant endocarditis, to exudative 
inflammation of the pleura, and to 
inflammatory processes in other 
parts of the body.3 
The gonococcus may in the pri- 
mary as well as in the secondary 
lesions be associated with the "pyo- 
genic cocci," the colon bacilli, or 
other micro-organisms. These as- 
sociations have been observed in 
cases of pyaemia following gono- 
coccal infection. The gonococcus is 
usually most abundant in the urethra during the acute stage of the 
inflammation. But long after the organisms have disappeared from 
the urethral discharge they may be present in small numbers in the 
deeper portions of the urethra or in the prostatic secretions whence, 
under favoring conditions, a fresh infection may arise. In the female 
the inflammation develops in the urethra and cervix, and, through the 
transportation of the gonococci, may extend along the mucous mem- 
brane to the uterus and into the Fallopian tubes. The germs may 
Fig. 125.-Micrococcus Gonorrhcej® in 
Cells.-Specimen from the Urethra. 
1 For a full resume of the studies on the pneumococcus see Neufeld and Handel, Kolle and Wasser- 
mann's "Handbuch der Mikroorganisinen," 2d edition, 1912, iv., 513. 
2 See Schottmuller, Munch, med. Woch., July 25th, 1905; also Buerger, Cbl. f. Bakt., I. Abth., Orig. 
Bd. xli., p. 314, 1906. 
3 Consult, for cases and bibliography, Young, "Welch Anniversary Contributions to the Science 
of Medicine," p. 677, 1900; also, Elting, Albany Med. Ann., Mar., 1900, bibl. 222 
THE INFECTIOUS DISEASES 
enter the peritoneum, inducing exudative inflammation. Hyperplasia 
and suppuration of lymph-nodes near the inflammatory region may 
occur. Gonorrhceal conjunctivitis is similar in origin and character to 
the inflammation of the urethra. 
Characters of the Gonococcus. 
The gonococcus is apt to occur in pairs, the apposed sides being more or less dis- 
tinctly flattened (Fig. 126). It stains readily with the anilin dyes, and differs from 
most known cocci which might be mistaken for it in that it is decolorized by the iodine 
solution in the Gram method of staining. It is well after the decolorization by this 
method, and before mounting in balsam, to make a contrast stain with a dilute aque- 
ous solution of Bismarck brown. Then the gonococci will be of 
light-brown color, while most other germs will retain the violet 
color. 
The gonococcus is non-motile and does not grow at ordinary 
room temperatures nor on the ordinary solid or fluid culture 
media. It may, however, be cultivated at the temperature of 
the body on human blood-serum or on a combination of this 
with agar. 
In serum-agar the surface growth of the gonococcus is in the 
form of small circular, sharp-edged, slightly raised, nearly trans- 
parent colonies, coarsely mottled in the central portion, finely 
granular toward the borders. The life of the colonies under artificial culture is 
short, but by frequent transference to fresh media it may be maintained indefinitely 
and gradually adapts itself to the artificial environment. 
The gonococcus is readily killed by heat and light and drying and is very vulnerable 
in the presence of many common disinfectants. 
It is probable that the organism has no natural habitat outside the bodies of 
human beings. The lower animals are not, as a rule, susceptible to inoculations of 
the mucous membranes with the gonococcus, but suppurative inflammation has been 
induced in mice and guinea-pigs by intraperitoneal injections. 
Inoculations of pure cultures of the gonococcus upon the urethral 
mucous membranes of man have been repeatedly made and were followed 
by a characteristic catarrhal inflammation. Thus the evidence is com- 
plete that the gonococcus is an excitant of the inflammation with which 
it is so constantly associated. But in what measure this germ, in what 
measure others, are responsible for the complicating inflammations 
when both germs occur together, is yet to be determined. The gono- 
coccus appears to act rather through its endotoxins than by soluble 
substances set free in its growth. 
Inasmuch as one or more forms of cocci and diplococci occurring in 
the normal and in the inflamed urethra are morphologically similar to 
the gonococcus, great caution should be exercised in doubtful cases in 
deciding upon the nature of suspicious micro-organisms in urethral 
discharges or other exudates. But the pronounced tendency of the 
gonococcus to gather within cells; the sometimes conspicuous but often 
ill-defined flattening of the apposed sides of the gonococci; the decolor- 
ization by Gram's method, which leaves most other germs apt to be 
associated with the gonococcus still stained, and whenever practicable 
Fig. 126.-Micro- 
coccus Gonorrhce.® 
(Gonococcus). 
From culture. THE INFECTIOUS DISEASES 
223 
the artificial'Culture characters-these all should be considered in the 
summary of evidence.1 
ACUTE CEREBRO-SPINAL MENINGITIS. 
This is an acute infectious process of which the characteristic lesion 
is an exudative inflammation of the pia mater of the brain and cord. 
As a rule the inflammation of the pia mater results in the production 
of serum, fibrin, and pus, which infiltrate the pia mater and accumulate 
in the ventricles, so that the gross appearance of the brain is character- 
istic. The exudation is often especially abundant at the base of the 
brain and over the posterior surfaces of the cord. In children the dis- 
tention of the lateral ventricles with purulent serum may be a marked 
feature, while in adults the quantity of serum is apt to be small. (For 
details of the lesions in exudative meningitis see Nervous System.) 
While the above are characteristic lesions of this disease, there are a 
number of secondary or associated septicsemic or toxsemic lesions in 
different parts of the body. There may be subserous punctate haemor- 
rhages in the endocardium; petechiae in the skin; acute arteritis; hyaline 
and granular degeneration in the voluntary striated muscle; occasional 
multiple abscesses in various parts of the body; suppurative inflamma- 
tion of the joints; albuminous degeneration of the heart, liver, and 
kidneys; and hyperplasia of the gastro-intestinal lymphatic apparatus 
and of the spleen. 
Cerebro-spinal meningitis may occur by itself or in connection with 
some other acute infectious disease, such as acute lobar pneumonia, 
mycotic ulcerative endocarditis, pyaemia, 
multiple suppurative arthritis, otitis media, 
puerperal fever, typhoid fever, etc. 
It may be epidemic, the lesions, however, 
being essentially similar to those in the simple 
acute form. 
The bacterial excitants of simple sporadic 
cerebro-spinal meningitis are most commonly 
the pneumococcus and Streptococcus pyo- 
genes. Of less frequent occurrence in the 
lesions are the influenza bacillus,2 the typhoid 
bacillus, and the gonococcus. Other bacteria have been recorded. 
Epidemic Cerebro-Spinal Meningitis.-This form of exudative inflam- 
mation of the meninges of the brain and cord is induced by an organism 
named by Weichselbaum Diplococcus intracellular is meningitidis (menin- 
gococcus) because of its form and its frequent presence within cells of the 
exudate (Fig. 127). While often occurring in epidemics, infection 
with the meningococcus may be sporadic. 
Fig. 127.-Diplococcus Intra- 
CELLULARIS. MENINGOCOCCUS. 
From fluid obtained by spinal 
puncture in case of epidemic 
cerebro-spinal meningitis. 
1 For summary of studies on the gonococcus with bibliography consult Koch and Bruck, in Kolle 
and Wassermann's "Handbuch der Mikroorganismen," 2d edition, Bd. iv„ p. 655 and 721. 
2 See Moore, Brit. Med. Jour., Oct. 25, 1913, bibl. 224 
THE INFECTIOUS DISEASES 
The lesions are in general similar to those above described in exuda- 
tive inflammation of the meninges with other excitants, but, in distri- 
bution and type, present some moderately characteristic appearances. 
The exudate, which is purulent, sero-purulent, or fibro-purulent, is 
usually most marked at the base of the brain and on the posterior 
surface of the cord. In death at an early period there may be simple 
hyperaemia with little exudate. The purulent exudate consists largely 
of polymorphonuclear leucocytes, but there may be large polyhedral 
Fig. 128.-Acute Endarteritis and Arteritis in Epidemic Cerebro-spinal 
Meningitis. 
The endothelium is raised from the membrana elastica by an accumulation of cells-shown in the 
next figure. The muscularis is also involved. 
cells mingled with them. These large cells, apparently derivatives of 
endothelium, are phagocytic and may contain leucocytes, red blood 
cells, etc. At later periods these large cells may preponderate in the 
exudate. The exudate may be present in the superficial layers of the 
brain and may involve the cranial nerves and the spinal nerve roots. 
There may be proliferation of neuroglia cells.1 Acute arteritis with 
the accumulation of leucocytes and the formation of new cells beneath 
the endothelium of the small arteries of the brain and cord (Figs. 128 
and 129) is often present in this disease. 
In the prolonged, so-called chronic cases there may be oedema and 
thickening of the pia mater and degeneration of the pus cells. 
1 For an epitome of lesions see Councilman, Jour. Amer. Med. Assn., vol. xliv., p. 997, 1905. THE INFECTIOUS DISEASES 
225 
Characters of Diplococcus Intracellularis Meningitidis. 
It is a diplococcus, considerably resembling the gonococcus, the 
pairs and tetrads being often flattened on the apposed sides. It is non- 
motile, not staining by Gram's method. It grows readily though not 
voluminously on appropriate culture media at body temperature. It 
is readily killed by exposure to sunlight, and by drying as well as by 
heat, cold, and the common disinfectants. 
While the meningococcus is most abundant in the meningeal exudate, 
and is obtained on lumbar puncture, it has been found in the blood1 
Fig. 129.-Endarteritis in Cerebro-spinad Meningitis-Epidemic. 
Leucocytes and polyhedral cells have gathered between the endothelium and the muscularis 
in this small artery. 
and in the nasal passages. Agglutinative substances are formed during 
the infection. 
Pathogenicity.-Inoculations of cultures into various animals, mice, 
rabbits, guinea-pigs, etc., show that it is moderately pathogenic, the 
effects seeming to be largely due to an endotoxin. Flexner has induced 
in monkeys lesions almost identical with those of man.2 
Source.-The frequent occurrence of the meningococcus in the 
nasal passages both in those suffering from epidemic cerebro-spinal 
meningitis at an early period and in those closely associated with them,3 
while it is usually absent in well persons not exposed to the disease, 
leads to the conclusion that the infectious material may be transmitted 
by the nasal secretion directly, or through the air in the spray caused by 
sneezing. There is reason for believing that entrance is gained through 
the naso-pharyngeal mucous membrane,4 and through the pharyngeal 
tonsil. This is obviously possible through the direct connections which 
exist between the meninges and the nasal mucosa by lymphatics which 
pass the cribriform bone with branches of the olfactory nerve. But the 
possibility of origin through the blood is to be held in mind.5 
1 Elser and Huntoon, Jour. Med. Res., xx., 377, 1910, bibl.; also, Davis, J. Inf. Dis., iv., 558, 1907. 
2 See Flexner, Trans. Assn. Am. Phys., vol. xxi., p. 378, 1906; also, Jour. Exp. Med., vol. ix., pp. 
105 and 142, 1907. 
3 See Weichselbaum and Ghon, Wiener klin. Wochenschr., June 15th, 1905, p. 625; also Goodwin and 
v. Sholly, Jour. Inf. Dis., Suppl. No. 2, Feb., 1906, p. 21; also Elser and Huntoon, 1. c. supra. For study 
of carriers see Chapin, Sources and Modes of Infection, 2d edition, New York, 1912. 
4 Westenhoeffer, Berl. klin. Wochenschr., June 12th, 1905, p. 737. 
5 For a study of cases with bibl. consult Councilmann, Mallory, and Wright, " Special Report of the 
State Board of Health of Massachusetts," 1898; also Elser, Jour. Med. Res., vol. xiv., p. 89, 1906. For 
agglutinative reaction see Jaeger, Zeitsch. f. Hygiene u. Infkr., Bd. xliv., 1903, p. 225. 226 
THE INFECTIOUS DISEASES 
Serum Therapy.-By the immunization of horses with dead and 
living cultures of meningococcus, and with extracts of the bodies, cura- 
tive sera have been prepared.1 Such sera injected intraspinously has 
been found after critical tests on a large number of cases to be an ex- 
tremely valuable curative agent.2 
Micrococcus Catarrhalis. 
Diplococci resembling the meningococcus and called M. catarrhalis have been 
found on respiratory mucous membranes. Their cultural characters are quite similar 
to those of the meningococcus, for which they may be easily mistaken. They are 
believed to be incitants of catarrhal inflammations. They are often associated with 
pneumococcus and the influenza bacillus. 
GLANDERS. 
Glanders is an infectious disease incited by the presence and growth 
in the body of the Bacillus mallei. 
It is most common in the horse, affecting the mucous membrane of 
the nose (when involving the skin the disease has been called farcy), 
and can be communicated to man and to certain other of the domestic 
animals by direct or accidental inoculations. 
Man is quite susceptible to glanders infection, and the disease is 
most frequent in those who come much into direct contact with horses. 
The seat of primary local infection is most often the skin, more rarely 
the mucous membranes about the nose and mouth. 
The local lesions are similar in man and the lower animals. In the 
presence of the Bacillus mallei there is usually a circumscribed or more 
rarely a diffuse infiltration of the tissue with leucocytes and young con- 
nective-tissue cells. These whitish foci of cell accumulation may be 
small and to the naked eye resemble miliary tubercles, or they may be 
larger and nodular. The tissues about them may be infiltrated with 
blood. But the accumulated cells are apt, in the presence of the bacilli, 
to become necrotic and disintegrate and thus lead to smaller and larger 
abscesses, or, if near the surfaces, to ulcers. If they occur on mucous 
membranes these lesions are often accompanied by intense diffuse 
catarrhal inflammation. 
As the glanders nodules soften, the bacilli are apt to diminish in 
number or in the capacity to stain, so that it may be possible to detect 
their presence only by inoculation or culture methods. 
The disease may begin at a single point, so that it may be mistaken 
for a carbuncle or gangrenous erysipelas. But the infection is apt not 
to remain local; the bacilli, finding their way along the lymph-channels 
into various parts of the body, set up fresh foci of inflammation and 
necrosis. Then the skin may be covered with a pustular eruption; 
furuncles, carbuncles, and abscesses may form beneath the skin and in 
the muscles. Nodules are found in the nasal mucous membrane, the 
1 Kolle and Wassermann, Deut. med. Woch. 1906, xxii., 609; Jochmann. Deut. med. Woch. 
1906, xxii., 788, who first reported good results from infraspinous injections; Flexner and Jobling, Jour. 
Exp. Med., x., 141, 1908. 
2 Flexner, Jour. Am. Med. Assn., liii., 1443, 1909, ibid., 1912, lix., 1371. THE INFECTIOUS DISEASES 
227 
lungs, kidneys, testes, spleen, and liver. The joints may be inflamed, 
and there may be osteomyelitis. Leucocytosis may accompany infection 
with the B. mallei. 
The glanders infection may, however, pursue a more chronic course, 
with hard, persistent nodules and sluggish ulcers. Under these condi- 
tions the detection of the bacillus in the tissue by a simple morphological 
examination may be difficult. 
While some forms of glanders nodules somewhat resemble in gross 
and microscopic appearance certain forms of miliary tubercles, the 
absence in the former of coagulation necrosis and of giant cells, and 
the tendency to rapid disintegration and softening in the latter, will 
usually suffice for the distinction between the two sets of lesions. But 
the demonstration of the bacilli characteristic of each is in all cases 
decisive. 
Characters of the Bacillus mallei.-The Bacillus mallei is a slender bacillus pro- 
portionately thicker than the tubercle bacillus, with rounded ends, occurring singly 
or in pairs (Fig. 130). It stains easily with the anilin dyes, but readily gives up the 
color in presence of even feeble decolorizing agents such as 
dilute alcohol or acids. It is left decolorized by Gram's method. 
It is non-motile, does not form spores, and frequently shows 
vacuoles and various involution forms. 
In the tissues the bacilli may be stained wdth Loffler's 
alkaline methylene blue. 
The glanders bacillus grows readily on almost all of the 
ordinary artificial culture media, and best at blood heat. The 
growths on solid media are apt to be viscid. On potatoes it 
forms in two or three days an, abundant yellowish pellicle which 
in a few days darkens and finally becomes brown in color. It gradually loses its 
virulence in successive generations of artificial cultures. The germ is easily killed by 
moist heat, by sunlight, drying, and the several germicidal chemicals.1 
Field mice and guinea-pigs are very susceptible to infection with the Bacillus 
mallei, and develop highly characteristic local and general lesions. 
Toxic Products and Immunity.-The toxic product of B. mallei is chiefly stored in 
the body of the organism as an endotoxin. On extraction by methods similar to those 
usedin the preparation of tuberculin, (p. 261), the product called mallein has been 
found useful as a means of diagnosis in glanders, affected animals showing local re- 
actions and a sharp rise of temperature, and marks of toxaemia. 
Immunity is not apparently secured by glanders infection and while antibodies- 
agglutinins-are formed, effective curative sera have not been prepared. 
Diagnosis.-In cases in which an early diagnosis is imperative it is well, in 
addition to the morphological examination and cultures of the suspected exudate, to 
inject a small amount into the peritoneal cavity of a male guinea-pig. If the virulent 
glanders bacilli be present, within two or three 'days the testicles will swell and 
develop an intense suppurative inflammation. 
Fig. 130.-Bacillus 
Mallei. 
Several bacilli, apparently related to the B. mallei, have been found in various 
lesions in men and lower animals. Thus an organism called Bacillus pseudotuberculo- 
sis has been found in certain nodular lesions somewhat resembling tubercles which are 
especially frequent in rodents. B. pseudotuberculosis liquefaciens has been described 
in a series of cheesy nodules of the peritoneum, pancreas, and liver in man. In this 
group also belong organisms which have been found in noma. 
Other Bacilli Related to Bacillus Mallei. 
1 For a resume of characters of the glanders bacillus see Wladimiroff in Kolle and Wassennann's 
" Handbuch der Mikroorganismen," 2d edition, Bd. iv., p. 1063. 228 
THE INFECTIOUS DISEASES 
Chancroid (Soft Chancre). 
Soft chancre or chancroid is an acute inflammatory lesion usually of the genital 
regions, at first pustular, then ulcerative. The infective agent is communicated by 
contact. Neighboring lymph-nodes are apt to suffer an acute hyperplasia passing into 
abscess. 
In the lesion of soft chancre and the discharge from it a small oval bacillus ("Du- 
crey's bacillus") has been frequently found either clustered or in chains. It stains 
readily with methylene blue, although it easily loses the color. It usually occurs 
with other micro-organisms, and has been found, though not commonly, in the buboes. 
It has been obtained in pure culture, in rabbit-blood agar and in human blood, and 
inoculation experiments in man and in monkeys indicate its pathogenicity.1 
This disease, which is much more common in the lower animals, 
especially the herbivora, than in man, is widely prevalent in Europe. 
It is comparatively rare in the United States, but in certain regions is 
more common than formerly. 
It is induced in man by accidental inoculation with the Bacillus 
anthracis, which also incites the disease in the lower animals. Inocu- 
lation may occur through the skin by the agency of flies and other 
ANTHRAX. (Splenic Fever; Malignant Pustule; Charbon; Carbuncle.) 
From a man who had been handling foreign hides in New York. Bacilli stained. 
Fig. 131.-Anthrax-Malignant Pustule-of the Skin. 
insects which have been feeding on animals infected with this disease, 
through abrasions or slight wounds on the hands of those handling 
their carcasses or hides, or in other ways. Following this skin inocula- 
tion a pustule is apt to develop-" malignant pustule"-and varying 
phases of an acute exudative inflammation, which may be haemorrhagic, 
sero-fibrinous, purulent, or necrotic, accompany the local proliferation 
of the germs (Fig. 131). Anthrax bacilli in large numbers may be pres- 
ent in the local lesion. From this local source a general infection may 
ensue. General infection may occur without evident external lesion. 
Infection with anthrax may occur through the lungs, most often 
among those who handle infected wool or hides, the dust from which is 
inhaled ("wool-sorter's disease"). Under these conditions there may 
1 See Davis, Journal of Medical Research, vol. ix., 1903, p. 401, bibl. THE INFECTIOUS DISEASES 
229 
be oedema, lobular pneumonia with involvement of the pleura, medias- 
tinum, and other adjacent structures. Infection through the gastro- 
intestinal canal takes place by the ingestion of food containing anthrax 
spores, and is apt to be accompanied with inflammatory and necrotic 
changes, which are described in detail among lesions of the intestine. 
This is a common mode of infection in animals. 
When general anthrax infection occurs the post-mortem appearances 
vary. Decomposition, as in other acute infections, generally sets in 
early. The blood is frequently not much coagulated and dark in color. 
Haemorrhages and ecchymoses are frequently found in the serous and 
mucous membranes and in various other parts of the body. 
Fig. 132.-Bacillus Anthracis Growing in the Blood-vessels of the Liver of a Mouse In- 
oculated with a Pure Culture of the Bacillus. 
The lungs may show small haemorrhages and oedema, and the bron- 
chi may be deeply congested. The pleural cavities may contain serum. 
The intestines may exhibit the lesions of the so-called intestinal mycosis. 
The bronchial and other lymph-nodes may be swollen. The spleen may 
be swollen, very dark in color, and soft, sometimes almost diffluent. 
The bacillus may be found, usually in large numbers, in the spleen 
and in the capillary blood-vessels, especially in the liver (see Fig. 132), 
lungs, kidneys, and intestine.1 
Characters of the Bacillus Anthracis. 
The Bacillus anthracis is from 5 to 20 y long and about 1 to 3 g broad, and is often 
uneven along the sides. The ends of the bacilli are square or slightly concave, and 
the bacilli often hang together end to end, forming thread-like structures (Fig. 133). 
While the bacilli in the vegetative condition are easily killed, they develop spores 
outside the body only, and these are very invulnerable to the ordinary germicidal 
1 For bibliography and resume of anthrax see Sobernheim, Kolle and Wassermann's " Handbuch der 
Mikroorganismen," 2d edition, 1913, iii., 583. 230 
THE INFECTIOUS DISEASES 
agents and to heat, resisting often for many days the action of from 2- to 5-per-cent. 
carbolic acid and defying for some minutes the action of live steam. Anthrax bacilli 
are immobile, sometimes capsulated, and are easily stained by the anilin dyes. They 
grow readily on artificial culture media at ordinary room temperatures, fluidifying 
gelatin. 
Subcutaneous inoculation of cultures of the anthrax bacillus into various species of 
animals induces characteristic lesions. White mice and guinea-pigs are especially 
susceptible, usually succumbing to the anthrax septicaemia in from two to four days. 
Serous exudations, often bloody and with many bacilli, develop at the seat of inocula- 
tion, while in the blood multitudes of the bacilli are found. 
Immunization.-If cultures of the anthrax bacillus be made at a temperature of 
about 42° C., growth occurs, but it is meagre. Spores are not formed as they are at 
body temperature, and the virulence of the germ dimin- 
ishes day by day, so that at last the most susceptible 
animals are not affected by large inoculations of the 
living organisms. If fresh cultures of these organisms 
be made in various stages of their diminishing virulence 
and maintained at their optimum temperature, spores 
will again form, the growth will become vigorous, and 
in morphology quite characteristic; but the physiolog- 
ical qualities which determine virulence will remain 
more or less in abeyance. 
By inoculation of animals with anthrax cultures, 
first w'ith those which had been kept at 42° C. for from 
fifteen to twenty days, and thus had but feeble virulence, 
and passing to those cultivated at 42° C. for a shorter time and which were thus more 
virulent, Pasteur secured immunity from anthrax in a series of the lower animals (see 
p. 162). Based upon these experiments a method of protective inoculation has been 
practised on a large scale among sheep and other animals in some parts of Europe 
which has been of great economic value. The death rate from anthrax has by these 
methods been reduced in sheep from 10 per cent, to about nine-tenths of 1 per cent., 
and in cattle from 5 per cent, to less than four-tenths of 1 per cent.1 
Little is known of soluble toxins or endotoxins of the anthrax bacillis. 
Fig. 133.-Bacillus Anthracis 
Containing Spokes. 
From a culture. 
ACTINOMYCOSIS. 
This disease, which is of occasional occurrence in man, but is more 
common in the domestic animals, especially in cattle and in horses, is 
most frequently characterized by a slow suppurative and proliferative 
process, often leading to the formation of large fungous masses which 
may become calcareous. 
In cattle, the new-formed tissue, which develops with especial fre- 
quency in the jaw, is apt to extend beyond the original site and to slough, 
so that not only may the tissues of the tongue, pharynx, larynx, etc., 
be involved, but secondary nodules of similar character may form in the 
lungs, gastro-intestinal tract, and skin. 
In man, suppuration with necrosis and the formation of abscesses, 
ulcers, and fistulse, are the most marked lesions in parts near the surface 
of the body. In the lungs the lesions may be essentially those of an 
acute general bronchitis or in the form of broncho-pneumonia (Fig. 134), 
with the formation of new tissue.3 
1 For a study of opsonic substances in dog serum favoring phagocytosis of anthrax bacilli see 
Hektoen, Jour. Inf. Dis., vol. iii., p. 102, 1906. 
2 For a detailed description of the lung lesions in actinomycosis, with general bibliography, see 
Hodenpyl, "Actinomycosis of the Lung," New York Medical Record, Dec. 13th, 1890. THE INFECTIOUS DISEASES 
231 
Abscesses and cavities may form which extend into adjacent parts. 
In intestinal actinomycosis nodular masses of new tissue with ulceration 
may develop in the mucosa and submucosa. Metastases have been 
described. The excitant of this disease-now most commonly called 
Actinomyces bovis-is a micro-organism which seems to be more closely 
related to the moulds than to the bacteria. It is, however, considered 
here because its botanical position is not yet clearly established, and it 
may be one of the so-called pleomorphous bacteria (see p. 135). 
Fig. 134.-Actinomyces Growing in Human Bronchus. 
(The bulbed ends of the filaments are seen in the borders of the colony. The bronchus, cut lengthwise, 
contains purulent exudate, and its wall is becoming involved.) 
The organism often grows in the tissues in the form of little rounded 
masses from a size so small as to be invisible to that of a pin's head. 
They may be transparent or grayish white or yellow or dark in color. 
Under the microscope these masses often appear in the form of a dense 
group of radiating filaments with more or less bulbous ends; hence the 
common name "ray fungus." 
Characters of Actinomyces. 
The organism when freed from other bacteria is readily cultivated at 37° C. It 
grows in delicate branching threads which show segments resembling bacilli and cocci 
besides bulbous or club-shaped forms, probably "involution forms." Successful 
inoculations of cultures have been made in animals. 
The organism is usually conveyed from one animal to another by inoculation or by 
contact of the growth with a wound or an abrasion of the mucous membrane. 232 
THE INFECTIOUS DISEASES 
In the examination of sputum, faeces, pus, etc., for the presence of actinomyces 
the naked-eye appearances may be of value, since the yellowish white granules are 
often quite visible, especially on a black background. Suspicious masses may be 
teased and studied unstained, or stained by Gram's method. Sections of tissue may 
be hardened in alcohol, and sections stained by Gram's method with contrast eosin 
stain. 
Many forms of micro-organisms of similar general characters to actinomyces have 
been described, some occurring in connection with infective processes in man and the 
lower animals of which they seem to be the excitants, others living as saprophytes in 
various situations. Among the apparently pathogenic forms we may mention the 
following: 
An organism somewhat resembling actinomyces and found in connection with a 
disease commonly called mycetoma or "Madura foot," frequent in the tropics and 
characterized by new nodular growths associated with suppuration and necrosis 
most often affecting the foot.1 
Another form has been described in connection with a peculiar form of erysipela- 
tous inflammation of the skin; another in the so-called farcin de boeuf, a disease of 
cattle in Guadeloupe; this has been called Streptothrix and now Nocardia. 
Several times organisms of this general character, but differing considerably from 
actinomyces, have been found in inflammatory and necrotic lesions of the lungs. 
Whether these are variants of that species or independent species, and how many such 
there are it is impossible at present to say.2 Many attempts have been made to 
classify these organisms but knowledge of them is still too incomplete to permit 
accurate distinctions. 
Other Organisms Resembling Actinomyces. 
In the last few years a considerable number of cases of a chronic fungoid process 
involving the skin and mucous membranes, and occasionally resulting fatally, have 
been described. Several types of organism, growing on ordinary media, have been 
isolated. The condition is known as sporotrichosis.3 (See also p. 149.) 
Sporotrichosis. 
Pharyngo-Mycosis Leptothrica. 
Certain filamentous micro-organisms called Leptothrix, whose botanical affiliations 
are not yet clear, are of common occurrence in the mouths of healthy persons. Occa- 
sionally, however, a persistently recurrent attack of "sore throat," with local tender- 
ness and sometimes cough and fever, is associated with the growth of masses of lepto- 
thrix in the crypts of the tonsils, at the base of the tongue, on the walls of the pharynx, 
or in the nose or superior portion of the oesophagus. The leptothrix masses or colonies 
form thick whitish pellicles or patches which may be superficial, or in tonsils may 
extend deep into the crypts. These masses are usually firmly adherent, often leave 
bleeding surfaces when removed, and the growth is apt persistently to recur. 
Microscopic examination of removed portions of the growth show tufts and bun- 
dles of the thread-like micro-organisms, growing among or directly out from flat epi- 
thelial cell masses and mingled with various other forms of micro-organisms, mostly 
cocci and short bacilli. There may be overgrowth of epithelium and collections of 
leucocytes in and about the leptothrix masses.4 
1 Consult Wright, Journ. Exp. Med., vol. iii., p. 421, 1898, bibl.; also in Jour. Med. Res., viii., 349- 
1905 and Osler's, "Modern Medicine, I., 327, 1907. 
2 For a description of two such cases, with a selected bibliography, see Norris and Larkin, Journ 
Exp. Med., vol. v., p. 155, 1900; also case by Tuttle, Med. and Surg. Rep., Presby. Hosp., N. Y., vol. 
vi., p. 147, 1904. 
For a critical summary of this group of organisms, with a full bibliography, see monograph by 
Lachner-Sandoval, "Ueber Strahlenpilze," Strasburg, 1898; see also Kolle and Wassermann's "Hand- 
buch der Mirkoorganismen," 2d edition, Bd. v., p. 267 and 365 
For a full treatment and bibliography consult the monograph on " Aktinomykose " by Schlegel 
in Kolle and Wassermann's "Handbuch der Mikroorganismen," Bd. v., p. 301; see also Musser, Pearce, 
and Gwyn, Trans. Assn. Am. Phys., vol. xvi., p. 208, 1901. 
3dFor further details and bibliography see de Beurmann and Gougerot, Traits des sporotrichoses, 
Paris, 1912. 
4 For further details and bibliography consult Campbell, Medical News. Apr. 4th, 1896; also Pearce, 
Bull, Univ. Penn., vol. xiv., 1901, p. 217; also Davis, Jour. Infect. Dis., 1914, xiv., 144. THE INFECTIOUS DISEASES 
233 
INFLUENZA. Epidemic Catarrhal Fever; La Grippe. 
This is an infectious disease characterized by fever, physical and 
mental prostration, and exudative inflammations in different parts of 
the body. Thus there may be exudative inflammation in the respiratory, 
digestive, and nervous systems, either singly or together. Sometimes, 
however, these local inflammations may be absent, when the disease may 
be marked by the characteristic prostration and symptoms of toxaemia. 
None of the lesions appear to be characteristic. The lesion of the 
lungs is usually of the broncho-pneumonic type and is apt to involve the 
interstitial tissue. The cut surface is smooth, the exudate is soft and 
contains relatively little fibrin. The lung resembles that of "purulent 
infiltration." 
The numerous bacterial studies which up to 1892 had been made on 
epidemic influenza had failed to reveal any micro-organism which could 
fairly be regarded as of etiological significance, although some of the 
complicating inflammations of the lungs had been shown to be very 
frequently associated with the pyogenic cocci-Staphylococcus pyogenes 
and Streptococcus pyogenes and the Diplococcus pneumoniae. 
Early in 1892, Pfeiffer, Kitasato, and Canon described the occurrence 
in the bronchial exudate and in the blood of influenza patients of a very 
small bacillus, hitherto unknown or possibly noted earlier by Babes. 
This bacillus-B. influenza-was sometimes present in the bronchial 
exudate in enormous numbers, and often with little or no contamina- 
tion with other germs. It was found at the seat of other local lesions, 
and the pus cells often contained many bacilli. It has been found to 
persist in the body long after the active processes have ceased.1 
Characters of the Influenza Bacillus. 
The influenza bacillus is very small-about 0.5 y long by 0.2 by 0.3 y in width- 
with rounded ends, non-motile and does not form spores. It stains with some 
difficulty with simple anilin dyes; but by Ziehl's solution (p. 258), or by warmed 
Loffler's methylene blue (p. 145), it is readily colored. It does not retain the stain 
well by Gram's method. The organism apparently dies after a few hours' drying in 
the air and soon in water and is readily killed by heat or cold or chemical germicides. 
This bacillus grows best at body temperature, on glycerin-agar whose surface has 
been smeared with blood-human, rabbit, or pigeon. It forms very small, scarcely 
visible, dewdrop-like colonies, which, although growing close together, do not tend to 
coalesce, as many micro-organisms do. It has been cultivated through several gene- 
rations, but usually dies soon. 
Animal inoculations have given diverse and not very marked results, most of the 
lower animals being apparently quite insusceptible except to very large doses of 
cultures which may have a toxic action upon them. In monkeys, however, influenza- 
like symptoms have been induced by application of cultures to the nasal mucosa. 
The evidence that the organism described above is the excitant of 
epidemic influenza rests largely upon its apparently constant presence, 
especially in the exudates of the nasal and bronchial mucous membranes, 
1 For a full resume of the characters of the influenza bacillus and its relation to various forms of the 
disease, with bibliography, see the articles by Scheller in Kolle and Wassermann's "Handbuch der 
Mikroorganismen," 2d edition, 1913, Bd. v., p. 1257. 234 
THE INFECTIOUS DISEASES 
where it may be present in enormous numbers and almost free from 
admixture with other germs. 
Cases of sporadic influenza are of frequent occurrence, especially in 
towns. These are often mixed infections, the influenza bacillus being 
associated with pneumococcus, streptococcus, etc. 
That the organism should have been occasionally found under other 
conditions,1 as in chronic pulmonary tuberculosis, does not at all militate 
against its significance in inciting the manifestations of influenza, since 
many parallel instances are known in other infectious diseases. The 
frequent discrepancy between the clinical and bacterial diagnosis in 
influenza is largely due to its varying and often obscure clinical manifes- 
tations which render possible and convenient the use of the name for 
many phases of catarrhal and other forms of inflammation. 
Immunity in any marked degree does not appear to be conferred by 
influenza. 
Source.-Material containing the influenza bacillus is readily and 
doubtless frequently conveyed from the victims of influenza or from 
those harboring the organism to the well in droplets and spray dispersed 
through the air by unguarded coughing and sneezing, as well as by 
direct personal contact and the use of contaminated utensils for food 
and drink. 
Other Organisms of the Influenza Bacillus Group. 
There are several organisms in the influenza bacillus group which considerably 
resemble it, some of which appear to be pathogenic, others not so. Thus several 
observers have found in exudates from various sources, but especially in the respira- 
tory passages, small immobile asporogenous bacilli growing best under conditions 
similar to those favorable to the influenza germ, the colonies being similar. They are 
somewhat larger than the influenza bacillus, and tend to form threads. This organism 
has been called the pseudo-influenza bacillus-B. pseudo-influenza. Its pathogenic 
capacities are not clear, but it evidently differs in this respect from the genuine influ- 
enza bacillus. In stained specimens of exudate the pseudo-bacillus may be mistaken 
for its relative. It seems probable that there may be several forms of organisms not 
distinguishable at present from each other and from the influenza bacillus, which 
have been grouped under the name B. pseudo-influenzse, so that the use of the name 
is of doubtful value.2 
Another bacillus of this group, B. conjunctivitidis-Koch-Weeks bacillus-has 
been found in conjunctival catarrh by several observers in various countries and is 
doubtless the inciting factor in a readily communicable form of conjunctival inflam- 
mation. This bacillus, resembling the influenza bacillus, is somewhat longer and 
grows on blood-free media. It may be differentiated by cultural characters. Animal 
inoculations have been negative. 
TYPHOID FEVER. 
Typhoid fever is an acute infectious disease incited by the Bacillus 
typhosus. The reaction of the body to this bacillus is usually mani- 
fested by characteristic lesions, especially by hyperplasia and necrosis 
1 See Park, "Pathogenic Bacteria and Protozoa," 4th edition, 1910, p. 353; see also for studies of 
this organism Lord, Bost. Med. and Surg. Jour., vol. clii., pp. 537 and 574, 1905, also Auerbach, Zeits. 
f. Hygiene u. Infkr., Bd. xlvii., p. 259, 1904; also Davis, Jour. Inf. Dis., vol. iii., p. 1, 1906. 
For a study of the influenza bacillus in inflammations of the respiratory tract in infants see Woll- 
stein, Jour. Exp. Med., vol. viii., p. 681, 1906. 
2 See ref. Wollstein above. THE INFECTIOUS DISEASES 
235 
in the lymphatic structures of the intestines and the mesenteric lymph- 
nodes, and in the spleen, as well as by the more general alterations 
incident to toxaemia and septicaemia; but the infection is occasionally 
of the septicaemic type without characteristic local lesions in the intes- 
tines, or mesenteric nodes, or other viscera. 
The Bacillus of Typhoid Fever. 
The presence of a bacillus, called Bacillus typhosus, in various parts 
of the body in typhoid fever, in a considerable proportion of the cases 
examined, has been well established. This bacillus does not occur in 
the body, so far as is known, except in connection with this disease. 
Characters of the Bacillus Typhosus. 
The typhoid bacillus is usually about three times as long as broad, being about one- 
third as long as the diameter of a red blood cell. It is rounded at the ends, motile, 
aerobic, facultative anaerobic, and asporogenous. 
It grows readily at room temperature on the ordi- 
nary media. In cultures the bacilli often cling 
together end to end, forming threads (Fig. 135). 
It is readily killed by heat, is fairly resistant to 
chemical germicides, and remains alive for some 
time frozen in ice. 
The inoculation of lower animals with the 
typhoid bacillus may result in various lesions, and 
prove fatal, but typical typhoid fever is not 
induced.1 
The typhoid bacillus in its growth in cultures 
does not seem to produce soluble toxins of 
marked potency in very considerable amount though there is evidence that some 
such poison is formed.2 On the other hand, there is stored up in the bodies of the 
bacilli a virulent endotoxin which has been largely used in artificial immunization. 
It is probable that the more characteristic symptoms and lesions of 
typhoid fever are largely due to the absorption of toxic substances which 
are produced as the result of the life processes of the bacteria at the 
point of their greatest accumulation and activity. It should be borne 
in mind that the typhoid bacillus, as is the case with many other bac- 
teria, may induce local changes by means of its endotoxins, which are 
set free as the organisms disintegrate after their death in the body.3 
Fig. 135.-Bacillus Typhosus. 
Primary Characteristic Lesions. 
We shall first consider the lesions which are most common and char- 
acteristic of typhoid fever. 
The Intestines.-The lesions of the intestines consist of an inflamma- 
tory enlargement (hyperplasia) of the solitary lymph-nodules and of 
the agminated lymph-nodules (Peyer's patches). Necrosis of the nod- 
ules with ulceration frequently follows the hyperplasia. 
1 For a study of experimental typhoid see Atlassoff, Ann. Inst. Pasteur, t. xviii., p. 701, 1904, bibl. 
2 For a study of the soluble poisons o the typhoid bacillus see Rodet, Lagriffoul, and Aly Wahby, 
Arch, de med. exp., t. xvi., p. 397, 1904. 
3 For a study of the typhoid bacillus, with reference to the pathology, diagnosis, and hygiene of the 
disease, see Hiss, Med. News, May 11th, 1901. 236 
THE INFECTIOUS DISEASES 
The process appears to begin with a catarrhal inflammation of the 
mucous membrane, accompanied or immediately followed by changes in 
the lymph-nodules. The lesions in the lymph-nodules begin early; 
they have been observed in persons who have died forty-seven hours 
after the commencement of the disease. The increase in size of the 
agminated and solitary nodules may be rapid or gradual. The nodules 
may be only slightly enlarged, or may project far into the lumen of the 
intestine. The enlargement is usually more marked in the agminated 
than in the solitary nodules. Usually the whole of a Peyer's patch is 
enlarged, but sometimes only a part of it. If the enlargement be 
gradual the different nodules which make up a Peyer's patch may 
enlarge, while the septa between them remain but little changed, thus 
giving the patch an uneven appearance. 
Fig. 136.-Hyperplasia of Peyer's Patches in Typhoid Fever. 
The patches which are only moderately enlarged are of reddish or 
reddish gray color, and soft and spongy, and their edges blend gradually 
with the adjoining mucous membrane. The patches which are more 
markedly affected are of grayish color, of firm consistence, and rise 
abruptly from the surrounding mucous membrane (Fig. 136) or even 
overhang it like a mushroom. The largest patches are sometimes 
more than three-eighths of an inch thick. 
The enlargement and infiltration may spread from the patches to 
the surrounding mucous membrane, so that the patches appear very 
large; a number of them may become fused together, and there may 
even be an annular infiltration entirely around the lower end of the 
ileum. The infiltration, limited at first to Peyer's patches, may extend 
outward into the muscular coat, and appear in the peritoneal coat as 
small, gray, rounded nodules. This condition is usually found only 
with a few patches in the lower end of the ileum; sometimes in the 
csecum and appendix vermiformis. 
The solitary nodules are affected in the same way as Peyer's patches. 
They may be hardly enlarged at all, or be quite prominent, or may be 
affected over a larger portion of the intestine than are the patches. 
Very rarely the solitary nodules are enlarged, while the patches are not 
at all or but slightly affected. THE INFECTIOUS DISEASES 
237 
The inflammation and enlargement of the agminated and solitary 
nodules may be followed by a healing process. The character of this 
process varies according to the intensity of the previous inflammation. 
If the reaction be slight and the enlargement of the nodules moderate, 
the enlargement gradually disappears, and they resume their normal 
appearance (resolution). In moderate enlargements of Peyer's patches 
resolution proceeds first in the nodules, leaving the septa between them 
for a time still swollen and prominent. This gives to the surface of a 
patch a reticulated appearance. After a time, however, the entire 
patch becomes flattened and uniform. On the other hand, the solitary 
nodules or the separate nodules of a patch may soften, break down, and 
their contents be discharged with 
some attendant haemorrhage. This 
leaves a bluish gray pigmentation, 
due to altered haemoglobin, in the 
situation of each nodule, and this 
may remain for years. 
In more severe types of the 
disease the enlargement of the 
nodules and Peyer's patches ends in 
ulceration. This takes place in two 
ways: 
(a) The enlarged nodules or 
patches become necrotic, soften, 
break down, and discharge into the intestine. In this way are formed 
small ulcers (Fig. 137). These ulcers increase in size by the same 
softening process, which gradually extends at their edges, and in this 
way ulcers of large size may be formed.1 The ulcers may extend out- 
ward to the muscularis or to the peritoneal coat, or they may involve 
the peritoneal coat also and perforate. 
(6) In the severest forms of the disease considerable portions of the 
enlarged patches may slough and become detached, leaving large ulcers 
with thick, overhanging edges (Fig. 138). The slough may involve 
only the nodules, or it may involve also the muscular and peritoneal 
coats, and perforation may occur. These ulcers also may afterward 
increase in size, and several of them may be joined together. When 
the ulceration leads to perforation, peritonitis and death are the usual 
result. In rare cases, however, the patient recovers and the perforation 
is closed by adhesions. 
If the patient recover, the ulcers are covered by granulation tissue, 
their edges become flattened, the granulation tissue becomes firmer and 
denser, and this new connective tissue is gradually covered with cylin- 
drical epithelium. 
The minute changes which take place in the development of the 
intestinal lesion are as follows: 
Fig. 137.-Hyperplasia of Peyer's Patch 
in Typhoid Fever, with Small Ulcers. 
The separate small ulcers are extending and 
have in part coalesced. 
1 Owing to the frequent involvement of Peyer's patches, the larger intestinal ulcers in typhoid 
fever are apt to have their longest diameter lengthwise of the gut in contrast to spreading tuberculous 
ulcers, which, owing to the extension of the local inflammation along the encircling lymph channels, 
are apt to have the longest diameter crossing the gut. But exceptions to this general rule are common. 238 
THE INFECTIOUS DISEASES 
At first the blood-vessels around the nodules are dilated and con- 
gested, while the nodules are swollen and the epithelium may fall off. 
Then the nodules increase in size, largely from a growth of new cells. 
This cell growth is essentially a hyperplasia of normal elements of 
Fig. 138.-Ulceration of Peyer's Patches and Solitary Lymph-nodules in Typhoid Fever. 
The swollen patches and nodules are necrotic except at their edges, the central portions forming a 
ragged slough. 
the lymphatic tissue, namely, the lymph cells and the endothelium of 
the trabeculae and sinuses. There are thus two main types among the 
new-formed cells: first, small cells with relatively large and deeply stain- 
ing nuclei; and second, larger polyhedral or rounded cells with more 
or less vesicular nuclei. The larger cells may contain foreign substances, 
Fig. 139.-Endothelial Cells in Hyperplasia of Peyer's Patch in Typhoid Fever. 
These exfoliated and newly formed cells contain various foreign substances-leucocytes, red 
blood cells, fragments of nuclei, etc. Some of them are necrotic and are degenerating. A mitotic figure 
is seen in one. 
such as red blood cells or leucocytes (Fig. 139). The occurrence of 
mitotic figures in the endothelial cells while these are in situ, and the 
position and grouping of the large cells, appear to prove their endothelial 
origin. The production of new cells is not confined to the nodules, but THE INFECTIOUS DISEASES 
239 
extends also to the adjacent mucous membrane and underlying tissue. 
In many cases also little foci of similar new-formed cells are found in 
the muscular, subserous, and serous coats. 
In this stage resolution may take place; then the new-formed cells 
degenerate and gradually disappear. In severer forms of the disease 
necrotic changes are apt to supervene, leading to the larger and small 
ulcers above described. The factors which determine the death of the 
hyperplastic tissues are not yet fully understood. It is believed by some 
to be directly due to toxic substances formed by the typhoid bacilli 
w'hich kill the tissue cells; others are inclined to attribute it to the pres- 
sure which the new-formed cells exert on the nutritive blood-vessels. 
Fig. 140.-Phagocytes in the Perifollicular Sinuses of a Mesenteric Lymph-node in 
Typhoid Fever. 
The large cells in the sinuses contain red blood cells and blood pigment. 
The conclusions on this point which Mallory draws from a long and 
interesting series of studies would indicate that a proliferation of the 
endothelial cells of the blood-vessels may lead to their occlusion. This 
observer describes the formation of occluding thrombi in the lymph- 
vessels and smaller veins. These are composed of the proliferated 
endothelial cells which have degenerated, together with fibrin whose 
formation these degenerating cells induce. The accumulation of serous 
and fibrinous exudate about these thrombi, and the necrosis of tissue 
which may now ensue may soon be followed by necrosis of the super- 
ficial epithelium and the development of ulcers. The accumulation of 
polymorphonuclear leucocytes may, according to Mallory, now occur, 
and, in cases which go on to recovery, healing follow'S by the formation 
in the usual way of granulation tissue with the ultimate restitution of 
the surface epithelium. Mallory lays great stress upon the phagocytic 
nature of the new-formed cells of the veins and lymph-vessels (Fig. 140 240 
THE INFECTIOUS DISEASES 
and Fig. 141). For the significance of this process and other interesting 
details we refer to the original paper.1 
The lesions which we have described are found most frequently and 
are most pronounced in the lower part of the ileum. They are not 
always, however, confined to this situation. Enlarged and ulcerated 
nodules may be found over the entire length of the ileum and even in 
the jejunum. They may also extend downward and be found in the 
colon, even as far down as the rectum. Similar changes may take 
place in the appendix vermiformis.2 A few cases are recorded in which 
local nodular foci of new cell production, necrosis, and ulceration are 
limited to the colon. Clusters of typhoid bacilli may be found in these 
nodules. These are usually irregularly scattered, are not limited to a 
hyperplasia of the lymph-nodules, and should be distinguished from 
simple nodular hyperplasia with ulceration.3 
Fig. 141.-Phagocytic and Necrotic Cells in Lymph-vessel near Peyer's Patch in the Wall 
of the Intestine in Typhoid Fever. 
Mesenteric Lymph-nodes.-The mesenteric nodes undergo changes 
similar to those in the nodules of the intestines, and are usually affected 
in a degree corresponding to the intensity of the intestinal lesion. 
The nodes are at first congested and succulent; then there is a pro- 
duction of lymphoid cells and large cells as in the intestinal nodules, 
and the node becomes enlarged. When the enlargement has reached 
its full extent, congestion diminishes, and the cells begin to degenerate. 
The degeneration may take place slowly, and then the node gradually 
returns to its normal condition; or more rapidly, and then little foci of 
necrotic, purulent material are formed. If the patient recover the 
small foci are absorbed, leaving a fibrous cicatrix; the larger foci may 
become dry, necrotic, and enclosed in a fibrous capsule. Intense exu- 
dative inflammation may occur in the nodes, which may be densely 
infiltrated with serum, fibrin, and pus. 
The Spleen.-In nearly every case of typhoid fever the spleen is 
enlarged. This enlargement begins, as a rule, soon after the commence- 
ment of the disease, increases rapidly until the third week, remains 
stationary for a few days, and then diminishes. The organ is congested, 
1 Mallory, Journal of Experimental Medicine, vol. iii., p 611, 1898. 
2 For a study of the distribution of typhoid ulcers see Baer, Am. Jour. Med. Sci., vol cxxvii., p. 
787, 1904. 
3 See Whipple, Johns Hopkins Hosp. Bull., vol. xvii., p. 281, 1906. THE INFECTIOUS DISEASES 
241 
of dark red color, and of firm consistence while it is increasing m size. 
After it has reached its maximum size, its consistence becomes soft, and 
there is a considerable deposit of brown pigment. The enlargement 
appears to be due to congestion and hyperplasia. 
Mallory describes proliferation of endothelial cells, especially in the 
blood-vessels and pulp spaces, and the formation of venous thrombi. 
In rare cases the softened spleen ruptures, with an extravasation of 
blood into the peritoneal cavity. There may be infarctions of the 
spleen, which sometimes soften and may apparently lead to peritonitis. 
The Liver.-The liver may present no apparent lesion. It is, how- 
ever, frequently large, pale and flabby, and in this condition the liver 
cells may be the seat of simple albu- 
minous degeneration. 
Less frequently there are present 
in the liver very small, soft, grayish 
nodules (Fig. 142). These focal 
lesions are sometimes too small to be 
distinguished by the naked eye. 
They may be situated about the 
branches of the portal vein or within 
the lobule. Some of these nodules 
consist of masses of small spheroidal 
cells, which may form a diffuse in- 
filtration along the small veins. 
Mallory distinguishes two distinct 
varieties of these focal lesions: one 
formed in the lymph spaces and vessels in the capsule of Glisson by 
a proliferation of the endothelium (Fig. 143); the other due to obstruc- 
tion of liver capillaries, in part by the proliferation of endothelium 
on the spot, in part by emboli of endothelial-cell origin, which are 
derived through the portal circulation from the vessels of the spleen 
and intestine. Necrotic changes may develop in and about these focal 
cell accumulations. 
Simple focal necroses of the liver and of other viscera, due to the 
action of toxic substances in the body fluids, may occur in typhoid fever 
as in many other infectious diseases.1 
While small foci of cell proliferation may be present in the kidneys 
as well as in other viscera, their occurrence is neither so frequent nor so 
characteristic as in the liver. 
In typhoid fever as in other infectious diseases toxsemia may be mani- 
fested by disturbances in the circulatory, respiratory, and heat-regu- 
lating mechanism, and in general metabolism, as well as by manifest 
lesions, such as albuminous or other degeneration of parenchyma cells 
throughout the body, and alterations leading to leucocytosis. 
Fig. 142.-Focal Area of Endothelial- 
cell Proliferation in the Liver in 
Typhoid Fever. 
1For fuller details of studies on these focal lesions in typhoid and other infectious diseases con- 
sult Mallory, loc. cit. Reed, Johns Hopkins Hosp. Rep., vol. v., p. 1895. Flexner, ibidvol 
vi., p. 259, 1897. 242 
THE INFECTIOUS DISEASES 
Secondary Lesions. 
In addition to the more characteristic lesions of typhoid fever which we have 
described, there are several of secondary or complicating nature. These are of suffi- 
ciently frequent occurrence in the disease to require brief mention. They are in part 
due to the direct action of the typhoid bacillus or its soluble poisons; in part, how- 
ever, are brought about by secondary bacterial infections.1 
The Digestive Organs.-In the intestine there may be gangrene, sometimes 
involving the tissues about the ulcers, sometimes apart from these. There may be 
croupous inflammation of the'intestinal mucous membrane of either the large or small 
intestine. A slight peritonitis sometimes accompanies the intestinal lesion. A severe 
peritonitis is usually due to perforation, less frequently to ulcers which reach the 
serous coat, but do not perforate. When there is infiltration of the serous coat with 
the new cell growth, described above, peritonitis may be associated with a produc- 
tion of little gray nodules of the same character throughout the peritoneum. In- 
Fig. 143.-Hyperplasia of Endothelium in the Liver in Typhoid Fever. 
This cut shows a more highly magnified portion of the focal lesion in Fig. 142. 
farctions of the spleen, inflammation of the ovaries, and perforation of the gall- 
bladder are sometimes the inciting factors in peritonitis. 
Haemorrhage from the intestines may be slight and due to the inflammatory 
swelling and congestion of the mucous membrane; or it may be due to the ulceration 
of the follicles and opening of the blood-vessels, and is then often profuse. 
There may be hyperplasia of the tonsils and of the lymphoid tissue at the base of 
the tongue. Gangrenous ulcers of the sides and floor of the mouth may be present. 
Catarrhal and croupous inflammation of the pharynx may be associated with super- 
ficial or deep ulceration. Inflammation of the parotid leading to suppuration is not 
infrequent. The submaxillary gland may be similarly affected. Enlargement and 
induration of the salivary glands and of the pancreas in typhoid fever have been 
described and are believed to be due to hyperplasia of the gland cells with accumula- 
tion of their secretion. This may be followed by degeneration. 
The Circulatory Organs.-The heart in many cases is the seat of albuminous, 
fatty, or hyaline degeneration, or of pigmentation. Myocarditis, endocarditis, and 
pericarditis are of occasional occurrence. Thrombi may form upon the valves or in the 
1 For bibliography of the extra-intestinal lesions induced by the typhoid bacillus, see Howard, 
Philadelphia Monthly Med. Jour. vol. i., No. 7. p. 402, 1899. THE INFECTIOUS DISEASES 
243 
heart cavities, and detached fragments of these may be lodged as emboli in various 
parts of the body. The arteries may be the seat of acute inflammation. If this in- 
volve the intima, an occluding thrombus may be formed which may lead to gangrene 
of the part supplied by the vessel, Thrombosis of the veins is common, and especially 
frequent in the femoral vein late in the disease.1 
The Respiratory Organs.-The larynx is frequently the seat of catarrhal 
inflammation, with or without superficial erosions. Less frequently there is croupous 
inflammation, followed in some cases by destructive ulceration; oedema of the glottis 
occasionally occurs. 
The Lungs- Catarrhal inflammation of the large bronchi is very common. Bron- 
cho-pneumonia occurs in two forms. There may be a severe inflammation of most of 
the bronchi of both lungs, with cellular infiltration of the walls of the bronchi and 
zones of peribronchitic pneumonia; or there may be an intense general bronchitis, 
with lobules of the lung corresponding to obstructed bronchi, either collapsed or in- 
flamed, or both. 
From the long-continued recumbent position of the patients, the posterior por- 
tions of the lungs become congested, dense, and unaerated. Sometimes, in addition 
to this, irregular portions of the lungs become hepatized. Less frequently there is 
acute lobar pneumonia. Infarctions are not uncommon, and gangrene occasionally 
occurs, either associated with lobular pneumonia or with infarctions, or as an indepen- 
dent condition. Fibrinous pleurisy and empyema are not infrequent.2 
The Genito-urinary Organs.-The kidneys are occasionally the seat of an acute 
inflammation. Catarrhal and croupous and nodular inflammation of the bladder may 
occur. Haemorrhage and gangrenous inflammation in the ovaries have been recorded; 
the uterus may be involved.3 Orchitis and epididymitis may develop during conva- 
lescence.4 
The Nervous System.-In addition to chromatolytic changes in the ganglion 
cells which are common to many infectious diseases,5 there may be thrombosis of the 
venous sinuses and obliterating endarteritis. Acute meningitis is rare.8 Degenera- 
tion and inflammation of the peripheral nerves may occur. 
Suppurative inflammation may occur in almost any part of the body in typhoid 
fever. This may be in the form of boils or of deep abscesses. Post-pharyngeal sup- 
puration is often one of the most serious of these complications. Post-typhoid bone 
lesions are often important.7 
Septicemic Forms of Typhoid Fever Without Characteristic 
Local Lesions. 
Typhoid fever may occur without the characteristic intestinal and 
associated lesions. In this septicaemia type of the disease there may be 
no demonstrable lesions other than those which are due to the toxaemia.8 
On the other hand, inflammatory processes in the viscera-lungs, kid- 
ney, spleen, etc.-may be dependent on the presence of the typhoid 
bacillus. The lesions in such cases are not, so far as we yet know, 
1 See an analysis of forty-two cases of venous thrombosis in typhoid fever, Thayer, Trans. Assn. 
Am. Phys., vol. ix., p. 164, 1904. 
2 For pulmonary complications see Robinson, Proc. Phila. Path. Soc., vol. viii., p. 141, 1905. 
3 Lartigau, New York Med Jour., vol. Ixxi., p. 944, 1900, bibl. 
4 See Kinnicutt, Trans. Assn. Amer. Phys., vol. xvi., p. 145, 1901. 
5 For a study of ganglion cells in cases of typhoid fever see Nichols, Jour, of Exp. Med., vol. iv., 
p. 189, 1899, bibl. See also Ewing, "Studies on Ganglion Cells," Archives of Neurology and Psycho- 
pathology, vol. i., p. 263, 1898. 
6 For study of typhoid meningitis see Cole, Johns Hopkins Hosp. Reports, vol. xii., p. 379, 1904. 
7 Parsons, Johns Hopkins Hosp. Rep., vol. v., p. 417, 1895. For a study of bone-marrow in 
typhoid and other infections see Longcope, Proc. Phila. Path. Soc., vol. viii., p. 49, 1905. 
8 Consult in this connection, for cases and bibl., Chiari, Zeitschrift f. Heilkunde, 1897; Lartigau, 
New York Med. Jour., vol. Ixx., p. 158, 1899; also Johns Hopkins Hosp. Bull., April, 1899; Ophuls, 
N. Y. Med. Jour., May 12th, 1900. 244 
THE INFECTIOUS DISEASES 
characteristic, and the post-mortem diagnosis depends largely upon the 
identification of the bacillus.1 
Distribution of the Typhoid Bacillus in the Body in Typhoid 
Fever. 
In the early stages of the disease the bacillus may be found in the 
lymphatic structures of the intestines and in the mesenteric lymph- 
nodes and the spleen. It may be present in lesions involving the bone- 
marrow, kidney, liver, lungs, pleura, uterus, 
testicle, and in the rose spots of the skin,2 
as well as in the blood, where it may be 
found in a large proportion of cases.3 
Typhoid bacilli have been found in the 
urine in about 20 per cent, of cases in the 
third and fourth weeks, and in the bile, 
and may persist in both of these and in the 
faeces long after the establishment of con- 
valescence.4 They may be found, though 
not in such abundance as was formerly 
assumed, in the intestinal contents after 
the disease has become well established.5 
Their abundance here appears to depend 
somewhat upon the degree of intestinal 
ulceration. In the viscera they are apt 
to occur in larger and smaller masses or clusters (see Fig. 144). The 
typhoid bacillus may be transmitted through the placenta to the foetus.6 
Typhoid bacilli may be present alone or in association with other 
germs in the foci of suppuration which so frequently complicate typhoid 
fever, also in the exudate in inflammations of the serous membranes 
and in the endocardial vegetations.7 
Mixed Infection.-Some of the inflammatory complications which 
occur in typhoid fever are due to the growdh of the bacillus in unusual 
places in the body; but many of them are due to a secondary infection 
with other germs, notably with the pyogenic cocci,8 also with the colon 
bacillus and the pneumococcus.9 
Fig. 144.-Cluster of Typhoid 
Bacilli in the Spleen. 
1 For summary of studies on the typhoid bacillus and typhoid fever, with bibliography., consult 
Dunbar, "Ergebnisse der allg. Aetiologie der Menschen- u. Thierkrankheiten," Jahrg. I., Abth. 1, p. 
605, 1896. 
2 See Pratt, Jour. Bost. Soc. Med. Sci., vol. iii., p. 170, 1899. 
3 See Coleman and Buxton, Jour. Med. Res., xvi., 83, 1909. 
* Gwyn, Johns Hopkins Hosp. Bull., vol. x., p. 109, 1899; also Curschmann, on typhoid cystitis, 
Munchener med. Wochenschr., October 16th, 1900. 
3 Hiss, Med. News, May, 1901. 
6 Ref. Lartigau, New York Med. Jour., vol. Ixxi., p. 944, 1900. 
7 See Flexner, Jour, of Path, and Bact., vol. iii., p. 202, 1895, and Johns Hopkins Hosp. Reports, 
vol v., p. 343; also Mace, "Traite de Bacteriologie," 1901. 
8 For full consideration of the pyogenic powers of the typhoid bacillus, consult Dmochowski and 
Janowski, Ziegler's Beitr. z. path. Anat., etc., Bd. xvii., p. 221, 1895. 
9 Keen, "Surgical Complications of Typhoid Fever," 1898. Hare, "The Medical Complications of 
Typhoid Fever," 1899. THE INFECTIOUS DISEASES 
245 
Modes of Infection with the Typhoid Bacillus. 
Infection with the typhoid bacillus seems usually to occur through the 
gastro-intestinal canal. In very many cases the bacilli are conveyed by 
means of food, especially of milk and drinking-water, which have been 
polluted with the excretions-faeces and urine-of persons suffering or 
convalescent from the disease. Many serious epidemics of typhoid fever 
have been traced to pollutions of milk and drinking-water from such 
sources.1 
Oysters which have been taken from grossly polluted waters, as near 
sewer openings, have been the means of conveying the germs.2 There 
is abundant evidence that flies convey the infectious material from 
undisinfected discharges.3 
In milk the typhoid bacillus not only remains alive for long periods, 
but undergoes active multiplication. It may remain long alive in water 
but in steadily diminishing numbers.4 In the soil and when dried it 
may remain alive for months. Frozen in ice it has been found alive after 
more than three months, but here also the bacilli are gradually reduced 
in number and finally die out. It is readily killed by exposure to strong 
sunlight. 
Typhoid Carriers.-While the presence of typhoid bacilli in the bile 
and gall-bladder has been recognized for some time, it is only compar- 
atively recently that it has become definitely and widely known that the 
typhoid bacilli may remain in the gall-bladder for many years. Park 
states that from 1 to 5 per cent, of typhoid convalescents may continue 
to pass typhoid bacilli for years.5 In these cases the bacilli may be 
continually discharged in the faeces. Such persons are called 11 typhoid 
carriers" and if they are of uncleanly habits or are engaged in handling 
foods as cooks, milkmen, etc., may lead to the infection of many persons. 
Immunity and Preventive Inoculations. 
One attack of typhoid successfully overcome gives a certain measure of protection, 
though this is not absolute, against another. Animal experiments have shown that 
it is possible to secure immunity against deadly doses of typhoid bacilli, either by the 
inoculation in increasing amounts with sensitized living typhoid-bacillus cultures, or 
by the injection of suspensions of the bodies of the dead bacilli. 
Preventive inoculations have been practised on a large scale in man by the method 
of Haffkine with apparently favorable results. In this method cultures of the bacillus 
are killed by heat and an emulsion in salt solution is injected subcutaneously.6 
1 Freeman, New York Med. Rec., Mar. 28th, 1896, bibl.; also Vaughan, Jour. Amer. Med. Assn., 
Apr. 19th, 1902, p. 979. For resume with bibl. of viability of typhoid bacillus under various conditions 
see Wheeler, Jour. Med. Res., vol. xv., p. 269, 1906. 
2 Freeman, Albany Med. Annals, vol. xviii., 1897, bibl. 
3 See reference, p. 151; also report on typhoid fever in U. S. Military Camps during Spanish War 
of 1898, by Reed, Vaughan, and Shakespeare, 1900; also experimental study by Ficker, Arch. f. Hygiene, 
Bd. xlvi., 1903, p. 274. 
4 See Jordan, Russell, and Zeit, Jour. Inf. Dis., vol. i., p. 641, 1904; also Russell and Fuller, ibid., 
Suppl. No. 2. Feb., 1906, p. 40. 
6 For typhoid carriers, see Park and Williams, Pathogenic Bacteria," p. 287, 1910; also Ledingham, 
Carrier Problem in Infect. Diseases, 1912, bibl.; Chapin, Sources and Modes of Infection, New York, 
1912; and Graham Smith, Flies in Relation to Disease, Cambridge, 1913. 
6 See for a review of this method, Wright, Practitioner, Mar., 1904, and Brit. Med. Jour., Nov. 12th, 
p. 1433, 1904. 246 
THE INFECTIOUS DISEASES 
There is a slight and temporary local and general reaction which may be mane- 
fested with diminished intensity on the subsequent injections made after a few days' 
interval. 
As the result of this method it has been found both by the English and by the 
German observers of the effects in the army and among attendants upon typhoid 
cases, that considered in a large way and comparing over a hundred thousand cases 
injected with dead bacilli with equal numbers not injected and exposed to similar 
conditions, there were fewer cases of typhoid among the inoculated than in the other 
group, and the disease when occurring in an inoculated subject was likely to be less 
severe in type than among the others. 
In the United States more recently this method of preventive inoculation has been 
practised on a large scale in the army with favorable results.1 
Agglutinins, Precipitins, and Opsonins. 
We have seen in an earlier section of this book (p. 179) that in the adaptation 
of a living body to certain alien organic substances, among which are bacteria and their 
toxins, the serum of the adapted-or in the case of micro-organisms, of the immunized 
-individual may contain substances which are agglutinative for the particular species 
of micro-organism involved. By the use of this phenomenon of agglutination, a 
method of clinical diagnosis of considerable value has been devised and much employed 
especially in typhoid fever.2 
Specific precipitins also are formed in the adaptation of the organism to the typhoid 
bacillus.3 
Opsonins are formed in animals artificially immunized to the typhoid bacillus and 
also in man during typhoid fever. But determination of the opsonic index is difficult 
owing to the rapid lysis of the bacilli in the serum and in the phagocytes. 
The Typhoid and Colon Bacillus. 
Much difficulty has been encountered in distinguishing between the typhoid 
bacillus and various forms of the colon bacillus when they occur together, as may be 
the case in contaminated water or in the dejecta of persons suffering from typhoid 
fever. As a result of this difficulty a very close relationship has been assumed between 
typhoid and colon bacilli. This assumption is not wholly justified by the facts, since 
many of the biological as well as some of the morphological characters of the two are 
quite dissimilar. 
The difficulty in distinction is largely limited to the identification of colonies on 
the common media usually employed in the gelatin and agar plates. Hiss has shown 
how by a slight modification of the common methods the growth of each form is quite 
characteristic, so much so that pure cultures may be made from the first mixed plates 
without difficulty.4 When once the two forms are separated, distinguishing characters 
are readily demonstrable.5 
Method of Staining the Typhoid Bacillus, 
The bacilli from artificial cultures stain readily with the ordinary anilin dyes, such 
as fuchsin and methylene blue. In sections, however, they do not stain so readily. 
1 See Russell, The Harvey Lectures, Philadelphia, 1912-1913, also Am. Journ. Med. Sci., 1913, 
cxlvi, 803. 
2 For further details of agglutination we refer to the works on clinical pathology, and for bibliog- 
raphy to Craw, Jour., of Hygiene, vol. v., p. 113, 1905. 
3 Norris, Jour. Inf. Dis., I., 463, 1904. 
4 Hiss, Jour. Exp. Med., vol. ii., p. 677, 1897; Jour. Med. Research., vol. viii., 9102, p. 148; also 
Hiss and Russell, Med. News, Feb. 14th, 1903. 
6 For a study of agglutinative reactions of the colon-typhoid group see Bruns and Kayser Zeitsch. 
f. Hyg. u. Infkr., vol. xliii., 1903, p. 401, bibl. THE INFECTIOUS DISEASES 
247 
They are decolorized by Gram. They may be stained by Ziehl's solution (see p. 258). 
Stain for half an hour, decolorize in alcohol, clear in oil of cedar, mount in balsam. 
The decolorization in alcohol should be carefully done to avoid the removal of too 
much color. Flexner recommends the staining in Loffler's methylene-blue solution for 
two hours; then put in acetic-acid solution 1:1,000 for several minutes; dehydrate in 
absolute alcohol; clear and differentiate in oil of cloves; mount in balsam. The aim 
in both of these methods is to leave the nuclei faintly colored, but not so much so 
as to conceal the clusters of more deeply stained bacilli. 
Bibliography of Typhoid.-For a resume of the studies on the typhoid bacillus 
and its relationship to this disease see Kutscher, Kolle and Wassermann's " Handbuch 
der Mikrooorganismen," 2d edition, 1913, Bd. iii., p. 717. For studies on various 
phases of typhoid infection see Johns Hopkins Hosp. Rep., vol. viii., 1900. 
Paratyphoid. 
Recently a group of cases of continued fever has been recognized which gives the 
general clinical picture of typhoid fever, but in which the serum does not agglutinate 
the typhoid bacillus, and cultures reveal a bacillus in some respects resembling but not 
identical with the typhoid bacillus, and apparently intermediate between this and the 
B. coli communis. This bacillus has been called the paratyphoid bacillus, and it is 
agglutinated by the serum of the cases in which it occurs. The intestinal and other 
lesions of this disease, which is called paratyphoid, so far as they are known, are not 
those characteristic of typhoid fever. The reports of autopsies are not yet numerous 
enough to furnish reliable data as to lesions which thus far have been slight and appa- 
rently insignificant.1 The limitations of this book do not permit us to enter in 
detail into the subject of paratyphoid and its bacillus, in which considerable uncer- 
tainty still prevails.3 Regarding the value and significance of the agglutination test 
the reader should consult works on clinical diagnosis. 
This form of infectious colitis is regularly associated with and doubt- 
less incited by bacilli of the colon-typhoid group, Bacillus dysenterise 
or Shiga's bacillus. It is a short rod, rounded at the ends, staining easily, 
decolorized by Gram's method, growing readily in cultures. There are 
several types of dysentery bacilli having somewhat different biological 
characters.3 
For the lesions of this disease see page 677. , 
DYSENTERY. 
ASIATIC CHOLERA. 
Asiatic cholera is a disease incited by the growth and proliferation 
in the intestines of a slightly curved or spiral-shaped bacterium, which 
is called the cholera spirillum-Spirillum cholera Asiaticoe (Vibrio 
choler® Asiatic®). This organism in the early and active stages of the 
disease may be present in enormous numbers in the contents of the 
small intestine, often penetrating the mucosa. It is usually confined 
to this situation. Its deleterious effects upon the body appear to be 
largely due to the production of toxic substances, which in addition to 
1 See Wells and Scott, Jour, of Infec. Dis., vol. i., 1904, p. 72; also Pratt, Bost. Med. and Surg. 
Jour., vol. cxlviii., p. 137, 1903. 
2 For a resume of this subject, see Libman, Jour, of Med. Research, vol. viii., 1902, p. 168; also 
Pox, Bull. Univ. Penn., vol. xviii., p. 52, 1905, and Proescher and Reddy, Arch. Int. Med., v., 263, 1910, 
bibl; also Kolle and Wassermann, 2d edition, 1913, iii., 1005. 
3 See Hiss and Zinsser, Text-book of Bacteriology, 2d edition, New York 1914. 248 
THE INFECTIOUS DISEASES 
serious intestinal irritation or lesion may on absorption incite those 
systemic disturbances which characterize profound toxaemia. 
Lesions of Asiatic Cholera. 
In some cases of cholera there are no marked changes to be found 
after death, and in no case are the lesions distinctive of this disease. 
If death occur during the invasion of the disease or in the stage of 
collapse, the appearances in the more marked cases may be summarized 
as follows: 
The bodies may remain warm for some time, and the temperature 
may rise for a short time after death. The rigor mortis usually begins 
early and lasts for an exceptionally long time. The muscles sometimes 
exhibit a peculiar spasmodic twitching before the rigor mortis sets in, 
especially the muscles of the hand and arm. 
The skin is of a dusky gray color; the lips, eyelids, fingers, and toes 
are of a livid purple. The ends of the fingers are shrivelled, and 
the cheeks and eyes sunken. 
The Brain.-The sinuses of the dura mater are filled with dark, thick 
blood. The pia mater may be normal, or cedematous, or ecchymotic, 
or infiltrated with fibrin. The brain is usually normal, but may be dry 
and firmer than usual. 
The lungs are retracted and anaemic, the pleura may be dry or coated 
with fibrin. The heart is normal. The peritoneum may be dry or coated 
with a layer of fibrin. 
The stomach is usually unchanged, but may be the seat of catarrhal 
inflammation. The Small Intestine.-There may be ecchymoses in the 
mucous membrane; the mucous membrane may be soft and cedematous; 
there may be general congestion, or the congestion may be confined to 
the peripheries of the solitary and agminated nodules, and these nodules 
may be swollen; or there may be croupous inflammation and superficial 
necrosis. All these changes are usually most marked at the lower end 
of the small intestine. There is apt to be post-mortem desquamation of 
the epithelium. The characteristic rice-water fluid may be found in the 
intestines after death, or, instead of this, dark-colored, bloody fluid. 
The large intestine is usually normal, but in some epidemics croupous 
inflammation occurs in a considerable number of cases. 
The spleen may be soft. The liver may show small areas of granu- 
lar or fatty or hyal'ne degeneration. 
The kidneys are often increased in size, with white and thickened 
cortex and congested pyramids. The epithelium of the cortical tubes 
may contain coarse granules and fat globules, or be necrotic. The tubes 
may contain casts and disintegrated epithelium. The uterus and ovaries 
may be congested and contain extravasated blood. 
If the patient do not die until the stage of reaction, the body does 
not present the same collapsed appearance, and there are often inflam- 
matory changes in different parts of the body, especially in the larynx, 
the lungs, the stomach, and the intestines. THE INFECTIOUS DISEASES 
249 
Characters of the Cholera Spirillum. 
The cholera spirillum, which was discovered by Koch in 1885, is a curved rod with 
rounded ends, from 0.8 to 2.0 p long, asporogenous, aerobic, and motile. When grow- 
ing under suitable conditions these rods are apt to cling together by their ends, forming 
S-shaped structures or spirals, often of considerable length (Fig. 145). The organism 
stains readily and grows abundantly on the ordinary culture media. The life period is 
short and various degenerative " involution " forms are apt to be present in old cultures. 
It grows best at about blood heat; growth ceases at about 16° C., but may survive a 
reduction of the temperature to -10° C. It is quickly killed by drying or by the tem- 
perature of boiling water. Acids are inimical to its growth. It may retain its vital- 
ity for a considerable time in water. On moist surfaces, 
such as damp linen, earth, vegetables, or in milk, it may 
rapidly proliferate. 
Pathogenesis.-The results of animal experiments 
with the cholera germ are not in themselves decisive in 
determining its relationship to this disease, since animals 
do not react in its presence as man does. However, the 
constant occurrence of this organism in Asiatic cholera, 
its absence from the body under other conditions, and 
the accidental laboratory infections which have several 
times occurred in men handling pure cultures of the 
germ, leave no doubt as to its significance as the excitant of this disease. 
Bacterial Diagnosis.-It is often of the highest importance to determine, at 
the earliest possible moment, whether or not a suspected case be one of Asiatic cholera 
or some other form of acute intestinal disorder, so that in the former case the proper 
measures may be instituted to prevent the spread of the disease. The characters 
which are developed in cultures of the cholera bacillus enable an expert bacteriologist 
to distinguish this organism from all other known forms. But the scope of this work 
does not permit a detailed description of the cultural peculiarities of the germ. Nor 
should the responsibility of such determinations be assumed without adequate pre- 
liminary laboratory experience. By taking together the morphological and biological 
characters, it is possible, usually on the second or third day, to determine whether the 
intestinal contents of a suspected case do or do not contain the bacillus of Asiatic 
cholera.1 
Fig. 145.-Spirillum Chol- 
em Asiatic^®. 
From a culture. 
Communicability.-Through milk or water or other uncooked food, 
contaminated with the dejections of those suffering from Asiatic cholera, 
epidemics are lighted up and maintained. After drying, there appears 
to be relatively little risk from cholera discharges. Individual sus- 
ceptibility plays an important role in this as in many other infectious 
diseases. For during cholera epidemics the spirillum has been found 
in many instances in the stools of apparently healthy persons. Such 
"cholera carriers" seriously complicate the problems of public sanita- 
tion and quarantine. The elements of susceptibility to Asiatic cholera 
are not yet understood, though it is commonly assumed that dietetic 
indiscretions and gastrointestinal disorders may be significant factors 
in the acquired disposition to the disease. 
A certain degree of temporary immunity is acquired through recovery 
from the disease. 
1 For characters of the cholera organism, methods of diagnosis, etc., see Kolle and Schiirmann in 
Kolle and Wassermann's "Handbuch der Mikroorganismen, "2d edition, Bd. iv., p. 1, 1912. 250 
THE INFECTIOUS DISEASES 
Toxic Products and Preventive Inoculation. 
Toxic Products.-The toxic substances formed by the cholera spiril- 
lum are apparently set free to some extent in soluble form, but are 
largely such as are stored in the bacterial cell itself-endotoxins. 
Pfeiffer has shown that the spirillum of Asiatic cholera, put into the 
peritoneal cavity of an artificially immunized guinea-pig, is quickly 
immobilized, swells and becomes granular, and soon disappears. A 
similar effect can be secured in tubes by a mixture of the immune serum 
and fresh serum to which the spirilla are added. This lytic effect of 
the immune serum upon the bacteria may be used as a test, on the one 
hand, of the specific character of a suspected spirillum; and, on the 
other, with a definitely known spirillum the lytic action of the serum 
in a suspected case of disease may be valuable as a diagnostic test. 
This bacteriolytic action of specific sera is not peculiar to the so- 
called anti-cholera serum, but has been observed in other cases-for 
example, in typhoid serum with the typhoid bacillus. Its nature and 
its bearing on immunity have been considered in an earlier section of 
this book (see p. 170). 
Agglutinative substances are also developed in Asiatic cholera which 
may be of value in diagnosis. 
Preventive Inoculation.-A large amount of work has been done 
looking toward artificial immunization of man against Asiatic cholera 
in the East, and preventive inoculation practised by the method of 
Haffkine appears to have given encouraging results. This method con- 
sists in the subcutaneous injection of cultures of the cholera bacillus; 
first, those whose virulence has been diminished, and then, those in 
which the virulence has been exalted by artificial means. 
But the Haffkine preventive inoculation with living cultures has 
been in a large measure superseded by the injection of a small amount 
of a fresh agar culture killed by heat. The dose is repeated after a few 
days. There is moderate local and general reaction to the injections. 
The serum of persons thus twice injected, after two or three weeks, may 
show the development of bactericidal substances exceeding in efficiency 
those present during convalescence from the disease. Such an active, 
artificial immunity may last for many months. The practical result 
of this form of preventive inoculation on a large scale in Japan has been 
a considerable reduction in the proportion of cases in the protected 
groups, as compared with others similarly exposed, as well as a reduction 
in the mortality of those who in spite of the protective attempt contracted 
the disease.1 
Other Spirilla Resembling the Cholera Spirillum. 
There are several fairly distinct forms of spirilla, some of which appear to be 
related to the cholera organism, which have been occasionally found in various situa- 
tions. One of these is the so-called Vibrio proteus or spirillum of Finkler and Prior. 
This organism was found by these observers in the dejecta of persons suffering from 
1 For a study of protective inoculations against Asiatic cholera see Hetsch, Kolle and Wassermann, 
2d edition, Bd. iv., p. 110, 1912. THE INFECTIOUS DISEASES 
251 
cholera nostras, shortly after the discovery by Koch of the cholera spirillum, which 
at first it was thought closely to resemble. The cultural characters, however, abun- 
dantly suffice to differentiate the organisms. The Vibrio proteus is slightly pathogenic 
for certain lower animals, but not for man. 
Several forms of spirilla of somewhat similar general characters have been found 
in various situations; thus in cheese, by Denecke, S. tyrogenum; in a chicken epidemic 
and in sewage, by Gamaleia and by Pfuhl, Vibro Metschnikovi; in the dejecta during 
a cholera epidemic at Massawah, Vibrio Massawah, etc. Spirillum sputigenum, 
of frequent occurrence about the teeth and in the saliva of healthy persons, is not 
pathogenic. 
Tuberculosis is an infectious disease characterized by inflammatory 
and necrotic processes in the body and incited by the presence and 
growth of the Bacillus tuberculosis (tubercle bacillus). The most dis- 
tinctive morphological feature of tuberculosis is the development under 
the influence of the tubercle bacillus of larger and smaller, gray or white 
or yellow, firm or friable masses of tissue called tubercles. 
The effect on the body-cells of the presence and growth of the tubercle 
bacillus varies considerably, depending upon the number and virulence 
of the germs present, the character of the tissue in which they lodge, 
and the vulnerability of the individual. In general, it may be said 
that tubercle bacilli may stimulate the connective-tissue cells in their 
vicinity to proliferation; or they may excite emigration of leucocytes 
from blood-vessels and lead to the production of other exudates; or 
they may cause death of tissue. Thus the phases of inflammation 
which are excited by the tubercle bacillus are productive, exudative, 
and necrotic. The tubercle bacillus may incite these changes separately 
or simultaneously, in the sequence just indicated or in some other; 
and now one, now another of them may preponderate. 
TUBERCULOSIS.1 
Morphology of the Lesions of Tuberculosis. 
Tuberculosis manifests itself most often in the form of an inflamma- 
tion affecting some one part of the body, as the lungs and bronchial 
lymph-nodes (the parts most frequently involved in adults), the gastro- 
intestinal tract or the skin-"localized tuberculosis." In a considerable 
proportion of cases the local lesions induced by the tubercle bacillus 
are in the form of circumscribed nodules or masses of new-formed cells 
or tissue which are called tubercles, or, if small, miliary tubercles.2 
Such a localized tuberculosis may retain throughout the characters 
1 Some authors are disposed to class together, under the name Infectious Granuloma, lesions in- 
duced by micro-organisms, certain phases of which are characterized by a localized, usually slow, nodular 
growth tending to necrosis. The more important of these are tuberculous, leprous, syphilitic, and 
actinomycotic. It may be doubted whether it is wise to group together, under a name suggesting 
tumor relationships, which do not exist, lesions of such diverse origin and clearly of infectious character. 
2 The term miliary tubercle, which arose from the coincidence in size between small foci of tubercu- 
lous inflammation and some forms of millet seed, is now very liberally applied to tubercles which are 
very much larger as well as to those which are very much smaller than millet seeds. It is convenient 
to designate a small mass of new tissue formed under the influence of the tubercle bacillus, whatever its 
minute structure, as a tubercle granulum (see Fig. 146). Very frequently two or more tubercle granula 
are joined together by a more diffuse formation of tubercle tissue to form larger or smaller miliary 
tubercles-conglomerate tubercles (see Fig. 147). 252 
THE INFECTIOUS DISEASES 
of a local inflammation, or it may be accompanied by the clinical evi- 
dences of systemic infection. It may give rise through metastasis to 
the successive development of tuberculous inflammations in other parts 
of the body, or to a sudden development of small foci of tuberculous 
inflammation in many parts of the body at the same time-general 
miliary tuberculosis. 
A general infection may occur by the diffusion through the body of 
bacilli derived from a local tuberculosis, such as tuberculous phlebitis 
or arteritis, tuberculous inflammation of the thoracic duct, or from the 
breaking into a vessel of a tuberculous lymph-node. It is probably 
seldom that a sufficient number of tubercle bacilli enter the blood chan- 
nels at once to account for the enormous numbers of tubercles which are 
sometimes found in acute general miliary tuberculosis; but it is not 
unlikely that, from the newly formed tubercles which develop in the 
walls of the smaller blood-vessels, new distributions of bacilli may take 
place from time to time as the tubercles mature. This probability is 
sustained by the frequent occurrence of miliary tubercles on the intima 
of the small arteries in the lung for example, as well as by the evidence 
of differences in age of the individual tubercles in generalized miliary 
tuberculosis.1 
Diffuse Tuberculosis.-In many cases, however, the lesion is not focal 
or circumscribed but diffuse, and more or less widely infiltrates or 
replaces the tissues involved. This is called diffuse tuberculous inflamma- 
tion. 
Miliary Tubercles.-Miliary tubercles are small nodules of irregular 
shapes (Plates IV., VI., and VII.), the smallest hardly visible to the 
naked eye. The smaller tubercles are gray and translucent; the larger 
are usually, especially in the central parts, opaque and white or yellow 
on account of the necrosis which is apt to commence here. 
In studying the reaction of the living tissues to the tubercle bacillus 
it should be always borne in mind that while, as a whole, the lesions 
produced are quite characteristic, there is still no one structural feature 
or combination of features of tubercles or tuberculous inflammation 
which is absolutely distinctive of the action of this bacillus. In doubtful 
cases the demonstration of the presence of the germ itself may be neces- 
sary for the establishment of the character of the lesion.2 
The experimental studies in animals, as well as the morphological 
data gathered from the examination of tuberculosis in man, show that 
when tubercle bacilli in moderate numbers lodge and develop in the 
living body one of the early local effects is a proliferation of the connective- 
1 It is well, in the endeavor to understand the occurrence of general miliary tuberculosis or of the 
less striking instances of distribution of the bacilli, to remember that two varying factors are constantly 
active and significant: first, the virulence of the bacilli, which may be slight or extreme; and, second, the 
vulnerability of the infected individual-i.e., his "predisposition"-which also may be slight or ex- 
treme. Thus the distribution of bacilli, be these few or many, from an infective focus, may be in dif- 
ferent individuals or at different times in the same individual of quite different significance. For a 
resume of the discussion as to the sudden or gradual origin of miliary tubercles see Ribbert, Deut. med. 
Woch., p. 5, Jan. 4th, 1906. 
2 The term tubercle tissue, which is in common use, indicates a tissue formed under the influence 
of the tubercle bacillus rather than a tissue which is morphologically characteristic of tuberculosis in 
distinction from other forms of new tissue. THE INFECTIOUS DISEASES 
253 
tissue and endothelial cells.1 These become larger and polyhedral, with 
conspicuous nuclei (Fig. 146). 
A new reticulum or stroma may form hand-in-hand with the growth 
This is growing in the liver; is composed mostly of new-formed polyhedral cells closely packed 
with little intercellular stroma. At the center, coagulation necrosis is commencing. 
Fig. 146.-A Small Miliary Tubercle. 
Fig. 147.-A Miliary Tubercle with Giant Cells. 
This tubercle is of the conglomerate type, made up of four granula, the larger one showing coagu- 
lation necrosis in the central portion. From the peritoneum. 
of these new cells, or the old stroma may persist, adapting itself in form 
and arrangement to the new conditions. 
1 The studies of Wechsberg indicate that in some cases, at least, the first effect of the tubercle bacillus 
upon the living tissue is destructive, so that the characteristic cell proliferation which follows may not 
be altogether due to a direct formative stimulus to cell proliferation furnished by the bacillus. See 
Wechsberg, " Beitrage zur Lehr. v. d. primaren Einw'irkung des Tuberkelbacillus," Ziegler's Beitrage zur 
path. Anat., Bd. xxix., p. 203, 1901. See further Herxheimer, Ziegler's Beitr., Bd. xxxiii., p. 363, 
1903, bibl. 254 
THE INFECTIOUS DISEASES 
Either after the connective-tissue cell proliferation or hand-in-hand 
with it, or preceding it, or altogether independently of it, emigration of 
leucocytes and extravasation of serum may take place from blood- 
vessels in the vicinity of the germs. During the more or less active 
cell proliferation which occurs under the influence of the tubercle bacillus, 
multinuclear cells-giant cells-may be formed (Fig. 147), either by 
persistent nuclear division in growing protoplasmic masses which do 
not divide into separate cells, or by the coalescence of the bodies of cells 
already formed. 
Showing polyhedral cells, small spheroidal cells, and giant cells, with coagulation necrosis at the centre. 
Fig. 148.-A Miliary Tubercle in the Lung. 
More or less new tissue with numerous small spheroidal mononuclear 
cells and little stroma may form in and about the tuberculous foci. 
Blood-vessels are not apt to develop under the influence of the tubercle 
bacillus. Old blood-vessels are, on the other hand, usually obliterated 
as the new tissue forms. 
Sooner or later under the influence of the tubercle bacillus, there is 
usually a damage of cell and tissue, which may lead to coagulation 
necrosis in the new-formed as well as in the old tissue of the infected 
region. This necrosis is more apt at first to manifest itself in the central 
portions of the tuberculous foci (Fig. 148) and may progress outward; 
the nuclei become fragmented or disappear, or fail to stain in the usual 
way, the protoplasm becomes more homogeneous, and cells and stroma THE INFECTIOUS DISEASES 
255 
form at last an irregularly granular mass of tissue detritus which tends 
to disintegrate (coagulation necrosis, cheesy degeneration, caseation), 
forming cavities or, if on free surfaces, ulcers. 
As coagulation necrosis progresses, the tubercle masses lose the gray 
translucent appearance which in their early stages they are apt to pre- 
sent to the naked eye and become more opaque and of yellowish white 
appearance at the centres. 
Finally dense fibrous tissue may form in and about foci of tuberculous 
inflammation, encapsulating or sometimes entirely replacing the more 
characteristic new-formed structures. It is in this way-by the forma- 
tion of connective tissue-that such repair as is possible after local tuber- 
culous inflammation, is brought about (Fig. 396, p. 623). 
Forms of Tubercles.-Before the discovery of the tubercle bacillus 
and while knowledge of the lesions of tuberculosis was largely limited 
to their morphology, it was natural that much stress should be laid upon 
the variety in structure which the nodular growths called tubercles 
present, and that elaborate classifications and groupings of tubercles 
were often deemed important. 
With an exact knowledge of the excitant of the new growths and of 
the varying phases of their development in the body, the morphological 
peculiarities of tubercles are not now to be regarded as of such extreme 
significance, since they for the most part indicate simply variations in 
the local effect of a definite poison. These variations are due, as we have 
seen, to differences in the amount and intensity of the poison, to the degree 
of susceptibility of the individual, to the structure of the particular 
tissue or organ involved, and to the extent and variety of local complica- 
tions caused by other agencies. 
It is, however, usually convenient and sometimes important to recog- 
nize structural types in miliary tubercles. Thus they may be composed 
wholly of small spheroidal cells-11 lymphoid tubercles," or of larger poly- 
hedral cells1-11 polyhedral-celled tubercles," or of both forms of cells 
together and with or without a new-formed stroma; or of any of these 
combinations with giant cells. Then coagulation necrosis, which may 
occur in tubercles of any type; development of new dense connective 
tissue; association with various phases of simple exudative inflamma- 
tion-all of these contribute to the variety in the structural types of 
miliary tubercles. 
Diffuse Tuberculous Inflammation (Diffuse Tubercle).-1. If the 
infection with tubercle bacilli be extensive, or if step by step the bacilli 
are distributed in the tissues about the primary seat of infection, con- 
siderable amounts of tubercle tissue of one or other form may develop 
and pass into the condition of coagulation necrosis, so that at length 
large necrotic masses, with a comparatively small amount of well- 
defined tubercle tissue, either diffuse or in the form of granula, may alone 
remain to indicate the character of old and slowly progressive local 
infection. This form of lesion is found in the large tuberculous masses 
in the brain, in the mucous membrane of the bronchi, in large flat masses 
1 Some of the larger cells are regarded by many as so-called "plasma cells" (see p. 74). 256 
THE INFECTIOUS DISEASES 
on the serous membranes, and in the diffuse, cheesy infiltration of the 
lymph-nodes, kidneys, ureters, bladder, prostate, testicle, and uterus. 
These large areas of tuberculous inflammation are apt to be white or 
yellow in the central and necrotic portions, which are sometimes dense, 
compact, and hard, sometimes soft and friable. These areas are not 
infrequently surrounded by an irregular gray zone of tubercle tissue or 
by a dense fibrous-tissue capsule. 
2. In marked contrast with the phase of diffuse tuberculous inflam- 
mation just described, though often associated with it, is that in which 
the formation of inflammatory exudates is a prominent feature. This 
exudative form of tuberculous inflammation is best exemplified in the 
Fig. 149.-Exudative Form of Tuberculous Inflammation Showing Tubercle Bacilli. 
From the lung of a child. The size of the bacilli has been slightly exaggerated in the cut. 
lungs by some of the forms of acute phthisis (see p. 627). The tuber- 
cle bacillus is under certain conditions markedly pyogenic, and when 
it rapidly develops in the air spaces of the lungs or suddenly gains access 
to them in large quantities pus, serum, fibrin, and exfoliated or pro- 
liferated epithelial cells may collect in and largely fill the air spaces, 
and then the whole new exudate and the old lung tissue may, over 
larger or smaller areas, rapidly undergo coagulation necrosis. (Plates 
VIII. and X.) 
Thus in one phase of tuberculous inflammation the intensity and 
rapidity of the local poisoning by the bacillus do not permit of the 
formation of organized new tissue at all, but only of exudative products 
which are apt soon to become necrotic (Fig. 149). Less intense degrees 
of exudative inflammation are liable to develop in the vicinity of miliary 
tubercles anywhere in the body. 257 
THE INFECTIOUS DISEASES 
Characters of the Tubercle Bacillus. 
The Bacillus tuberculosis is a long, slender bacterium varying in length from 2 to 
4 [i (from one-quarter to one-half the diameter of a red blood cell) and in breadth from 
0.2 to 0.5 /£. It is frequently more or less curved, and the individual bacilli may cling 
together end to end, forming threads or chains. It may occur in branching forms.1 
The bacillus (Fig. 150) is stained with difficulty by the anilin dyes (see below), and 
when stained often presents an irregular beaded or knobbed appearance, due to an 
unevenness in the coloring of the protoplasm, or to involution changes. It is immobile, 
and spores have not been demonstrated in it. 
At the temperature of the body it can be grown on many of the artificial culture 
media. The growth of the tubercle bacillus in cultures is very slow in comparison with 
that of most of the pathogenic micro-organisms. After several weeks' growth it forms 
Fig. 150.-Tubercle Bacilli in Sputum from a Case of Pulmonary Tuberculosis 
Showing the bacilli stained with fuchsin, and pus cells stained for contrast with methylene blue. 
dry, scaly masses or thin, wrinkled pellicles on the surface of the media (Figs. 151 and 
152.) It requires a certain amount of oxygen for its growth, and thrives best in the 
dark. 
When brought in direct contact with various chemical disinfectants it is readily 
killed, but when enclosed in mucus, as in sputum, it may be quite resistant. It is 
killed by an exposure of a few hours to direct sunlight, or if moist is killed by an ex- 
posure of from ten to fifteen minutes to 70° C. On the other hand, it may long retain 
its vitality in the dried condition.2 
Cultures can be continued indefinitely from generation to generation with a slowly 
diminishing virulence which finally is largely lost. Under certain conditions the 
virulence may be restored or enhanced by successive inoculations into susceptible 
animals. 
The tubercle bacillus does not, so far as we know, grow in nature outside of the 
1 Branching forms of the tubercle bacillus have been frequently seen, and while their significance 
is not yet altogether clear, the tendency at this time is to separate this organism with the diphtheria 
bacillus and the so-called streptothrix or actinomyces forms into a group called higher bacteria. 
Whether, as many think, they are more closely allied to the moulds than to the bacteria, or whether, 
they should be considered in a class by themselves, is a problem still unsolved. For the present, we 
may wisely consider the tubercle bacillus as one of the bacteria. 
For studies and bibliography on this subject consult Schulze, Zeitsch. f. Hyg. u. Inf. Krank., Bd. 
xxxi., p. 153, 1899; and Lubarsch, ibid., p. 187. 
2 For a study of the viability of the tubercle bacillus see Rosenau, Hyg. Lab. U. S. Mar. Hosp. Ser. 
Bull., 57, 1909. 258 
THE INFECTIOUS DISEASES 
bodies of men and certain warm-blooded animals. It is thus apparently strictly 
parasitic. 
Inoculation of various animals, especially of guinea-pigs, rabbits, and monkeys, 
may be followed by lesions similar to those of man. 
Methods of Staining the Tubercle Bacillus. 
In Fluids.-For the examination of fluids, such as sputum,1 etc., the material 
should be spread in a thin layer on a cover-glass, dried in the air, and then passed thrice 
through the flame (see p. 143). 
While, as has been said above, the tubercle bacillus is stained much less easily with 
the anilin dyes than are most bacteria, it can be deeply colored by the use of accessory 
Fig. 151.-Culture of Tubercle Bacillus 
on Glycerin Agar. 
Fig. 152.-Culture of Tubercle Bacillus 
on Glycerin Agar. 
From tuberculosis in man. 
From tuberculosis in bird. 
agents which intensify the stains or render the protoplasm of the bacilli more accessi- 
ble to them. But when once stained the tubercle bacillus clings with great tenacity to 
its color in the usual decolorizing agents. 
A variety of methods are in vogue for staining the tubercle bacillus, most of them 
being more or less unessential modifications of the original process formulated by Koch 
and Ehrlich. Ziehl's solution is among the most useful. This is made by adding to a 
five-per-cent, aqueous solution of carbolic acid about one-tenth its volume of saturated 
alcoholic solution of fuchsin. This carbolic fuchsin will keep unchanged for a long 
time. 
1 It is well in obtaining sputum for examination in cases of suspected pulmonary tuberculosis to 
secure that which has been raised during several hours, including the early morning discharge. THE INFECTIOUS DISEASES 
259 
The prepared cover-glass is floated in a watch-glass or porcelain capsule-speci- 
men side down-on this coloring fluid, and gently heated almost to boiling for from 
three to five minutes. 
The entire specimen is thus completely stained, tubercle bacilli, tissue elements, 
and other bacteria which may be present, all in the same way. The next step is to 
remove the color with acid from all the structures which may be intermingled with 
the tubercle bacilli; the latter, owing to the tenacity with which they retain the color, 
being but slightly affected. This is done by dipping the cover-glass into an aqueous 
or alcoholic solution of five-per-cent, sulphuric acid, and shaking it about for a few 
seconds. Under the influence of the acid the specimen on the cover-glass loses its red 
color and becomes gray or colorless. It is then thoroughly rinsed in three or four suc- 
cessive portions of alcohol, and finally in water. By this manipulation the red color 
may be to a slight extent restored. 
Care should be taken not to expose the specimen too long to the action of the acid, 
because then the bacilli may be also partially or completely decolorized. A little 
experience will enable the experimenter to judge of the proper time for the action of 
the acid. The specimens may be studied in water with the use of an oil immersion 
lens and the Abbe condenser, or they may be dried in the air and mounted in balsam 
before examination. 
Inasmuch as not infrequently some other bacteria besides the tubercle bacilli 
retain a slight red color, it is well, after the specimen is rinsed in water, to float the 
cover-glass for a few minutes in a dilute aqueous solution of methylene blue, which will 
replace the red color in all of the bacteria except the tubercle bacilli, which might 
be mistaken for it, forming a marked color contrast between them. The contrast stain 
should not be intense. 
Pappenheim's Method.-After staining in the hot carbol-fuchsin as above, im- 
merse the specimen without washing in the following solution: 1 per cent, alcoholic 
solution rosolic acid saturated with methylene blue, adding 20 per cent, of glycerin. 
In this method of staining the tubercle bacilli are red, while smegma bacilli (see p. 
267), are blue. 
In Sections.-Thin sections of tuberculous tissue which has been hardened in 
alcohol are stained in the same way, except that instead of drying and fixation by heat 
the sections should be fixed to the cover-glass by means of the albumen fixative (see 
p. 1034), and then cover-glass and section are manipulated together. 
When differentiation is complete, the section is cleared in oil of origanum and 
mounted in balsam. 
For purposes of simple recognition of the bacilli in sections it seems to the writer 
usually better to have no color in the preparation other than that which the tubercle 
bacilli possess. But it is often convenient to demonstrate the nuclei of the cells at the 
same time, and this may be accomplished by staining lightly afterward with a dilute 
solution of some color which will contrast with that of the bacilli, such as methylene 
blue. 
In the examination of urine for the presence of the tubercle bacillus it is well to 
collect the sediment by means of a centrifugal machine. In the examination of milk 
or other fat-containing fluids for tubercle bacilli, it is well, after the film has been 
formed upon the cover-glass and before staining, to rinse with chloroform followed by 
alcohol, and this by water. 
Occasionally one finds in urine acicular crystalline bodies considerably resembling 
the tubercle bacillus in size and shape, and retaining a red color after the decolorization 
of the specimen. A careful study of the form, however, will suffice to prevent mistakes. 
The only other bacilli which are liable to be mistaken for the tubercle bacilli are 
the bacillus of leprosy and the so-called smegma bacillus which sometimes occurs be- 
neath the prepuce. The lepra bacillus may be distinguished from the tubercle bacillus 
by the following differential staining process: If the lepra bacillus be stained for ten 
minutes in a dilute alcoholic solution of fuchsin (five drops of saturated alcoholic solu- 
tion of fuchsin to 3 c.c. of water), and then rinsed for a few seconds in a solution of 
nitric acid (one part) in alcohol (ten parts), it will retain a red color, while under the 
same treatment the tubercle bacillus remains uncolored. For differential stains for 
the smegma bacillus see p. 267. 260 
THE INFECTIOUS DISEASES 
Antiformin in Sputum Examinations.-Antiformin is a patented preparation 
containing sodium hydroxide and sodium hypochlorite. When mixed with sputum 
in such proportion that the antiformin is present in about 15 per cent, the sputum is 
softened and most bacteria except the tubercle bacilli'are killed. After the softening 
of the sputum it is diluted with water or alcohol and spun in the centrifuge, the sedi- 
ment gathered and respun, the final sediment is used for smears and stained in the 
usual way. By the use of antiformin and centrifugation a "concentrate" of the 
bacilli from sputum may be secured for diagnostic inoculation of guinea-pigs. 
While many of the lower mammalia are susceptible to inoculations with tubercle 
bacilli derived from man, the bacilli obtained from spontaneous tuberculous lesions in 
the lower animals may present noteworthy variations in form and growth from the 
human type. Thus Theobald Smith and others1 have pointed out marked peculiarities 
of the bovine bacillus which would lead to the conjecture that though not a separate 
species it is probably a distinct variety of the organism. Although the cultural char- 
acters of the bovine bacillus seem to suffice for its distinction from the human variety, 
man, especially children, appears to be susceptible to the bovine organism.2 Theobald 
Smith has determined that the bovine bacillus is in general more highly pathogenic 
for mammals than is the human variety. 
Still more marked are the differences between mammalian and avian,3 or bird tuber- 
cle bacilli, and the tubercle bacilli of fish. Whether in this case also the differences 
are to be regarded as specific or within the limits of variational sway is not yet clear. 
Although the subject is important from the standpoint of prophylaxis and interesting 
from the point of view of the variations of bacteria under changes of environment, 
the attempts by experimental means to convert one form into the other have thus far 
been too few to lead to definite conclusions. 
Varieties of Tubercle Bacilli. 
Toxic Products of Tubercle Bacilli. 
While there is evidence that some soluble toxic substances are given 
off from the tubercle bacillus in its growth and activities, it is to its 
endotoxins that its chief poisonous capacities seem to be linked. 
It has been found that tubercle bacilli which have been killed by 
boiling or otherwise, when introduced into the body of the rabbit either 
beneath the skin, or into the serous cavities, or into the blood-vessels 
and the air spaces of the lungs, are capable, as they slowly disintegrate, 
of stimulating the cells of the tissues where they lodge to proliferation, 
and to the production of new tissue morphologically similar to tubercle 
tissue in its various phases4 (Fig. 153). Necrosis of the new-formed 
cells may occur, but this differs in some respects from the coagulation 
necrosis induced under the usual conditions. Dead tubercle bacilli 
are also, markedly chemotactic and capable of causing local suppuration 
and abscess. 
1 Sea Smith, Jour. Med. Res., vol. xiii., p. 253, 1905; also Wolbach and Ernst, Jour, of Med. Re- 
search, vol. x., 1303, p. 313, bibl.; also Ravenel, Medicine, July and August, 1902; see also reference to 
Ravenel, p. 266. 
2 See ref. 1, p. 266. 
3 For bibliography of animal tuberculosis see Eber, Lubarsch u. Ostertag, Ergebnisse d. allg. Path., 
1897, iv., 859. For a study of avian tuberculosis see Hastings, Halpin, and Beach, Jour. Infect. Dis., 
1913, xiii., 1; also Himmelberger, Centralbl. f. Bakteriol. I Abt., Orig., 1914, Ixxiii., 1. 
4 For further details concerning the effects of dead tubercle bacilli in the body see Prudden and 
Hodenpyl, N. Y. Med. Jour., June 6th and 20th, 1891, and Prudden, ibid., Dec. 5th, 1891. For summary 
of later work, with bibliography, see Herxheimer, Ziegler's Beitr., Bd. xxxiii., p. 363; also Miller, 
Jour. Path, and Bact., vol. x., p. 351, 1905, bibl. THE INFECTIOUS DISEASES 
261 
It would seem probable then that while the power of the tubercle 
bacillus to induce necrosis and the fever which in many cases indicates a 
systemic intoxication may be due to metabolic products of the living 
germ, the local lesions characteristic of exudative and productive inflam- 
mation may be due to a peculiar bacterial proteid which is set free by 
the disintegration of the bacilli in the tissues. But the products of 
autolysis in the necrotic tissue cells may contribute to the toxaemia. 
Fig. 153.-Inflammatory Nodule (Pseudo-tubercle) in the Liver of the Rabbit Induced 
by the Intravenous Injection of Dead Tubercle Bacilli. 
Most of the dead bacilli have disintegrated, setting free the bacterial proteid which has stimulated the 
new cell growth. A few fragments of the bacilli, however, still remain. 
Agglutinating Substances. 
The serum of tuberculous animals and men may contain agglutinating substances. 
The reaction, however, frequently fails and is not at present of much diagnostic value. 
Tuberculin. 
When the tubercle bacillus is grown on glycerinated nutrient broth certain meta- 
bolic products are formed and pass into solution in the fluids. If after some weeks of 
vigorous growth the germs are separated by filtration and the broth is concentrated 
by evaporation, a dark brown fluid results which is called tuberculin. This substance 
-at one time believed by many, and still by a few observers, to possess distinct cura- 
tive properties in certain forms of tuberculosis-has assumed great economic impor- 
tance on account of its value as a diagnostic agent in bovine tuberculosis. For if 
administered subcutaneously in small quantity to cattle a marked temperature re- 
action follows in tuberculous animals, while those which are sound are unaffected. 
The existence of even very slight lesions may be detected in this way. In man also 
tuberculin has proved of value in cases in which the efforts to establish a diagnosis 262 
THE INFECTIOUS DISEASES 
by the usual method have failed. The new tuberculin "T. R." contains the dead 
bodies of tubercle bacilli.1 
Immunity and Therapeutic Use of Tuberculin in Tuberculosis. 
The fact that so large a percentage as from sixty to ninety of human beings dying 
from all causes have been shown by autopsies to have been at some period and in 
some measure affected with tuberculosis, while the mortality from tuberculosis as com- 
pared with death from all other causes is not far from fourteen per cent, indicates 
that man enjoys a marked degree of natural immunity to the incursions of the tubercle 
bacillus. The clinical data are not very convincing as to the acquirement of increased 
immunity after successfully coping with the disease. However, experiments on 
animals, those of Trudeau and others, have shown that by the repeated inoculation 
of small doses of tubercle bacilli of attenuated virulence, rabbits may be largely pro- 
tected, though not rendered wholly immune, from the full effect of later injections of 
virulent bacilli. Behring has apparently succeeded by intravenous injections into 
young cattle of some product or derivative of the tubercle bacillus in rendering them 
highly, and it is claimed permanently, immune. Similar results have been obtained 
by others.2 
Many attempts have been made to secure artificial immunity in man either by 
the injection of products of the growth of the tubercle bacillus, or by the use of the 
dead bodies of the bacilli. Wright and his followers have reported marked success in 
the use of a form of tuberculin called new tuberculin or " T. R., "3 which contains the 
bodies of the dead bacilli, especially in localized tuberculosis. This is administered in 
accordance with the indications of a rise or fall of the ' ' opsonic index " of the serum (see 
p. 187), determined by the degree of phagocytosis, the opsonic index marking the 
immunizing effect of the injection. Trudeau seems also to have obtained favorable 
results from the artificial immunization with the dead bodies of the bacilli, "T. R.," 
controlling the administrations of the very potent agent by careful clinical observa- 
tions. 
Altogether, then, it appears that a certain measure of active artificial immunity to 
tuberculosis may be secured in man. Attempts to secure passive immunity in tubercu- 
losis by alleged antitoxic sera do not seem to have been notably successful.4 
Complex Factors in the Tuberculous Process. 
It is well in studying the characters of tuberculous inflammation to remember 
that in its progressive phases there are two factors at work: first, those which lead 
to cell proliferation and new tissue formation, which is apparently a reparative and 
conservative process; second, those which are inhibitory or damaging or destructive; 
and, finally, that both sets of factors are commonly active together. It may still 
be considered doubtful whether the tubercle bacillus furnishes a direct formative 
stimulus, or whether such is furnished by damaged cells, or whether the cell pro- 
liferation may not be an expression of reparative activity in the presence of damaged 
tissue made possible by disturbed organic control (see p. 351). In any event the 
new tissue which forms under the influence of the tubercle bacillus apparently owes 
its morphological as well as biological characteristics to impulses toward tissue forma- 
tion which are exerted in the presence of agencies-doubtless poisons-restraining 
within narrow bounds the new connective-tissue growth, no matter how extensive or 
persistent this may be, and tending constantly to its destruction. 
1 See Allergy, p. 190, also Baldwin, Bull. Johns Hopkins Hosp., 1913, xxiv., p. 220. 
2 See review of animal immunization against tuberculosis, Pearson, Second Ann. Rept. of the Phipps 
Inst., p. 311, 1905. 
3For a resume of various tuberculin preparations, see Hiss and Zinsser, "Text-book of Bacteri- 
ology, 2nd edition, 1914. 
4 See for the bearing of the parasitism of the tubercle bacillus on infection and immunity Th. Smith, 
Jour. Am. Med. Assn., Apr. 28, 1906. THE INFECTIOUS DISEASES 
263 
It is interesting in this connection to note that when lesions in many respects 
similar to those of the ordinary tuberculosis are induced experimentally in animals 
with dead tubercle bacilli (see above), the poisonous substances leading to necrosis 
are not produced continually and for indefinite periods, as is the case in infection 
with living bacilli, but are soon exhausted, so that after a certain amount of initial 
necrosis the new tissues go on to develop in the usual reparative way, blood-vessels 
are formed, and healing by a cicatrix under favorable conditions regularly takes place. 
It is probable that effective healing in tuberculosis in man takes place only after 
the local production of destructive poison ceases through the death and completion 
of the lysis or the diminished virulence of the tubercle bacilli present. 
On the other hand, it is important to bear in mind that while the formation of 
new cells and tissue on the part of the body in tuberculosis marks a protective adapta- 
tion to new and harmful conditions, the tubercle bacilli themselves are also subject to 
adaptive changes which on their side are protective. Thus through what has been 
called selective adaptation of both host and microbe a condition of balanced para- 
sitism may be brought about in which there may be a reduced mortality, but not a re- 
duced morbidity, since in the processes of adaptation the microbe has won capacities 
for harm which may be very potent and significant in individuals not adapted to it.1 
The Number of Tubercle Bacilli in Lesions. 
The number of bacilli which are present in the lesions of tuberculosis 
is subject to great variation. They are usually abundant in the walls 
and contents of phthisical cavities, and in tubercle tissue which is under- 
going cheesy degeneration and disintegration. In these situations they 
may be found in myriads, forming sometimes a large part of the disin- 
tegrated mass. They are found in cells and scattered among them. 
Sometimes they are present in considerable numbers in the giant cells of 
miliary tubercles. In the acute general tuberculosis of children they 
are often present in large numbers, particularly in the lungs (Fig. 149). 
They may be found in tuberculous inflammation in any part of the body, 
and are often demonstrable in the blood. The bacilli are constantly 
discharged in the sputa of patients suffering from pulmonary tubercu- 
losis, often in enormous numbers-from one to four billion in twenty- 
four hours, according to Nuttall's estimate-and their presence some- 
times affords valuable diagnostic aid in early stages of obscure forms 
of the disease. 
Under a variety of conditions, especially in the older tuberculous 
lesions, the bacilli may not be demonstrable. This apparent occasional 
absence of the bacilli is probably due either to their disappearance as 
the process grows older or to some unknown changes which interfere 
with the ordinary staining procedures. 
Frequency of Tuberculosis in Man and the Lower Animals. 
Tuberculosis is a very common disease not only of man2 but also of 
many of the lower animals, especially of cattle, and inasmuch as the 
1 For a consideration of the mutual relationship of microbe and host see Th. Smith, Jour. Amer. 
Med. Assn., April 28th., p. 1247, 1906. 
2 Carefully prepared statistics show that tuberculous lesions are present in the body in more than 
ninety per cent, of the cases examined at autopsies. See for a thorough and suggestive analysis of five 
hundred autopses Naegeli, Virchow's Archiv, Bd. clx., p. 426, 1900; also Necker, Verhl. Deutsch. Path. 
Ges., viii., p. 129, 1904. For a study of frequency of tuberculosis in children see Winkler, Verhl. Deut. 
Path. Ges., viii., p. 129, 1904. 264 
THE INFECTIOUS DISEASES 
victims of this disease, both men and animals, are apt, as stated above, 
to throw off enormous numbers of the bacilli in the sputum and other 
excreta, the germ is widely dispersed in inhabited regions, especially in 
buildings frequented by uncleanly tuberculous persons or by infected 
cattle. 
Among the lower animals, guinea-pigs, rabbits, monkeys in confine- 
ment, and cattle are particularly susceptible to the action of the tubercle 
bacillus. Although tuberculosis is widespread in man, he is not, as 
compared with some of the lower animals, particularly susceptible. 
While the tuberculous process presents some differences in different 
animal species in rate of development, amount of necrosis, tendency to 
softening, calcification, etc., the fundamental effects are similar in man 
and in the lower animals. 
Portals of Entry, Distribution of Lesions, and Sources of the 
Tubercle Bacilli. 
Portals of Entry and Distribution.-The question of the chief portals 
of entry of the tubercle bacillus has given rise to much discussion and 
much experiment. So far as the lungs are concerned, in which tuber- 
culosis is common, it has been assumed that infection is most frequently 
direct, the bacilli gaining access through the respiratory passages to 
the alveoli. Others have contended that lung infection is most often 
secondary to the entrance of the bacilli through the gastro-intestinal 
canal with or without local lesions. Still others believe that tuber- 
culosis of the lung is commonly secondary to tuberculous lesions of the 
bronchial lymph-nodes, or that the bacilli may enter through the tonsils, 
or that they often enter through the placenta. To the advocates of 
the latter views the blood-vessels and lymphatics play a predominant 
role in the distribution of the infective agents.1 
While it is probable that all of these portals of entry are of importance, 
it would seem well established that direct inhalations are the most 
frequent occurrence, while entrance through the intestinal mucosa is 
very common, especially in infancy.2 
We may assume, then, that the tubercle bacillus most frequently 
enters the body through the respiratory organs, including tonsils and 
pharynx, and through the gastro-intestinal canal. Traumatic infection 
1 For a study of tubercle bacilli in the blood see Anderson, Hyg. Lab. U. S. Mar. Hosp. Ser. 
Bull., 57, 1909; Klopstock and Seligmann, Ztschr. f. Hyg., 1913, lxxvi.,7; and Klemperer, Berl. klin. 
Wchnschr., 1914, li, 436. 
2For a full discussion of this subject see Lubarsch, Fortschr. d. Med., Bd. xxii., pp. 669, 701, 1914. 
For experimental tuberculosis in young guinea-pigs with reference to portals of entry see Bartel and 
Spieler, Wiener klin. Woch. p. 155, 1905 and p. 25, 1906. For a resume of studies on the tubercle 
bacillus and its portals of entry, Baumgarten, Verhl. Deut. Path. Ges., Bd. ix., p. 5, 1905; Aufrecht, 
"Pathologic and Therapie der Lungenschwindsucht," Wien, 1908; Ravenel, Am. Jour. Med. Sei., 
cxxxiv., 469, 1907. For mode of tubercle-bacillus infection in young see W estenhoeffer, Berl. klin. 
Woch. 1904, pp. 153 and 191. For intestinal origin of pulmonary tuberculosis see Calmette and Guerin 
Ann. Inst. Pasteur, vol. xix., p. 601, 1905 and Calmette, Medical Record, 1908, Ixxiv., 741. For a study 
of mode of infection of the lungs by way of the mouth and pharynx see Beitzke, Virch. Arch., Bd. 
clxxxiv., p. 1, 1906. THE INFECTIOUS DISEASES 
265 
through the skin is of relatively infrequent occurrence, as is apparently 
the congenital transmission.1 
In adults the lungs, in children the bronchial lymph-nodes, are the 
most frequent seat of tuberculous lesions.2 
Many observations on the occurrence of tuberculous bronchial, 
cervical, and mesenteric lymph-nodes in persons exhibiting no appre- 
ciable tuberculous lesions elsewhere would indicate the frequency of 
access of the bacilli to the lymph channels without primary lesion at 
the portal of entry in the pharynx, tonsils, respiratory passages, intes- 
tinal mucosa, or elsewhere.3 A considerable percentage of persons dying 
from other diseases have been found to have tuberculous lesions often 
healed in the lungs or bronchial lymph-nodes. 
Sources of Tubercle Bacilli.-Tubercle bacilli are frequently trans- 
mitted to the well from the victims of tuberculosis by means of the 
sputum which is cast off, allowed to dry, and becomes pulverized and 
is then inhaled as dust. 
But this source of infection is perhaps not as significant as was 
formerly believed from analyses of material gathered from walls and 
floors of contaminated rooms. For it has become clear that not all the 
infectious material which may be cast out of the body as sputum is 
always readily and speedily transformed into dust. In the drying of 
the mucus with which much of this material is mingled, a process ordi- 
narily rather slow, the bacteria are closely imprisoned so that only 
under certain conditions, such as the rubbing and beating of soiled 
clothing, the shuffle and tread of feet over contaminated floors, dry 
sweeping, and the like, is the excretion sufficiently comminuted to float 
in the air as dust. Even when this is the case, it has been found that a 
large part of such pulverized excreta is still in too large particles to 
remain long suspended on the air. 
This condition of affairs was not appreciated in the earlier studies 
on dust infection, and in many instances the material called dust, col- 
lected in various places for analysis, was evidently not in such form as 
would have remained long in suspension. Thus it is that while the 
earlier identification of various pathogenic micro-organisms in the dust 
of rooms was correct, the inference as to the constant risk of dust infec- 
tion in such places was frequently at least somewhat overestimated. 
On the other hand, Fliigge and others4 have found that not only in 
sneezing and coughing, but also in ordinary speech, the secretions 
of the nose, mouth, and throat may be cast forth in considerable quantity 
for a distance of several feet, not only in the form of visible droplets, 
but as a more or less abundant, invisible spray, which may remain sus- 
1For a study of placental and congenital tuberculosis see Warthin and Cowie, Jour. Inf. Dis., 
vol. i., p. 140, 1904. 
2 For studies in the frequency, localization, and modes of dissemination of tuberculosis, with 
special reference to its occurrence in the lymph-nodes and during childhood, see Harbitz, Jour. Inf. Dis., 
vol. ii., p. 143, 1905, bibl. For a study of localization in infants and young children see Wollstein, 
Arch. Int. Med., iii., 221, 1909. 
3 See ref. foot note, p. 592. 
4 For the studies of Fliigge and his assistants see Zeitschr. f. Hygiene u. Infkr., vol. xxx., 1899, 
and vol. xxxviii., 1901. 266 
THE INFECTIOUS DISEASES 
pended for from half an hour to several hours, and may be carried for 
long distances on such slowly moving air currents as are common in 
inhabited rooms. 
Thus, fully virulent, infectious material may be transmitted directly 
through the air in coughing and sneezing; indirectly through dried 
infectious sputum ground to dust and floating in the air. Less fre- 
quent is the conveyance of tubercle bacilli through soiled utensils. 
The transmission of this germ through contaminated milk1 and the 
meat of tuberculous cattle2 is a mode of infection of great importance, 
especially the use of contaminated milk by young children.3 
Whichever way the tubercle bacilli enter the body, whether directly into the 
lungs, or by the pharynx or tonsils, or through the intestinal mucosa, or in rarer cases 
through wounds or through the placenta, they are transported by the blood- and 
lymph-vessels to lymph-nodes or to the tissues, where they lodge and grow and incite 
the formation of tubercles. These again if in the blood- or lymph-vessels, when they 
soften and set the bacilli free by ulceration into the channels, afford fresh foci of dis- 
tribution. So that in cases of disseminated tuberculosis the process of distribution 
is more or less gradual. In the meantime the progress of the lesions dependent in their 
topography upon the fortuitous character of the distribution of the infective agent is 
marked by the protective adaptation of the body-cells expressed by the formation of 
the tubercles and the development of immunizing substances; while, on the other 
hand, the bacillus itself is undergoing these adaptative modifications of its own bio- 
logical characters which are expressed in what we call its virulence. 
Statistics show, as we have seen, that in the majority of cases in man the pro- 
tective agencies of the body suffice to localize the lesions, surround the bacilli by 
necrotic masses in which they do not flourish, or enclose them in a fibrous envelope. 
Thus it appears that it is largely the chances of a wide or a continued distribution of 
the infective agent, or an unusual susceptibility of the host or exalted virulence of the 
bacilli, or the occurrence of fresh infection, that makes tuberculosis now and then so 
formidable a malady to man. 
While it is not impossible that future research may lead to the development of 
effective methods of artificial immunization to tuberculosis, it is to preventive meas- 
ures that we must look for the largest success in the suppression of this scourge of the 
human race. By proper disposal of the sputum; by providing against aerial disper- 
sion of infective material through unguarded coughing and sneezing; and by such intelli- 
gent methods of cleaning and disposal of dust as shall safeguard the respiratory organs; 
together with an enlightened supervision of the supplies of meat and milk, it should 
be possible even in crowded communities largely to reduce both the morbidity and 
the mortality of tuberculosis. 
Concurrent Infection in Tuberculosis. 
A concurrent infection with the tubercle bacillus and the pyogenic 
micro-organisms is of extreme significance in that phase of tuberculous 
1 Many cases of infection of human beings, especially children, with bovine bacilli, have been 
reported and in children abdominal tuberculosis and tuberculosis of the cervical lymph-nodes is most 
frequent. Park estimates that about 10 per cent, of tuberculosis in children under five years is due to 
bovine infection. See for tables of observations, Park and Williams, "Pathogenic Bacteria," p. 323, 
1910, and for comprehensive study of bovine and human types of tubercle bacilli, Park and Krumwiede, 
Jour. Med. Res., xxiii., 205,1910; ibid., 1912, xxvii., 109; see also Lewis, Jour. Exp. Med., xii., 82, 1910; 
Mitchell, Brit. Med. Jour., 1914, p. 125; and Fraser, ref. p. 888. 
2 See Kober, Amer. Jour. Med. Sc., vol. cxxvi., 1903, p. 684, bibl. For the intercommunicability 
of human and bovine tuberculosis see Ravenel, Proc. Path. Soc. Philadelphia, May, 1902; also resume by 
Bovaird, Med. Record, vol. Ixvii., p. 283, 1905. 
For a study of tubercle bacilli on books see Mitulescu, Zeitschr. f. Hygiene u. Infkr., Bd. xliv., p. 
397, 1903. 
3 For a study on flies and tuberculosis see Lord, Bost. Med. and Surg. Jour., vol. cli., p. 651, 1904. THE INFECTIOUS DISEASES 
267 
inflammation of the lungs commonly called phthisis.1 While the so- 
called cold abscesses may be caused by the tubercle bacillus alone, this 
germ is not infrequently found under these conditions to be associated 
with other pyogenic micro-organisms, especially the streptococcus and 
staphylococcus.2 
There are several species of bacteria which after deep staining resist the decoloriz- 
ing action of dilute acids. These have been called, collectively, "acid-resisting" or 
acid-proof bacteria.3 We shall consider only two of these. 
The Smegma Bacillus.-This organism is often present and sometimes in large 
numbers in the preputial smegma and elsewhere about the external genitals. It so 
closely resembles the tubercle bacillus in size, shape, and staining reactions that it is 
liable by morphological examinations alone to be mistaken for it. It has been culti- 
vated on artificial media and is not pathogenic. The smegma bacillus, when stained as 
above recommended for the tubercle bacillus, resists the decolorizing action of the 
acid; but it is usually decolorized by prolonged exposure to alcohol, thus differing 
from either the tubercle bacillus or the leprosy bacillus. But this color reaction is not 
certain; individual bacilli not infrequently remain unstained. Various special 
methods for differentiation have been suggested.4 In doubtful cases, and when 
serious operative procedures are dependent upon the bacterial diagnosis, recourse 
should be had to animal inoculations. 
The "Hay Bacillus."-This resembles the tubercle and smegma bacilli in form 
and staining peculiarities. It is called the "hay bacillus" or "grass bacillus" because 
of its common occurrence upon grass-heads in the fields. It is not pathogenic and is 
readily cultivated. 
Similar organisms have been frequently fourid in milk and butter, also in the 
sputum in gangrene of the lung. 
Bacteria Resembling the Tubercle Bacillus. 
Local tuberculous inflammation of the skin may occur in the form of small nodules 
or wart-like thickenings, as the result of accidental inoculation. Local skin infection 
may occur about the orifices of the body in tuberculous persons from contact with 
secretions or excretions containing the tubercle bacilli, or about sinuses leading to 
tuberculous abscesses, joints, etc., or in the vicinity of tuberculous lymph-nodes. 
A chronic form of tuberculous inflammation which presents special clinical features 
has long been known under the name of lupus. 
Lupus.-This form of inflammation most frequently occurs in the skin of the face, 
but also in the mucous membrane of the mouth, pharynx, conjunctiva, vulva, and 
vagina. The lesion consists of small, multiple nodules of new-formed tissue, in the 
cutis or mucosa and submucosa. By the formation of new nodules and a more diffuse 
cellular infiltration of the tissue between them the lesion tends to spread, and by the 
confluence of the infiltrated portions a dense and more or less extensive area of nodular 
infiltration may be formed. There may be an excessive production and exfoliation of 
epidermis over the infiltrated area, or an ulceration of the new tissue. 
Microscopical examination shows the lesion to consist of small spheroidal cells in- 
termingled with variable numbers of larger, polyhedral cells and cell masses, and in 
Lupus and Other Forms of Tuberculosis of the Skin. 
1 See Spengler, Zeitschr. f. Hygiene, etc., Bd. xviii., p. 343, 1894, bibliography. See reference to 
Prudden, p. 631. 
2 For a study of the simultaneous occurrence of tuberculosis and cancer see Weinberg, Munch, 
med. Wochenschr., p. 1473, 1906; for bibliography see Oertel, Jour. Med. Research, 1912, N. S., xx., 305. 
3 See for resume and bibliography Abbott and Gildersleeve, Trans. Assn. Amer. Phys., vol. xvii., p. 
37, 1902; also Rosenberger, Proc. Path. Soc. of Phila., January, 1904. 
4 Critical review, with bibl., Dahms, Jour. Am. Med. Assn., vol. xxxiv., pp. 983 and 1045, 1900. 
Consult also Cowie, Jour. Exp. Med., vol. v., p. 205, 1900. 
For the method of Pappenheim, which is said to be more reliable than the alcohol decolorization, see 
p. 259. 268 
THE INFECTIOUS DISEASES 
many cases giant cells (Fig. 154). In some cases a well-marked reticulum is present 
between the new cells, and these are often grouped in masses around the blood-vessels. 
In some cases there is, without previous ulceration, a formation of new connective tis- 
sue in the diseased area, and a well-marked cicatrization; in other cases the cells and 
intercellular substance undergo a disintegration which leads to ulceration. Tubercle 
bacilli in small numbers may be found in these lesions. In the clinical group of dis- 
eases called lupus there are other forms of lesion which are not incited by the tubercle 
bacillus. 
Fig. 154.-Lupus of Face. 
Bibliography of Tuberculosis. 
The announcement of the discovery of the Bacillus tuberculosis by Koch was made 
in the Berliner klin. Wochenschrift, 1882, No. 15. A most elaborate and valuable 
article on the same subject by Koch is contained in the " Mittheilungen aus dem Kaiser- 
lichen Gesundheitsamte," vol. ii. 
The abundant literature on the subject of the tubercle bacillus -which has accumu- 
lated since 1882 is for the most part scattered through the German, English, and French 
journals. 
An excellent critical resume of the subject by Lartigau, with selected bibliography, 
may be found in the "Twentieth Century Practice," vol. xx. 
In the large work of Straus, "La Tuberculose," 1895, the experimental aspects of 
the subject are fully considered. 
In the work of Cornet, "Die Tuberculose," together with the general and clinical 
consideration of the disease, the modes of infection and prophylaxis are set forth, 
with bibliography. See also Kolle and Wassermann's " Handbuch der Mikoorganis- 
men,'" 2d edition, 1913, v., pp. 391-746. An excellent summary of the tubercle 
bacillus and its biological characters is in Kolle and Hetsch, " Experimentelle Bak- 
teriologie und die Infectionskrankheiten," 3d edition, 1911. THE INFECTIOUS DISEASES 
269 
Leprosy is characterized by the development of nodular and some- 
times diffuse masses of tissue, consisting of larger and smaller cells of 
various shapes-spheroidal, fusiform, and branched, with a fibrous 
stroma-the whole somewhat resembling granulation tissue. The new 
tissue is most frequently formed in exposed parts of the skin, as the 
face, hands, and feet, but it may occur in the skin of any part of the 
body. It is formed more rarely in the subcutaneous connective tissue, 
in intrafascicular connective tissue of nerves, in the viscera, and in the 
mucous membranes. The mucous membranes most frequently affected 
are those of the eye, nose, mouth, and larynx. The nodules may be 
very small or as large as a walnut, and may be single or joined together 
in groups or masses. The tissue of the part in which the new formation 
occurs may be atrophied and replaced by, or may remain intermingled 
with, the leprous tissue, or it may be hyperplastic. The nodules may 
persist for a long time without undergoing any apparent change, or they 
may soften and break down, forming ulcers; but ulceration, except in 
the mucous membranes, is said usually to occur as the result of injury 
or unusual exposure. The leprous tissue may change without ulceration 
into cicatricial tissue, or cicatrization may follow ulceration. 
Various secondary lesions and disturbances of nerve function are 
associated with the formation of leprous tissue in the nerves and central 
nervous system, but these we cannot consider here. 
In all the primary lesions of leprosy, bacilli are said to be present, 
mostly in the cells, and particularly in the larger transparent spheroidal 
forms, but sometimes free in the intercellular substance. The bacilli 
have been found in the skin, mucous membrane of the mouth and 
larynx, in peripheral nerves, in the cornea, in cartilage, in the testicles, 
kidney, liver, and in the blood and lymph-nodes. Sometimes the cells 
contain but few bacilli, but they are frequently crowded with them. 
LEPRA (Leprosy). 
The bacilli are from 4 to 6 n long and very slender. They are sometimes pointed 
at the ends and sometimes present spheroidal swellings (Fig. 155). In their com- 
portment toward staining agents, as well as in 
general morphological characters, they consider- 
ably resemble the Bacillus tuberculosis, but they 
are more readily stained. They may be stained 
with fuchsin or gentian violet by the ordinary 
method, or by the method employed for staining 
the tubercle bacillus (see p. 258). 
Cultures and Pathogenesis.-Various reports 
of success in the artificial cultivation of the lepra 
bacillus have been made but confirmation has 
not followed. Quite recently, however, Clegg1 
and others have apparently succeeded in securing cultures with amoebae, and their 
symbiotic bacteria. Finally Duval2 records his success in pure cultures and his 
confirmation of the work of Sugai in securing positive results by the inoculation of 
cultures in the Japanese dancing mouse. 
Characters of the Lepra Bacilli. 
Fig. 155.-The Bacilli of Leprosy 
From a nodule in the skin, showing the 
bacilli free and within cells. 
1 Clegg, Phillipine Jour. Sci., iv, 403, 1909; also Currie, Brinckerhoff, and Hollman, Public Health 
Reports, U. S. Mar. Hosp. Ser., xxv., 1173, 1910. 
2 Duval, Jour. Exp. Med., xii., 649, 1910; Duval and Wellman, Jour. Infect. Dis., 1912, xi., 116. 270 
THE INFECTIOUS DISEASES 
The structure of the new tissue growth, the absence of coagulation 
necrosis, and the peculiar grouping of the bacilli in the large transparent 
cells are characters which usually clearly distinguish the lesions caused 
by the leprosy bacillus from those of tuberculosis. 
Leprosy is common in India and in other hot countries. It is infre- 
quent in America, but in the Gulf States, in Mexico, among the Nor- 
wegians in the Northwest, and in the eastern British provinces a con- 
siderable number of cases are grouped. Isolated cases are, however, 
encountered now and then in various parts of the United States.1 
Communicability.-So long as the leprous tissue is intact the bacilli 
are closely enclosed by it. But when necrosis and ulceration occur, as on 
the skin or the mucous membranes, the bacilli may be widely distributed; 
from ulceration nodules in the nose and pharynx, for example, in sneez- 
ing and coughing. But even persons exposed to infective exudates are 
so seldom infected that one is forced to assume special predisposing 
factors which we do not understand when infection does occur. Under 
proper sanitary conditions leprosy is not to be regarded as readily 
communicable.2 
SYPHILIS. 
It has been found convenient to consider the lesions of syphilis as 
occurring in three stages, primary, secondary, and tertiary. These 
stages may perhaps mark epochs in the development of the infective 
agent or phases in the protec- 
tive action of the body-cells in 
the course of their adaptation 
to the parasitic organism. Or, 
finally, the stages of syphilis 
may bear some relationship to 
the adaptive processes of the 
infective organism itself. 
It may be said in general 
that the characteristic lesions of 
syphilis consist in a more or 
less circumscribed formation of 
new tissue. This may be made 
up largely of small spheroidal 
cells or of these with polyhedral 
cells (Fig. 156), and of occa- 
sional giant cells. The new 
tissue, which may be diffuse or 
in more or less clearly circumscribed masses, contains, as a rule, few 
blood-vessels, and is prone to undergo coagulation necrosis. This 
tendency is most pronounced in the circumscribed masses. 
The endothelial cells of the blood-vessels in and near the inflammatory 
Fig. 156.-New-formed Tissue in Syphilitic 
Inflammation. 
From a "hard chancre," showing swollen endo- 
thelium in a small blood-vessel. 
1 For a study of leprosy in the United States, see Brinckerhoff, Public Health and Marine Hospital 
Service, vi., 1909. 
2 For bibliography of leprosy consult Morrow, "Twentieth Century Practice," vol. xviii. THE INFECTIOUS DISEASES 
271 
foci in this form of inflammation are not infrequently swollen and may 
proliferate (Figs. 156 and 157, B). The vessels may otherwise undergo 
extensive changes. 
Primary Lesions.-At the point of inoculation in a few weeks a focus 
of inflammation develops-the initial sclerosis. This may be in the 
form of a papule or a vesicle, and in either case erosion of the surface is 
apt to occur and a hardening of the deeper tissues, leading to the so- 
called chancre. In this primary lesion, in addition to more or less 
Fig. 157.-Section of a Portion of a Syphilitic Condyloma of the Mucous Membrane. 
A, (Edematous papilla; B, swollen endothelial cells in small blood-vessels of a papilla; C, pus 
cells in the submucous connective tissue; D, pus cells in the epithelium; E, disintegration of the epithe- 
lium in the superficial portion of the mucous membrane. 
fluid and cellular exudate, there may be obliterating endarteritis, a 
small spheroidal-cell infiltration of the connective tissue, proliferation of 
connective-tissue cells, especially near the blood-vessels (Fig. 158), 
swelling of the vascular endothelium, and an occasional development 
of giant cells. This new tissue may become fibrous and the initial 
lesion heal. 
Usually in connection with, or following the development of, the 
initial lesion there is a hyperplasia of the lymph-nodes belonging to the 
anatomical district of the lesion. These become hard and swollen. 272 
THE INFECTIOUS DISEASES 
These hyperplastic lymph-nodes, called buboes, are not apt to suppurate 
except as the result of concurrent infection with pyogenic bacteria, but 
the swelling gradually subsides. 
Secondary Lesions.-After six or seven weeks the so-called secondary 
stage of syphilis, now called constitutional syphilis, is entered upon. 
This is characterized by various forms of eruption on the skin and 
Fig. 158.-Section from a Primary Syphilitic Nodule of the Mucous Membrane of the 
Mouth. 
Showing collections of cells about the blood-vessels in the submucous tissue. 
mucous membranes-macules, papules, and pustules. Periostitis is not 
infrequent. At this period there often develop on the mucous membranes 
or where these join the skin, circumscribed areas of exudative and pro- 
ductive inflammation of the papillary layers with necrosis and exfolia- 
tion of the epithelium. The papillae are enlarged, the epithelium swollen 
and opaque. These local areas of inflammation and necrosis are called 
mucous patches. Of similar character are the elevated areas of the skin 
common about the generative organs in secondary syphilis, called con- 
dylomata. Here also there is at the base the characteristic cell prolifer- THE INFECTIOUS DISEASES 
273 
ation with swelling of the papillae, thickening and exfoliation of the epithe- 
lium, and there may be an abundant infectious exudate from the surface. 
Tertiary Lesions.--One of the most characteristic phases of the 
tertiary inflammations of syphilis is the formation in the periosteum 
or in the viscera, especially in the liver, lungs, heart, brain, and kidney, 
of masses of new tissue called gummata. 
The smaller gummata consist of a mass of small spheroidal and epi- 
thelioid cells (see Fig. 159). As these cell masses grow larger they are 
apt to become necrotic and caseous at the centre, and we mav then 
have, as seen by the naked eye, a grayish white, usually firm mass, with 
a more or less dense and irregular granular centre and a translucent, 
often radially striated border of dense fibrous tissue (see Fig. 160). 
Fig. 159. 
Fig. 169. 
Fig. 159.-Small Nodule of Syphilitic Inflammation (Miliary Gumma) in the Liver. 
Fig. 160.-Syphilitic Gumma in the Liver. 
Showing necrotic caseous centre merging into the new-formed cellular and fibrous tissue in the 
periphery. This gumma was much larger and is much less magnified in the cut than Fig. 159. 
Gummata vary in size from those invisible to the naked eye to 
those several centimetres in diameter; they are usually single, but may 
be multiple, and occasionally several coalesce. The border zone of the 
gumma usually consists of granulation or fibrous tissue and may be 
regarded as due to the reparative reaction of the surrounding tissues. 
The necrotic portions of gummata may be absorbed and the whole 
replaced by a mass of cicatricial tissue; or strands of fibrous tissue enclos- 
ing irregular islets of caseous material may long persist at the original 
seat of the gummata. In some instances the syphilitic inflammation 
may be diffuse, with or without marked necrosis. In the lungs, the 
liver, and the walls of the arteries the later stages of syphilitic infection 
may be marked by the diffuse formation of fibrous tissue. 
Congenital Syphilis.-The lesions of congenital syphilis are those of 
the secondary and tertiary stages, and may be present at birth or develop 
at a later period. Various phases of malnutrition are often obvious. 274 
THE INFECTIOUS DISEASES 
There may be pemphigus of the hands and feet or elsewhere, with vesicles 
or blebs containing variously colored or bloody fluid. Pustules, usually 
about the buttocks; various erythematous rashes; coryza; inflammations 
of the bones, joints, and cornea, etc., are frequent. Irregularities in 
the ossification of the long bones (see p. 889), gummata and cirrhosis of 
the liver, enlargement of the spleen, various inflammatory and degener- 
ative lesions of the kidney, and obliterating endarteritis are among the 
more common marks of congenital syphilis. 
Diagnosis.-The nodular lesions of syphilis are in many respects 
structurally similar to those of tuberculosis, so that it is sometimes 
difficult to distinguish them on morphological examination alone. But 
the greater variety in the developmental stages of the tuberculous foci 
which may be found in a single individual, the grouping of the lesions 
in a manner indicative of local infections, and in the last resort the 
demonstration of the presence of the tubercle bacillus, will usually suf- 
fice to distinguish the tuberculous from the syphilitic lesion, even with- 
out recourse to the clinical history. 
For further details regarding syphilitic lesions of the viscera see 
Part II. For many details regarding syphilis, its symptomatology and 
lesions, its effects upon gestation and the infant, etc., reference is made 
to special works on the subject.1 
Animal Inoculations.-It has been shown by Metchnikoff and Roux2 
and by Neisser,3 that successful inoculations of apes may be made with 
the virus of syphilis. It has been found that while cutaneous inocula- 
tion with material from primary and secondary lesions gives positive 
results, subcutaneous and intraperitoneal introduction of similar mate- 
rial does not. Rabbits have also been successfully inoculated.4 
Treponema pallidum (Spirochaeta pallida).-In 1905 Schaudinn and 
Hoffmann5 described the occurrence in primary lesions of syphilis of a 
slender, spiral organism (Figs. 161 and 162) of about the length on the 
average of the diameter of a red blood cell, which they called Spirochaeta 
pallida. It is sharply curved, corkscrew like, having from three to ten 
or more curves, and is pointed at the ends. It is mobile, rotating on 
the long axis, and moving in both directions. This organism at first 
called Spirochaeta was afterward renamed Treponema. 
The Treponema pallidum is stained with difficulty by the ordinary 
reagents and is thus frequently difficult of detection. It may be mixed, 
especially when on the ulcerating surfaces of syphilides, with coarser 
and more readily stained spiral organisms, particularly Spirochaeta 
refringens, and with various other saprophytic bacteria. It is most 
readily detected in material from the depths of such lesions as con- 
dylomata and mucous patches. 
1 For critical summary of syphilis with recent bibliography see Lang and Ullmann in Lubarsch and 
Ostertag's " Ergebnisse," Jahrg. v. for 1898, p. 481. 
For a study of blood-vessel changes in syphilis with bibliography see Abramow, Ziegler's Beitrage, 
Bd. xxvi., p. 202, 1899. 
2 Ann. Inst. Pasteur, t. xvii., p. 809, 1903. 
3 Deut. med. Woch., xxx., pp. 1369 and 1431, 1904; and Neisser and Baermann, ibid., xxxi., p. 
48, 1905. 
4 Bertarelli, Central, f. Bak., xli., 320, 1906. 
6 Arbeiten a. d. Kais. Gesundheitsamte, Bd. xxii.. p. 527, 1905; also Deut. med. Woch., p. 711, 1905. THE INFECTIOUS DISEASES 
275 
The Treponema pallidum has been found in condylomata and in the 
primary macules, papules, and pustules. It has been found in the 
internal organs, in the lymph-glands of involved regions, in the spleen, 
adrenals, and liver, and in the blood. 
The organism has also been found in the secondary lesions of syphilis, 
even at a late period, and in tertiary lesions and in the brain in paresis. 
It also occurs, sometimes in large numbers, in the lesions of the skin and 
in the internal organs of the victims of congenital syphilis. 
It has been found possible by inoculating monkeys and rabbits, the 
latter preferably in the testicle, with human syphilitic material, to obtain 
characteristic lesions containing the treponema, and 
also to induce similar lesions with pure; cultures 
obtained directly from human tissues. The blood 
of infected monkeys also gives the Wassermann 
reaction. There is, therefore, no longer any doubt 
that the organism is the inciting agent of syphilis. 
Its exact classificatory relationships are as yet a 
matter of discussion, but it is generally regarded as 
a special order of the protozoa.1 
Communicability.-The infective agent of sy- 
philis is readily and most frequently conveyed in 
man by direct inoculation with the exudate from 
some lesion of a victim of the disease. This most 
frequently occurs during sexual intercourse, but 
may take place in many other ways, either through 
direct or indirect transmission to abraded or 
wounded surfaces of the infective exudate. 
Syphilis may also be congenitally transmitted, 
apparently, either from the father or the mother. 
But the transmission of the infective agent through the placental blood 
is the more common. 
Immunization.-Though many attempts have been made to secure 
active and passive immunity, none has been successful. 
Fig. 161.-Treponema 
Pallidum 
(Spirochaeta pallida.) India 
ink stain. 
The material is most readily obtained from the primary ulcerated lesions by gently 
scraping with a platinum loop after a preliminary cleansing of the surface, or from 
mucous patches by a deep scraping with a sharp spoon. From papules, pustules, and 
roseolae one may obtain material by expressing fluid through a superficial incision; 
from lymph-nodes by the hypodermic needle. 
Living Organisms.-By the use of the special condenser for dark field illumination 
in a fresh preparation, by the arc light one may see the refractile unstained spiral 
organisms in rapid motion across the dark field. 
Staining.-Smears of the material should be made very thin. After fixation in 
strong methyl alcohol for ten minutes, the Treponema pallidum can be stained by the 
Giemsa method (page 1037) or the azure-eosin method of Wood (page 317). With the 
Giemsa method it is well to stain for from twelve to twenty-four hours; with the 
Wood method a warm preparation can be stained in ten minutes. 
Demonstration of Treponoma Pallidum. 
1 For cultural methods see Noquchi, Jour. Exper. Med., 1912, xv., 90. For a general review with 
bibliography see Sobernheim, in Kolle u. Wassermann, Handbuch, 2d edition, 1913, vii, 745; Doflein, 
Lehrbuch d. Protozoenkunde, 3d edition, Jena, 1911; Levaditi and Roche, La syphilis, Paris, 1909. 276 
THE INFECTIOUS DISEASES 
In tissues, the treponema is best demonstrated by the silver impregnation method 
of Cajal, as modified by Levaditi and others. This is as follows: 
1. Fix slices of tissue not over 2 mm. thick in a solution of 1 part formalin and 9 
parts water, for twenty-four to forty-eight hours. 
2. Harden in 96-per-cent. alcohol for twenty-four hours. 
3. Wash in distilled water until the fragments sink. 
4. Impregnate with the following solution: 
Pyridin 10 c.c. 
Silver nitrate, 1-per-cent. aqueous sol 90 c.c. 
Tightly stoppered bottles are maintained at a temperature of 50 to 55° C. in a paraffin 
oven for five hours. 
5. Wash in distilled water and reduce in the following mixture at room temper- 
ature : 
Pyridin 17 c.c. 
Acetone 10 c.c. 
Pyrogallic acid , 4-per-cent. in dist. water 90 c.c. 
Stained by the silver method. Preparation of Dr. Noguchi. Showing enormous numbers of 
spirochetes in the smear of material from syphilitic lesion. 
Fig. 162.-Treponema Pallidum. 
The tissue should be kept in the dark and reduction carried out for several hours. 
6. Dehydrate in alcohol, embed in paraffin, and cut sections not over 5 microns 
thick. 
If a counterstain is desired, use toluidin blue or Unna's alkaline methylene blue, 
and differentiate with glycerine-ether. 
^Noguchi1 states that in the use of the Levaditi method certain modifications are 
necessary if satisfactory results are to be obtained. The preliminary fixation of the 
cerebral tissue in formalin should be very thorough, a period of six months to a year 
giving the best results. Slices of brain tissue, 5 to 7 mm. thick, are placed in the follow- 
ing mixture: 
Formalin lOparts 
Pyridin 10 parts 
Acetone 25 parts 
Alcohol 25 parts 
Distilled water 30 parts 
1 Noguchi, Munchen, med. Wchnschr., 1913, lx., 737. THE INFECTIOUS DISEASES 
277 
In this they remain at room temperature for five days. They are then washed in 
distilled water for twenty-four hours; transferred to 96-per-cent. alcohol for three days; 
washed in distilled water for twenty-four hours; soaked in 1.5-per-cent. aqueous solu- 
tion of silver nitrate for three days at 37° C. or for five days at room temperature; 
washed in distilled water for two hours; reduced in 4-per-cent. pyrogallic solution to 
which has been added 5-per-cent. formalin, for twenty-four to forty-eight hours at 
room temperature; washed thoroughly in distilled water; transferred to 80-per-cent. 
alcohol for twenty-four hours; then to 95-per-cent. alcohol with daily renewals for 
three days; and absolute alcohol for two days; and embedded in paraffin. Sections 
should be cut about 3 to 5 microns thick, and should be taken from different portions 
of the block in order that areas may be obtained in which the neuroglia fibers are not 
deeply stained and the treponema is black. 
By this method the spirals are more or less definitely black, the tissues pale yellow. 
Double staining reveals the relationships of the organism to the tissue cells. 
India Ink Stain.1-An effective method of demonstrating the syphilis organism in 
smears is as follows: 
The fluid squeezed from a syphilitic lesion on to a slide with as little blood as pos- 
sible is mixed with a drop of India ink (Chin-Chin waterproof ink manufactured by 
Gunther Wagner), and the mixture spread as in making blood smears. After dry- 
ing, which is almost immediate, the specimen examined directly with an oil immer- 
sion lens shows the organism, if present, as unstained in a black field (see Fig. 161). 
WASSERMANN'S TEST IN THE DIAGNOSIS OF SYPHILIS. 
General Considerations.--The principles on which this test is based have been 
considered on page 189 under the heading Fixation of Complement. We have 
there seen that when a substance capable of inciting the body-cells to the formation of 
antibodies, i.e., an antigen, is mixed with its corresponding heated serum, i.e., 
antibody or amboceptor, in the presence of complement, the latter is so "fixed" in 
combination with the antigen that it is no longer free to enter into any other combina- 
tion. This is shown by the fact that if such a mixture be placed in contact with 
the sensitized red blood cells, no haemolysis is produced. 
If, in the above reaction, the heated serum contained no antibody, the comple- 
ment would not be fixed and haemolysis would take place on the addition of the 
sensitized red blood cells. 
In this way one may determine the presence in given fluids of specific antibodies, 
on the one hand, or of antigens on the other, if he have at hand the homologous 
antigens or antibodies as the case may be. For antigens one may use bacteria or 
bacterial extracts. 
In Wassermann's test it was assumed that syphilitic organs might contain uncom- 
bined portions or products of Spirochseta (Treponema) pallidum, i.e., free syphilitic 
antigens, and thus extracts in salt solution or alcohol were made of organs-spleen, 
liver, etc.-of a syphilitic foetus. But it was discovered later that specific antigens 
are not necessary for the reaction; that extracts of normal organs, liver, spleen, heart, 
human or animal, or lecithin in solution can act as antigens in the tests. 
Details of the Test.-Five elements enter into the Wassermann test-antigen, 
haemolytic serum, complement, blood corpuscles, and the serum to be tested for 
syphilitic antibody. 
I. The Antigen.-Of the large number of antigens proposed by different workers 
for use in the Wassermann test, the following have been found by the writer to be the 
most useful. • 
A. Alcoholic extract of syphilitic organs. The liver of a syphilitic foetus is 
chopped fine, and absolute alcohol is added in the proportion of 9 c.c. to each gram of 
liver. The mixture is shaken with glass beads in a shaking machine for twenty-four 
hours, and then filtered through paper. The extract is most useful in amounts of 
from 0.2 to 0.3 c.c. 
B. Alcoholic extract of normal organs. Guinea-pig or human heart, ground fine, 
is extracted with 5 c.c. of 95-per-cent. alcohol to each gram of material. The extrac- 
1 Burri, Das Tuscheverfahren, Jena, 1909. 278 
THE INFECTIOUS DISEASES 
tion may be done in a water bath at 60° C. for ten to twelve hours or at 37.5° C. or 
room temperature for longer periods, up to two weeks. Such extracts are most often 
used in amounts of from 0.03 to 0.3 c.c. 
C. Fractionated lipoids. Noguchi1 recommends the use of the alcohol and ether 
soluble but acetone insoluble fraction of the heart, liver, or kidney of man or various 
animals, as the ox, guinea-pig, rabbit, etc. Fresh beef heart is generally available and 
gives a fair proportion of satisfactory results. 
The finely minced organ, freed from fat, is extracted for several days at 37.5° C. 
with ten parts of absolute alcohol. The resulting alcoholic extract is evaporated 
to dryness with the aid of an electric fan. The residue is taken up in ether and the 
turbid solution is allowed to stand until the insoluble portion has settled, leaving a 
clear supernatant fluid. The clear portion is decanted and concentrated to a small 
volume by evaporation. This is mixed with ten volumes of acetone, when a precipi- 
tate will form which settles to the bottom of the vessel. The supernatant fluid is 
decanted and the brownish sticky precipitate is retained. Three-tenths gram of 
this material is dissolved in about 1 c.c. of ether and 9 c.c. of methyl alcohol are added. 
A slight precipitate results, which is removed by sedimentation. This solution is per- 
manent. For use in the test a 0.3-per-cent. emulsion is made by mixing 1 c.c. of the 
alcoholic stock solution with 9 c.c. of salt solution. Titration usually shows that 
0.1 c.c. of this emulsion will give satisfactory results. 
D. Cholesterinized extracts.2 Finely minced guinea-pig hearts are extracted 
with 95-per-cent. alcohol for two to three weeks at 37.5° C. To the filtered extract 
is added 0.4-per-cent. cholesterin. For use the antigen is diluted with salt solution. 
One c.c. of a 1 to 10 dilution is usually found satisfactory. 
In preparing antigens it is found that even with identical technique the results 
vary greatly, some preparations proving absolutely worthless. The substances 
used as antigen occasionally have lytic properties for red blood corpuscles and fre- 
quently have the power when used in too large quantities of themselves binding 
complement. It is necessary, therefore, with each antigen to determine the largest 
quantity which can be used without causing lysis of sheep corpuscles or exerting an 
anticomplementary action; i.e., which will not of itself inhibit haemolysis. For these 
tests the required amount of antigen is diluted with three parts of 0.9-per-cent. salt 
solution. To test the lytic power, graded amounts of this antigen emulsion are 
mixed with 0.25 c.c. of a 5-per-cent. suspension of washed sheep corpuscles and 
sufficient salt solution is added to make the total volume of each tube 1.25 c.c. 
These tubes are placed in a water bath for one hour at 37.5° C. To test for 
anticomplementary properties graded amounts of the antigen emulsion are added 
to 0.25 c.c. of a 1 to 10 dilution of guinea-pig serum, with sufficient salt 
solution in each tube to make the total volume 0.75 c.c. The tubes are placed 
in a water bath for one hour at 37.5° C. At the end of this time 0.5 c.c. of ac- 
tivated sheep cells are added to each tube, and the mixtures returned to the water 
bath for one hour. The activated sheep cells are prepared by mixing equal parts 
of a 5-per-cent. suspension of washed sheep cells and a dilution of rabbit serum 
haemolytic for sheep corpuscles, of such strength that in the resulting mixture the 
sheep corpuscles shall contain two units of sheep amboceptor. As a general rule, the 
amount of antigen used in the test should not be more than half the largest amount 
found by the previous titration not to be of itself anticomplementary. For use in the 
Wassermann reaction it is advisable to dilute the antigen with salt solution so that 
1 c.c. of the emulsion shall contain the proper amount of the extract. The extract 
should then be tested in this and smaller amounts, using the regular Wassermann 
technique, with several positive sera to prove the presence of antigenic properties 
in sufficient amount. The postulate of Noguchi3 that an antigen should not be 
anticomplementary or lytic in four times the dose used and should contain at least 
five antigenic units, i.e., should give a positive reaction with one-fifth the amount 
used, is empirical, but is a good rule to follow for the fractionated lipoid antigens. 
If the antigenic properties of an antigen are not sufficiently strong the complement 
1 Noguchi, Serum Diagnosis of Syphilis, 3d edition, 1912. 
2 Walker and Swift, Jour. Exper. Med., 1913, xviii., 75. 
3 Noguchi, Serum Diagnosis of Syphilis, 3d edition, 1912. THE INFECTIOUS DISEASES 
279 
may be only partially fixed even with strongly positive sera and a weak reaction may 
result, while with weakly positive sera the reaction may be entirely missed. 
The presence in many human sera of natural sheep amboceptor necessitates the 
use of an antigen of several antigenic units, if the best results are to be obtained from 
the original Wassermann technique. Within certain limits the quantitative relation- 
ship between the absolute amounts of amboceptor and of complement necessary to 
produce complete haemolysis is such that an increase of one, as amboceptor, permits 
of the use of a smaller amount of the other, that is, complement. As, in the final stage 
of the Wassermann reaction, we add two units of sheep amboceptor, the presence of 
natural sheep amboceptor in the human serum causes an excess of this factor, which 
in some cases is considerable. To avoid the dangers of negative reactions with posi- 
tive sera because of an excess of amboceptor, several modifications of Wassermann's 
original technique have been devised, as those of Noguchi,1 Bauer,2 and Jacobaeus.3 
The modifications of Noguchi and Jacobaeus are efficient in precluding this possibility. 
If, however, an antigen of high antigenic power is used the number of positive sera 
which will give a negative reaction with the regular Wassermann technique because 
of the presence of natural sheep amboceptor is very small. 
Cholesterinized antigens give a larger percentage of frankly positive reactions than 
do antigens made by other methods; and sera which with other antigens give only a 
doubtful or weakly positive reaction are apt with the cholesterinized antigen to give 
much stronger reactions. Some workers, however, believe that some of the sera 
which give positive reactions with this antigen only are not luetic. It is always ad- 
visable in the Wassermann test to use more than one antigen, inasmuch as the results 
with different specimens vary. At least, until a greater number of observations with 
cholesterinized antigens have been recorded, it is particularly advisable that when 
this antigen is being used the results be in every case controlled by a reliable antigen 
made by one of the older methods. 
II. The Haemolytic Serum.-The haemolytic amboceptor, for the reaction, is 
obtained by injecting into rabbits the washed red blood corpuscles of a sheep. A 
50-per-cent. emulsion of the corpuscles is made and of this 5 c.c., 10 c.c., and 15 c.c. are 
injected at intervals of five or six days. Three or four graded injections of this kind 
are usually sufficient to furnish a serum of adequate haemolytic power. The injections 
may be made intraperitoneally, subcutaneously, or intravenously. If intravenous 
injections are given the doses should be smaller than the above. About nine or 
ten days after the last injection of corpuscles, a small amount of blood is withdrawn 
from the ear vein, and a preliminary titration of the serum is made. If the serum is 
of sufficiently high potency, the rabbit may then be bled from the carotid artery, 
and the serum withdrawn from the clot, inactivated by heating for twenty minutes 
at 54° C., and sealed in small sterile tubes. 
It is best to have a haemolytic serum of high potency in order that the quantities 
used for the reaction may be as small as possible This is desirable because of the 
fact that the serum may contain small amounts of precipitins for sheep's serum, due 
to insufficient washing of the corpuscles employed in the immunization. If such 
precipitins should be present in any quantity in the serum used for the reaction, 
precipitates might be formed, and these, as we know, have a tendency to carry down 
complement from a mixture. 
For the Wassermann test most workers use two ha; moly tic units. A haemolytic 
unit is the quantity of inactivated immune serum which in the presence of complement 
suffices to cause complete haemolysis of 1 c.c. of a 5-per-cent. emulsion of washed 
blood corpuscles. This must be accurately determined. 
For this purpose mixtures are made in a series of tubes of uniform amounts of 
complement and sheep cells with diminishing quantities of the inactivated haemolytic 
serum. For the sake of economy all titrations are set up with one-fourth the amount 
of reagents used in the Wassermann test. 
The smallest amount of the immune serum which gives complete haemolysis is 
considered one unit; in the given case this is 1 c.c. of a 1 to 1,200 dilution. In the 
1 Noguchi, Jour. Exper. Med., 1909, xi, 392. 
2 Bauer, Semaine med., 1908, xxviii., 429. 
3 Jacobaeus, Ztschr. f. Immunitatsforsch., Orig., 1911, viii., 615. 280 
THE INFECTIOUS DISEASES 
Wassermann test two units are used; i.e., 1 c.c. of a 1 to 600 dilution. It is not neces- 
sary to titrate the amboceptor each time that it is used, as its strength remains 
practically constant for a long period. 
Tube 
num- 
ber 
Immune 
rabbit 
serum 
Salt solu- 
tion 0.9 % 
i Guinea-pig 
serum 1-10 
Sheep cor- 
puscles 5 % 
suspension 
Haemolysis 
Correspoding dilution 
for whole units 
1-300 
1 
0.75 
0.25 
0.00 
0.25 
None 
Control 
2 
0.75 
0.00 
0.25 
0.25 
Complete 
1-100 
3 
0.25 
0.50 
0.25 
0.25 
Q 
Complete 
1-300 
4 
0.13 
0.62 
0.25 
0.25 
00 
Complete 
1-600 
5 
0.09 
0.66 
0.25 
0.25 
Complete 
1-800 
1-3000 
6 
0.75 
0.00 
0.25 
0.25 
5 
O 
Complete 
1-1000 
7 
0.63 
0.12 
0.25 
0.25 
Complete 
1-1200 
Almost 
8 
0.52 
0.23 
0.25 
0.25 
§ 
Complete 
1-1400 
9 
0.47 
0.28 
0.25 
0.25 
Partial 
1-1600 
10 
0.41 
0.34 
0.25 
0.25 
s 
Very slight 
1-1800 
11 
0.38 
0.37 
0.25 
0.25 
None 
1-20000 
12 
0.00 
0.75 
0.25 
0.25 
None 
Control 
III. The Complement.-The complement for the Wassermann reaction is used in 
the form of fresh guinea-pig serum. This may be obtained in the following way: A 
guinea-pig may be killed by an incision in the throat and the blood allowed to flow 
into a large Petri dish or centrifuge tube. This is set away in the ice chest until the 
clear serum has separated from the clot. After twelve to twenty-four hours the serum 
is carefully removed with a pipette. 
Some workers always use 1 c.c. of a 1 to 10 dilution of guinea-pig serum as a unit 
for the Wassermann reaction. Inasmuch as the amount of complement in guinea- 
pig serum varies somewhat, the sera from several pigs should be mixed if this amount 
is to be used without preliminary titration. It is best, however, always to titrate the 
complement before use against one unit of amboceptor as previously determined. 
This may be done as follows: 
Tube 
num- 
ber 
Guinea- 
pig serum 
1-10 
Salt 
solution 
Immune rab- 
bit serum 1 
c.c. = 1 unit 
e.g. 1-1200 
dilution 
Sheep cor- 
puscles 5 % 
Haemolysis 
Corresponding amounts 
of 1-10 dilution of 
guinea-pig serum for 
whole units 
C.C. 
C.C. 
C.C. 
1 
0.375 
0.38 
0.25 
0.25 
5 
Complete 
1.5 
2 
0.3 
0.45 
0.25 
0.25 
*0 
Complete 
1.2 
3 
0.25 
0.5 
0.25 
0.25 
Complete 
1.0 
4 
0.2 
0.55 
0.25 
0.25 
Partial 
0.8 
5 
0.125 
0.63 
0.25 
0.25 
o 
Slight 
0.5 
6 
0.06 
0.7 
0.25 
0.25 
a 
>-< 
None 
0.24 
7 
0.0 
0.75 
0.25 
0.25 
None 
Control 
In the above case 1 c.c. of a 1 to 10 dilution represents one unit, and this quantity should 
be used in the test. 
IV. The Sheep Corpuscles.-The sheep corpuscles for the actual reaction are 
obtained by receiving the blood of a sheep in a small flask containing a sterile solution 
of a 1 per cent, sodium citrate and 0.85-per-cent. sodium chloride, or into one contain- 
ing glass beads or short pieces of glass tubing. In the former case, the citrate solution 
prevents clotting and the corpuscles may be washed free from the citrate solution and 
emulsified in salt solution before use in the test. In the latter case, it is necessary to 
shake the blood in the flask immediately after taking, and to continue the shaking 
motion for about ten minutes. At the end of this time, the blood will be defibrinated 
and the corpuscles are washed free from serum by centrifugalization in salt solution. 
A 5-per-cent. emulsion of the corpuscles in salt solution is employed for the test, made THE INFECTIOUS DISEASES 
281 
by measuring the bulk of centrifugalized corpuscles and adding nineteen parts of 
sterile salt solution. Thorough washing of the corpuscles is essential to preclude the 
occurrence of precipitates. 
V. The Serum to be Tested for Syphilitic Antibody.-The serum of the patient upon 
whom the test is to be made is best obtained in the same way that blood is obtained 
for blood cultures. After surgical precautions as to sterilization, a needle is plunged 
into the median basilic vein and 3 or 4 c.c. of blood are removed. Whenever circum- 
stances do not permit such procedure, blood may be obtained from the finger or the 
ear, always in sufficient quantity to furnish at least 1 c.c. of clear serum. Before use 
for the test, the patient's serum must be inactivated by heating in a water-bath to 
56° C. for twenty minutes to half an hour. As, according to some observers, 56° C. 
destroys the syphilitic antibody in part, Noguchi advises inactivation at 54°C. 
The Test.-In a test tube of suitable size are mixed 0.2 c.c. of the suspected serum, 
previously inactivated, 1 c.c of a 1 to 10 dilution of guineaj?ig serum, or such amount 
as has been determined by previous titration to be suitable and sufficient salt solution 
to make the total volume 3 c.c. The mixture is thoroughly shaken and placed for 
one hour in a water bath or incubator at 37.5° C. At the end of this time there are 
added 1 c.c. of a 5-per-cent. suspension of sheep corpuscles and 1 c.c. of amboceptor 
dilution of such strength as to contain two hsemolytic units. The mixture is then 
shaken and returned to the water bath for one hour at 37.5° C. 
If antibody is present in the suspected serum no haemolysis takes place; if it is 
absent, haemolysis is complete. 
No test is of use unless suitable controls are made. The controls set up should be 
as follows: 
Control 1.-For each serum tested the mixture described above, but omitting 
antigen and using double the quantity of suspected serum, i.e., 0.4 c.c., to preclude 
the possibility of the fixation of complement by serum alone. 
Controls 2 and 3.-The mixture made up as in the test, but (2) with a known 
syphilitic serum, and (3) omitting antigen and using double the quantity of syphilitic 
serum. 
Controls 4 and 5.-The mixture made as in the test, but (4) with normal serum, 
and (5) omitting the antigen and using double the quantity of normal serum. 
Control 6.-Complement and twice the quantity of antigen used in the test, but no 
human serum, incubated for one hour before the addition of sheep cells and ambo- 
ceptor, in order to preclude the possibility of the antigen itself fixing the complement. 
Control 7.-Complement and salt solution alone, incubated for an hour before the 
addition of sheep cells and amboceptor, in order to show that the haemolytic system is 
in working order. 
It is convenient to set up the tubes in two rows in a rack, those in the front row 
containing antigen, those in the back row containing the same mixtures without 
antigen. 
In a positive test, the test itself and Control 2 alone should show inhibition of 
haemolysis. All the other tubes should show complete solution of the haemoglobin. 
Noguchi's ModificationA-Noguchi has modified the original Wassermann technique 
in several particulars. Inasmuch as the inactivation of syphilitic sera weakens to 
some extent their complement-binding properties, he uses the sera in an active state. 
To avoid the possibility of obtaining negative reactions in syphilitic sera because of the 
presence of natural sheep amboceptor in human sera, he employs human corpuscles 
and the sera of rabbits immunized against them. He also uses small amounts of 
reagents and the antigen and amboceptor in a dry state. Pieces of filter paper are 
soaked with these reagents and allowed to dry. After drying the strength of antigen 
and amboceptor are determined by titration, using small measured pieces of filter 
paper of different sizes. These reagents may, however, be used in the liquid form, as 
in the Wassermann technique, if desired. 
Luetin Test 
From cultures of Treponema pallidum Noguchi prepared an emulsion of the killed 
organisms which he called luetin.2 By the use of this an important allergic test for 
1 Noguchi, Jour. Exper. Med., 1909, xi., 392; Serum Diagnosis of Syphilis, 3d edition, 1912. 
2 Noguchi, Jour. Exper. Med., 1911, xiv., 557; Jour. Amer. Med. Assn., 1913, Iviii., 1163. 282 
THE INFECTIOUS DISEASES 
syphilis is possible, which has proved to be of practical value in diagnosis, as it incites 
specific reactions in the skin of infected individuals even when the Wassermann test is 
negative. 
Rhinoscleroma. 
This disease, which occurs especially in eastern Europe and occasionally in other 
parts of the world, is a chronic inflammation of the nasal, pharyngeal, and laryngeal 
mucous membrane. In this inflammation a diffuse or nodular formation of new 
tissue somewhat resembling granulation tissue, occurs, which tends to assume a dense 
cicatricial character. (Fig. 163.) 
A bacillus called Bacillus rhinoscleromatis is often found in the lesion. In most of 
its morphological and biological characters it closely resembles the pneumobacillus of 
Friedlander (B. mucosus capsu- 
latus), growing readily on the 
common culture media and de- 
veloping a capsule, and it may 
be identical with it. The rela- 
tionship of this bacillus to the 
lesions of rhinoscleroma does 
not appear to be as yet defi- 
Fig. 163.-Rhinoscleroma Showing Large Clear Cells 
of Mikulicz, Filled with Bacteria Not Showing in the 
Photograph. 
Fig. 164.-Fibrin in Diphtheri- 
tic Membrane undergoing Coa- 
gulation Necrosis. 
nitely established, since inoculations in men and animals have not given positive 
results.1 
DIPHTHERIA. 
Diphtheria is an acute infectious disease incited by the Bacillus 
diphtherice (Loftier), and usually characterized by a pseudo-membranous 
inflammation on some of the mucous membranes or occasionally on 
the surface of wounds, and by immediate or remote effects of absorbed 
toxic substances. The mucous membranes which are the most fre- 
quently affected in diphtheria are those of the tonsils, pharynx, soft 
palate, nares, larynx, and trachea; less frequently those of the mouth, 
gums, conjunctiva, oesophagus, and stomach. 
Morphology of the Lesions 
The local lesions in mucous membranes may present various phases. 
Thus there maybe a simple redness of the affected surfaces which leaves 
no trace after death. On the other hand, in the more marked forms of 
1 See Babes, Kolle and Wassermann, Handbuch, 1913, 2d edition, v., 1237. THE INFECTIOUS DISEASES 
283 
the lesion there may be a fibrinous exudate which infiltrates the mucous 
membrane, or, intermingled with pus cells, epithelial cells, red blood cells, 
bacteria, and granular material, forms a thick or thin pellicle on the affect- 
ed surfaces (see Fig. 123, p. 213). This pellicle may undergo coagulation 
necrosis (Fig. 164), and with this there may be superficial or deep necrosis 
of the mucous membrane. The false membrane in diphtheria is thus 
formed by a combination of inflammatory products and necrotic tissue, 
the extent of the necrosis and the amount of inflammatory products 
varying in different cases. The membrane may disintegrate or exfoliate, 
with or without loss of tissue in the underlying mucous membrane. 
Phlegmon, abscess, and oedema are liable to occur as local complications. 
Adjacent and distant lymph-nodes are apt to be swollen, and often 
show, on microscopical examination, endothelial-cell hyperplasia with 
small foci of cell necrosis and disintegration.1 Similar foci of cell hyper- 
plasia with necrosis with small spheroidal-cell accumulation and fatty 
degeneration may be 
found in the kidney, 
spleen, and liver. Al- 
buminous degenera- 
tion in the kidney and 
acute nephritis are 
not infrequent. 
Small haemorrhagic 
foci may be present 
in the liver and kid- 
neys. Degeneration 
of the heart muscle 
may occur.2 The ex- 
act nature of the 
nerve lesions which 
may be associated 
with the late paral- 
yses of diphtheria is not yet clear, but degeneration of the peripheral 
nerves and chromatolysis of the ganglion cells occur, indicating the ac- 
tion of an absorbed toxic substance in the body fluids. Leucocytosis 
may be present. 
Catarrhal bronchitis and broncho-pneumonia or simple lobular pneu- 
monia frequently complicate diphtheritic lesions of the upper air pass- 
ages and fauces. 
Fig. 165.- Diphtheritic Inflammation of the Tonsil. 
Showing Loffler's bacilli in the pseudo-membrane. 
Bacteriology of the Disease 
Although bacteria of various forms are commonly present in the 
false membrane, and some of them penetrate deeply into the underlying 
1 Consult Waschkewitsch Virch. Arch., Bd. clix., p. 137, 1900. 
2 For studies of the lesions of the myocardium in diphtheria consult Scagliosi, Virch. Arch., Bd. 
cxlvi., p. 115, 1896; also Thomas and Hibbard, Reports of Boston City Hosp., 1900, p 204, bibl.; for a 
study of nerve lesions with bibl. see Batten, Pediatrics, vol. vii., p. 97, 1899; also Rainy, Jour. Path, 
and Bact., vol. vi., p. 435, 1900. For a comprehensive study of the bacteriology and pathology of 
two hundred and twenty fatal cases of diphtheria see Councilman, Mallory, and Pearce, Jour. Boston 
Soc. Med. Sci., vol. v., p. 139, 1900. 284 
THE INFECTIOUS DISEASES 
tissue, the primary and specific excitant of this disease is the Bacillus 
diphtheriae of Loffler. 
In man the diphtheria bacilli are largely confined to the seat of local 
lesion, and sometimes occur here in enormous numbers, especially in 
the older layers of the pseudo-membrane (see Fig. 165). But they may 
become widely distributed through the body. This appears to be espe- 
cially the case when the pyogenic cocci are associated with the diphtheria 
bacillus at the seat of local lesion. The systemic effects in diphtheria 
appear to be largely due to the absorption into the body of toxic material 
elaborated locally by the germs. Septicaemia or acute visceral inflam- 
mations, particularly of the kidney, may occur without evidence of an 
external local lesion or of the portal of entry of the bacillus.1 
Concurrent Infections. 
The very frequent association of the pyogenic cocci and other bacteria 
with the diphtheria bacillus gives rise to a series of changes which make 
the clinical picture and the lesions of diphtheria sometimes very com- 
plex. Thus the complicating bronchitis and broncho-pneumonia, as 
well as pysemic symptoms and lesions, may be due to the diphtheria 
bacillus alone. But these secondary lesions may be due to the presence 
in the pseudo-membrane, and the entrance into the deeper air passages 
and the blood, of Streptococcus pyogenes, Staphylococcus pyogenes, 
Diplococcus lanceolatus, Bacillus coli communis, and other bacteria, 
or of these together with the diphtheria bacillus.3 
This organism, first described and definitely associated with this disease by Lbffler, 
is a slender rod, in general about 3 n long, but sometimes shorter and sometimes grow- 
ing into threads. It occasionally grows in 
branching forms,3 and is characterized mor- 
phologically by marked irregularities in its form 
(Fig. 166). While the typical form is that 
of a round-ended, straight, or slightly curved 
bacillus, it is very apt--perhaps as a result 
of degeneration-to appear club-shaped or 
pointed at the ends, irregularly segmented, 
and to develop at the ends or elsewhere a 
strongly refractile material which stains more 
deeply than the rest of the protoplasm. 
The diphtheria bacillus is immobile, 
asporogenous, grows best at blood heat, and 
thrives on most of the artificial culture media. 
In fluids it may be killed by an exposure of 
ten minutes to a temperature of 58° C.; or of 
one minute to boiling, but it may remain alive 
Characters of the-Diphtheria Bacillus. 
Fig. 166.-B. Diphtheria. 
X 1000 
1 For a resume and bibliography of studies relating to diphtheritic septicaemia see Brown and 
Thiry, Gazette des H6pitaux, May 2d, 4th, and 9th, 1899. 
2 For a study of the presence and action of the diphtheria bacilli in the lungs see Flexner and 
Anderson, Johns Hopkins Hosp. Bull., vol. ix., p. 72, 1898. 
For a summary of the association of diphtheria and tuberculosis see Councilman, Mallory, and 
Pearce, reference p. 283. 
3 The branching forms which are occasionally observed in the diphtheria as well as in the tubercle 
bacillus, together with certain other characters, have led some observers to the belief that these organ- 
isms are related to streptothrix and to the moulds rather than to the bacteria. But, for the present 
at least, it seems wiser to consider them in their more generally acknowledged relationships. THE INFECTIOUS DISEASES 
285 
for weeks, or even months, in fragments of dried membrane. It may be stained 
with Loffler's alkaline methylene-blue solution or by Gram's method. 
It is subject to extreme variations in virulence, forms occurring which with all the 
usual cultural characteristics are not at all virulent.1 
Action of the Bacillus in Animals. 
Inoculations of virulent cultures subcutaneously in guinea-pigs are followed by a 
localized haemorrhagic cedema with a variable amount of whitish exudate. Death 
usually occurs in from two to five days. In addition to the local lesions there may be 
-but this is not constant-swelling of the adjacent and of the abdominal lymph-nodes, 
serous effusions into the pericardial, pleural, and peritoneal sacs: swollen spleen, 
albuminous and fatty degeneration in the liver, kidney, and heart muscles; congestion 
and sometimes haemorrhage of the suprarenals. Microscopical examination shows, 
in a considerable proportion of cases, fragmentation of nuclei and other evidences of 
cell death at the seat of inoculation and in the viscera, as well as chromatolysis of gan- 
glion cells in the anterior horn. Animals which survive the inoculations may later 
develop paralysis, and a similar result may follow the injection into rabbits of culture 
fluids. The bacilli do not usually gain access to the body at large, but may be found 
at the seat of inoculations. Inoculation into the mucous membranes of rabbits, 
pigeons, and certain other animals may result in the development of a pseudo-mem- 
brane somewhat resembling that of the disease in man. 
Diphtheria Toxin and Antitoxin and Diagnosis. 
In its growth under artificial culture some strains of the diphtheria bacillus de- 
velop and set free in the culture media toxic substances whose chemical composition 
is as yet unknown. It is this toxic material which is used in the production of diph- 
theria antitoxin (see p. 164). 
Communicability.-While the possibility of the transmission of the diphtheria 
bacillus by domestic animals to man cannot be doubted, the usual source of infective 
material is the exudates of victims of the disease, or virulent bacilli from the mouths 
of healthy persons to those disposed to the infection. This conveyance may take 
place directly by contact, or by coughing and sneezing, or through contaminated 
clothing, bedding, or various utensils, or through "carriers,"3 The susceptibility to 
diphtheria is greatest in the young. 
It is important from the prophylactic standpoint to remember that the Bacillus 
diphtherias may remain alive in the mouth of the human subject for many weeks after 
recovery from the local lesions of the disease, and also that healthy persons when the 
disease is prevalent may harbor the virulent bacilli in their mouths. 
Other Bacteria of the Diphtheria-Bacillus Group. 
While the diphtheria bacillus varies greatly in the physiological capacities which 
determine its virulence, its general morphological and cultural characteristics are 
fairly constant. There are, however, non-virulent bacilli occurring on mucous mem- 
branes under normal as well as abnormal conditions which considerably resemble 
this, but which differ somewhat in both morphological and biological characters from 
the true diphtheria bacillus and its variants. Such organisms have been called pseudo- 
diphtheria bacilli (Bacillus Hoffmani). These non-virulent forms may be regarded as 
attenuated varieties of the diphtheria bacillus.3 
The so-called Xerosis bacillus, which has been repeatedly found in xerosis con- 
junctivae, is apparently a member of the diphtheria-bacillus group.4 
1 For a study of varieties of the B. diphtheria, see Williams, Jour. Med., Res., 1902, N. S. iii., 83; and 
Kolmer, Jour. Infect. Dis., 1912, xi., 56. see also for full summary of studies on the diphtheria bacillus 
and its toxins, Neisser and Gins, Kolle u. Wasserman, Handbuch, 2d edition, 1913, v., 931. 
2 For a study of diphtheria carriers, see Page, Arch. Int. Med., 1911, vii., 16; and Chapin, Sources and 
Modes of Infection, 2d edition, 1912. 
3 For a study of virulent "pseudo-diphtheria" bacilli see Hamilton and Horton, Jour. Inf. Dis., vol. 
iii., p. 128, 1906. 
4 Graham-Smith., Jour, of Hygiene, vol. iv., p. 306, 1904. 286 
THE INFECTIOUS DISEASES 
TETANUS. (Lockjaw.) 
This disease, which is especially marked clinically by muscular 
spasm, is due to infection by the Bacillus tetani. This organism is rather 
widespread and in some places very abundant, occurring with other 
germs in the soil, especially in manured soil, and gaining entrance to 
the body through wounds, which are often very slight. The soil in 
certain regions appears to harbor in especial abundance the tetanus 
organism or its spores. Thus in certain districts on Long Island and in 
New Jersey slight injuries are frequently followed by tetanus. The 
liability to infection from the spores is greatly enhanced by their associa- 
tion with other organisms or with dirt, splinters, etc., in the wound. 
The Lesions of the Disease. 
The local lesion in tetanus is usually slight and not characteristic, 
often consisting only in a slight suppuration. 
The morphology of the lesions of the nervous system to the existence 
of which the symptoms of tetanus so directly point is yet obscure. Over- 
filling of the blood-vessels, cellular exudate into the perivascular spaces, 
chromatolysis of the ganglion cells of the spinal cord are common. The 
bacillus remains for the most part at the seat of local lesion and induces 
its effects by the elaboration of most intense poisons or toxins, called 
tetano-toxins. The action of this toxic substance appears sometimes to 
continue in the body after the death of the organisms which have elab- 
orated it. This infectious disease affords a most typical example of 
toxaemia. 
Characters of the Bacillus Tetani. 
It is 2 to 5 fi long, slender, and motile, often growing in pairs or threads and prone 
to develop a spore in one end (Fig. 167), in which condition the bacillus is larger at 
this end, being club- or racket-shaped. It is readily stained. At the room tempera- 
ture it grows on artificial culture media, and is strictly anaerobic, flourishing in an 
atmosphere of hydrogen, but may be artificially adapted 
to other conditions. 
The spores of the tetanus bacillus are very resistant 
to drying, to heat, and to various chemical disinfectants. 
Characteristic tetanic symptoms followed by death 
may be induced in mice, guinea-pigs, and rabbits by 
subcutaneous inoculation of cultures. Man and the 
horse are markedly susceptible to tetanus; birds are as a 
rule insusceptible. If the tetanus bacillus be grown in 
nutrient broth at blood heat out of contact with oxygen 
the toxin is developed and mingles with the fluid. This 
toxin when freed from living germs is capable of induc- 
ing the symptoms of the disease. Broth cultures may, after some weeks, have 
acquired such an extreme intensity that the dried poisonous material, separated 
from the inert fluids and partially purified, may be fatal to a mouse weighing 15 gm. 
in a dose of 0.00000005 gm. Estimating according to the relative weights of the 
subjects, the minimal fatal human dose would be about 0.00023 gm. This toxin is 
rendered inert by a temperature above 65° C. and by light. 
Fig. 167.-Bacillus Tetani. 
From a culture; showing club- 
shaped ends with spores. THE INFECTIOUS DISEASES 
287 
Tetanus Antitoxin. 
By procedures similar to those described in diphtheria immunization 
(p. 164), the tetanus toxin has been used to secure artificial immunity 
in dogs, goats, and horses, and here also the blood serum of the immu- 
nized animals has been prepared and employed in man for therapeutic 
purposes with some degree of success.1 
The tetanus toxin induces its effects in the body chiefly by its action 
on the central nervous system. It has been shown to reach the nerve 
centres from the seat of growth of the bacillus, by way of the axis cylin- 
ders of the motor nerves. The tetanus antitoxin, on the other hand, 
which may be injected for protective purposes, is not taken up by the 
nerves, but passes into the blood- and lymph-vessels and tissue fluids. 
The power of the antitoxin to neutralize toxin is apparently limited to 
that portion of the latter which has not been absorbed by the nerves, 
but is still free either at the seat of production or in the blood or lymph. 
The theoretical promise of the tetanus antitoxin for therapeutic 
purposes in man is thus in practice rendered in a large measure futile, 
because the existence of the disease is not recognizable until the tox- 
aemia is sufficiently marked to produce the nervous symptoms, at which 
time, union of the toxin with the nerve tissues having been effected, 
the usefulness of the antitoxin is limited to the neutralization of the 
unabsorbed toxin. Statistics are as yet too meagre to justify a final 
opinion as to the practical value of tetanus serum therapy, but it appears 
to be definitely useful, especially when applied directly to the nerve 
tissues. 
Diagnosis. 
For purposes of diagnosis it may be necessary to inoculate a white mouse at the 
base of the tail with suspicious material at the same time that morphological examina- 
tion and anaerobic cultures are made. Should tetanus develop in the mouse within 
a few days, control cultures may be made from the exudate at the seat of inoculation.2 
Other Bacilli of the Tetanus Group. 
Several bacterial species are already known which may be classed in the tetanus 
group. While varying in size, these bacilli are in general rather large; spores form in 
their thickened ends; they are facultative anaerobes; some do, others do not fluidify 
gelatin; and they retain the stain by Gram's method. They are mostly saprophytes 
and have been found in milk and milk products, in excrement and sewage, etc. None 
is known to be pathogenic in man. The most noteworthy among these is Bacillus 
pseudo-tetanicus, Sanfelice, which in morphology and growth characters resembles the 
Bacillus tetani, but does not form the toxin. 
This disease, which has been most frequently observed along the shores of the 
Mediterranean and in India, and occurs in South America and the West Indies is 
characterized by prolonged pyrexia with irregular remissions. In the rather rare 
Malta Fever. 
'Fora critical resume of tetanus and its treatment with the antitoxic serum, with bibliography, 
see Moschcowitz, Ann. of Surg , vol. xxxii., p. 219, 1900. 
2 For resume of characters of the tetanus bacillus and its toxin see von Lingelsheim, Kolle and 
Wassermann's "Handbuch der Mikroorganismen," Bd. ii., p. 566. 288 
THE INFECTIOUS DISEASES 
fatal cases there may be considerable enlargement of the spleen, albuminous degenera- 
tion in the liver and kidneys. Acute nephritis may occur. 
It is said that there are constantly present in the spleen in this disease small 
bacilli so short as to have been mistaken for cocci, stained by Gram, readily cultivated 
on artificial media. The result of inoculations of pure culture into monkeys and 
other animals tends to confirm the pathogenic significance of the organism, which has 
been called Micrococcus melitensis.1 
BUBONIC PLAGUE. (Oriental Plague; Black Death.) 
Types of the Disease.-This disease presents three main types-the 
bubonic, pulmonary, and septicaemic. 
The most common is the bubonic, which is characterized by an intense 
inflammatory hyperplasia of the lymph-nodes, most frequently the 
inguinal or axillary. The surrounding tissue may be involved; haem- 
orrhage, necrosis, or suppuration in the nodes may occur. Coincident 
with these local reactions there may be albuminous degeneration, focal 
necrosis, and leucocytosis from toxaemia, or secondary foci of inflamma- 
tion in the spleen or lungs or liver. A second type of the infection is the 
pulmonary, in which larger or smaller areas of the lungs are involved in 
broncho-pneumonia with associated secondary involvement of the 
bronchial lymph-nodes. In the septiccemic type of bubonic plague 
there may be a general involvement of the lymph-nodes and -nodules of 
the body with the marks of toxaemia, without an indication of the point 
of primary infection.2 
In all these various phases of the disease the plague bacillus may be 
present often in enormous numbers in the primary buboes and in the 
secondary lesions and in the viscera; in the consolidated areas and in 
the sputum in the pulmonary type, and in the septicaemic phases in 
the blood. 
Characters of the Plague Bacillus. 
The plague bacillus was discovered in 1894 by Kitasato and Yersin, and its role as 
the excitant of the disease was soon established. It is a short, thick, motile, round- 
ended bacillus, often staining more deeply at the ends than in the middle. It some- 
times grows in chains and may be capsulated, not forming spores; it is decolorized by 
Gram's method. It grows readily though not voluminously on the ordinary culture 
media at blood heat.3 This organism is killed by drying for a few days and by expos- 
ure to sunlight for a few hours. Subcutaneous inoculations in guinea-pigs and 
rabbits is followed by local haemorrhagic and serous inflammation with typical involve- 
ment of the regional lymph-nodes and by septicaemia. Death may follow in from one 
to five or six days, with albuminous degeneration of the viscera, hyperplasia of the 
spleen, and petechial haemorrhages. 
Portals of Entry.-The chief portals of entry in man are abrasions 
or wounds of the skin, the lungs, and the intestines. The spread of the 
infectious material in overcrowded and unsanitary districts may readily 
take place by rats, which are very susceptible to the disease and may 
1 Consult Birt and Lamb, Lancet, 1899, ii., p. 701, bibl. 
2 For a resume of lesions of plague see Flexner, Trans. Assn. Am. Phys., vol. xvi., p. 481, 1901. 
3 See article by Dieudonni and Otto, in Kolle and Wassermann's "Handbuch der Mikroorgan- 
ismen," 2d edition, Bd. iv., p. 155. THE INFECTIOUS DISEASES 
289 
be infected by feeding.1 Through mosquitoes and flies also the bacilli 
may be conveyed from man to man or from dead rats or their dejecta 
to man.2 
Preventive Inoculation has been largely practised in the East by the 
Haffkine method. This consists in the subcutaneous injection of beef- 
tea cultures of the plague bacillus, which have been killed by heating. 
Moderate local inflammatory reaction and slight fever may follow the 
injection. The statistics seem to indicate that among exposed persons 
the mortality may be considerably reduced by this preventive inocula- 
tion.3 
An anti-plague serum, prepared by the immunization of horses, has 
been used by Yersin with at least promising results.4 
HEMORRHAGIC SEPTICEMIA. 
Many of the lower animals are victims of acute infections, septicsemic in character, 
often with petechial haemorrhages in the viscera and serous membranes and marked 
intestinal disturbances. These are called "haemorrhagic septicaemias." 
Associated with these and doubtless their inciting agents are several bacilli which 
may be classed, as is done by Hueppe, Kruse, and others, with the plague bacillus 
under the designation, the haemorrhagic septicaemia group. These are mostly small, 
short, sporeless forms growing readily on the ordinary media as facultative anaerobes, 
not fluidifying gelatin and decolorizing by Gram. Some of these are motile, others 
not. Among these may be mentioned the bacillus of mouse typhus (B. typhi murium), 
the bacillus of chicken cholera (B. choleric gallinarum), the bacillus of swine plague 
(B. suisepticus). Several species related to these and to the plague bacillus are 
pathogenic in man; thus the B. hcemorrhagicus septicus of Babes, the B. hcemorrhagicus 
of Kolb, the B. hcemorrhagicus velenosus of Tizzoni and Giovanni. 
The recognition of these and related species may be of especial significance in con- 
nection with the diagnosis of bubonic plague by cultures and animal inoculations.5 
Bacillus Aerogenes Capsulatus (Bacillus Welchii, Gas 
Bacillus). 
This bacillus was described in 1891-92 by Welch and Nuttall. Later 
studies of Welch and Flexner and many others have confirmed the orig- 
inal belief that the bacillus is a frequent excitant in man of a serious 
infectious disease, characterized by a local widespread serous and 
emphysematous phlegmonous inflammation, frequently associated with 
gangrene and general symptoms of a profound toxeemia. 
The Bacillus aerogenes is rather large, on certain media spore-form- 
ing, is often encapsulated, and occasionally forms chains. It retains the 
stain by Gram's method. It is anaerobic, growing readily in a variety 
of artificial culture media. 
Rabbits are not susceptible to even large intravenous injections of 
1 The ground squirrels along the Pacific Coast are widely infected with plague bacilli and are a 
menace to that region, see Pub. Health Repts., U. S. Mar. Hosp., xxv., 27, 1910. 
2 On insects as plague-carriers see Herzog, Am. Jour. Med. Sci., vol. cxxix., p. 504, 1905. 
3 For summary of result of the Haffkine method see Forsyth, Lancet, vol. ii., p. 1646, 1903; also 
Slaughter, Johns Hopkins Hosp. Bull., vol. xiv., 1903, p. 307. 
4 Critical summary and bibl., Netter, Arch, de med. exp., t. xii., p. 86, 1900. 
6 For studies on various forms of h®morrhagic infection see Babes, Verh. d. deutschen path. 
Gesellsch., Bd. ii., p. 262, 1900; also Hutyra, Kolle and Wassermann's "Handbuch der Mikroorgan- 
ismen," 2d edition, 1913, vi., p. 64. 290 
THE INFECTIOUS DISEASES 
pure cultures. But if they be killed soon after such inoculation, within 
a few hours, at room temperatures, an abundant development of gas 
occurs throughout the body. On the other hand, the subcutaneous 
injection of a very small quantity of the fresh cedematous exudate is 
followed by the typical local and general marks of infection. Guinea- 
pigs are more susceptible than rabbits to inoculation, either with cultures 
or fresh material, and develop characteristic lesions. 
While infection may occur without gas, in most cases before death 
and especially after, there is an abundant formation of gas in the tissues. 
This is largely hydrogen formed through the splitting by the bacillus 
of either sugar or proteins. While the gas may be present in any of 
the tissues, in the body cavities, and in the blood-vessels, it is especially 
in the liver after death that the marks of gas accumulation are most 
striking. This organ may be riddled with small holes, presenting an 
appearance which has been characterized as "foamy liver" (Fig. 485, 
p. 738). 
Infection may occur through wounds or injuries in any part of the 
body. It has been frequently observed in pregnant and puerperal 
women.1 Ulcers of the stomach and intestine or of the urinary tract 
may be portals of entry. One of the more common forms of local 
infection is the so-called gaseous phlegmon or emphysematous gangrene. 
Pulmonary and pleural lesions, appendicitis, and peritonitis are described, 
as well as gaseous abscesses and purulent meningitis. While the usual 
action upon the tissues is the induction of bloody oedema and necrosis, 
this bacillus is also occasionally pyogenic. 
The natural habitats of the organism are the soil and the intestinal 
canal. This accounts for the relative frequency of infection through the 
intestinal and genito-urinary tracts and through wounds contaminated 
with dirt. 
Infection, especially from the intestinal canal, may apparently occur 
during the later hours of life, with or without symptoms and with a 
post-mortem formation of gas. It is often difficult to determine, since 
gas formation occurs so early and so extensively after death, whether the 
entrance has or has not been effected during life. It seems fair to infer, 
as the result of animal experiments, that when the gas formation, even 
after death, is widespread, ante-mortem infection has occurred. 
Concurrent infection with other organisms, especially the pyogenic 
cocci, is frequent. 
Welch and Nuttall early called attention to the importance of recog- 
nizing the possibility of infection with this bacillus in judging of a cer- 
tain class of cases of alleged air embolism. 
It is probable that the Bacillus aerogenes capsulatus is identical with 
forms which have been described under various names in connection with 
cases of gaseous phlegmon, or so-called malignant oedema.2 
1 For a study of B. capsulatus in puerperal infections see Little, Johns Hopkins Hosp. Bull., vol. 
xvi., p. 136, 1905. 
2 For an excellent critical resumi of this subject, with bibliography, see Welch, Johns Hopkins 
Hosp. Bull., vol. xi., p. 185, 1900; also Ghon and Sachs, Cbl. f. Bak., Abth. I., Orig. Bd. xxxv., p. 665; 
Bd. xxxvi., p. 1, 1904. THE INFECTIOUS DISEASES 
291 
Malignant (Edema. 
This disease is of occasional occurrence in man and certain domestic animals, 
horses, cattle, sheep-usually following some form of traumatism. It is a septicaemia 
with local, often haemorrhagic oedema, visceral degeneration, etc. 
The bacillus of malignant oedema, Bacillus oedematis maligni, which is frequently 
present in dust, in putrefying substances, and in soil, considerably resembles the 
Bacillus aerogenes capsulatus in both its morphological and biological characters. It 
is, however, more slender, and more apt to form threads; spore formation occurs 
readily in the ordinary media. It decolorizes partially by Gram's method. Other 
differential characters are to be made out in cultures. It is an excitant of haemor- 
rhagic oedema in animals, but with slight if any development of gas. 
Other Bacteria which may Induce Haemorrhagic Septicaemia. 
Nearly related to the Bacillus aerogenes capsulatus and to the bacillus of malignant 
oedema are several other spore-forming anaerobic bacilli occurring especially in the 
earth, in excrement, and in various rotting substances. Some of these appear to be cf 
pathogenic significance in the lower animals under both natural and experimental 
conditions. 
Thus the Quarter-evil (Rauschbrand; charbon symptomatique), especially in 
Europe, is a serious infectious disease of sheep, goats, and cattle. At the seat of 
infection, often in the legs, there is a haemorrhagic oedema with gas formation, the 
involved region often becoming much swollen and black in color ("black leg"). The 
bacillus which is the excitant of this disease is known, and preventive inoculation has 
been practised. 
Howard has described a group of cases of haemorrhagic septicaemia characterized by 
haemorrhages into the skin, serous membranes, and viscera, in which capsulated bacilli 
apparently related to the above-described bacillus of Friedlander (p. 216) have been 
found. For the details of these cases and their relationship to other forms of septi- 
caemia we refer to the original paper.1 
Meat Poisoning. 
Meat poisoning may be due to some strain of Bacillus enteritidis 
which infects various animals. The meat of these diseased animals is not 
abnormal in appearance or taste but may contain the organism, and if 
not thoroughly cooled may induce serious gastrointestinal disorders in 
man. The meat of diseased cows and calves most frequently has been 
the source of infection. The infection is most common in summer and 
the infective agent may apparently be conveyed from man to man 
through excreta. 
Several other forms of meat poisoning, some resembling typhoid 
fever, others involving a mild or violent gastro-enteritis, others especially 
characterized by toxaemic symptoms have been attributed to the pres- 
ence of various bacterial organisms which we cannot consider further 
here.2 
Botulism. 
This is a toxaemia characterized by chills, giddiness, trembling, headache, and 
sometimes vomiting followed by symptoms such as loss of accommodation, dilated 
pupils, ptosis, aphonia, etc., referable to the action of some toxic substance. Death 
1 Howard, Jour, of Exp. Med., vol. iv., p. 149, 1899; also Blumer and Laird, Johns Hopkins Hosp. 
Bull., vol. xii., 1901, p. 45. See also Typhus and Rocky Mountain Spotted Fever. 
2 For a brief resume of this group see Hiss and Zinsser "Text-book of Bacteriology," 2d edition, 
1914, and ref. therein. 292 
THE INFECTIOUS DISEASES 
may follow general motor paralysis and dyspnoea. Visceral hypersemia, petechial 
haemorrhage, and albuminous degenerations may be found. The disease has been 
shown to be due to an anaerobic, readily cultivated bacillus, B. botulinus, first isolated 
by van Ermengem from a contaminated ham which had poisoned many persons. 
It is believed that the toxins inducing this condition are formed in the contamin- 
ated meats-ham, canned meat, and sausages-before their ingestion. 
RELAPSING FEVER. (Typhus Recurrens; Famine Fever; Spirillum Fever; Seven- 
Day Fever.) 
This disease is common in India, Africa, and many tropical countries, 
and has occurred in Russia and in the United States.1 It is characterized, 
apart from the fever and associated symptoms, by the presence in the 
blood at certain periods of a spiral organism discovered by Obermeier in 
1873. Some six closely related species of spirochetes inducing the 
different forms of the disease have been described, of which the Spiro- 
chaeta Obermeieri and the Spirochaeta Duttoni are the best known. 
The Lesions of the Disease. 
There may be albuminous degeneration in the viscera, leucocytosis, 
catarrhal or croupous inflammation of the mucous membranes of the 
respiratory and digestive organs, ecchymoses in the skin and in the 
mucous and serous membranes. There may be pneumonia and pleurisy, 
degeneration of the cardiac muscle, hyperplasia of the mesenteric 
lymph-nodes. The spleen may be large and flabby, this change being so 
extreme that rupture has occurred during life; it may also be the seat of 
infarctions, and these have given rise to peritonitis. 
Characters of the Spirochaeta Obermeieri. 
In the blood of all parts of the body during the febrile attacks may be found, in 
very large numbers, a long, slender spiral called from its discoverer Spirochaeta Ober- 
meieri (Sp. recurrentis) (Fig. 168). The organisms dis- 
appear from the blood during the afebrile intervals, and 
it has been shown that at this time they accumulate in 
the spleen, where they are destroyed in large numbers, 
apparently through the action of phagocytic cells. The 
organism is in general from 7 to 9 p in length, some- 
times longer, and performs rapid, undulating movements. 
The inoculation of healthy men and of 
monkeys with the blood of relapsing-fever pa- 
tients which contains the organism induces a 
similar disease. Norris and Pappenheimer have 
made successful inoculations of white rats with 
a Spirochaeta believed to be of this species.2 Pure cultures of these 
organisms through several generations have been made,3 and for the 
Fig. 168.-Spirochaeta 
Obermeieri. 
1 Carlisle, Jour. Inf. Dis., vol. iii., p. 233, 1906, bibl. (describes two cases). 
2 Norris, Pappenheimer and Flournoy, Jour. Inf. Dis., vol. iii., p. 266, 1906. 
8 Noguchi, Jour. Exper. Med., 1912, xvi., 199 THE INFECTIOUS DISEASES 
293 
reasons indicated, and since the organism has never been found ex- 
cept in connection with the disease, there is every reason for believ- 
ing that the Spirochaeta Obermeieri is the excitant of relapsing 
fever.1 The organisms are considered to be protozoa by many ob- 
servers, though Novy regards them as definitely bacterial in nature. 
Tick Fever.-This is a disease of Uganda, Abyssinia, and the Congo 
region in Africa. The parasite has been studied by Novy and Knapp,2 
and designated by them Spirochaeta Duttoni. The pathological changes 
induced in the body by the parasite are the same as those caused by the 
presence of the Spirochaeta Obermeieri. The organism is transferred by 
the bite of the Ornithodorus moubata, a tick in which it can live for a 
long time. 
Dutton and Todd3 have been able to induce the disease in monkeys 
by causing these animals to be bitten by the infested ticks. 
Morphologically the parasite resembles very closely the Spirochaeta 
Obermeieri, except that the organisms are somewhat thicker. 
VINCENT'S ANGINA.4 
This is an inflammation of the mouth, pharynx, and tonsils, often 
associated with a pseudo-membrane and sometimes leading to ulceration. 
There is usually but moderate systemic disturbance. While in the 
lesions there are frequently many bacteria, two forms usually associated 
are most commonly found, one spindle-shaped resembling a bacillus, 
the other spiral-shaped, longer than the first, with shallow irregular 
curves, and staining with difficulty. 
These two organisms have been cultivated under anaerobic conditions. 
But their relationship to Vincent's angina and to each other is not yet 
clear.5 
YAWS (FRAMBCESIA TROPICA). 
This disease of tropical and subtropical countries is characterized 
chiefly, by a papular eruption, with ulcerations suggestive of a relation- 
ship to syphilis. In the lesions, Castellani in 1905 demonstrated spi- 
rochetes resembling Treponema pallidum; and the observation has been 
repeatedly confirmed. The infective agent can be transmitted to mon- 
keys and to rabbits by inoculation of material from the lesions.6 It 
seems clear that though the inciting agent of yaws, Spirochaeta pertenuis 
1 See for resume, Novy and Knapp, Jour, Inf. Dis., vol. iii., p. 291, 1906; also Muhlens in Kolle and 
Wassermann's "Handbuch der Mikroorganismen," 2d edition, vii., 864, 1913, bibl. 
2Novy and Knapp, Jour. Inf. Dis., 1909, iii., 379., Todd and Wolbach, Jour. Med. Res., 1914, 
N. S. xxv., 27. 
3Dutton and Todd, Brit. Med. Jour., 1905, ii., 1259; Ross and Milne, Brit. Med. Jour.,.1904, ii., 
1453. . ' 
4 Vincent, Ann. de 1'inst Pasteur, xiii., 606, 1899, and ibid, Lancet, 1905, vol. i., p. 1260. 
5 For a study of fusiform bacilli see Dick, Jour. Infect. Dis., 1913, xii., 191; Krumweide and Prait, 
1913, xii., 199; ibid., 1913, xiii., 438, and Larson and Barron, ibid., 1913, xiii., 429. For cultures of 
spiochetes see Noguchi, ref. p. 647. 
6 See for a study of experimental yaws in the monkey and rabbit, Nichols, Jour. Exp. Med., xii., 
616, 1910. 294 
THE INFECTIOUS DISEASES 
(Treponema pertenuis) resembles the syphilis organism, the diseases are 
entirely distinct. Salvarsan, however, is therapeutically beneficial. 
HYDROPHOBIA. (Rabies.) 
Morphology of the Lesions. 
This is an infectious disease occurring most frequently in the car- 
nivora, and especially common in dogs and wolves and usually com- 
municated to man by bites of the rabid animals. 
The lesions are not constant nor are they characteristic. Though 
well marked in some cases, in others they are but very slightly developed. 
Changes, when present, are apt to be most pronounced in the medulla 
oblongata and pons, but they may be present in the spinal cord. They 
Fig. 169.-Hydrophobia. Transverse Section of Small Blood-vessels in the Spinal Cord. 
Showing accumulation of leucocytes and proliferation of connective-tissue cells in the adventitia of 
the vessels. 
consist of small haemorrhages, accumulation of leucocytes in the peri- 
vascular lymph spaces about the blood-vessels (Fig. 169) and around 
the ganglion cells, of thrombi in the smaller blood-vessels, and finally of 
chromatolysis of the ganglion cells.1 
Changes have been described in the intervertebral ganglia and in 
the plexiform ganglia of the pneumogastric nerve, which, although not 
limited to rabies, are yet so frequently present as to be apparently of 
value in diagnosis. The lesions consist in degeneration or atrophy or 
destruction of the ganglion cells with a proliferation of the endothelial 
cells lining the capsule.2 
1 Bailey, Jour. Exp. Med., vol. v., p. 581, 1901. 
2 See Ravenel and McCarthy, University Med. Mag., vol. xiii., p. 766, 1901. THE INFECTIOUS DISEASES 
295 
Animal Inoculations. 
Since the infective agent of rabies is present in the central nervous 
system of victims of the disease, this material, i.e., brain and spinal-cord 
tissue, especially from the cord, is used in experimental work. This 
is called the "virus" of rabies. Rabbits and guinea-pigs, as well as 
various other animals, are susceptible to subdural injections, after tre- 
phining, of a small amount of emulsion of the infective nerve tissue. 
After an incubation period varying in different animals, these succumb 
with characteristic symptoms and lesions.1 
The Excitant of the Disease. 
The infective agent appears to be carried especially along the nerves 
from the point of inoculation to the central nervous system, where it 
seems to develop. It is not present in considerable quantity in either 
blood or lymph. 
It is known that the infective agent is in the saliva and salivary 
glands of rabid animals, and that it may be present in the saliva of the 
dog from three to five days before the symptoms of the disease appear. 
It seems to be especially concentrated in the central nervous system. It 
is readily rendered inert by corrosive sublimate and other germicides. 
It resists cold even to -20° C. but loses virulence after one hour's 
exposure to 50° C. It is preserved for some time in glycerin. 
It has been found that the rabic virus may pass the pores of an un- 
glazed porcelain filter not pervious to ordinary bacteria, so that some 
form or developmental phase of the organism must be extremely minute. 
Negri Bodies.-In 1903 Negri announced that he had seen in sections 
of the central nervous system of rabic animals within the ganglion 
cells, rounded bodies from 1 y to 23 /z long, containing vacuoles and 
granules often grouped around a larger central structure. These bodies 
he regarded as parasites belonging among the protozoa and believed 
them to be the specific inciting factors in hydrophobia. These intra- 
cellular structures, now called "Negri bodies," have been the object of 
many careful researches, and the observations of Negri have been in 
general confirmed and extended. 
The "Negri bodies" are, as a rule, most abundant in the large 
ganglion cells of the Hippocampus major (Ammon's horn), but occur 
in ganglion cells of the cerebral cortex and elsewhere. They are readily 
stained and appear to consist of a rounded or oval, homogeneous base- 
ment substance containing a central body surrounded by variously 
shaped granules (Fig. 170). They occupy central or peripheral posi- 
tions in the ganglion cell and vary greatly in number in different cases 
of rabies. 
Similar cell inclusions have been found in animals inoculated with 
"fixed virus" (see below), but they are smaller and more difficult of 
detection than in street rabies and in animals inoculated with the street- 
rabies virus. Negri bodies have been found in nearly all cases of street 
1 For further data see epitome in Kolle and Hetsch, " Bakteriologie," 3d edition, 1911. 296 
THE INFECTIOUS DISEASES 
rabies examined for them, and in no infective or other disease than 
rabies. Their constancy in street rabies has led workers in this field 
to regard them as of the utmost diagnostic value. While their nature is 
not yet definitely established, their morphology and staining qualities 
seem to be consistent with the assumption of their protozoan character. 
They have indeed been named by Williams Newroryctes hydrophobia. 
Their uniform presence in street rabies and the frequent presence of 
Fig. 170.-Negri Bodies. 
In smears from Ammon's horn of rabic dog. 
sm.aller similar structures in fixed virus and in animals inoculated with 
this, together with their absence in diseases other than rabies, seems to 
justify the tentative assumption of a specific etiological relationship to 
hydrophobia.1 
Preparation and Staining of "Negri Bodies." 
Williams-Lowden Method.-While the earlier studies were made on sections, 
Williams and Lowden have shown that in stained smears of the nerve tissue made 
upon slides, which is much simpler than sectioning, the "bodies" are more clearly- 
demonstrated, and that this method for diagnostic and other purposes is to be 
preferred. The technique of making and staining smears as devised by Williams and 
Lowden is in outline as follows: 
On a clean slide a small bit of the gray matter is placed, and a cover-glass is lightly 
pressed upon it, spreading it into a thin layer, then moved along the slide, leaving a 
uniform thin smear of the substance. The smears are dried in the air. 
Staining may be done by the Giemsa solution (p. 1037) or by the eosin methylene- 
blue stain of Mallory. The latter is effected as follows: 
1 For a resume and study of "Negri bodies" see Williams and Lowden, Jour. Inf. Dis., 1906, iii., 452, 
bibl.; and Watson, Jour. Exper. Med., 1913, xvii., 29. For the preliminary announcement of a study 
of rabies with a special culture medium in which granular and larger nucleated bodies were found, see 
Noguchi, Jour. Exper. Med., 1913, xviii., 314. THE INFECTIOUS DISEASES 
297 
Fix smears in Zenker's fluid for one-half hour; rinse and place in iodinized, 95-per- 
cent. alcohol for fifteen minutes; in 95-per-cent. alcohol and absolute alcohol, success- 
ively, one-half hour each; aqueous eosin solution, twenty minutes; rinse in water; 
place in Unna's alkaline methylene-blue solution (methylene blue, 1; carbonate of 
potash, 1; water, 100) diluted 1-5 or 1-10 for fifteen minutes; differentiate in 95-per- 
cent. alcohol from one to five minutes; dry with filter paper; balsam. By this method 
the cytoplasm of the Negri bodies is magenta in color, the central bodies and 
associated granules dark blue, the ganglion cell-body light, and its nucleus a darker 
blue.1 The red blood cells are a brilliant eosin pink. 
Frothingham's Impression Method.-To avoid the distortion of the ganglion cells 
and the disturbance of their relationships inevitable in the "smear" method, and 
to enable the operator to recognize the topography and thus select for examination 
the larger cells lying just outside the hilus in which Negri bodies are more commonly 
found, Frothingham recommends the following procedure for rapid diagnosis.2 
Dissect out the Ammon's horn, removing extraneous tissue from the edges. With 
scissors cut out a small disc at right angles to the long axis of the organ from any 
part desired and place it upon a board near its edge so that one of the flat surfaces of 
the disc rests upon the board, the other being exposed. The grouping of nerve cells 
may now be seen in distinct white lines. 
Place a thoroughly cleaned slide upon this disc of tissue, press it gently and lift sud- 
denly. The disc adheres to the wood, and an impression of its upper surface is left 
upon the glass. Repeat, using a new portion of the slide and a little more pressure. 
A third impression is made, using still more force, and a fourth using sufficient 
pressure to flatten the disc almost completely. 
Before these impressions have dried, place in methyl alcohol for 1/2 to 2 minutes 
or longer. Remove from the alcohol and cover with Van Gieson stain. Warm gently 
for 1/2 to 2 minutes till a light vapor rises. Wash in water, dry with filter paper, and 
examine without cover, first with low power to locate best cells, then with oil immer- 
sion. 
Frothingham slightly modifies Van Geison's stain, using water 20 c.c.; saturated 
alcoholic solution of fuchsin, 3 drops; saturated aqueous solution of methylene blue, 
1 drop, prepared fresh each day. The Negri bodies are stained pale pink to pinkish 
red, the ganglion cells are bluish. 
Preventative Inoculation. 
Notwithstanding his total ignorance of the micro-organisms con- 
cerned in inciting hydrophobia, his genius in wise experiment enabled 
Pasteur to establish a method for artificial immunization against the 
disease, which has proved most beneficent. 
He first obtained a virus of high and definite intensity. This was 
accomplished by a series of inoculations beneath the dura mater in 
rabbits of portions of the spinal cords of rabid animals. This was called 
"virus fixe"-fixed virus. It was found that by drying in the air, 
spinal cords of rabbits having definite and high virulence-fixed virus 
-with due protection against aerial contamination, the virulence 
diminished day by day. With virus thus obtained of virulence ranging 
from that which is practically inert to that of the utmost potency, it 
has been found possible, by subcutaneous injections, safely to accustom 
both animals and men to the presence of amounts of hydrophobia virus 
contained in the spinal cord emulsion, which under ordinary conditions 
1 For the details of the Giemsa staining and a new and promising stain for Negri bodies suggested 
by Van Gieson, see Williams and Lowden, Jour. Inf. Dis., vol. iii., p. 452, and foot-note p. 461, 1906. 
2 See Frothingham, "The Rapid Diagnosis of Rabies," Jour. Med. Res., vol. xiv., p. 471, 1906 
also Am. Jour. Pub. Hygiene, Feb., 1908. For a study of virus freed from cells of host see Poor and 
Steinhardt, Jour. Infect. Dis., 1913, xiii., 263. 298 
THE INFECTIOUS DISEASES 
would prove speedily fatal. In other words, it has been found possible 
to confer artificial immunity against the disease. 
This process occupies several days, and immunization must be com- 
pleted before the disease has begun to manifest itself; but as the incu- 
bation period in hydrophobia is fortunately a long one-the average 
is about forty days-it has been possible, in a large and increasing 
number of cases, to save the lives of persons bitten by rabid animals.1 
This work is now done in laboratories maintained for the purpose 
and requires care and experience in the preparation of the virus as well 
as in diagnosis. 
Diagnosis. 
In view of the importance of diagnosis in animals which have died 
or have been killed under suspicion of rabies, the brain, spinal cord, 
medulla, and ganglia should be saved. 
The presence of Negri bodies is believed to be diagnostic for rabies, 
so that these should be sought for in the fresh tissue by the methods 
indicated above. But considerable experience is required for this work. 
The examination of the plexiform and other ganglia, and of the 
perivascular tissue and ganglion cells in hardened tissue for possible 
changes, may be useful in cases of doubt, though not in themselves 
positively diagnostic. Finally, it may be necessary to have recourse 
to the so-called biological test by the subdural inoculation of suscep- 
tible animals with fresh material from the medulla of the suspect. Por- 
tions of the fresh medulla in watery emulsion are inoculated beneath the 
dura mater of three healthy rabbits or guinea-pigs, and the develop- 
ment of rabic paralysis and other symptoms awaited. This operation 
for diagnostic purposes should be done only by one experienced in this 
subject.2 
It is always wise not to kill animals suspected of rabies, but to keep 
them under observation in confinement. Rabies being always fatal, 
recovery from a suspicious disease excludes it, so that further pro- 
tective measures may be clearly unnecessary. On the other hand, the 
carefully observed symptoms of a suspected animal may even in the 
event of a fatal termination afford valuable evidence. If the laboratory 
for diagnosis be accessible, it is well, if the suspected animal should die 
or be killed, to send the whole animal or the head cut off low down, 
packed in ice. Cold does not rapidly diminish the virulence of the 
rabic virus. If the material is to be transmitted for a long distance, 
after the preparation of impressions or smears from the gray matter of 
Ammon's horn, the brain of the animal with the medulla, carefully 
removed to avoid contamination, may be sent in a sterilized bottle con- 
taining a mixture of equal parts of glycerin and water, which has been 
sterilized by boiling and cooled. 
1 See, for details of preventive inoculations, Park and Williams, "Pathogenic Bacteria and 
Protozoa," 1910; also for general summary and bibl. Stimson, Pub. Health and Mar. Hosp. Ser., Bull. 
65, 1910. 
2 For further details of diagnosis, see ref. to Williams and Lowden, p. 295; Frothingham, ref. 
p. 296; and Park and Williams, I. c. THE INFECTIOUS DISEASES 
299 
It has been found that by the cauterization of the wounds, made by 
rabid animals, with fuming nitric acid, the infective agent may be 
destroyed even after the lapse of several hours. 
ACUTE ANTERIOR POLIOMYELITIS. (Infantile Paralysis.) 
Acute anterior poliomyelitis is an infectious disease occurring in 
epidemic and sporadic forms, affecting especially young children, and 
definitely, though apparently not readily, communicable. 
While before 1907 epidemics of this disease were infrequent in the 
United States, since that time it has widely prevailed. In Europe also 
within the past few years the disease has been of frequent occurrence 
and widespread. It is characterized by an exudative inflammation of the 
meninges, and of the interstitial tissue of the brain, and especially the spinal 
cord, which may lead to destructive changes in the ganglion ceils, par- 
ticularly of the anterior horns, and to paralysis, atrophy, and contracture 
of the associated muscles. 
Although a series of earlier studies had shown that the disease could 
be incited in monkeys by the 
intraperitoneal injection of an 
emulsion of nerve tissue from 
fatal cases of infantile paralysis, 
it was not until 1909 that Flex- 
ner and Lewis1 succeeded in car- 
rying the infective agent from a 
human case on through monkeys, 
by the intracranial inoculation 
of nerve tissue of infected ani- 
mals, in a series which is now 
extended and apparently may 
be indefinitely prolonged. Then 
it was discovered that experi- 
mental infection can be secured 
by inoculation into the subcuta- 
neous tissue, blood-vessels, and 
nerves, and it now seems probable that under all these conditions 
the course of infection is through the nerves. It has been found also, 
that the infective material may be present, not only in the brain, spinal 
cord, and the sensory and sympathetic ganglia, but also in the blood, 
spinal fluid, naso-pharyngeal mucous membranes and lymph nodes.2 
The infective agent belongs among the so-called "filterable viruses" 
for it passes through the pores of the Berkefeld filter. Its virulence per- 
sists after drying and after long preservation in glycerin-two years or 
more. It is readily killed by heat-45° to 50° C. for thirty minutes, but 
sustains prolonged cold, though less resistant to this than to long immer- 
sion in glycerin. 
Fig. 170a.-Organism Isolated from Case of 
Poliomyelitis. 
From a preparation of Dr. Noguchi. X 1000. 
1 Flexner and Lewis, Jour. Exper. Med., 1910, xii, 227. 
2 For a study of the distribution of the virus from the blood see Flexner and A moss, Jour. Exper. 
Med., 1914, xix., 411. 300 
THE INFECTIOUS DISEASES 
Flexner and Noguchi1 have cultivated from the brains of human 
cases of poliomyelitis as well as from the brains of experimentally in- 
fected monkeys, a minute organism which induces characteristic symptoms 
and lesions in monkeys. This spheroidal organism occurs in masses or 
pairs or chains, depending upon conditions of culture. (Fig. 170a.) The 
individual bodies are about 0.2 micron, in diameter, which is much smaller 
than known bacterial cocci, and close upon the limits of visibility. 
Cultures were at first secured from fragments of infected brain, in 
human ascitic fluid to which had been added a fragment of sterile tissue, 
such as fresh rabbit kidney, for example, oxygen being excluded by cover- 
ing the liquid in the tube with a thick layer of sterile paraffin oil. The 
growth of the organism is manifested by a gradually increasing opales- 
cence of the fluid. After the adaptation of the organism to the above 
culture medium, it may be transferred and grown on agar and under other 
conditions. Cultures have been carried forward through twenty genera- 
tions still maintaining the capacity, under the requisite conditions, of 
inciting the disease in monkeys. 
In experimentally infected monkeys the symptoms and lesions of the 
disease in man are fairly reproduced. The lesions in the monkey are, 
primarily and chiefly, cellular infiltrative changes in the perivascular 
lymph spaces of the arteries and of the interstitial substance of the nerve 
tissues. (Fig. 671a.) This leads to temporary occlusion of the vessels, 
focal haemorrhage and oedema, and degeneration of the nerve tissues with 
necrosis and disintegration. While the brain may be involved, the lesions 
are especially marked in the spinal cord and medulla. 
For details of the lesions in man, see page 967. 
Communicability.-Clinical evidence of the communicability of 
epidemic poliomyelitis is abundant. Since it has been shown by Flexner 
and Lewis, not only that the naso-pharyngeal mucosa in animals arti- 
ficially infected by intracranial injections may contain the infective 
agent, but that on rubbing the virus from an infected animal over the 
scarified naso-pharynx of monkeys characteristic paralysis may follow, 
one is at present led to assume that the discharges from the mouth and 
nose of victims of the disease should be properly cared for.2 
Immunity.-Flexner and Lewis have shown that a certain immunity 
is secured in monkeys by a successfully weathered artificial infection. 
But the nature of this immunity is not yet quite clear, nor are the pre- 
liminary studies on the production of immunizing sera sufficiently 
advanced to justify very confident prediction of success in the imme- 
diate future.3 
TYPHUS FEVER. (Hospital Fever; Spotted Fever; Jail Fever; Ship Fever, etc.) 
This communicable disease has no characteristic lesion save the pete- 
chial skin eruption; but after death the body may present lesions com- 
mon to many of the infectious diseases. The disease may be classed 
among the haemorrhagic septicaemias. The isolation of an anaerobic 
1 Flexner and Noguchi, Jour. Exper. Med., 1913, xviii., 461. 
2 For a consideration of the naso-pharyngeal mucosa as a portal of entry, see Flexner, Jour. Am. 
Med. Assn., 1910, lv., 405 
3 For an interesting risum( of the nature, prevalence, and prevention of the disease, see Frost, Pub. 
Health Repts. U. S. Mar. Hosp. Service, xxv., 1663, 1910. THE INFECTIOUS DISEASES 
301 
pleomorphic bacillus, alleged to be its inciting agent, has been reported 
but the report has not as yet been confirmed.1 
The infective agent has been conveyed from man to monkeys2 and also 
to guinea-pigs. 
A mild form of typhus fever has been described in Mexico under 
the name Tabardillo, and in New York under the name Brill's disease. 
The conveyance of the infective agent seems to take place through the 
bites of body lice, Pediculus vestimenti.3 
ROCKY MOUNTAIN SPOTTED FEVER. (Tick Fever.) 
This infectious febrile disease, occurring chiefly in the spring in 
Montana and adjacent Rocky Mountain States, is often fatal, not com- 
municable, and without obvious characteristic lesions save petechial 
and other spots of the skin which mark it as one of the group of haemor- 
rhagic septicaemias. 
Ovoid bodies in the red blood cells of persons suffering from the disease 
have been described4 and have been believed to be protozoa, and small 
bodies resembling short bacilli have also been reported,5 but there is no 
evidence at present to show that they are the specific infective agents. 
The disease can be transmitted to guinea-pigs, rabbits, and monkeys, and 
is probably conveyed to man by the bite of infected ticks, Dermacentor 
occidentalis.6 
YELLOW FEVER. 
Lesions of the Disease. 
Yellow fever is endemic in tropical America, occurs on the west coast 
of Africa, and occasionally invades the temperate zones of America and 
Europe. 
This infectious disease of man is without characteristic lesions save 
for the haemorrhages and pigmentation in the skin. Such other lesions 
as commonly exist are those common to toxaemia. The following con- 
ditions are, however, frequently present after death: 
Rigor mortis is marked and occurs early. 
The brain and its meninges are usually congested. The skin is of a 
yellow color from the presence of the bile pigment, and may be mottled 
by ecchymoses. Ecchymoses are frequent in the mucous and serous 
membranes. 
The heart is of a pale or brownish yellow color. Its muscular fibres 
may be the seat of fatty degeneration. The lungs may be congested. 
The stomach often contains a characteristic dark fluid, due to altered 
blood pigment, similar to that which is vomited during life-black 
vomit. Its mucous membrane may be congested, softened, and is 
sometimes eroded. The intestines are dark-colored, often distended 
1 Plotz, Jour. Amer. Med. Assn., 1914, Ixii., 1556. 
2 Nicolle, C. R. Acad. Sci., 1909, cxlix,, 157. Anderson and Goldberger, Jour. Med. Research, 1910, 
N. S. xvii., 469. 
3 Ricketts and Wilder, Jour. Amer. Med. Assn., 1910, liv.,463,1304, 1373. McCampbell, Jour. Med. 
Research, 1910, N. S. xviii., 71. 
4 Wilson and Chowning, Jour. Infect. Dis., 1904, i., 31. 
6 Ricketts, Jour. Amer. Med. Assn., 1909, lii., 379. 
6 Ricketts and Gomez, Jour. Infect. Dis., 1906, iv., 141. 302 
THE INFECTIOUS DISEASES 
with gas, and sometimes contain blood. The liver in the earlier stages 
of the disease may be intensely congested. More frequently it con- 
tains but little blood, is of a light yellow color, and the hepatic cells 
show the changes of an intense albuminous degeneration, often much 
more marked than are found in any other disease except acute yellow 
atrophy of the liver. Areas of focal necrosis may be present. The gall- 
bladder is apt to be contracted. 
The spleen shows no marked changes. The kidneys present an 
intense albuminous degeneration. The tubules usually contain masses 
of hyaline material. 
The Excitant of the Disease 
While its mode of occurrence and the characters of its symptoms and 
lesions indicate that yellow fever is an acute infectious disease, none of 
the various studies which have been made upon its etiology has as yet 
revealed the presence of any micro-organism which can be confidently 
accepted as its excitant.1 
The Mode of Infection. 
It has been shown by Reed and his colleagues, Carroll and Agramonte, 
that the infectious agent in yellow fever may be transmitted by the sub- 
cutaneous injection into a healthy individual of a small quantity of blood 
drawn from a patient in the early stage-first three days-of the disease. 
It has, furthermore, been shown by repeated and abundantly confirmed 
experiments that yellow fever may be induced in a non-immune indi- 
vidual by the bite of the mosquito-Stegomyia calopus-which has pre- 
viously-at least twelve days-bitten a patient in an early stage of the 
disease. Practical sanitary procedures, based upon the hypothesis that 
this mosquito acts as an intermediate host in which the (unknown) 
yellow-fever parasite passes one of its developmental cycles, have 
furnished strong evidence that it is through the intervention of this 
mosquito, and thus only, that the disease is conveyed. For it has been 
possible, by the prevention of access of this mosquito to yellow-fever 
patients through the use of netting and other precautionary measures, 
practically to suppress the disease in Havana, where it was formerly 
endemic, and to stifle epidemics elsewhere.2 It has been further demon- 
strated in the most conclusive way that the infectious agent in yellow7 
fever is not conveyed directly through the air or by fomites.3 That it is 
1 The various studies of Sternberg, who isolated a bacillus which he called "Bacillus x," and of 
Sanarelli, who found a bacillus which he named Bacillus icteroides, are the most noteworthy earlier con- 
tributions to the subject. A later study and references to the bibliography of this subject may be found 
in an article by Reed and Carroll, Jour. Exp. Med., vol. v., p. 215, 1900. 
2 For a summary of observations relating to the mosquito as an intermediary host of the infectious 
organism in yellow fever, see Reed, Carroll, and Agramonte, Phila. Med. Jour., October 27th, 1900; also 
Jour. Am. Med. Assn., vol. xxxvi., p. 431, 1901; Amer. Med., vol. ii., p. 15, 1901; Guiteras, Amer. Med., 
vol. ii., p. 809, 1901; Durham, Thompson Yates' Laboratories Report, vol. iv., 1901, p. 485; Reed and 
Carroll, Amer. Med., vol. iii., p. 301, 1902; also Carroll, Jour. Am. Med. Assn., vol. xl., p. 1429, 1903. A 
summary and bibliography by Goldberger is in Bull. No. 16 of the Yellow Fever Institute, 1907. 
3 For a brief resume of the reasons for the belief that the mosquito is the sole agent in the convey- 
ance of the infectious agent in yellow fever, see Carter, Bull, of the Yellow Fever Institute, No. 10, 
July, 1902, Bureau of Public Health and Marine Hospital Service, U. S. A. For a description of the 
mosquito Stegomyia calopus and modes of prevention in yellow fever see Reed and Carroll, Med. 
Record, vol. lx., p. 641,1901. For the bearing of this subject upon quarantine regulations see Doty, Med. 
Record, vol. lx., p. 649, 1901. THE INFECTIOUS DISEASES 
303 
an extremely minute organism is shown by the fact that it can pass 
through the pores of a Berkefeld filter. 
Smallpox is an acute, readily communicable, infectious disease,, 
especially characterized anatomically by an inflammation of the skin 
which passes through a series of more or less distinctive phases of papule,, 
vesicle, pustule, with a final drying of the exudate and necrotic tissue 
constituting the crust. 
Various phases of the exanthem are used to designate forms of the- 
disease. 
Secondary lesions are diffuse suppurative inflammation of the skin, 
congestion, inflammation, and ulceration of the mucous membranes,, 
haemorrhages in various parts of the body, swelling and ulceration of 
the lymphatic tissues, albuminous degeneration of the kidney, liver, and 
spleen, and leucocytosis. 
VARIOLA. (Smallpox.) 
Fig. 171. -A Smallpox Vesicle of the Skin. 
The skin lesion shows in general at first circumscribed areas of inflam- 
mation above the ends of the papillae, with the development of a fluid- 
filled reticulum, so that vesicles more or less umbilicated are formed 
(Fig. 171). These at first contain a clear fluid, but by the gathering of 
pus cells the fluid becomes turbid and accumulates to form a pustule. 
Hand-in-hand with these changes the papillae and adjacent layers of the 
corium may become infiltrated with cells. The contents of the pustules 
and the necrotic tissue above dry and form the crusts. When the 
changes are largely confined to the epidermis, the lesion may leave no 
deformity. But if the changes in the cutis are considerable, cicatricial 
tissue may form, leaving scars. The association of local haemorrhage 
with the above changes gives rise to the haemorrhagic form of exanthem. 
Artificial Immunization in Smallpox. 
Smallpox affords one of the most striking examples of positive and 
prolonged acquired immunity conferred by a successfully weathered, 
attack of an infectious disease. 304 
THE INFECTIOUS DISEASES 
In the early days attempts were made to mitigate the virulence of 
smallpox acquired by exposure in the usual ways by artificial inoculation 
of material-virus-taken from a smallpox pustule. The usually 
relatively mild form of the disease induced in this way also conferred 
immunity. But the individual was during his immunization a source of 
danger to others. The great discovery of Jenner that by inoculation 
with virus from cowpox, immunity was secured against smallpox need 
not be considered in detail here. The immunity secured in this way, 
while not absolute, is usually effective and involves as a rule but slight 
indisposition. By revaccination after an interval of a few years prac- 
tical protection is secured, so that the occurrence of smallpox epidemics 
to-day is possible only through neglect of simple and positive protective 
measures. 
The more recent view of the immunity conferred by vaccination 
against smallpox is based upon the demonstration that the disease 
variola in man and the disease vaccinia in the bovine species are of 
the same nature and not different, as was formerly believed. This 
has been established by numerous inoculation experiments. The disease 
in the cow is a modified form of the human disease. The effect of the 
passage of the unknown micro-organisms through the insusceptible 
bovine-thus runs the rationale in the new light-is so to diminish the 
virulence of the germ that by its subsequent inoculation in man immu- 
nity is secured without the profound disturbance which infection with a 
germ of unmitigated virulence would involve.1 
The Excitant of Smallpox. 
Bacteria.-The large number of studies which have been made of the 
skin lesions of smallpox and of vaccine lymph have shown that bacteria 
of various kinds are frequently present.2 Streptococci and staphylo- 
cocci are especially common in the pustules and may be present in the 
blood in later stages of severe or fatal cases.3 It is probable that the 
pyogenic cocci are of great importance as complicating factors in the 
disease. But there is no evidence at hand that these or any other bac- 
teria are its primary excitants. 
Protozoa.-While it was natural that the most painstaking search 
should be made for bacteria in the lesions of smallpox, there have been 
from the first many obvious reasons for the conjecture that this disease 
1 In diphtheria the perfection of the process of artificial immunization and the establishment of 
a precise and successful curative method are the direct results of a long, patient, logical series of anima 
experiments with a definite end in view, and by the use of the absolutely identified and well-known 
germ which induces the disease. On the other hand, it is not a little curious that in smallpox and in 
hydrophobia effective methods of immunization should have been perfected without precise knowledge 
of the micro-organisms which incite the diseases, and yet by procedures which, though somewhat em- 
pirically hit upon, are nevertheless in close accord with those which the most recent studies on immunity 
in general have shown to be effective. Thus in both smallpox and hydrophobia the material used 
for protective inoculation is that which has been artificially reduced in virulence; in the one case-small- 
pox-by its passage through the body of a relatively insusceptible animal; in the other-hydrophobia- 
by drying in the air. 
2 See Huguenin, Lubarsch and Ostertag's "Ergebnisse," Jahrg. iv., p. 387, bibl. 
3 See report by Ewing, Trans. Assn. Am. Phys., vol. xvii., 1902, p. 213; also Perkins and Pay, Jour. 
Med. Res., vol. x., 1903, p. 180. THE INFECTIOUS DISEASES 
305 
as well as the other exanthemata might be incited by organisms of a 
different nature. In fact, as early as 1886 and 1887 bodies were found 
in the pustules by Van der Loeff and L. Pfeiffer, which they conjectured 
to be protozoa. It was not until 1892, however, when Guarnieri under- 
took a series of noteworthy experiments in animals, that the nature of 
the suspected structures in vaccine lymph became clearer. Guarnieri 
inoculated vaccine lymph into the cornea of rabbits and noted the 
appearance after a few days in increasing numbers in the epithelial 
cells of the structures which had been previously discovered in the con- 
tents of smallpox pustules. In some of these bodies he believed that he 
saw amoeboid movements. These bodies, which were called "vaccine 
bodies," he regarded as protozoa and named the species Cytoryctes 
vaccince.1 
These observations of Guarnieri on the vaccine bodies found in the 
lesions of both vaccinia and variola were confirmed by Wasielewski2 
and many other observers. 
The vaccine bodies of Guarnieri are spheroidal, oval, or irregular 
structures from 1 y to 4 or even 8 y in diameter, staining readily with 
various dyes, the central portion giving in general the staining characters 
of nuclear substance, a peripheral zone being sometimes differentiated 
by cytoplasmic stains. The bodies often lie close upon the border of 
the nucleus of the epithelial cells, sometimes lying in a depression of the 
nuclear border. They may, however, lie in other parts of the epithelial 
cytoplasm. They are frequently surrounded by a clear space, which may 
become of considerable size. They have not been found in the nucleus. 
Hand-in-hand with the increase of these bodies there are progressive 
degenerative processes in the epithelium of the inoculated region, with 
the formation of various structures characteristic of the degeneration 
of protoplasm under a great variety of conditions. 
While many observers following Guarnieri have felt justified, largely 
on morphological evidence, in the belief that the vaccine bodies are pro- 
tozoa, others have been led to the conclusion that many, if not all, the 
appearances presented can be accounted for by protoplasmic degen- 
erations induced by other agencies. Several experimenters, indeed, 
by the introduction into the rabbit's cornea of chemical and other sub- 
stances not at all related to the vaccine virus, have been able to induce 
degenerative protoplasmic structures resembling the vaccine bodies. 
The studies of Ewing on this subject are of especial significance.3 
It is evident that the proof on morphological grounds alone of the 
protozoan nature of such minute structures is a task of extreme difficulty, 
associated as they frequently are with the readily stained products of 
protoplasmic degeneration. 
In April, 1903, Councilman announced the results of a long series of 
studies by himself and his associates, Magrath, Brinckerhoff, and Tyzzer, 
1 This name was given because the bodies frequently lay in small spaces in the cell protoplasm, 
which he assumed to have been formed by the destructive action of the parasite. 
2 Consult for a most admirable summary of the subject, with original studies, photographs, and 
bibliography, Wasielewski, Zeitsch. f. Hyg., Bd. xxxviii., 1901, p. 212. 
3 See Ewing, Jour. Med. Res., vol. xii., p. 509, 1904; also ibid., vol. xiii., p. 233, 1905. 306 
THE INFECTIOUS DISEASES 
on the excitant of smallpox.1 The observations of Guarnieri, Wasie- 
lewski, and others, on the vaccine body, were in the main confirmed. 
These observers found the vaccine bodies in the lower layers of skin epi- 
thelium before the production of the vesicles and in the advancing 
edges of the young vesicles. They found morphological evidence of the 
segmentation of the bodies and the formation of round, spore-like 
structures about 1 /z in diameter. Councilman further announced 
the discovery of other bodies, not before described, within the nucleus 
of the epithelial cells in the infected region in man. These intranuclear 
structures are circular, ring-like, with a central dot, and may be seen 
singly or in clusters. They are' from 1 to 1.5 p in diameter. These 
intranuclear bodies Councilman regards as a further stage and as repre- 
senting a second complex cycle of development of the smallpox parasite. 
The intranuclear structures he believes to be developed from the spore- 
like bodies, resulting from the segmentation of the intracellular vaccine 
body, which penetrate the nucleus. Councilman finds the vaccine bodies 
both in the epithelial cells of the smallpox lesion in man and in the lesion 
induced by vaccination of the rabbit and calf. But the intranuclear 
forms have not been found in the latter animals. After inoculation of 
the monkey with the contents of smallpox pustules, both the intracellular 
and the intranuclear forms wrere found. He believes it to be probable 
that in smallpox the parasite undergoes complete development, passing 
through two cycles, an intracellular and an intranuclear, while in vaccinia 
only one, the primary, cycle is achieved.2 
Calkins, from an independent study of the material furnished by 
Councilman, is convinced of the protozoan nature of the organisms in 
question and now groups them among the rhizopods.3 
It is clear that final judgment upon the nature and significance of 
these minute structures must be suspended until further experiments 
upon suitable animals shall have furnished fuller biological data than 
are yet at hand, which may sustain the evidence, still largely morpho- 
logical, on which these suggestive conclusions are based.4 
SCARLET FEVER. (Scarlatina.) 
This is an infectious, readily communicable disease characterized by 
a diffuse skin eruption, and frequently accompanied by inflammation, 
either catarrhal, or croupous, or gangrenous, of the tonsils, pharynx, 
and larynx. Focal necroses, albuminous degeneration in the viscera, 
and leucocytosis with moderate eosinophilia may occur. 
There may be acute hyperplasia or suppuration of the cervical lymph- 
nodes. There is very frequently an acute exudative or an acute diffuse 
1 "Studies on the Pathology and on the Etiology of Variola and Vaccinia," Jour, of Med. Res., 
vol. xi., 1904; see also summary by Councilman, Am. Med., vol. x., p. 689, 1905. 
2 For studies on experimental variola and vaccinia in monkeys see Brinckerhoff and Tyzzer, Jour. 
Med. Res., vol. xiv., p. 209 et seq., 1906. See also, for studies on reaction of variola virus to external 
conditions, ibid., p. 352. 
3 Calkins, Protozoology, 1909, 308. 
4 Consult for general bibliography Freeman, article on vaccination in "Cyclopedia of the Diseases 
of Children," vol. v., suppl., p. 263; or Moore, in "Twentieth Century Practice," vol. xiii. THE INFECTIOUS DISEASES 
307 
nephritis.1 The spleen may be enlarged. Broncho-pneumonia, endo- 
carditis, and pericarditis may complicate the disease. 
The exanthem or skin eruption in scarlatina is a simple dermatitis, 
as the result of which the papillae and subpapillary stratum become 
infiltrated with fluid or leucocytes, or both, the leucocytes being gathered 
especially about the blood-vessels. There may be small haemorrhages, 
and the acute phase of the inflammation is followed by an increased 
production of epithelium and an exfoliation of the superficial layers. 
These lesions of the skin may be, excepting the haemorrhages, very 
slightly marked after death. 
The Excitants of Scarlatina.-That the disease is due to some form 
of micro-organism there can be no doubt. The exact nature of this 
organism is not yet known. The acute nephritis and the marks of 
degeneration and focal necrosis so often present appear to be due to some 
poison formed in the body during the disease. 
Mallory2 has described bodies in and between the epithelial cells of 
the epidermis and free in the superficial lymph-vessels and spaces of 
the corium in scarlet fever which he believes to be protozoa and to bear 
an etiological relationship to the disease. Most of these bodies are 
from 2 to 7 in diameter and stain with methylene blue. A series of 
forms are found, including rosettes, which are said to resemble the series 
in the asexual development of the malarial parasite. Further studies 
will be required to establish the protozoan nature as well as the signifi- 
cance of these structures.3 
One of the most marked features of the disease is the predisposition 
which it entails to the incursions of pathogenic germs other than that 
which we believe to be its excitant. Thus an infectious croupous inflam- 
mation of the mouth, tonsils, pharynx, larynx, and trachea, due to a 
streptococcus (see p. 212), is a frequent complication. True diphtheria 
due to the Loftier bacillus is also prone to establish itself upon the vul- 
nerable inflamed mucous membranes. So also the frequently associated 
pneumonia, the inflammatory hyperplasia and suppuration of the lymph- 
nodes, suppurations in various parts of the body, the endocarditis and 
pericarditis which are not uncommon, may all be due to a secondary 
infection with the pyogenic cocci. 
TRACHOMA 
The inflammation of the conjunctiva, known as trachoma, has long 
been suspected to be of infective nature. But it was not until 1907 that 
Halberstaedter and v. Prowazek,4 and Greff5 described the occurrence in 
1 For a special study of kidney lesions in scarlatina see Chapman, Jour, of Path., vol. xi., p. 276, 
1906, bibl. 
2 Mallory, Jour, of Med. Res., vol. x., 1904, p. 483. On the demonstration of the alleged parasites 
of scarlatina in blister fluids see Duval, Univ. Penn. Med. Bull., Nov., 1904; also Williams and Lowden, 
Studies Res. Lab. of the N. Y. City Health Dept., iii., 42, 1907, and Field, Jour. Exp. Med., 1905, vii., 
343. 
3 For a study of intraleucocytic inclusions (Dohle bodies) see Glomset, Jour. Infect. Dis., 1912, xi., 
468. For a study of the alleged incitement of scarlet fever in monkeys see Draper and Hanford, Jour. 
Exper. Med., 1913, xvii., 517. 
4 Halberstaedter and v. Prowazek, Deut. Med. Wchnschr., xxxiii., 1285, 1907. 
5 Greff, Ibid, 914, 1907. 308 
THE INFECTIOUS DISEASES 
the epithelial cells of the conjunctiva in the early stages of the disease of 
extremely minute, rounded or oval bodies, smaller than the smallest cocci, 
not staining with Gram, but reddish or violet with Giemsa. 
These bodies are surrounded by a clear mantle, staining blue with 
Giemsa, and are often paired. They are called Trachoma Granules or 
Bodies. The trachoma granules are found chiefly in the epithelial cells, 
Conjunctiva. From a preparation of Dr. Noguchi. The bodies are in a small cluster near the 
nucleus of the cell near the centre of the cut. The outline of the cell-body has been lost in the repro- 
duction of the photograph. 
Fig. 172.--Trachoma Bodies. 
often grouped in concentric masses, close to the nucleus (Fig. 172). 
They sometimes fill and distend the cells (Fig. 173). They vary con- 
siderably in size. They increase rapidly within their mantles which 
presently they replace. 
These bodies were called Chlamydozoa because of the surrounding 
mantle. They are not very abundant and may soon disappear. Their 
significance and nature do not seem at present clear.1 
1 For a study and bibl. see Noguchi and Cohen, Jour. Exper. Med., 1913, xviii., 573; and Wolbach 
and McKee, Jour. Med. Res., 1911, N. S. xix., 259. THE INFECTIOUS DISEASES 
309 
MEASLES. 
A readily communicable infectious disease, the most prominent 
features of which are an intense hyperaemia with inflammation of the 
skin, associated with catarrhal inflammation of the mucous membrane 
of the air passages. The inflammation of the skin is anatomically of 
the same general type as that in scarlatina.1 Albuminous degeneration 
Conjunctiva. From a preparation of Dr. Noguchi. The "bodies" nearly fill the cell near the centre 
of the cut and partly surround the nucleus. 
Fig. 173.-Trachoma Bodies. 
of the kidney or acute exudative nephritis may occur. Focal necrosis 
in the liver and kidneys have been described by Freeman.2 
The more common secondary lesions are broncho-pneumonia, pseudo- 
membranous inflammation of the pharynx and larynx, suppurative 
inflammation in various parts of the body, and diphtheria. These compli- 
cations, as in scarlatina, are doubtless, in part at least, due to secondary 
infection with other germs than those causing the disease itself. 
The excitant of measles is not known. 
1 For a study of epithelial cell changes in measles, see Ewing, Jour. Inf. Dis., vi., 1, 1909. 
2 Freeman, Arch, of Pediatrics, February, 1900. 310 
THE INFECTIOUS DISEASES 
Canon and Pielicke in 18921 recorded the discovery in the blood in fourteen cases 
of measles of very small bacilli, about as long as the radius of a red blood cell, but 
varying considerably in size. These bacilli were sometimes abundant, sometimes 
scanty in the blood, lying singly or in heaps. Meagre cultures were obtained in three 
cases in beef tea. They did not seem to grow on the ordinary solid media. Bacilli 
similar in form were found in the exudate from inflamed mucous membranes in 
measles. The observations of these writers are interesting and suggestive, but until 
they shall have been confirmed by others and greatly extended nothing can be assumed 
as established regarding the etiological significance of the germs. 
Inoculation of Measles.-Although readily conveyed in natural ways 
from one human being to another predisposed individual, the attempts 
at experimental inoculation of the infectious agent in measles in man 
have not led to very definite conclusions. Hektoen succeeded in two 
cases in inducing typical measles by the injection of material derived 
from the blood at an early stage of the disease.2 
MALARIA. 
The Lesions of Malaria. 
The characteristic lesions of acute malarial infection are found in the 
blood, the liver, spleen, kidneys, and brain. 
The alterations in the blood are chiefly confined to the diminution in 
number of the red corpuscles, due to their destruction by the parasites 
developing in them and to a reduction in the haemoglobin content of 
those which do not contain parasites. These changes are apparently 
due to some toxic agent, for which there is additional evidence in the 
polychromatophilia and granular degeneration of the body of the red 
cell so often present in severe malarial infections. The evidence of some 
poison acting on the protoplasm of the red cells is found, not only in 
those cells in which the organism is developing, but more abundantly 
in those cells in which no plasmodia are present. 
The leucocytes show slight qualitative changes, there being usually 
present a relative increase in the large mononuclear cells. Pigmented 
leucocytes are often seen, and in very severe infections large macrophages 
loaded with pigment may be seen in the circulating blood. In severe 
cases the pigment, which is derived from the haemoglobin of the blood 
corpuscles and forms the granules in the body of the parasite, may be 
found free in the general circulation, but is usually soon removed by 
the leucocytes and the phagocytic cells of the liver, spleen, and bone 
marrow. The brain in cases of pernicious aestivo-autumnal fever is 
often much congested, and the smaller capillaries may be filled with 
enormous numbers of the plasmodia in various phases of development; 
there may also be small punctate haemorrhages in the white matter. 
The deposition of the malarial pigment in the cortex may give to the 
latter a dark reddish brown color, or it may be almost black. The spinal 
cord shows similar changes. 
1 Berliner klin. Wochenschr., Apr. 18th, 1892. 
2 For a resume of earlier attempts at inoculation of measles and his own experiments see Hektoen, 
Jour. Inf. Dis., vol. ii., p. 238, 1905. For an experimental study of measles in monkeys, see Lucas and 
Prizer, Jour. Med. Res., 1912, N. S. xxi., 181. THE INFECTIOUS DISEASES 
311 
The liver in acute cases may show focal necroses resembling those 
present in other infectious diseases. The endothelium of the liver 
capillaries may contain much pigment (see Fig. 473, p. 721), while 
the lumina of the capillaries may be stuffed with plasmodia in various 
stages of development. The kidneys may show albuminous degenera- 
tion, and while the intertubular capillaries may be filled with pigmented 
leucocytes there is not, as a rule, a great accumulation of plasmodia in 
the vessels. A moderate diffuse nephritis is occasionally seen. The 
capillaries of the mucosa of the stomach and the intestines may be filled 
with parasites in cases with choleraic symptoms, and there may be a 
considerable amount of necrosis in the epithelium of the mucosa of the 
intestines. The bone marrow usually contains large numbers of the 
plasmodia, chiefly segmenting forms. A good deal of pigmentation is 
present, and an active phagocytosis is carried on, mainly by the giant- 
cell macrophages present in the marrow. Crescentic organisms may be 
present in the marrow even if these have not been present in the blood 
during life. 
The spleen is increased in size, the pulp is softened and very dark, 
the Malpighian bodies are not well marked. Microscopically, the organ 
is greatly congested; many of the red cells are invaded by the plasmodia 
which are often in the segmenting stage. There is a very active phago- 
cytosis by the macrophages present, often so extensive as to include the 
red cells with their contained parasites. 
In the chronic cases the patient may become extremely anaemic with 
nucleated red cells in the blood and a great reduction in the number of 
erythroblasts. The spleen is greatly enlarged, the capsule thickened and 
adherent to the surrounding tissues. The cut section of the organ is of 
a dark brown or slaty black from the deposit of pigment. The Mal- 
pighian bodies are well marked. The fibrous-tissue trabeculae are 
thickened, as is the reticulum of the pulp; the pulp cells are pigmented. 
The liver shows a marked pigmentation, especially in the endothelium 
of the capillaries and in the so-called perivascular cells described by 
Kupffer, while occasionally there is a moderate amount of new connec- 
tive tissue, which, however, does not follow, as a rule, the anatomical 
distribution of the connective tissue in the usual atrophic cirrhosis. In 
chronic poisoning the kidneys may show a chronic diffuse nephritis. The 
bone marrow may remain fairly normal except for the deposition of pig- 
ment, or there may be seen a marked hyperplasia with replacement of 
the normal fatty marrow of the shafts of the long bones with red marrow 
containing normoblasts or even megaloblasts if the disease has been 
long-continued and severe. 
The Excitant of Malaria. 
The excitant of the disease long known clinically as malaria is a small 
animal parasite, the Plasmodium malariee, which enters the red corpuscles1 
1 While it is generally known that a few of the parasites adhere to the outer surface ot the red cells, 
the theory of Rowley Lawson (Jour. Exper. Med., 1914, xix, 450), that the parasites are always external 
to the red cells, has received little or no acceptance. 312 
THE INFECTIOUS DISEASES 
of the blood and in the course of its development destroys them. The 
destruction of each cell is coincident with the maturation of its con- 
tained parasite, a phenomenon which is also coincident with the clinical 
appearance of the chill and its accompanying fever.1 
These parasites of the red cell are protozoa belonging to a special 
sub-group, the hoemo sporidia. For purposes of description these hsemo- 
sporidia of human malaria may be classified into three species or types, 
each of which incites a different clinical form of disease and each of 
which also differs from the other types in its morphology. These types 
are the tertian, the quartan, and the aestivo-autumnal parasites. 
Tertian and Quartan Types.-If the blood of a patient suffering from 
tertian fever be examined shortly after a chill, a number of the red 
cells will be found to contain small, highly refractile, actively amoe- 
boid bodies which are the early forms of the plasmodia or merozoites. 
The latter often take the form of small rings surrounding a central clear 
space especially well seen in stained specimens (Plate I., Figs. 1-4). If 
the blood be examined some hours later, the small forms have grown 
and small brown or black granules will be noted in the body of the plas- 
modium, having a very rapid motion inside the body of the parasite. If 
the blood be examined at the end of forty-eight hours the organism may 
be seen to have grown so large as to occupy nearly the whole of the red 
cell (Plate I., Figs. 5-12), which becomes somewhat swollen and pale, 
the latter effect being due to the destruction of the haemoglobin of the 
cell by the parasite, which thus produces the pigment granules of melanin 
with which it is filled. The pigment now occupies the centre of the organ- 
ism, which has ceased its active amoeboid motion. Now small pale spots, 
which are the nuclei of the segmenting mature form, become easily visible 
(Plate I., Fig. 16), and finally the red cell bursts, and the small merozoites, 
each containing a nucleus, are set free to enter other red cells and to 
repeat the cycle. A certain portion of the free merozoites are destroyed 
by the phagocytic leucocytes and other cells. The free pigment left after 
the segmentation of the mature forms is also collected by these phago- 
cytes. Thus after severe and prolonged attacks of malaria the leucocytes 
are frequently filled with pigment. 
The quartan organism goes through a cycle similar to that of the 
tertian, except that the time required is seventy-two instead of forty- 
eight hours. There are also a few minor differences in the morphological 
appearance of the two organisms. Thus the small early amoeboid 
forms of the plasmodium are much more active in their movements in 
the tertian than in the quartan. The pigment in the tertian is very 
fine; in the quartan it is often in small blocks or rods and is much coarser 
(Plate I., Figs. 22-25). The mass of segmenting merozoites in the 
tertian organism is quite irregular in shape and contains from fifteen to 
twenty individuals, while that of the quartan is a regular rosette in 
shape and the merozoites average from six to twelve (Plate I., Figs. 
26-28). 
1 For cultivation of the parasite see Bass, Jour. Am. M. Assoc., 1912, lix., 936. THE INFECTIOUS DISEASES 
313 
^stivo-autumnal Type.-The parasite of the sestivo-autumnal fever 
develops in the blood in much the same way as the other forms, with 
the exception that the amoeboid rings are, as a rule, smaller. The 
signet-ring shape is more marked, and the pigment is less abundant 
(Plate I., Figs. 31-34). Another peculiarity of this organism is that 
the development of the larger amoeboid forms takes place chiefly in the 
bone-marrow and the spleen, while that of the tertian and quartan is to 
be seen in the blood. Thus as soon as the plasmodium of the sestivo- 
autumnal type has grown sufficiently to occupy about one-fourth of 
the red cell, it disappears from the peripheral blood and can be found 
developing in the blood obtained by puncture of the spleen, or, in fatal 
cases, from the bone-marrow (Plate I., Figs. 35, 36). In such prepara- 
tions the mature plasmodia may be found and the segmenting process 
followed (Plate I., Figs. 37-39). The organism is not as large as the 
tertian, as the segmenting form usually occupies only about one-half 
of the somewhat shrunken red corpuscle. The number of merozoites 
formed is about fifteen. The time of the developmental cycle in the 
blood is forty-eight hours. 
In the blood of a patient infected with the sestivo-autumnal parasite, 
there are always found within a few days after the beginning of the 
disease a moderate number of crescent-shaped bodies with pigmented 
centres and the remnant of a red cell about them (Plate I., Figs. 43, 44). 
They are devoid of amoeboid motion. The exact nature of these cres- 
centic bodies was quite unknown until very recently, when it was dis- 
covered that they are cells with sexual capabilities, whose function 
seems to be the prolongation of the species in a cycle outside of the human 
body. It had long been known that certain of the large mature amoe- 
boid forms of the tertian and quartan organisms and the crescents of 
the aestivo-autumnal species did not undergo segmentation into mero- 
zoites, but remained circulating in the blood. When, however, the 
blood containing these forms was examined in a fresh condition on a 
slide, and especially if the blood before being covered was allowed to 
remain in a moist chamber for a few minutes, changes could be seen to 
take place which had not been observed in perfectly fresh preparations. 
Certain of the mature organisms set free long, actively motile flagella 
which entered other mature forms. In stained preparations it could be 
seen that each flagellum contained some of the nuclear chromatin of 
the organism from which it arose, and that this flagellar chromatin 
united with the chromatin of the body which the flagellum entered. 
The crescentic forms under suitable conditions go through the same 
process, the male crescent giving off flagella, one of which in turn fer- 
tilizes another crescent of slightly different morphology. 
Evidently this is a sexual process, and its occurrence only in blood 
which has been drawn from the body suggested the probability that 
under ordinary circumstances it takes place outside the human host. 
The truth of this conjecture has recently been established, and the proc- 
ess of fertilization and maturation of the fertilized organism has been 
found to occur in the stomach of a particular genus of mosquito, the 314 
THE INFECTIOUS DISEASES 
Anopheles. No other type of mosquito is capable, according to our 
present knowledge, of acting as host to the plasmodium of human malaria, 
though the organism which induces malaria in birds can develop in a 
mosquito of the genus Culex. Whether the plasmodium can carry out 
its sexual cycle under other conditions than in the stomach of the 
Anopheles is as yet unknown. If an Anopheles bites a patient with 
malaria, the blood with its contained organisms is drawn into the stom- 
ach of the mosquito, the flagella are given off from the gametes and enter 
other mature forms and fertilize them. The fertilized organism goes 
through a complicated development, and the resulting sporozoite finds 
its way in the course of a few weeks to the salivary glands of the mos- 
quito host, to be injected into the blood of the next person bitten. 
The sporozoites enter the red cells, becoming the small amoeboid forms 
or merozoites already described.1 
The details of the process of fertilization and the formation of the 
sexual cells which are capable of carrying on the cycle in the mosquito 
have been best observed in the aestivo-autumnal fevers, so that the 
stages will be here described in connection with the development of the 
crescent gametes. These crescents are formed chiefly in the bone 
marrow from the small ovoid, intracellular bodies, which can early in 
their development be distinguished from the ordinary amoeboid forms 
by their more abundant coarse pigment and oval outline. 
The adult crescents are quite constantly present in well-developed 
cases, and are often found in the blood after treatment with quinine has 
caused the disappearance of the amoeboid bodies, the power of resisting 
the action of drugs being much more marked in the crescents than in 
any other form of the plasmodium. Two types may be distinguished, 
both of which begin as small amoeboid forms and gradually mature into 
oval or crescentic organisms. One of these, the microgametocytes, or 
the cells producing the male elements, develops and gives off the flagel- 
lum (microgametes); the other, the macrogametes (female elements), 
neither form nor give off flagella. According to Marchiafava and Big- 
nami2 the microgametocytes are distinguished from the macrogametes 
by the fact that in the former (the male form) the pigment is gathered 
in a fairly compact mass in the middle of the crescent, the chromatin 
is more abundant, and the entire body stains faintly; while in the female 
form, the pigment surrounds the rather scanty nuclear chromatin in 
a ring form, the cell body stains deeply, and no flagella are given off. 
The crescents in the fresh blood show no amoeboid motion, and even the 
pigment is motionless. They are either crescentic in form with the 
pigment collected at the centre, or they may be spindle-shaped with 
somewhat scattered pigment, or finally short, thick ovoid bodies with 
pigment irregularly scattered or more frequently gathered into a ring 
about the nucleus. They are all contained in red blood cells (endo- 
globular), the faint remnant of the red cell often being seen as a delicate 
line stretching between the two horns of the crescent. 
1 For details of the process see Schaudinn, Arbeiten aus dem Kais. Gesundheitsamte, 1902, p. 169. 
2 Other observers claim that the pigment in the male forms is scattered throughout the plasmodium. Description of Plate I. 
Haematozoa of Tertian Malaria. 
Figs. 1 to 4 Small ring-shaped merozoites of tertian malaria; 2 and 3, multiple 
invasion of a single red cell. 
" 5 to 12... .Amoeboid forms of gradually increasing size. 
Fig. 13 Large amoeboid form in which the pigment is beginning to collect 
as a preliminary to segmentation. 
" 14 Pigment still more clumped, and the pale areas representing nuclei 
begin to be marked. 
" 15 Segmenting form with an irregular mass of merozoites. 
" 16 More symmetrical type of segmentation with central block of 
pigment. 
" 17 Free merozoites after leaving the red cell. 
" 18 Gamete. 
" 19 Microgametocyte with flagella or microgametes. 
Haematozoa of Quartan Malaria 
Figs. 20 and 21. .Small ring form of merozoites. 
" 22 to 25... .Amoeboid forms with coarse pigment. 
" 26 to 28.. . .Segmenting forms. 
" 29 Gamete. 
" 30 Microgametocyte with microgametes in the process of formation 
Haematozoa of TEstivo-Autumnal Malaria. 
Figs. 31 to 34... .Small ring forms, some of them on the surface of the corpuscle; 32 
and 33, multiple invasion of the red cell. 
" 35 and 36. .Amoeboid forms found in the peripheral circulation. 
" 37 to 39.. . .Large amoeboid forms and segmenting parasites found only very 
rarely in the peripheral circulation, but abundantly in the spleen 
and bone marrow. 
" 40 to 42.. . .Young crescentic forms not found in the peripheral circulation, 
but chiefly in the bone marrow. 
" 43 and 44..Adult crescents or gametes, found abundantly in the peripheral 
blood. 
" 45 and 46. . Microgametocytes becoming oval and preparing to give off microga- 
metes. 
Fig. 47 Microgametocyte giving off microgametes. Pathology-Delafield & Prudden. 
Pl ATE I 
Heematozoa of Tertian Malaria. 
Haematozoa of Quartan Malaria. 
Htematozoa of Aestivo-Autumnal Malaria. THE INFECTIOUS DISEASES 
315 
The formation of flagella (microgametes) does not take place in 
the circulating blood; it begins only after the blood has remained on 
a slide for a few minutes or has remained for some time in the stomach 
of the mosquito. These flagella, usually about four in number, bud out 
from the periphery of one of the microgametocytes, which has assumed 
a spherical instead of a crescent shape, and grow to a length of three to 
five times the diameter of the red cell. They are either pointed or 
bulbous at their extremities, or they present swellings at irregular inter- 
vals. Their motion in warm-stage preparation is rather rapid, and they 
finally become detached and move about free in the serum (Plate I., 
Figs. 45, 46, 47). The pigment during this process usually remains at the 
centre of the spherical microgametocyte and is actively motile, but in 
preparations stained to show the nuclear chromatin the latter may be 
seen to penetrate the flagella in the form of long thin rods which remain 
after the flagella become detached. The shell of the red cell in which 
the crescent has developed can rarely be seen in fresh preparations of 
the flagellate forms. These flagella penetrate the body of one of the 
macrogametes present on the slide and fertilize it. 
This process, which we have followed in an artificial preparation, 
seems necessary for the continuance of the race, and is normally carried 
out in the middle intestine of the mosquito of the genus Anopheles. 
The actual entry of the microgamete (spermatozoon) into the macro- 
gamete has been observed by MacCallum1 and others in fresh-blood 
preparations. 
If a patient in whose blood mature crescents are present is bitten by 
the mosquito, the parasites develop in the intestine of the insect, and at 
the end of two days the fertilized forms may be found adherent to the 
wall of the intestine as small pigmented oval bodies quite similar to the 
early forms of the crescents developing in the human bone marrow. 
Two days later the parasites or oocysts are much larger and have a dis- 
tinct capsule, while by the sixth day they may measure from 60 to 80 
y in diameter. They contain numerous small particles which are nuclei 
due to the frequent division of the original nuclear material, and the 
capsule is much thicker. At the end of a week the parasite contains a 
large number of slender thread-like rods with pointed extremities, each 
one of these rods having nuclear chromatin. The parasite or oocyst 
projects through the wall of the intestine into the coelom cavity of the 
mosquito host, and when it ruptures these minute rods or sporozoites 
are carried by the lymph currents to the salivary glands, from which 
they may be injected with the saliva when the female Anopheles bites 
another subject. 
The sporozoites, after entering the circulation of man, attack the 
red cells, and become the small amoeboid forms described above. In 
two or three weeks the formation of the gametes takes place, and the 
crescent forms appear in the blood. 
That the infection of man in this way is possible has been abundantly 
1 MacCallum, "On the Hsematozoan Infections of Birds," Jour, of Exp. Med., vol. iii., 1898, p. 
117. 316 
THE INFECTIOUS DISEASES 
proven by allowing mosquitoes infected with sestivo-autumnal organisms 
to bite healthy persons, who, after a period of incubation of about ten 
days, are seized with an sestivo-autumnal type of fever, and the char- 
acteristic organisms, though not present previously, are now to be 
found in the blood. The mature forms of gametes of the tertian and 
quartan fevers undergo a course of development very similar to that of 
the sestivo-autumnal fever, and are derived from the blood qf the infected 
patient by the female of the same genus of mosquito, the Anopheles 
(Plate I., Figs. 19 and 30). The sporozoites find their way to the sali- 
vary glands of the mosquito and enter the blood of the person infected 
while the Anopheles is biting. These sporozoites then enter the red 
cells as the small amoeboid forms and carry on the sexual cycle in the 
blood until either the tissues of the body finally overcome the parasite, 
or treatment with quinine destroys the merozoites by means of its toxic 
action on these immature forms.1 
Methods of Examination of the Blood in Malaria. 
There are two methods of examining the blood for plasmodia, in fresh preparations 
and in stained smears. Both require considerable training, as the artefacts produced 
by imperfect technique have often been mistaken for organisms. 
The Examination of Fresh Blood.-To examine the fresh blood, a puncture 
is made in the pulp of the finger and a perfectly clean cover-glass just touched to the 
top of the drop of blood which exudes from the puncture. The cover is then dropped 
without pressure on a clean slide. The diameter of the drop on the cover-glass should 
never exceed 2 mm., because if more be taken the corpuscles cannot spread out in a 
perfectly thin layer, but will overlap each other and the preparation will be useless. 
The search for the organism should be made with a one-twelfth oil-immersion lens and 
a moderate illumination. The organisms are best recognized by the actively motile 
pigment in the clear, highly refractile cell body. 
The Examination of Blood After Fixation.-If the examination cannot be 
made at once, stained preparations may be made. The smear should be made on a 
slide or large cover-glass. It is best fixed in strong methyl alcohol for three minutes. 
The organisms are most satisfactorily demonstrated by stains which color the chro- 
matin as well as the protoplasm. For this purpose a very satisfactory stain is that 
devised by Giemsa.2 The staining solution contains azure eosin and azure II dissolved 
in glycerin and methyl alcohol. It is difficult to prepare and had best be bought from 
Griibler. It must be kept in tightly stoppered bottles. 
In order to stain a fixed blood smear, a dilution of the stock solution is made by 
adding 1 drop of the dye to 1 c.c. of distilled water. If the smear is on a cover-glass, 
10 c.c. of the dilution should be placed in a shallow dish and the cover floated, blood 
side down, on the mixture. For staining slides a Coplin jar is convenient. As this 
holds about 50 c.c., 50 drops of the concentrated stain should be added slowly to the 
water with constant stirring with a glass rod. The slides are left for an hour, then 
washed with a strong stream of water, dried in the air without heat, and mounted 
and examined. If intended for permanent preservation they should be embedded in a 
neutral gum dammar dissolved in xylol. Slides more than a few days old do not stain 
1 A general bibliography of malaria to 1895 is contained in the excellent monograph of Thayer and 
Hewetson, "The Malarial Fevers of Baltimore," Johns Hopkins Hosp. Rep., vol. v., 1895. The more 
recent literature, especially that relating to the development of the organisms in the mosquito, is in 
Marchiafava and Bignami, article "Malaria" in "Twentieth Century Practice," New York, 1900, 
and also Liihe, " Neuere Sporozoenforschung," Centralbl. f. Bakt., Bd. xxvii., pp. 367 and 436, and Bd. 
xxviii., p. 384, 1900. For a study of structure and biology of Anopheles see Nuttall and Shipley, Jour, 
of Hyg., vol. i., p. 4, 1901. For practical directions for the identification and study of mosquitoes see 
Alcock, Entomology for Medical Offices, London, 1911. 
2 Giemsa, Centralbl. f. Bakt., I Abt. Orig., 1904, xxxviii., 308. THE INFECTIOUS DISEASES 
317 
well. After a year it is necessary to use a more dilute stain and afterward decolorize 
with distilled water or even methyl alcohol, as the blue component overstains all the 
cells. 
By adding an equal volume of pure methyl alcohol to the stock solution of the 
Giemsa stain, it is possible not only to shorten the time, but also to avoid separate 
fixation of blood smears.1 
The blood smear is placed in a Petri dish and 10 to 15 drops of this new mixture 
are placed on the slide and allowed to act for half a minute. About 10 to 15 c.c. of 
distilled water are poured into the Petri dish and the whole is agitated until the stain 
is thoroughly diffused through the entire fluid. The slide remains in this mixture for 
five minutes. A longer period increases the intensity of the stain. 
A simpler method has recently been published,2 which is better adapted for clinical 
work. The smear is fixed for two minutes or more in methyl alcohol, then stained for 
ten seconds with a 1 : 1,000 aqueous eosin solution, the latter allowed to run off the 
slide, and the smear again covered with a few drops of a 1 /4-per-cent. solution of 
methylene azure I. In about from five to fifteen minutes the staining is complete. 
The slide should be washed in distilled water, dried, and examined directly with an 
oil-immersion lens, no cover-glass being necessary. 
WHOOPING-COUGH. (Pertussis.) 
Whooping-cough is a readily communicable, infectious disease 
usually associated with catarrhal inflammation of the upper respiratory 
passages. It may be complicated by bronchitis or pneumonia. Hyper- 
plasia of the lymph-nodes of the laryngeal and bronchial districts may 
occur. Immunity is usually secured by an attack. 
The organism described by Bordet and Gengou3 seems most probably 
to be the specific agent. This organism is a small, ovoid, short bacillus 
showing irregular staining. It stains with some difficulty, requiring the 
use of dilute carbol-fuchsin or other strong stains to color it satisfactorily. 
Mallory4 has shown that the bacilli can be demonstrated in large 
numbers lying among the cilia of the tracheal and bronchial mucosa. 
The disease can be transmitted to young dogs and monkeys, with the pro- 
duction of the same lesions; and a complement fixation can be demon- 
strated between the organs and the blood of infected animals and of 
children suffering from whooping-cough. 
The poles often stain more deeply than the centres. The bacillus is 
negative to Gram. The organism is grown only with difficulty and upon 
a special medium of glycerinated extract of potato to which has been 
added an equal volume of sterile defibrinated rabbit or human blood. 
The organism is strictly aerobic and in ascitic broth may remain alive 
for some months.5 Bordet and Gengou report that a specific comple- 
ment fixation can be obtained in the serum of patients suffering from 
the disease. 
While the excitant of acute rheumatism is unknown, there is much 
reason to believe that some phases of it at least should be classed among 
ACUTE RHEUMATISM. 
1 Giemsa, Munchen, med. Wchnschr., 1910, Ivii., 2476. 
2 Wood, Medical News, vol. Ixxxiii., p. 248, 1903. 
3 Bordet and Gengou, Ann. de 1'Inst. Pasteur, 1906, xx., 731. 
4 Mallory and Hornor, Jour. Med. Research, 1912, N. S. xxii., 115; Mallory, Hornor, and Henderson, 
ibid., 1913, N. S. xxii., 391. 
5 Wollstein, Jour. Exper. Med., 1909, xi., 41. 318 
THE INFECTIOUS DISEASES 
the infectious diseases. There are no characteristic lesions; but various 
joints are frequently the seat of slight exudative inflammation, serous 
or fibrinous in character. Albuminous degeneration of the visceral 
cells with hyperplasia of the spleen has been noted. The disease is not 
infrequently complicated by endocarditis or pericarditis, by exudative 
inflammation of the lungs or pleura. Various micro-organisms have 
been found in the body in acute rheumatism; of these the pyogenic 
cocci have been most frequently isolated, but these are probably to 
be regarded only as excitants of the suppurative or other complications. 
It is possible that more than one form of infection is embraced under the 
designation rheumatism.1 
BERI-BERI. 
Beri-beri is a disease of warm climates, due to the use of rice from which the hulls 
have been removed. These contain a substance called a vitamine, which is apparently 
a simple organic compound. If the disease is not too far advanced it can be cured 
by adding fresh meat to the dietary.2 The lesions are often not well defined. There 
are in some cases subcutaneous oedema and dropsy. There is often degeneration of 
the peripheral nerves and of the heart and voluntary muscle. 
PELLAGRA. 
Pellagra is a disease especially of the rural districts, long prevalent in Europe, and 
now of serious extent and import in the southeastern portions of the United States. 
It is characterized by protean symptoms and lesions of the nervous, digestive, and 
cutaneous systems, such as neurasthenia, ataxias and paralyses; erythema and 
dermatitis; and profound disturbances of nutrition. It is not communicable, nor is 
evidence at hand that it is infectious. Its inciting agents or factors are not definitely 
known. But unbalanced food ration, some toxic substance or organism in the spoiled 
maize or Indian corn, which is often an important feature in the dietary of those 
affected, and many other factors and agencies are current in accounting for pellagra.3 
INFECTIOUS DISEASES OF UNKNOWN ORIGIN. 
Protozoa.-Notwithstanding the great increase in our knowledge of infection 
within the past few years, there are still several diseases obviously of this class whose 
inciting factors are unknown to us. We are now beginning to realize that we must 
not confine our search in this class of diseases to the bacteria alone; but that among 
the protozoa may be found most important infective agents. In this latter group of 
organisms the culture methods applicable to the bacteria do not furnish the necessary 
data for the establishment of etiological relationships. While the pathogenic signi- 
ficance of the malarial protozoan has been determined without cultures, and has 
1 For summary and studies of etiology of acute rheumatism see Cole, Jour. Inf. Dis., vol. i., p. 714! 
1904; Beattie, Jour. Med. Res., vol. xiv., p. 399, 1906; Frissell, Med. Record, vol. Ixix., p. 737, 1906- 
bibl.; Meakins, Med. and Surg. Repts. Presbyterian Hospital, N. Y., viii., 1908. For a study of the sub- 
miliary myocardial nodules of Aschoff, most frequently found in the walls of the left ventricle in 
rheumatic infection, see Thalhimer and Rothschild, Jour. Exper. Med., 1914, xix., 417 (bibl.). See also 
for bibl. of infective agents, ibid., p. 429. 
2 Vedder, Beri-beri, New York, 1913; Funk, Die Vitamine, Wiesbaden, 1914. 
3 See the books of Niles, 1912 and of Roberts, 1912, on Pellagra for summaries and bibl.; also 
resume by Bartholow, N. Y. Med. Jour. vol. xcviii., p. 1262, 1913; and First Report of the Thompson-Mc- 
Fadden Pellagra Commission of the N.Y. Post-Graduate Medical School by Siler and Garrison, Am. 
Jour. Med. Sci. vol. cxlvi., pp. 42 and 238, 1913. 
For rtsum# and bibl. of experimental work see Bailey and Miller, "Text-book of Embryology.'' 
1909. THE INFECTIOUS DISEASES 
319 
become probable on morphological grounds in several other diseases, the desirability 
of artificial culture methods in the study of protozoa is daily becoming clearer. But 
it is well to remember that many protozoa pass through complex life cycles so that 
simple cultures cannot be expected to yield as illuminating results as do cultures of the 
more lowly organized bacteria and yeasts. 
Ultra-microscopic Micro-organisms.-In the search for the inciting agents of 
infectious diseases which have as yet baffled investigation, it should be borne in mind 
that it is quite possible that bacterial and other micro-organisms may exist which are 
ultra-microscopic; that is, so small as to be invisible with such microscopic resources 
as we at present possess. In one instance, the infectious peripneumonia of cattle, 
Nocard and Roux by a special technique1 have been able to isolate an organism so 
small that its morphological characters could not be learned even with the highest 
available magnification/ Experiments with the filtration of infectious material, 
especially from certain communicable diseases of animals, through porcelain filters 
whose pores are so fine as to retain ordinary bacteria, have shown that the infective 
agent may pass these filters and, though revealing no morphological elements, is still 
virulent. Among the more important of the ultramicroscopic infective agents which 
have been found to pass the pores of porcelain filters are those inciting contagious 
pleuro-pneumonia of cattle, anterior poliomyelitis, yellow fever; foot-and-mouth dis- 
ease and rinderpest of cattle. The possibility of the existence of ultra-microscopic 
organisms must then be held in mind in our summaries of infectious diseases 
whose inciting factors, though persistently sought, are still unknowm.2 
THE INFECTIOUS DISEASES OF ANIMALS. 
The study of comparative pathology is of great and increasing importance, and 
already much light has been thrown on the nature of human diseases by the study of 
the diseases of the lower animals. 
The scope of this book does not permit of more than an occasional reference to 
animal diseases, but the reader may consult: Moore, "The Pathology of the Infectious 
Diseases of Animals," 1906; Nocard and Leclainche, "Les Maladies Microbiennes des 
Animaux," Paris, 1898, and Frieberger and Frohner, "Lehrbuch der speciellen Path- 
ologic und Therapie der Hausthiere," 1896; also Kitt, "Text-book of Comparative 
General Pathology," Eng. Trans, by Smith and Cadbury, 1906. 
BIBLIOGRAPHY OF THE INFECTIOUS DISEASES. 
For a fuller treatment of the themes considered in this chapter the reader may con- 
sult among the larger works: 
Kolle and Wassermann, "Handbuch der Mikroorganismen, " 3d edition, 1908-13. 
Kolle and Hetsch, " Experimentelle Bakteriologie u. d. Infectionskrankheiten," 
1906. Gives excellent summaries. 
Among the smaller works may be mentioned: 
Hiss and Zinsser, "Text-book of Bacteriology," 1914. This admirable work pre- 
sents a concise but comprehensive epitome of modern bacteriology, especially in 
those aspects which are of practical value to students and practitioners of medicine. 
Park and Williams, "Pathogenic Bacteria and Protozoa," 1910. Presents impor- 
tant hygienic and public-health aspects of the subject. 
1 For a description of coilodium sacs used in the study of ultra-microscopic organisms, agglutina- 
tion, and for other purposes see McCrae, Jour. Exp. Med., vol. v., p. 635, 1900; also Rosenau, " Labora- 
tory Technique," Bull. No. 7, Hygienic Labty., U. S. Marine Hosp. Ser., 1902. 
2 For a summary of investigations on infectious diseases of unknown origin see Hektoen, Jour. Am. 
Med. Assn., vol. xli., pp. 405 and 493, 1903; see also Roux, " Invisible Microbes," Bull, de 1'Inst. Pasteur, 
tome i., 1903, pp. 7 and 49, bibl.; see also Wolbach, Jour. Med. Research, 1912, N. S. xxii., 1. CHAPTER X. 
MALFORMATIONS. 
General Considerations. 
The classification of malformations is difficult, both because of the 
complexities of development not yet wholly understood, and because 
of our ignorance of many subtle phases of nutrition and inheritance in 
general. We shall here attempt little more than a catalogue of some of 
the more striking or common developmental defects, with a suggestion 
of grouping for convenience rather than for scientific accuracy.1 
The individual may be subject to abnormal conditions during embry- 
onic life which lead to changes analogous to those which the body may 
suffer from injuries after birth. But these various lesions are compli- 
cated in the embryo by the fact that it is in a state of active growth and 
development, so that even slight injuries to the embryo may result in 
malformations of the most extreme character, especially when the 
injuries are inflicted in the earlier periods of its life. 
Among the abnormal and harmful conditions to which the embryo 
may be subjected may be mentioned first those which relate to the 
mother, such as infectious or other diseases, disturbances of nutrition, 
psychic impressions, etc. To these may be added local interference 
with development, such as pressure upon the uterus, circulatory and 
other disturbances of the placenta and membranes, an abnormal accu- 
mulation of amniotic fluid, adhesions between the embryo and the 
membranes of the placenta, as well as various forms of trauma. 
On the other hand, there are many abnormalities in development 
which must be referred back to inherited defects transmitted through 
the maternal or paternal cells. 
While one may catalogue in a general way many of the conditions 
leading to malformations, the rationale of the process in many instances 
is still obscure. In recent times much light has been thrown on the 
subject by a host of experimental studies on the ova of the lower animals 
by shaking, dissection, and other mechanical interferences. But into 
this field the scope of this book does not permit us to enter. 
i Many malformations are so extreme or involve such vital organs 
that extrauterine life is impossible. Such are some of the malformations 
of the nervous system or of the circulatory apparatus, occlusions of the 
1 The reader is referred for details to Thoma, "Pathology and Pathological Anatomy," Eng. Trans., 
bibl., or to other special works, such as Marchand, "Missbildungen," in Eulenburg's Real Encylopadie 
der gesammten Heilkunde, Bd. xv., 1897, and Schwalbe, "Die Morphologic der Missbildungen des 
Menschen und der Tiere," 1906 to 1913; Ballantyne, Manual of Antenatal Pathology," 1902 and 1904. 
For a discussion of the embryological side, see Broman, Normlae und abnorme Entwicklung des 
Menschen, Wiesbaden, 1911. 
320 MALFORMATIONS 
321 
gastro-intestinal canal, etc. Some of the abnormalities of development, 
on the other hand, while not fatal, predispose to disease. Such are the 
embryonal displacements of groups of cells which predispose to tumor 
formation. It is customary to speak of the lesser defects as congenital 
anomalies. Such are congenital angiomata, naevi, and certain dermoid 
cysts. 
Malformations may involve a single individual or embryo or they 
may concern two or more, which are variously united. 
Malformations Involving Single Individuals.1 
The types of such malformations are various. Thus, there may be 
a failure to develop a part or organ. This is called aplasia or agenesia. 
For example, the upper or lower extrem- 
ities may be absent (Fig. 174). 
When an organ or part is formed, but 
remains small or undeveloped, we speak 
of hypoplasia. A common example of 
this is the hypoplasia of the aorta in the 
status lymphaticus (see p. 439). 
Sometimes a part of the body re- 
mains at an early developmental stage. 
Under these conditions, however, the de- 
velopmental arrest may not involve ces- 
sation of growth. Examples of this form 
of lesion are the various fissures and clefts 
which occur in the median line or other 
parts of the body, due to some interfer- 
ence with the closure of the invaginations 
of the germinal layers which should take 
place at an early foetal period-the me- 
dullary groove, intestinal groove, facial 
and branchial clefts. 
From fissures in the facial region arise 
such malformations as absence of the 
whole or parts of the face (Fig. 175), 
various forms of harelip (Fig. 176), etc. 
Defects of closure in the cervical and 
thoracic region lead to many forms of 
fissures, fistulse, cysts, etc., of the neck 
and chest, such as the so-called branchial 
cysts, branchial fistulse, auricular appen- 
dages, tracheal fistulee. The lower jaw may be absent (agnathia). 
Under these conditions the mouth may be represented by a small opening 
and the ears are placed low down and near the median line (synotia) 
Fig. 174.-Abbachius. 
The arms are absent. 
1 Many of the developmental defects occurring in a single foetus are considered somewhat more 
in detail in the part of this work dealing with the special organs, to which the reader is referred. 322 
MALFORMATIONS 
Fig. 175.-Facial Fissure. 
Owing to imperfect union in the anterior median line of the body, in the facial region the larger 
irregular cleft persists. There is also absence of the vault of the skull-cranioschisis. 
Fig. 176.-Double Harelip. 
There is bilateral fissure extending into the hard palate. MALFORMATIONS 
323 
(Fig. 177). There may be fissure of the sternum, sometimes with pro- 
trusion of the thoracic viscera, among others the heart-ectopia cordis. 
Fissure of the diaphragm may occur with that of the sternum and per- 
mit displacement of the abdominal and thoracic viscera. The imperfect 
closure of the abdominal wall leads to various forms of lesions. Thus 
The rudiments of two eyes are fused and occupy a common orbit. A wart-like process lies above 
tfie orbit. The lower jaw is absent-agnathia. The mouth is small. The ears are low and near the 
middle line between the upper jaw and the neck-synotia. 
Fig. 177.-Synophthalmia, Agnathia, and Synotia. 
there may be a patent urachus, the formation of a Meckel's diverticulum 
(see p. 667), umbilical hernia, or, when there is large deficiency of the 
abdominal wall-complete abdominal fissure-there may be prolapse 
of the abdominal viscera (Fig. 178). Fissure of the lower portion of the 
abdominal wall may lead to prolapse of the bladder, and the bladder 
itself may be fissured so that the interior of the prolapsed organ is 324 
MALFORMATIONS 
exposed-inversio vesicce. Such fissures in the anterior median line 
may involve the urethra, leading to epispadias or hypospadias. 
A failure of the walls of the medullary groove in the posterior median 
line of the body to fuse properly leads to significant malformations of 
the central nervous system. This failure may be complete-cranior- 
rhachischisis totalis (Fig. 179). There is a wide irregular groove involving 
the dorsal aspect of the head and trunk. In this condition, however, 
Prolapse of the abdominal viscera through imperfect closure of abdominal wall. 
Fig. 178.-Abdominal Fissure. 
the anterior portions of the brain, with the nose and eyes, may be formed, 
though distorted. 
But there may be only a partial failure in the closure of the medullary 
groove, limited to longer or shorter segments, especially in the cervical 
and sacral regions. Thus arise various forms of myelomeningocele, in 
which, the pressure from within not being sustained by vertebral arches, 
often forces the skin and underlying soft parts outward in the form of a 
pouch or sac (Fig. 180). 
A local failure in the closure of the anterior portion of the medullary 
groove may lead to many malformations of the brain-cranioschisis, 
hemicephalia, acrania-and to various forms of meningocele. Thus in MALFORMATIONS 
325 
fissures of the skull there may be prolapse of parts of the brain and its 
membranes, forming with the enclosing skin pendent pouches of various 
forms-encephalomeningocele (Fig. 181). The vault of the skull may 
be absent, and on the base there may be small amounts of brain substance, 
or this may be entirely absent-anencephalia (Fig. 182). For the 
details of these lesions we must refer to the chapter on the Nervous 
System and to special works on malformations. 
In many of the developmental lesions of the brain, the anterior 
parts, especially the optic vesicles and the olfactory bulbs, are often 
A failure to close of the medullary groove along a portion of the posterior median line. 
Fig. 179.-Craniorrhachischisis. 
but little affected. But we may note here one of the striking mal- 
formations which results in the fusing of the eyes into one placed in 
the forehead near the median line. This condition is called synoph- 
thalmia or cyclopia (see p. 927). 
Finally, there may be an arrest of development, more or less com- 
plete, of the brain or some of its parts-micrencephalus. 
In one phase of malformation involving single individuals, paired 
organs may be grown together, for example in the so-called "horse- 326 
MALFORMATIONS 
shoe kidney" (Fig. 183). Or single organs may retain lobular forms 
belonging to an early period of life-tabulated kidney. 
There may be supernumerary parts, such as fingers, toes, etc., or 
organs-spleen, adrenals, lungs, pancreas. There may be fusion of 
fingers and toes, frequently involving all of the extremities. Various 
congenital malformations commonly due to arrest of development are 
exemplified in the diverse phases of "club-foot"-talipes-and "club- 
hand "-talipomanus. 
Foetal structures which in the normal development should make way 
Fig. 180.-Myelomeningocele Sackalis-Spina Bifida. 
From a partial failure in the closure of the medullary groove, this sac is formed containing fluid and the 
lower portion of the spinal cord. 
for adult organs may persist. Thus the urachus, the Wolffian ducts, 
parts of the branchial clefts, may remain. 
Through adhesions of the membranes or by abnormal winding of 
the umbilical cord about the neck or the extremities (Fig. 184), partial 
decapitation or amputation of a limb may take place (Fig. 185). So 
also by adhesions of the surface of the embryo and the placenta or 
the membranes, various disturbances of growth may occur. MALFORMATIONS 
327 
Normal and Pathological Conditions in which Two or More Individuals 
Develop Together. 
Two or more individuals may develop together, the bodies being 
separated as in normal twins, triplets, etc., or the individuals being more 
or less closely joined or merged. This duplication may be evident, so 
that the nature of the complexity is clear; or one of the individuals 
may develop greatly in excess of the other. 
There is afissure on the posterior aspect of the skull, out of which the imperfect brain and its membranes 
protrude, filling the pouch of the scalp. 
Fig. 181.-Encephalocele. 
Twins, Triplets, etc.-Pregnancies may be complicated by the devel- 
opment in the uterus of two or more embryos. These are called twins, 
triplets, etc. This duplication may arise by the development of separate 
ova or the formation of more than one embryo from one ovum. 
Twins and triplets developed from one ovum-homologous twins- 
are always of the same sex; and if both develop normally they usually 328 
MALFORMATIONS 
closely resemble each other. But the individuals, if born alive, often 
do not develop equally; one may be less well nourished than the other, 
from a disturbance of the vascular supply, for example. 
One of the twins may die early in pregnancy and suffer varying 
degrees of degeneration into a shapeless mass, or may die later and be 
born prematurely or at the delivery of the living twin (Fig. 186). Some 
of these abortive forms are without a heart or have only a rudiment 
of that organ. These are called acardiac monsters (foetus acardiacus) 
They may consist of connective tissue, rudimentary bones, and portions 
of intestine, and are covered by skin with hair-acardiacus amorphus 
Or there may be a more or less distinctly formed head without a corre 
Fig. 182.-Cranioschisis. 
The vault of the cranium is absent. There is a small reddish mass at the base representing the rudi- 
ment of a brain. 
spending trunk-acardiacus acormus. There may be a fairly well 
developed trunk with viscera and a rudimentary heart, but no head- 
acardiacus acephalus. Finally, there may be a relatively well developed 
trunk with defective extremities and a rudimentary heart-acardiacus 
anceps. 
In all of the above duplications the fusion is confined to the placenta 
and its appendages, the bodies of the twins being separate. 
Double Monsters (Monstra duplicia).-The union to any considerable 
extent of the embryos themselves is pathological, and the malformations 
are classified as double monsters. 
In these unions of twins there may be: 1, complete duplication 
of the axis of the germinal area, so that there is a double development 
of the central nervous system, while the remaining parts are more or MALFORMATIONS 
329 
less fused; or, 2, there may be only a partial duplication of the axis, 
so that either of the head or in the sacral region there may be double 
development, while at the other extremity the body is single.1 
We shall now look briefly at some of the forms of double monsters 
in which the individuals are more or less symmetrically united. 
There may be fusion of the bodies in the thoracic region. The 
ensiform processes are united by cartilage, union of the soft parts extend- 
ing over the umbilical region. The thoracic and abdominal cavities 
The kidneys are in place in the body of the young child. They are lobulated with the large adrenals 
above them. 
Fig. 183.-Horseshoe Kidney. 
are separate. This malformation is called xiphopagus. Such were 
the celebrated Siamese twins who lived to the age of sixty-three. In 
other cases there is a common thoracic cavity, usually with two hearts 
and two pairs of lungs more or less malformed (Fig. 187 and Fig. 188). 
The abdominal cavities may also be united. Parts of the intestine may 
be common to both twins. These monsters are called thoracopagus. 
They do not long survive birth. The fusion may, however, extend 
1 See Thoma, l.c., foot-note p. 320. 330 
MALFORMATIONS 
upward so that two upper extremities may fuse-thoracopagus tribra- 
chius; or two of the lower extremities may fuse-thoracopagus tripus; 
or, finally, the fusion may embrace the head so that the faces are more 
or less united-prosopothoracopagus. The cephalic and thoracic regions 
may remain separate while fusion takes place from the umbilicus to the 
pelvic region. The spinal column is duplicated while there is a common 
pelvic ring-ischiopagus. 
There may be fusion of the otherwise separate twins in the cranial 
Fig. 184.-Foetus, with Umbilical Cord Coiled Around the Neck and Leg. 
region-craniopagus. The union is usually only of the scalp and cranial 
bones. 
The head and the upper part of the body may be single, or the head 
alone may be single, while the abdomen and pelvis are separate. There 
may be four or less lower extremities. Such malformations are called 
dipygi. 
There may be union of the head, neck, or chest, so that there are two 
faces more or less symmetrical looking in opposite directions-janiceps 
or janus. MALFORMATIONS 
331 
In cases in which there is only a partial duplication of the axis, this 
may be most marked at the cephalic or caudal extremity. Thus may 
be formed an individual with duplication of the face-diprosopus. Thus, 
depending upon the degree of duplication, arise diprosopus distomus; 
d. diophthalmus; d. triophthalmus; d. tetraophthalmus. But this anterior 
duplication may extend to the whole head. Thus arise the two-headed 
monsters-dicephalus-which according to the degree of duplication 
Fig. 185.-Partial Intra-uterine Amputation of the Leg. 
of the upper extremities are called dicephalus tribrachius; dicephalus 
tetrabrachius. 
Finally, the bodies are united posteriorly in the region of the sacrum 
and coccyx. This malformation is called pygopagus. The individuals 
may live for years. 
In the double malformations which we have thus far considered 
there has been a more or less symmetrical development of the physically 
joined twins. But for various reasons it often happens that one of the 
individuals is arrested in its development, while the other continues. 
This condition is analogous with that already considered in which the 332 
MALFORMATIONS 
arrest of development involved an independent acardiac individual 
which was not viable. But in the present case the arrested twin is 
joined to the other as a part of a living organism, and its life is thus 
maintained by the more favored relative. Under these conditions 
the more completely developed twin is called the autosite, the arrested 
embryo, the parasite (Fig. 189). 
The rudimentary structure, the parasite, may be variously developed. 
It may have extremities, various forms of tissue, nerve, muscle, intestine, 
Fig. 186.-Twins. 
The individuals are separate. One died early in utero and is only partially developed and mummified 
etc. It may be formed of a jumble of tissues with cystic cavities which 
may be lined with epithelium. Its size varies; it may be as large as the 
body of the autosite. Thus may be formed the parasitic thoracopagus, 
attached to the sternum, or the parasitic ischiopagus and parasitic 
craniopagus. So also are formed the epignathus, in which an acardiac 
parasitic rudiment is attached to the autosite in the facial region. The MALFORMATIONS 
333 
rudimentary embryo may be attached in the sacral region, forming 
sacral appendages or tumors-sacral teratomata. 
Finally, the second individual may be much less developed than 
in the cases which we have thus far surveyed, and may be represented 
Fig. 187.-Thoracopagus. 
only by formless appendages or by inclusions in different parts of the 
body, which are made up of various and often complex tissues-fibrous 
tissue, nerve tissue, bone, teeth, cartilage, muscle, glands. These are 
called teratoids, dermoids, fcetal inclusions, congenital teratomata. They 
may occur in the ovaries, or testicles,or about the head, in the medias- 334 
MALFORMATIONS 
tinum, or in the sacral region, and elsewhere. They often become 
cystic and may give origin to various forms of tumors. 
The teratomata are apparently derived either from impregnated 
polar globules or more probably from a portion of the blastoderm sep- 
arated at an early period from the cell complex which goes to form the 
Fig. 188.-Skeleton of Thoracopagus-Pig. 
developing foetus. The separated cells may long remain latent, finally 
beginning to grow with the power to form complex tissue and structure, 
but only in a jumbled mass, embraced within or attached to the developed 
individual. Some of the teratomata are comparatively simple in struc- 
ture. Their nature is often revealed by the heterologous character of 
their component structures. The ectodermal elements are often most 
conspicuous (see p. 358). MALFORMATIONS 
335 
We thus see in summary of this brief survey of complex malforma- 
tions in general that under normal conditions two or more individuals 
may develop together in the uterus-twins, triplets, etc. Under patho- 
logical conditions the individuals may be more or less united, forming 
double monsters. The duplex individuals may develop more or less 
Fig. 189.-Child with Acardiac Parasite Attached Posteriorly. 
One of the twins, the autosite, has developed; the other only partially. 
symmetrically with independent cerebrospinal axes and various degrees 
of union. Or the development may be very unequal, so that one is a 
more or less obvious appendage to the other. Finally, one of the indi- 
viduals may exist as a mere complex rudiment attached to or within its 
more favored mate. CHAPTER XI. 
TUMORS. 
The Nature and Characters of Tumors in General. 
The word tumor, which was originally applied to any swelling, has 
become more and more strictly limited in meaning until it is now com- 
monly used to designate certain more or less circumscribed new tissue 
growths or neoplasms. But the formation of new cells and new tissues 
is of such common occurrence under normal as well as under various 
abnormal conditions that it is desirable for us to fix, if possible, upon 
some features by which the tissue growths called tumors may be distin- 
guished from other normal or abnormal new-formed tissues. In the 
first place tumors, like all tissues formed in the body after embryonic 
ife, are produced by the proliferation of cells of normal types, each of 
ts kind. 
It would be well in this connection to remember that a given cell of whatever 
type, be it of connective tissue, muscle, gland, or nerve, can fully maintain the char- 
acters of its type only so long as the conditions of its life do not greatly differ from 
those under which by adaptation to environment the type was finally fixed. The 
characters of cells are largely shaped by heredity, and these characters are maintained 
with great tenacity, but both in form and function cells may be largely swayed by 
external influences. The marks of departure from the type in cells subjected to an 
unusual environment may be evident when expressed in form or structure, and some- 
times in function, but it is well not to forget that even our most refined methods of 
study of cells leave by far the greater part of their metabolic performances wholly in 
the dark, while we seem as yet to be only on the threshold of knowledge of their 
structural details. 
These considerations are especially important in the study of tumors as of all 
new tissue formations, because the key to our understanding of these lies largely in 
the appreciation of the fact that every cell in the differentiated tissues comes from a 
cell of the same type. But this, which is sometimes called the principle of legitimate 
succession in cells, assumes that the conditions under which the life of the new cell is 
maintained shall not depart too widely from the normal, that is, the usual. The 
bearing of this limitation will be evident as we proceed in our study of tumors. 
The capacity for cell proliferation is most marked in the embryo and 
during the earlier periods of individual life. When the body attains its 
development, the power of cell reproduction, as we have seen (see 
Regeneration, p. 64), is largely limited to special forms of tissues, such 
as connective tissue, the blood, and certain kinds of epithelium. This 
constant normal regeneration makes good the wear and tear of normal 
cell life. But here the capacity for multiplication in the cells is closely 
confined to the requirements of the body. A definite physiological con- 
trol is evident, similar in character to that under which in normal develop- 
336 TUMORS 
337 
ment the amount of new tissue is limited and its adaptation to the 
organism as a whole secured. 
Under normal conditions, furthermore, there may be a very large 
new formation of tissue under special physiological excitation, as in the 
mammary gland and the uterus in pregnancy. But here also the char- 
acter and amount and the functional capacity of the new tissue are 
strictly limited and subservient to the welfare of the individual. 
Let us now turn from these normal new tissues to those which are 
abnormal. We have already seen, especially in our study of inflamma- 
tion, that new tissues may form even in considerable amount under 
abnormal conditions, such as injury with subsequent repair; degenera- 
tions and destruction of parenchyma, prolonged hyperaemia, and in 
compensatory hypertrophies. But under these various conditions also 
the tissue growth is local, approximately typical in structure, usually 
limited in amount, and in most cases appears measurably to accord in 
nature and distribution with the maintenance of the structural integrity 
and general welfare of the individual. The new tissue, in other words, 
maintains under these varied conditions a definitely co-ordinated 
relationship to the body as a whole. 
While it is as yet impossible to define tumors in such a way as abso- 
lutely to distinguish them from such other new tissue formations as we 
have just cited, they are in general characterized by such independence 
and by such irregularity in growth both in structure and extent; by 
such a lack of relationship to the functional requirements of the indi- 
vidual;1 by such an emancipation from that subtle physiological restraint 
which limits cell growth and proliferation in the normal body, and in 
the new tissue formation in repair, that their distinguishing character 
is perhaps best indicated by the word autonomy, or by the more striking 
suggestions of the term cell-anarchy. 
The autonomous or independent character of tumors, as has been 
very clearly formulated by Thoma, is especially manifested in the dis- 
tinct limitation of the growth at the start; in the tendency to variation 
in the structural type; in various functional aberrations of the new cells; 
in their interference by compression or otherwise with adjacent parts; 
in their proneness to multiply through local or distant transplantation 
of cells; and finally, in their liability to various forms of degeneration and 
necrosis. Furthermore, the independent character of tumors is marked 
by the fact that the characteristic cells forming the tumor are the prog- 
eny of the earlier cells in which the tumor starts, so that the tissues 
in which the tumor may be placed share only in a secondary way in its 
structure. But tumors are of course dependent for their nutrition upon 
the general blood supply and upon the suitable conditions for growth 
which their situation among other tissues alone makes possible. 
The reason why we cannot more accurately characterize tumors in 
distinction from other new tissue formations is chiefly because we do not 
1 An example of a certain physiological independence in tumors is seen in lipomata, in which a 
large amount of fat tissue may persist in an ill-nourished individual whose fat has otherwise almost 
wholly disappeared; or in myomata of an extremely atrophied uterus. 338 
TUMORS 
yet know what are their immediate excitants. To this subject we shall 
presently return, but we must first look at the general characters of 
tumors. 
Tissue Types in Tumors.-Tumors, as we have seen, are composed of 
the same types of tissue as those normally existing in the body, and from 
the latter they are derived by a proliferation of pre-existing cells. Thus, 
tumors of the connective-tissue type originate in connective-tissue cells, 
of the epithelial-tissue type in epithelium, of muscle in muscle, etc. 
While the general types of tissue are maintained in tumors, there are 
many more or less well-defined departures from these. It should be 
remembered that the formation and maintenance of typical cell forms, 
and of typical topography in organs, are closely dependent upon many 
factors, for example upon mechanical pressure, nutritive conditions, 
relationship to surrounding parts, nerve relations, and many others. 
But under the conditions in which tumors grow, all these factors may 
suffer most significant disturbances, so that the shape, size, structure, 
and mutual relationship of cells, their grouping, gland types, and various 
functional characters, may suffer such modifications that great diffi- 
culties are often encountered in the attempt to classify tumors in accord- 
ance with the established tissue types. Tumor cells also depart from 
the type in that they often represent embryonic or reversion forms. 
Tumors are not only analogous to the normal tissues of the body in 
structure, but their life history is manifested under the same general 
laws of nutrition, growth, reproduction, etc. They are supplied with 
blood-vessels which grow into them from adjacent healthy parts, just as 
these do, for example, into granulation tissue, so that they may finally 
possess a more or less independent vascular system. 
The blood-vessels, however, especially of rapidly growing tumors, 
are in many respects' atypical and not as sharply differentiated into 
arteries, veins, and capillaries as are the vessels of normal tissues. Many 
vessels with wide lumina have thin walls, with few muscle or elastic 
fibres in them. Thus the blood-vessel system of such tumors is often 
made up of an irregular meshwork of vascular trunks, which in their 
branchings, anastomoses, width of lumen, and thickness and structure 
of their walls are quite abnormal, and in which the blood is conveyed 
in most unsystematic fashion from its diverse entrance channels to its 
irregular exits. The cells, especially of malignant tumors, often grow 
much more rapidly and are larger in the vicinity of blood-vessels than else- 
where (Fig. 203). Tumors have lymph-vessels, and some of them nerves.1 
The intercellular framework of tumors may be in a measure fur- 
nished by the connective tissue of the part in which they grow. The 
tissues by which tumors are connected with surrounding parts or are 
more or less definitely encapsulated, most commonly originate from 
without. The tumor in many instances bears the relationship of a 
foreign body to its surroundings, and a reaction to its presence is incited, 
quite analogous with that which we have already seen in the case of 
alien substances in an earlier chapter. 
1 For a study of nerves in tumors see Young, Jour. Exper. Med., vol. ii., p. 1, 1897, bibl. TUMORS 
339 
While the cell divisions by which tumors grow exhibit m general the 
same minute phenomena as does cell division in normal tissues (see p. 
66), abnormal mitosis is frequent. Thus it may be multipolar; the 
chromatic substance may 
present great irregularity 
in form and amount (Fig. 
42, p. 67); there may be 
incomplete nuclear divi- 
sion, or the new nuclei may 
vary in size and form. 
While all these abnormali- 
ties may occur in other new 
tissue formations and may 
be experimentally incited, 
they are unusually frequent 
in certain tumors and mark 
one of the ways in which 
the lawlessness of tumor 
growths is manifested. 
Degenerative and Destructive Processes in Tumors.-Tumor tissues 
are subject to the same degenerative changes as other tissues; they may 
become fatty or calcified, ulcerated, gangrenous, pigmented, etc. By 
Fig. 190.-Multiple Nodular Sarcomata of the Skin. 
Fio. 191.-Sarcoma of the Forearm. 
A tumor of the lobulated type. 
necrosis a tumor may be largely destroyed, though complete obliteration 
rarely occurs in this way. They are liable to undergo the ordinary in- 
flammatory changes, granulation tissue may form in them, and abscesses 
and cicatrices. 340 
TUMORS 
The rapidity of growth of tumors varies greatly; some grow very 
slowly indeed and may change but imperceptibly in size and appearance 
for years, while others grow so fast that they do not acquire solidity, and 
their elements remain in an incompletely developed condition and are 
thus more liable to destructive changes than are normal tissues. In 
healthy tissues the blood-vessels are supported by surrounding elements, 
which aid them in sustaining 
the blood pressure from within. 
In rapidly growing tumors this 
external support is often lack- 
ing, and, as the walls of the 
blood-vessels are themselves 
often badly formed, the result 
is that the walls are apt to be- 
come pouched or aneurismal, 
and they often burst, giving rise 
to larger or smaller interstitial 
haemorrhages. 
Shape, Size, and Modes of 
Extension of Tumors.-Tumors 
have various shapes: nodular, 
tuberous, fungoid, polypoid, 
papillary, dendritic, lobulated, 
etc. (see Figs. 190, 191, 192). 
Tumors may occur singly or 
in greater or less numbers in the 
same or in different parts of 
the body. If they be multiple 
they may have occurred simul- 
taneously or at different times 
as independent structures. Or, 
multiple tumors may occur as 
the result of the dissemination 
in the body, from a primary 
tumor, of cells which form a 
starting-point for new tumors. 
Many tumors are sharply cir- 
cumscribed, may be even encap- 
sulated, and influence surround- 
ing parts only by the pressure which they exert upon them. In this 
way they may cause displacement, atrophy, or necrosis; they may, by 
pressure on neighboring vessels, induce oedema, thrombosis, etc.; they 
may in the same way lead to dislocation and caries of bones. But 
tumors may damage their surrounding tissues by the phagocytic action 
of their cells, by the products of their perverted metabolism, imperfect 
secretions or degenerative material, or directly as foreign bodies. Thus 
various phases of inflammation and tissue destruction may occur in 
the neighborhood. Leucocytes may enter the tumor from without, 
Fig. 192.-A Nodular Polypoid Tumor- 
Fibroma-Hanging from the Vulva. TUMORS 
341 
and through these and other phagocytes the tumor tissue itself may 
suffer damage. 
Tumors may grow largely by increase of elements within them, thus 
simply expanding; this is called central or expansive growth. They may 
grow in part or largely at the surface-peripheral growth. In this case 
the growth may be a direct, continuous enlargement of the mass at or 
near the periphery, the tumor tissue growing in among the surrounding 
parts. In this case certain tumor cells, especially those of the connective- 
tissue type, may "emigrate" and may act as phagocytes. This is called 
infiltrating peripheral growth. On the other hand, peripheral growth 
may take place by the formation of secondary nodules near the primary 
growth, which, gradually enlarging, finally coalesce with the latter, 
forming a part of the nodular tumor. This mode of enlargement is 
called discontinuous peripheral growth, and is due to the dissemination 
of cells from the mother tumor into the adjacent tissue through the 
blood- or lymph-channels and their proliferation at the points of lodg- 
ment. This dissemination may occur by the agency of blood or lymph 
currents or by the amoeboid movements of the cells. Those new cells 
formed in tumors which are characteristic of the growth are, it should be 
remembered, all descendants of the cells in which the neoplasm starts and 
maintain their general type. But the old tissue of the part in which the 
tumor grows may remain with its vessels and form a matrix whose in- 
terstices are filled with the new tumor tissue; or the old tissue may 
furnish the starting-point for a new 
growth of a fibrous and vascular nutrient 
and sustaining stroma. 
Metastasis of Tumors.-All tumors 
are not limited, as we have seen, to that 
part or region of the body in which they 
first occur. Sooner or later secondary 
nodules resembling the first may be 
found in distant parts of the body, some- 
times singly, sometimes in great num- 
bers. These may grow like the parent 
tumor, and themselves form foci for new 
disseminations. 
This dissemination of tumors is one 
of the important elements of malignancy, 
and is called metastasis, the secondary 
tumors being called metastatic tumors. Metastasis usually occurs by the 
transportation of tumor cells through the blood or lymph channels (Fig. 
193). Since the tumor itself may contain new and badly formed blood- 
and lymph-vessels, and its structures be in close contact with the vessels 
of the tissue in which it grows, the cells of the primary tumor may, by 
ulceration through or by atrophy of the walls, readily find their way into 
the lumen of the vessels and be swept away by currents as emboli, and, 
finding lodgment, proliferate and grow, forming secondary tumors; or 
the proliferation may occur in the vascular endothelium itself, when the 
Fig. 193.-A Tumob-cell Embolus 
Growing in a Blood-vessel at a Dis- 
tance from the Primary Carcinoma in 
the Mamma. 342 
TUMORS 
formation of emboli is easy to understand. When carried through the 
lymph-vessels the tumor cells may for some time be kept from the larger 
channels and from general dissemination by lodgment in the lymph- 
nodes, where they may establish independent tumors. 
The tumors in which metastasis most frequently occurs are, as a 
rule, those which grow rapidly, are vascular and succulent, and contain 
many cells in proportion to their sustaining connective or indifferent 
tissues. The parts of the body in which metastatic tumors are most 
apt to form depend, of course, upon the situation of the primary tumor 
and the distribution of the vascular channels through which dissemina- 
tion occurs in accordance with the general principles of embolism. 
Another form of metastasis is seen in the dissemination of tumors over 
serous surfaces, the peritoneum for example, in which the mode of dis- 
tribution from a primary ulcerating tumor may be obvious. An inter- 
esting example of this type of metastasis is the frequent bilateral oc- 
currence in the ovary of metastatic carcinomata originating from the 
mucous membrane of the stomach. In many of these cases no macro- 
scopic growths can be found on the surface of the peritoneum and the 
tumor in the gastric mucous membrane may be very small, although 
the ovary shows extensive involvement. The possibility of implanta- 
tion of tumor cells upon the skin or mucous membranes should also be 
mentioned. 
Metastasis affords one of the most noteworthy examples of the great 
proliferative capacity of the cells of malignant tumors. For in the 
metastasis of normal tissue cells, such as not infrequently occurs after 
injuries to the bones or the liver, for example-the so-called parenchyma- 
cell emboli-the transported cells usually soon die and are disposed of as 
foreign bodies. But the exalted proliferative capacity of detached 
tumor cells enables them, in spite of adverse conditions, to establish and 
maintain fresh foci of vigorous tissue growth.1 
The Malignancy of Tumors.-Not less variable than the size, mode of 
growth, and structure of tumors is their significance in the organism. 
It is customary to classify tumors, for practical purposes, as malignant 
and benign, and for a long time malignant tumor and cancer or carcinoma 
were synonymous terms. Now we know that other tumors as well as 
carcinomata are malignant, and, furthermore', contrary to the former 
belief, that malignancy does not depend upon any specific extracellular 
agent in the tumor. By the malignancy of a tumor is not meant merely 
the gravity of its presence, for a simple fat tumor, by pressing on the 
trachea, may lead to suffocation, and any tumor may secondarily cause 
death by haemorrhage. The more obvious marks of malignancy in a 
tumor are: 1. Invasion of adjacent tissues by eccentric or peripheral 
growth. 2. The tendency to local recurrence after removal. 3. The for- 
mation of metastases. 4. An interference with the nutrition and general 
well-being of the body, which may give rise to a condition known as cachexia. 
The modes of invasion of surrounding tissues and the formation of 
1 For a study of metastasis in histologically benign tumors see Borrmann, Ziegler Beitr., Bd. xl., 
p. 372, 1906. TUMORS 
343 
metastases have been considered above. The tendency to local recur- 
rence after removal is probably, in most cases, due to the incomplete 
removal of the peripheral infiltrating cells. These may be very few in 
number and lacking in characteristic structural features, but they are 
none the less endowed with the capacity of proliferation and develop- 
ment into a new and similar tumor at or near the seat of the one extir- 
pated. The infiltrating peripheral cells may remain dormant for a long 
time after an operation, or may immediately commence to grow. But 
the mere fact that a second tumor develops in the place of one removed 
does not imply malignancy, since this may result from a continuance of 
the conditions which induced the first. 
The drain upon the system by the rapid growth of a tumor, together 
with the absorption from it into the body of deleterious materials, from 
sloughing, ulceration, and degeneration, or the occurrence in it of local 
infection with various micro-organisms may give rise to fever and other 
constitutional disturbances. Or, the tumor may induce feebleness, 
anaemia, and that general impairment of the nutritive functions of the 
body known as cachexia. This condition is frequently rendered worse 
by the mental status of the patient in the presence of such a traditional 
object of alarm. 
It should be remembered, however, that so long as they are localized 
and have not undergone degenerative changes, even the most malignant 
tumors do not usually give rise to a cachexia, since the drain upon gen- 
eral nutrition by their simple growth is not, under ordinary conditions, 
very great. When the system is deteriorated by the absorption of septic 
materials from tissue degeneration, however, this may become a very 
important factor. 
This condition of cachexia, with our present knowledge, so evidently 
secondary to the growth and degeneration of the tumor, was formerly 
termed a dyscrasia or diathesis, and was supposed to precede and induce 
the growth of malignant tumors, particularly cancers. 
It will be seen from what has been said about malignancy in tumors 
that the distinction between the malignant and the benign, while of 
great practical importance, is not fundamental, since the elements of 
malignancy are largely factors of the mode and extent of growth, and 
all tumors at an early stage are in a clinical sense benign. It is in the 
last analysis by their apparently almost unlimited potency of growth 
that the malignancy of tumors is marked.1 
It is finally to be noted that the fragments of tumors which have 
found access to the vessels may act as simple emboli leading to imme- 
diate death, or, if infected, may incite metastatic abscesses. 
It was formerly supposed that the cells of malignant tumors, particularly of 
carcinomata, had a characteristic structure and appearance, and that by the examina- 
tion of single or of a few separated cells the nature of the tumor could be determined. 
From the above considerations it will be evident, since all tumor cells have their pro- 
totypes in the normal body, that there is nothing pathognomonic in the appearances 
of single cells. It is by a study of the general structure and of the topography of 
1 See potency of growth in transplanted tumors, p. 354. 344 
TUMORS 
tumors as well as of the characters of the individual cells, that we are enabled to 
determine their nature. And even then we must often bring to our aid the clinical his- 
tory and gross appearances of the growth before a definite conclusion can be reached. 
We may indeed sometimes, aided by the clinical history or gross appearances, be 
able, by microscopical examination of scrapings from a tumor or of fluids from an 
internal cavity in which it is growing, to form a reasonable conjecture regarding its 
nature. As a rule, the peripheral portions of the more rapidly growing tumors are 
best adapted for microscopical examination, because here secondary degenerative 
changes are less likely to have occurred than in the central parts. 
Etiology of Tumors. 
The etiology of tumors is one of the most complex and in many ways 
difficult subjects in general pathology, and with the limitations which 
the character of this work imposes we can touch only briefly upon some 
of its more important aspects, referring to more extended works and to 
monographs for a vast amount of statistical and experimental data. 
General Conditions Relating to the Occurrence and Growth of Tumors. 
-We shall first consider some of the general conditions which seem 
to have a bearing upon the occurrence of tumors. 
Age.-While it may be said in general that tumors are most frequent 
in adult and advanced life, it is noteworthy that tumors of the connective- 
tissue type are -apt to develop earlier, while the epithelial tumors are 
more frequent in the later periods. Thus, in one thousand and sixty- 
three cases of epithelial tumors analyzed by Gallard, only six occurred 
in the first ten years of life. The most common situation of tumors 
differs also in the young and in the old. Thus, in the earlier years, as 
statistics show, the most frequent seat of tumors is the eyes and their 
adnexa, the kidneys, bones, and testicles; whereas in adults and the 
aged, the stomach, uterus, liver, and mamma are most commonly 
involved. Carcinoma of the rectum, however, is an exception, for it is 
relatively frequent in early life. 
Sex.-Sex is also a significant factor in the development of tumors, 
especially of those which are malignant. Thus, in general, it may be 
said that the statistics indicate malignant tumors to be about twice as 
frequent in females as in males. This proportion, howevey, does not hold 
good for tumors of the individual organs. For example, tumors of the 
stomach and of the tongue and lips are more frequent in men than in 
women. On the other hand, tumors of the breast are far more common 
in women than in men. 
Heredity.-While the influence of heredity is difficult to estimate 
accurately, there are a few recorded instances of the remarkable preva- 
lence of malignant tumors in families within a few generations. The 
general facts, however, are not so striking. The statistics of Williams 
showed that in two hundred and thirty-five cases of carcinoma of the 
uterus or breast, about nine per cent, gave a history of carcinoma in 
father or mother, while in nearly twenty per cent, there was evidence of 
carcinoma in the family. In the estimates of other observers, the heredi- 
tary influence seemed evident in about one-third or one-fourth of the 
cases. It is, however, instructive in this connection to note that in a TUMORS 
345 
study by Snow of seventy-eight healthy persons there was evidence of 
carcinoma in the family in about one-fifth of the cases. In the mouse^ 
at any rate, it has been demonstrated that animals of recent cancerous 
ancestry are more apt to develop the disease than those of less pro- 
nounced taint (page 354). 
It is clear, therefore, that while such statistics are suggestive and on 
the w'hole indicate that an hereditary predisposition to the development 
of tumors may exist, this does not in any way account for the immediate 
incitement of the growth of tumors, and is indeed, as Menetrier has urged, 
but one of many examples of hereditary predisposition which is observed 
in many forms of disease, such as infections, cerebral apoplexy, etc. 
The influence of climate, food, race, and social condition has been 
invoked as bearing upon predisposition to the growth of tumors; but 
the evidence is not convincing that these are very significant in etiology. 
Local Predisposing Factors in the Development of Tumors.-When 
wre turn from the general to the local conditions bearing upon the origin 
of tumors, we find an imposing array of instances in which tumors, and 
especially malignant tumors, follow local injuries, either mechanical or 
toxic, or are associated with chronic inflammatory processes. Bruises 
or contusions, particularly those involving the bones, are not infre- 
quently followed by malignant tumors, and it is noteworthy that these 
tumors are most apt to be of the connective-tissue type-sarcoma, 
osteo-sarcoma, chondroma, etc. Epithelial tumors, on the other hand, 
are more frequently developed at the seat of repeated injury or long- 
continued irritation. Thus, epitheliomata are common in the mouth, 
near a rough ulcerated tooth, on the lips of pipe smokers, and on the 
abdomen in Hindus owing to irritation produced by fire baskets which 
they wear about the body, at the edges of chronic ulcers, on the skin of 
workers exposed to various chemical or mechanical irritants, in cicatrices, 
at the orifices of the stomach and at the anus. Finally, the frequent 
occurrence of carcinoma of the liver with cirrhosis, though less easy of 
interpretation than many instances of the association of tumors with 
chronic inflammation, is worthy of notice in this connection. 
Before concluding this brief survey of the relationships of tumors to 
trauma, prolonged irritation, and chronic inflammation,1 it may be wise 
to remind the reader that undue significance should not be attached to 
this occasional association, since in the great majority of cases these 
conditions are not followed by tumors, nor, furthermore, has it ever been 
possible to induce genuine tumors experimentally under these readily 
secured conditions in animals. The bearing of trauma upon the origin 
of tumors is to be held in mind in estimating the influence of sex, since 
males are in general more liable to injuries than females. 
The relatively common development of tumors in pigmented and 
other naevi of the skin illustrates the significance of local malformations 
as predisposing factors in the origin of tumors.2 
1 For an interesting study of the relationship of trauma to malignant tumor formation see Brosch, 
Virchow's Arch., Bd. clxii., p. 32, 1900, bibl. 
2 It should be remembered that many of the complex tissue growths often reckoned among tumors 
and called teratomata are really embryonic rudiments of another individual. While such rudimentary 346 
TUMORS 
Several cases have been recorded in which through injury there has 
been a mechanical displacement of cells-heterotopia-from which in 
their new situation tumors have developed. These cases, which have 
been in a measure paralleled by experiments in animals, illustrate an 
important class of congenital tumors, often cystic in character, which 
arise from embryonal cell displacement, or, as is the case in many of the 
tumors of the neck at the site of the branchial clefts, from an imperfect 
closure of embryonal openings. 
Cohnheim's Hypothesis of Superfluous or Displaced Embryonal Cells.- 
We have seen that such evident malformation as the nsevi of the skin 
may form the starting-point of malignant tumors. We know that in 
many cases cells or tissues or parts of organs displaced during embryonal 
life, as in the branchial clefts or in the kidney, may later develop into 
tumors. Cohnheim has gone further than this and framed an hypothesis 
to the effect that all true tumors arise in faulty embryonal develop- 
ment. In accordance with this hypothesis, cells which in the course of 
the development of the body may be displaced or become superfluous 
or do not undergo the usual differentiation, may remain for long periods 
unaltered but liable in later life, from whatever reason, to commence 
growing with all the potencies of lowly organized cells, in the midst of 
the mature tissues. The apparent influence of heredity in the occurrence 
of some tumors, the congenital nature and early development of others, 
their atypical structure in general, the formation in one organ of tumors 
of types belonging to another, for example adrenal tumors in the kidney, 
and the tendency of many forms to occur in situations in which during 
the development of the embryo considerable complexity exists, as well 
as their frequent primary multiplicity-all of these characters of tumors 
lend considerable plausibility to Cohnheim's hypothesis, and it appears to 
be applicable in certain cases. But it still lacks a morphological basis, 
since no one has seen the postulated, strayed, or dormant embryonic 
cells; again, it by no means follows because tumors often develop at 
the seat of malformations or may arise in embryonal heterotopias that 
all tumors are thus associated; and finally, the frequent origin of epi- 
theliomata in cells which have been formed in adult life, in cicatrices, 
for example, is evidence that this hypothesis is not in any event of 
universal application. 
We have now reviewed a series of conditions which appear more or 
less directly to bear upon the development of tumors: general conditions, 
such as age, sex, hereditary influences, etc.; local conditions, such as 
congenital or acquired malformations, injuries, long-continued irritation, 
inflammatory processes, surplus or displaced embryonal cells with 
foetal potencies of growth. But when all these are taken into the 
account, we do not appear to have gained a definite clew to the immediate 
actual excitant of the new growths. Given any or all of the varied 
predisponents, why do the cells, which under any of these favoring con- 
embryos may be large and present such diversity and arrangement of tissue as to render the character 
of the growth obvious, they may, on the other hand, be very simple in character, as in some of the so- 
called dermoid cysts. These are all to be regarded rather as malformations than as genuine tumors. TUMORS 
347 
ditions may have remained long inactive, and indeed usually do so, 
presently begin to proliferate and continue this new activity beyond the 
limitations of structural types or physiological correlation? It would 
appear that either there are external excitants of cell growth, as yet 
unknown to us, which suddenly become active, or else we are face to 
face with the fundamental problem as to the nature of the normal 
physiological impulses to cell growth and proliferation1 and the restrain- 
ing influences to which these are subject. 
The Excitants of Tumors.-If now we turn from the various general 
and local factors which appear to influence the occurrence of tumors 
to the views which are held as to the actual excitants, we find that these 
may in general be grouped in two classes. The first class of views 
involves the assumption of some form of living micro-organism capable, 
under suitable conditions, of inciting the body-cells to the proliferative 
capacities which are the chief characteristic of tumors. This is called 
the theory of the parasitic origin of tumors. Those who hold this view 
regard the processes by which tumors are formed as analogous with those 
involved in the infectious diseases. 
On the other hand, those who hold the second class of views regard- 
ing the excitants of tumors do not believe that tumors of any kind, 
even the most malignant, are induced or perpetuated by processes 
analogous with those involved in infection, but that the excitants to 
tumor formation are to be sought in the inherited and inherent potencies 
of the bQdy-cells themselves set free from their normal physiological 
restraints under a variety of external conditions. This is called the 
theory of the biological origin of tumors, or the theory of intrinsic excitants 
of tumors. 
Micro-organisms as Excitants of Tumors. Bacteria.-It is not sur- 
prising that micro-organisms should have been thought of as possibly 
direct excitants of tumors, especially in view of a certain crude analogy 
between some phases of tumor growth and metastasis and some forms 
of infection with metastasis. Bacteria of many kinds have, in fact, been 
frequently found in tumors of many sorts; but there is no conclusive 
reason at hand for the belief that they are ever of any direct significance 
save as chance contaminations of vulnerable tissues or as incitants of 
secondary and complicating lesions. 
Protozoa.-A great deal has recently been written about certain 
structures which are not infrequently found in or between tumor cells, 
especially in the carcinomata, which have been hastily assumed to be 
parasites and supposed to be protozoa. These cell "inclusions" ("can- 
cer bodies," "Plimmer bodies," "Bussell bodies," etc.) are for the most 
part larger or smaller rounded bodies (Figs. 194 and 195); with or with- 
out nuclei; sometimes with double contours, sometimes not; usually 
sharply outlined against the cell protoplasm in which they lie; often 
crowding the nucleus to one side, often situated within the nucleus, or 
apparently replacing it. Some of them are cell secretions or degener- 
ation products, some are invaginated epithelial or other cells, or cell 
1 See Regeneration, p. 64. 348 
TUMORS 
nuclei which have undergone various degenerative metamorphoses, 
fragmentation, etc. Some of the questionable structures appear to be 
the metamorphosed nuclei of the tumor cells themselves. They may 
be single or there may be several in a cell. They are especially common 
in gland-celled carcinomata. Similar objects are to be found in other 
than tumor tissues. They are not present in some forms of carcinoma. 
They are readily stained, with varying degrees of intensity, by haema- 
toxylin, eosin, safranin, or fuchsin. There is, in the writer's opinion, 
no evidence either that these are living organisms or that they have 
anything to do with the origin of tumors. 
Fig. 194.-"Plimmer's Bodies" in Carcinoma Mammae. 
While coccidia or allied organisms, with which these "cancer bodies" 
have been compared, are capable of inciting the growth of a small amount 
of new connective tissue and sometimes lead to hyperplasia1 of epithe- 
lium, such growths are apparently inflammatory in character, as are 
those other new tissue formations incited by the tubercle bacillus, the 
lepra bacillus, etc., which have sometimes been improperly classed with 
tumors and called infectious granulomata. The reader is referred to 
the sections dealing with the nature of the inflammatory process in 
general (p. 81), and to the introductory section in the present chapter 
for a review of the differences in the conception of the inflammatory 
processes and tumor formation. 
1 See Tyzzer, Jour. Med. Res., vol. vii., p. 235, 1902. TUMORS 
349 
Yeasts.-Attention has been called, in connection with tumors, to 
certain forms of yeasts or blastomycetes as excitants of new tissue 
growths, but these also appear to be inflammatory. The cultivation 
of yeasts from the tissues of malignant or other tumors is of no more 
significance than the cultivation of bacteria under similar conditions. 
The nearly uniform failure in the attempts to transplant tumors from 
one species of animal to another, although the morphological characters 
of such tumors occurring spontaneously appear to be identical, and the 
absolute failure to cultivate, either directly or by inoculation, any con- 
stant organisms from them which are capable of inducing experimental 
tumor growths; the difference in the nature of metastases; the failure 
Fig. 195.-Epithelial-cell "Inclusions" in Tumors. 
Showing various forms. From carcinoma. 
of statistical data to substantiate the claims made for the increase of 
cancer and its endemic occurrence, all speak with much force against 
the notion of the parasitic origin of malignant tumors. Moreover, the 
great diversity in the character and in the inconstancy of occurrence of 
the objects which have been regarded as of possible significance in 
tumors, as well as their occurrence elsewhere, greatly diminishes the 
plausibility of the claims which have been made for them.1 
It is much to be regretted that most of those who advocate the para- 
sitic nature of tumor excitants should be so engrossed with the alleged 
parasites that they largely ignore the dominant characters and the life 
history of the tumors themselves, especially of malignant forms, and the 
fundamental distinctions between these and such inflammatory growths 
as may superficially resemble tumors and which are undoubtedly often 
incited by various kinds of micro-organisms. 
One does not, of course, assert that tumors cannot be incited by para- 
1 For an interesting critical study of the so-called infectious lympho-sarcoma of dogs see Beebe 
and Ewing, Jour. Med. Res., vol. xv., p. 209, 1906. 350 
TUMORS 
sites, but at present no adequate reason appears to exist for believing 
that they are.1 
It is indeed not improbable that a local predisposition to tumor 
formation akin in nature to that which now and then is attributable to 
trauma occasionally may be induced by micro-organisms. But this it 
remains for future researches to demonstrate. 
The Intrinsic Excitants of Tumors.-"Biological Origin." 
The Complexity of the Problem.-It seems to the writer that to seek 
for a single external excitant or group of excitants for the aberrant tissue 
growths which we call tumors is to ignore the many still obscure influ- 
ences which are at work in all tissue growth, especially those physiolog- 
ical agencies which foster cell proliferation and tend, under the influence 
of heredity, to specialization in form or function. On the other hand, 
not to be ignored are those influences, whether of nutrition or pressure 
or exposure, which mould the cell growth under normal conditions 
into fixed and useful forms. It is rather a matter for surprise that 
ever-changing, self-regenerating living tissue does not oftener go astray 
in its activities than that it should only now and then do so. This 
latter somewhat inverted point of view may be useful in calling away 
the attention, in discussing the etiology of tumors, from a too close regard 
to extraneous factors, and directing it to the many still unexplored 
fields in cell physiology with which we must perhaps become familiar 
before we can with fair hope of success attack the serious problems of 
both the excitation and the prevention of tumors. 
No adequate conception can be gained of the complexity of the prob- 
lem involved in the origin of tumors or of the directions in which the 
highest promise of experimental research lies without a recognition of 
the new cell lore derived from a study of the lower and simpler forms of 
life. 
The more commonly accepted and time-honored view of the imme- 
diate excitation of tumors is that they are due to some stimulus- 
"formative stimulus"-by which the proliferative capacity of the cells 
is increased. What the nature of this postulated stimulus may be, where 
it comes from, and how it is brought to bear upon the transformations 
of energy which, through the subtle mechanism of the cell, are manifested 
in proliferation, is in no wise clear. 
The Relation of Abnormalities in Mitosis to Tumors.-It has become 
evident from the many illuminating studies which have been made 
during the last few years upon the phenomena of mitosis, that through 
the character and performances of the chromatic substance of nuclei and 
in the chromosomes many of the potencies and peculiarities of cells 
may find expression. It is natural, therefore, that studies should have 
been made upon the nuclear characters of rapidly growing tumors. 
Thus, v. Hansemann2 records observations upon the mitotic figures 
1 For a study of the nature of the cell inclusions of cancer see Greenough, Jour. Med. Res., vol. xiii., 
p. 137, 1905. 
2 v. Hansemann, Biol. Centrbl., Bd. xxiv.. No. 5, 1904. TUMORS 
351 
of malignant tumors which led him to assume that they have suffered 
modifications characterized by a loss of differentiation, a condition 
which he calls anaplasia. It is assumed that the cells of malignant 
tumors have acquired embryonic characters expressed by their inde- 
pendence and increased power of proliferation and of destruction of 
surrounding tissues. But this view, even if sustained, does not throw 
light upon the inciting factors in tumors. 
Similarly Farmer, Moore, and Walker,1 studying the phenomena of 
mitosis in malignant tumors, have asserted that there is in this mitosis 
a reduction in the numbers of chromosomes similar to that occurring 
in the maturation of sexual cells, the reduced cells having half the num- 
ber of chromosomes of the somatic cells. Thus in accordance with this 
view, malignant tumors arise from the metamorphosis of differentiated 
somatic tissues into a special form of reproductive tissue to which these 
observers attribute the independence and proliferative capacity marking 
malignancy. But this conception of the nature of the departure from 
the normal in malignant tumors, even if the alleged facts upon which 
it is based were established-which does not seem to be the case since 
reduced numbers of chromosomes may not be present in parts of such 
tumors-does not reveal the inciting factors in these growths. 
Cohnheim's Hypothesis.-The hypothesis of Cohnheim, which we 
have considered above, while in accord with many facts bearing upon the 
morphology, clinical manifestations, and experimental observations of 
tumors, really relates to the predisposing conditions of tumor forma- 
tion rather than to the actual excitants. It was, in fact, necessary for 
Cohnheim to assume, as possible final excitants of tumor growth from 
his displaced or belated cells, a local hyperaemia or a diminished resist- 
ance to their growth on the part of surrounding tissues.2 
Ribbert's Hypothesis.-A more subtle and perhaps more compre- 
hensive view of the agencies which must be taken into the account in 
the excitation of tumors is that especially advocated by Weigert3 and 
Ribbert.4 These observers and those in sympathy with their views do 
not admit a new formative stimulus into their conception of the origin 
of tumors, but regard the usual potencies of the cells in this respect to 
be sufficient if the natural restraints to over-proliferation be in any way 
diminished. 
Ribbert has, perhaps more definitely than any other, framed a work- 
ing hypothesis along these lines which is at least suggestive. He lays 
stress in his conception of the origin of tumors upon the intimate asso- 
ciations of the cells of the normal body as parts of an organism, whose 
varied capacities are normally held in some fashion under mutual restraint 
in subservience to their common welfare. This mutual relationship, 
however, once destroyed, for example, by the separation of cells or 
cell groups from their organic associations, they assume less highly 
1 See Farmer, Nature, Feb. 4th, 1904; also Bashford and Murray, Proc. Roy. Soc., January 21st, 
1904. See also Boveri, Zur Entstehung Maligner Tumoren, Jena, 1914. 
2 For a further discussion of these various views see Nichols, Jour. Med. Research, 1905, N. S., 
viii, 187. 
3 Weigert, "Neue Fragestellungen in path. Anat.," Deut. med. Wochenschr., 1896, p. 635. 
* Ribbert, "Geschwulstlehre," 1904; or "Lehrbuch d. allg. Pathologie," 1905. 352 
TUMORS 
differentiated characters, their physiological capacities are no longer 
held in leash, and these, if the nutritive and other conditions be favor- 
able, may express themselves in exaggerated fashion by excessive growth 
and proliferation. 
Ribbert explains the way in which he conceives that the process of 
cell disassociation and release from restraint may occur. Since he does 
not admit a primary increase in the inherent proliferative capabilities 
of the cells, he cannot assume, as is commonly done, that the process is 
initiated, in carcinoma for example, by the epithelial cells. He assumes 
that the process may start in the connective tissue, which is liable to 
increase in amount in response to a variety of influences, notably those 
which involve trauma, or simple inflammation, or replacement hyper- 
plasia. In the starting of carcinoma of the stomach or intestine, for 
example, Ribbert asserts that, in many cases at least, the new-formed 
connective tissue cuts off cells or cell groups from their organic connec- 
tions, and claims that in this way alone we may account for the required 
release from the restraints of the organic association and the exuberant 
aberrant growth which follows. 
This view is interesting in connection with the frequent association of 
carcinoma with chronic inflammation, which has been already noted. 
Ribbert also insists upon the embryonic displacements or superfluous 
cells of Cohnheim as important predisposing factors in /the release of 
tissues from organic control. 
It is assumed by those who adopt the hypothesis of Ribbert that the 
localized groups of cells, in which tumors originate during their growth 
under the conditions associated with their emancipation from organic 
control, have so adapted themselves to abnormal nutritive and other 
adverse conditions that the transportation to a new site as tumor cells 
can more readily be endured than by cells which have not enjoyed this 
preliminary adaptation to nutritive and environmental hardships- 
parenchyma-cell emboli for example.1 
Ribbert's views on this subject are summarized by himself sub- 
stantially as follows: 
All tumors originate in cells which have been separated from their normal relation- 
ships. 
This separation occurs either by a disturbance of the embryonal or post-foetal 
developmental processes, or by trauma, or by processes of growth which are the ulti- 
mate results of inflammation. 
1 Fischer has recently shown that the injection beneath the skin of the ear of the rabbit of a mixture 
of oil and Scharlach R is capable of inciting a downward growth of epithelium in branching plung resem- 
bling in structure the epithelial reticulum of epitheliomata. These structures maintain their characters 
and growth for a considerable time, but when the colored oil is extracted the epithelium passes on to its 
mature condition, and becomes cornified, and the growth ceases. 
The structures formed are limited in growth and are not, therefore, to be properly classed with 
malignant tumors. Fischer assumes that the injected colored oil is chemotactic and postulates for malig- 
nant tumors the presence in the body of some substance which he names attraxine, which through its 
persistent action incites the continuous cell growth marking malignancy. But this opinion has not 
stood criticism, the incitation to growth being due largely to increased blood supply. When Schalacht 
oil is injected with tumor material it diminishes the percentage of positive inoculations because it incites 
an excessive tissue reaction which causes absorption or destruction of the tumor cells. We refer for 
further details of these experiments to the original article, Munch, med. Woch., 1906, p. 2041. TUMORS 
353 
The dissociated cells grow independently and in limitless fashion, because the 
organism has lost control over them. 
The differences in the types of tumors are accounted for by the character of the 
originally separated cells and the conditions under which these have grown. 
The Ultimate Problems in Tumors.-When all has been said about 
general and local predisposing factors in tumors; when through obser- 
vation and experiment all possible light has been thrown upon the na- 
ture of their immediate excitants, we are still face to face with a host of 
problems relating to tumors as organized entities showing complex tissue 
adjustments and revealing specific inherited qualities and powers.1 
These all in the end carry us back to the fundamental questions in 
biology and the mechanism of development with which students of all 
forms of life are more or less directly engaged; back even to the poten- 
cies which dominate and characterize life itself, and are handed on from 
cell to cell through the long line of inheritance. It may be that from 
the chromosomes and their abnormalities with which the cytologist is 
so eagerly engaged to-day is to be derived the knowledge through which 
we shall arrive at a more definite comprehension of tumors. Thus it is 
evident that here as elsewhere in pathology we are dealing, not with 
independent problems, but with specific outlooks only on the wider 
field of general biology. 
The Need of New Research in Tumors. 
It has become evident of late that much of the statistical lore of 
tumors, especially of malignant types, which has been handed on from 
one writer to another, is in need of a critical revision, and that many of 
the current opinions regarding malignant tumors are based upon alleged 
observations of doubtful validity and upon inferences hastily and illogi- 
cally drawn. Among these opinions needing revision may be mentioned 
the alleged relative rapid increase in the frequency of cancer, which rests 
upon data obviously faulty; the contention that metastases in malig- 
nant tumors are closely analogous with metastases in infective processes 
and indicate the infective nature of the former; the view that carcinoma 
has been in many instances directly conveyed by contact from a victim 
of the disease to a well person; the successful inoculation of carcinoma 
of man into the lower animals. None of these points has been sustained 
by reliable data. 
It has become evident that a new departure is necessary in the study 
of tumors and that this is especially urgent along two lines: first, in 
the collection of more reliable statistics,2 which shall embrace not only 
1 For a suggestive study of this subject see Albrecht, " Entwicklungsmechanische Fragen der 
Geschwulstlehre," Verh. Deutsch. Path. Ges., Bd. viii., p. 89, 1904. 
2 For a study of the statistical investigation of cancer see Bashford and Murray, Report of Imp. 
Cancer Research Fund, No. 2, Part I., 1905. 354 
TUMORS 
man, but the lower animals as well; and, second, the initiation of care- 
ful and extended experimental studies of the tumors, especially the 
malignant tumors, of the lower animals, in which such growths frequently 
occur spontaneously. 
When along these lines the data relating to the biology of tumors 
shall have been gathered on a large scale the outlook will be brighter 
for the study of the fundamental problems of the inciting factors in 
tumors and of promising measures for their treatment. 
The Transplantation of Tumors. 
We have seen in an earlier part of this book (p. 78) that it has been possible to 
transplant living tissues from one animal to another of the same species; that when 
this is done there may be at first a slight proliferation at the new site and, in the case 
of epidermal structures, a considerable growth, so that new epidermis may form in 
skin grafts, while cyst-like structures may develop when epidermal tissues are em- 
bedded in the tissues of the host. It has even been possible to transplant whole organs, 
ovary, testicle, and kidney, which have maintained for a short time some of their 
structural and functional qualities at the new site. But in general the fate of trans- 
planted normal tissues is sooner or later to undergo necrosis or to fall under the sway 
of the protective agencies of the host, and either by the action of lytic fluids or by 
phagocytosis to disappear. Transplantation of normal tissue to animals of another 
species is not successful. 
Turning now to tumors, we find that the study of those occurring in the lower 
animals has opened up a wide field of observation, in which a number of important 
facts have already been discovered.1 
Many of the new growths encountered in man are found among animals also, down 
to, but not including, the reptiles, and, as in man, they are most common in the later 
years of life. But it is to the neoplasms of tame mice and rats, especially carcinoma, 
adenocarcinoma, and sarcoma, that attention has been particularly directed, because 
of the facility with which small animals can be stored and handled. 
In the mouse, the usual site of origin is the female mammary gland, and the clinical 
course of the disease closely follows that in the human subject. Metastasis is common, 
taking place generally by way of the blood-stream, or, more rarely, by the lymphatics, 
and true infiltrative growth is easily demonstrable. 
Murray2 has conducted experiments concerning the hereditary transmission 
of a tendency to develop these spontaneous cancers, which have led to the discovery 
that mice whose mothers or grandmothers developed malignant new growths are 
themselves more liable to fall victims than those with a non-cancerous ancestry. The 
percentage of cases among mice of cancerous heredity was found to be 20.5, while in 
those with non-cancerous antecedents it was but 11.6. This information may be 
applied to man, however, only with the greatest reservation, because, in the experi- 
ment just mentioned, animals with a concentrated cancerous ancestry were selected 
and bred together, and the tendency in the offspring was accordingly greater than 
ever it would be in man except in rare cases and as a result of the most unfortunate 
coincidence. 
It has been found that if small particles of a spontaneous mouse tumor be inserted 
under the skin of healthy young mice of the same race, the implanted cells will grow 
in a few of them, say about five-per-cent., and within from three weeks to several 
months produce new tumors similar in character to the original. Thus, from animal 
to animal the tumors may be propagated through long series to an extent which, so far 
as is now known, is without limit. The most striking feature of these transplantations 
is the apparently boundless capacity of the cancer cell for proliferation, for it will 
1 For a resume of the work that has been accomplished in this field, and for bibliography, see Woglom, 
The Study of Experimental Cancer, New York, 1913. 
2 Murray, Fourth Sci. Report, Imperial Cancer Research Fund, Lond, London, 1911, p. 114. TUMORS 
355 
readily be seen that if a few cells can, within a relatively short time, produce a mass as 
large as the growth from which they came, the amount of new tissue would be pro- 
digious almost beyond belief1 if all the tumors in every generation were to be trans- 
planted. 
The existence of certain hereditary factors tending to make some mice naturally 
more, and others less refractory to transplanted cancer, has been intimated, and 
susceptible and non-susceptible strains have been bred. 
Examples of the "contagion" of cancer through the medium of "cancer cages" 
have been recorded in the literature from time to time, and have been regarded by 
some observers as evidence of a parasitic etiology. Still, the animals in which the 
disease appeared were nearly always old female mice, and in most, if not all instances, 
she neoplasms occurred in the mamma. That old animals should have been affected 
at the site where cancer ordinarily develops suggests that these alleged epidemics can 
be explained by the sudden outcropping of a number of spontaneous new growths, 
and renders superfluous the assumption of an infectious etiology. 
Furthermore, the hypothesis which would ascribe malignant growths to the inter- 
vention of a parasite was dealt a heavy blow when Jensen, and afterward Bashford, 
Murray, and Cramer,2 showed that the parenchymal cells of a propagable carcinoma 
are not furnished by the host, but are the progeny of transplanted elements and, carried 
through however many generations, the lineal descendents of the cells of the original 
spontaneous tumor. In the infectious diseases with which we are so far acquainted, 
on the contrary, the lesions are produced solely by the tissues of the host, acting under 
the agency of the micro-organism in question. 
The stroma of a propagable carcinoma, however, in contrast to the parenchyma, is 
provided anew by the host at each transplantation; within the first few days after the 
insertion of the graft, fibroblasts and blood-vessels penetrate it in large numbers, 
replacing the old stroma, which gradually dies, and supporting and nourishing the 
new tumor. 
It is to the failure of this specific stroma reaction that Russell3 refers the acquired 
immunity shortly to be described. 
Ehrlich4 and others have shown that the cells of a few carcinomata have the power 
to transform the connective-tissue stroma into a sarcoma, which also is capable of 
continued propagation, and which tends to overgrow the epithelial portion of the 
tumor. 
It is possible that the combination of carcinoma with sarcoma which is occasionally 
encountered in human neoplasms, may be the outcome of a similar power on the part 
of the epithelial portions of these growths. At any rate, the phenomenon as a whole 
is probably of the same order as that observed when a carcinoma or sarcoma develops 
from normal cells in an otherwise healthy individual, following repeated trauma or 
chronic irritation. 
During continued propagation, a mouse tumor usually "takes" in a progressively 
larger number of animals until finally 90 or even 100 per cent, of success may be ob- 
tained. The percentage does not remain permanently at this level, however, but 
fluctuates with more or less regularity, and, it would seem, without relation to unavoid- 
able minor variations in technique. Whether increased power to grow in a foreign soil 
is due to heightened virulence, or to increased ability of the tumor cell to adapt itself 
to an unfamiliar environment, is a question which has been earnestly debated. 
Transplanted tumors may continue to grow until they ulcerate and kill the animal, 
or they may proliferate for a time and then recede, and it may be said in a general way 
that such biological characteristics as these are retained during propagation. The 
1 For a calculation of the possibilities of such growth see Apolant and Ehrlich, Berl. klin. Woch., 
1905, p. 871; ibid., 1906, p. 37. 
Certain experiments, however, in which normal tissue has been grown in vitro, suggest that this, 
too, may be capable of indefinite proliferation under suitable conditions. 
2 Bashford, Murray, and Cramer, Sci. Reports of the Imperial Cancer Research Fund, London. 
3 Russell, Sci. Reports, Imperial Cancer Research Fund, London. 
4 Ehrlich, Exp. Carcinoma Studien an Mausen, Sep. Abdr., Arb. a. d. Konigl. Inst. f. exp. Therapie, 
Heft 1, 1906. M 356 
TUMORS 
histology, also, of the original growth is adhered to more or less faithfully in the subse- 
quent generations of its daughter tumors. 
In contrast to the comparative difficulty of getting spontaneous growths to estab- 
lish themselves in new hosts, is the readiness with which they will succeed in the ani- 
mals that developed them, for almost without exception they-will proliferate if re- 
introduced into the organism to which they are native. This is not because the bearer 
of a spontaneous neoplasm offers a more favorable soil for tumor growth in general, 
but because the cells need make no great effort to adjust themselves to their environ- 
ment, as it is necessary for them to do if they are to survive introduction into another 
animal. 
Acquired Immunity to Tumors.-This is brought about in an animal by the absorp- 
tion of cells from another of the same species, and persists for as long as two or three 
months. Whether the material employed for its production be normal cells or cells 
from a tumor, is immaterial; the only requisite is that they shall be living when they 
are introduced. Thus, animals have been rendered refractory to transplantation 
by the inoculation of embryonic tissues, or adult spleen, kidney, etc., as well as by 
unsuccessful inoculation with tumors, but it has not been possible to obtain immunity 
by the injection of juices or extracts from a tumor, or by introducing serum from 
animals possessed of natural or acquired resistance. Experiments in which this out- 
come has been claimed are vitiated by lack of care in obtaining such uniform experi- 
mental conditions as a pure strain of animals,1 equal dosage, etc. Apparently nothing 
short of the living cell is capable of producing true resistance, and the reaction is so 
delicate that, as has been said, only tissues of the same species are potent. Those 
of the individual itself, however, are devoid of all immunizing power. 
The immunity thus effected is valid only against, a graft which is in the act of 
establishing itself in a new host, exerting not the slightest influence upon a more 
advanced tumor; nor does it prevent the development of a spontaneous new growth. 
Hence, there is no justification for the treatment, by analogous methods, of tumors in 
man, which, indeed, would be still less likely to yield, since they are composed, not of 
cells foreign to the organism, as is a transplanted mouse tumor, but, on the contrary, 
of native elements. Being so constituted, a spontaneous neoplasm is vulnerable, 
so far as we know at present, only to agents which are equally injurious to the cells of 
the body at large, a fact which explains the difficulty of finding some means to attack 
a tumor other than the comparatively crude and incomplete method of extirpation. 
The Technic of Transplantation. 
The mouse bearing the growth is dispatched as painlessly as possible and placed 
for a few moments in two per-cent, lysol. It is then pinned out on a cork block, after 
which the tumor is removed with sterile instruments. Two ways are available for 
transplantation. Small fragments about 1-2 mm. in diameter may be introduced 
with a coarse platinum-iridium needle and trocar, or the tumor may be emulsified by 
repeatedly snipping it with a pair of sharp curved scissors, without the addition of any 
fluid; in the latter event, inoculation is carried out with a graduated glass syringe. 
The former method, as a rule, gives better results. 
In either case, the needle is inserted under the skin of the groin, in an area that 
has been mopped off with alcohol, and pushed upward toward the axilla, where the 
implant is deposited. 
The best results are obtained by inoculating a tumor that has grown steadily for 
some time. Young tumors are not so suitable, while those that have remained sta- 
tionary in size, or have become smaller, are not apt to grow in a new host. Ulceration, 
of course, renders a growth entirely unfit for propagation, since the mice inoculated 
with it generally die of infection. 
1 It has been repeatedly observed that mice and rats of different strains, or obtained from different 
parts of a country, show marked variations in susceptibility to inoculation with the same tumor under 
precisely the same conditions. TUMORS 
357 
Classification of Tumors. 
It is not possible to-day to make a satisfactory scientific classification 
of tumors; but the fact that they are composed of structures which 
resemble the various morphological types of tissue found in the normal 
body suggests a grouping of the various forms which may be regarded 
as a useful and suggestive catalogue. 
It should be remembered that the usual separation of the normal 
tissues into groups is useful, rather because it facilitates their study than 
because it expresses absolute and fundamental distinctions; and the 
same may be said of all the classifications of tumors. An increase of our 
knowledge concerning their structure and genesis will doubtless lead to 
a more accurate grouping of tumors; but for the present such an arrange- 
ment as that indicated below will be found of practical value for the 
purposes of study.1 
CONNECTIVE-TISSUE TYPE. 
Normal Tissue. 
Fibrillar connective tissue. 
Mucous tissue. 
Embryonal connective tissue. 
Endothelial cells. 
Fat tissue. 
Cartilage. 
Bone. 
Neuroglia.2 
Tumors. 
Fibroma. 
Myxoma. 
Sarcoma. 
Endothelioma. 
Lipoma. 
Chondroma. 
Osteoma. 
Glioma. 
MUSCLE-TISSUE TYPE-MYOMATA 
Normal Tissue. 
Smooth muscle tissue. 
Striated muscle tissue. 
Tumors. 
Leiomyoma. 
Rhabdomyoma. 
NERVE-TISSUE TYPE-NEUROMATA. 
1 The attempt has often been made to classify tumors with reference to the developmental history 
of the tissues represented, and it has been generally believed that cells once differentiated in the primary 
embryonic layers cannot again be merged in type. While this principle holds good in general, espe- 
cially for highly differentiated forms, certain recent studies have seemed to indicate that even this dis- 
tinction may not be inflexible. However this may be, it is certain that the cells derived from one 
embryonic layer may under special conditions come so closely to resemble in morphology those of 
another layer that a structural differentiation, with our present resources at least, is not always possible. 
While, therefore, this, which is called the histogenetic principle of classification, is most suggestive 
and may be useful in connection with other data in the study of tumors, it seems to the writer that it 
is wiser for the present not to base our classification too largely upon embryological data in several 
particulars still subject to controversy. 
Consult in this connection the resume of Marchand on "The Relationship between Pathological 
Anatomy and Embryology," Verb. d. deutschen path. Gesellschaft, Bd. ii., p. 38, 1900. 
See also the admirable address by Minot on "The Embryological Basis of Pathology," Science, 
March 29th, 1901. In this paper, p. 487, the tissues are classified in accordance with their genetic 
relationships. 
2 The neuroglia, as well as the tumors derived from it, presents marked peculiarities in structure. 
While the neuroglia is closely related in genesis to the nervous system, being of ectodermal origin, its 
structural and functional alliance with the connective tissues of the mesoderm seems to the writers to 
justify for the present purpose its grouping among the latter. See ref. to Mallory, foot-note, p. 388. 358 
TUMORS 
VASCULAR-TISSUE TYPE-ANGIOMATA. 
Normal Tissue. 
Blood-vessels. 
Lymph-vessels. 
Tumors. 
Angioma. 
Lymph-angioma. 
EPITHELIAL-TISSUE TYPE. 
Normal Tissue. 
Glands. 
Various forms of epithelial cells 
and associated tissues. 
Tumors. 
Adenoma. 
Carcinoma. 
Tumors Formed by Various Combinations of Tissue Types.-Mixed Types. 
In a considerable proportion of tumors more than one type of tissue 
is present, and it is customary to indicate this by compound names, such 
as osteosarcoma, adeno-carcinoma, etc. Discrimination is necessary in 
the use of such names, however, and one should be clear as to what he 
wishes to express in this way. All tumors have a certain amount of 
fibrous stroma which carries the blood-vessels and forms a sustaining 
framework. In the early stages of tumor growth this matrix may be the 
tissue in which the tumor starts, which is either not increased in amount 
or is hyperplastic. Thus in carcinoma of the stomach, the stroma may 
be fibrous if the mucosa or composed of smooth muscle if the stomach 
wall be involved; but such growths would not be called either fibro- 
carcinoma or myo-carcinoma. It is only when the new tissue assumes 
the characters of an independent growth that it can be justly indicated 
in the compound name. This may not be easy or always possible to 
determine, but the desirability of doing so should be held constantly in 
mind. Unfortunately the compound name is by some writers used to 
indicate simply the seat of a tumor growth; in this sense osteo-sarcoma 
means simply sarcoma of the bone and not an association of osteoma 
and sarcoma. 
It should also be remembered in this connection that a tumor of 
mixed types does not always, perhaps not often, start as such, but may 
assume this character by metaplasia (see p. 62) within the limits of a 
tissue group. Thus the establishment in fibroma of bone or cartilage 
growth and the assumption by the adenomata of the carcinomatous 
type are common. Furthermore, although these mixed forms of tumors 
may arise secondarily by metaplasia, the more or less distinct forms of 
tissue may finally become so independent of one another that some of 
the metastases from such a mixed tumor may show only one tissue type. 
The possibilities in tissue metaplasia should be taken into the account 
before assuming, as is too often done, that the multiplicity of related 
tissue forms in a tumor point toward embryonal origin. 
Complex Congenital Growths-Teratoma. 
These are tumors which frequently contain a great number of differ- 
ent forms of tissue, such as various forms of fibrillar connective tissue, TUMORS 
359 
cartilage, bone, teeth, hair, skin, muscle, and glands. They are formed 
in the ovary, testicle, mediastinum, brain, in the sacral region,1 about 
the neck, in the retroperitoneal tissue, etc. They arise by an inclusion 
of portions of another foetus, and are thus rather malformations than 
tumors in the limited technical sense. But they may give rise to tumors, 
some of them malignant: such are chorion-epitheliomata and sarcomata. 
Among these are sometimes classed other and simpler congenital anom- 
alies, such as dermoid cysts, congenital angiomata, and the so-called 
pigmented nsevi or moles.2 
Special Tumor Types. 
There are types of tumors which are not readily brought into the 
usual general classifications, since they are formed of special kinds of 
tissue. These have received distinctive names. Thus there are peculiar 
tumors formed of placental tissue called chorion-epithelioma or deciduoma; 
of tissue resembling the adrenals, hypernephroma, etc. 
Lubarsch's Grouping of Tumors for Practical Purposes. 
Lubarsch has suggested the following grouping of tumors for practical purposes, 
without special reference either to their histogenetic or histological characters: 
1. Tumors which, although differing from the tissues in which they originate in 
the arrangement of their elements, usually increase in size but slightly or temporarily. 
In this group are the teratoid growths and those originating in embryonic displace- 
ments, such as congenital naevi, certain gland-like tumors, myoma, fibroma, lipoma, 
chondroma, and osteoma. Such tumors are usually of little practical importance. 
2. Tumors which, although conforming in general to the normal tissue type in 
growth and structure, still reveal a considerable independence of their surroundings; 
such are larger myomata, adenomata, angiomata, lipomata, which may grow slowly 
and with interruptions, and may when growth ceases through degenerative processes 
or necrosis undergo retrogression or even disappear altogether. 
3. Tumors which seem to be largely emancipated from the usual physiological 
control of normal tissues, both in the rapidity and extent of growth and in the fixity 
of the cell type in form and function. In this class are the tumors which are destruc- 
tive and invasive in their growth, especially the sarcomata and carcinomata. 
These three classes may in reality be considered to represent only stages in the 
growth of tumors in general; since the more destructive forms may in early stages 
conform to the characters of the other groups, while, on the other hand, tumors of the 
less aggressive types may assume the autonomy and significance of the malignant 
forms. These classes of tumors are not of course distinct, and many intermediate 
types may occur, but this grouping seems to the writer fairly to indicate a real differ- 
ence in character and significance in tumors as a whole which it is of practical ad- 
vantage to recognize, and which is often lost sight of in the more technical classi- 
fications. 
Cysts. 
These structures, for the sake of convenience, are often classed among 
the tumors, although in general characters, structure, and genesis they 
are usually of entirely different nature. 
1 For a critical summary, with bibliography, of tumors of the sacral region see Borst, Centralbl. 
f. Path., Bd. ix., p. 449, 1898. 
2 For the relationship of teratoma to other malformations see p. 334. 360 
TUMORS 
They may be divided into two classes: 
I. Cysts which develop from pre-existing cavities. 
II. Cysts which originate independently as the result of pathological 
changes. 
I. CYSTS WHICH DEVELOP FROM PRE-EXISTING CAVITIES. 
1. Retention Cysts.-These are chiefly formed by the accumulation 
in glands or their secretory ducts of the more or less altered secretion of 
the gland. They usually occur as the result of a hinderance to the nor- 
mal discharge, as from inflammatory contractions, pressure, etc. The 
contents of such cysts are usually mucous, sebaceous, serous, or of a 
mixed character. Their walls are the more or less altered walls of the 
original structure. To this class belong comedones, milium, atheroma, 
chalazion, ranula, the ovula Nabothi, milk cysts, and certain serous 
cysts of the ovaries, Fallopian tubes, gall-ducts, and uriniferous tubules. 
2. Transudation Cysts.-These arise usually, though not always, as 
the result of a chronic inflammatory process in lymph-spaces or serous 
sacs, and among them are to be classed the so-called ganglia, hydrocele, 
etc. Certain of the so-called haematoceles, in which blood is extrava- 
sated into closed cavities, form a variety of the cysts of this group. 
II. CYSTS WHICH ORIGINATE INDEPENDENTLY AS THE RESULT OF PATH- 
OLOGICAL CHANGES. 
1. Cysts Formed by the Softening and Disintegration of Tissue.-Such 
cysts may at first be small and have very meagre contents and no well- 
defined wall. A wall may finally be present either as an entirely new- 
formed structure, or the more or less modified capsule of the organ in 
which they occur may partly or entirely form the wall. The contents of 
such cysts are usually the more or less altered detritus of the tissue by 
whose disintegration they are formed. Such cysts are very apt to occur 
within true tumors, particularly those which are succulent and of rapid 
growth, since these, as above stated, are very liable to degeneration. Old 
abscesses may change into well-defined cysts of this kind. 
2. Cysts Formed around Foreign Bodies.-The inflammatory reaction 
induced by the presence of foreign bodies of various kinds, parasites, 
masses of extravasated blood, etc., frequently results in the formation of 
well-defined encapsulated cysts. 
3. Cysts Formed by a New Growth of Tissues in Whose Spaces Various 
Kinds of Fluid Accumulate.-These spaces may or may not be lined with 
epithelium and have something of the glandular character. Such forms 
are exemplified in some of the compound ovarian cysts-the so-called 
ovarian cystomata; but these are really adenomata. 
4. Congenital Cysts.-These are of various forms, and their mode of 
origin is in most cases but imperfectly understood. Some of them are 
properly grouped among the teratomata. The so-called dermoid cysts 
of the subcutaneous tissue (Fig. 196) and ovary are marked examples 
of this class. The dermoid cysts of the skin are probably all formed TUMORS 
361 
from an embryonal displacement of the epidermal structures. The 
simplest forms, called epidermoid cysts, are lined with epithelium of the 
squamous type and largely filled with a mass of flat desquamated cells. 
In the more complicated forms, hair follicles, and sebaceous and sweat 
glands are present in the lining epidermal membrane. Certain congenital 
cysts of the kidney and other internal organs are conveniently grouped 
here, although it is probable that some of them at least originate during 
Fig. 196.-Dermoid Cyst of the Skin. 
This small cyst beneath the skin above the eyebrow is lined with epithelial cells, in places cuboidal 
in form, but mostly merged into an irregular cell mass. The fibrous-walled cyst contained a clear 
fluid and a little granular cell detritus. 
foetal life in one or the other of the above-described ways, and hence are 
not essentially different in nature from some of the cysts of other classes. 
For the mode of formation of certain cysts of the neck see page 647? 
For cysts of the viscera see Special Pathology. 
Various Lesions Sometimes Described as Tumors. 
There are certain enlargements of the lymph-nodes which are in reality hyper- 
plasias, sometimes inflammatory in character and sometimes not, and which are often 
grouped among the tumors as lymphomata. They are not true tumors, and will be 
considered under the lesions of the lymph-nodes. In the same group are often classed 
the enlargements of the lymph-nodes in leukaemia and in other general diseases, which 
are considered in another part of this book. 
Another group of tumors sometimes called lymphomata are in reality sarcomata, 
and these will be described under the latter heading. 
There is also a group of nodular new formations, the so-called "infective granulo- 
mata," which in earlier days were classed among the tumors. These are found in 
tuberculosis, lupus, leprosy, syphilis, glanders, actinomycosis, and probably include 
the nodes of Hodgkin's disease. They are, however, inflammatory new formations, and 
as our knowledge regarding them has increased, many of them have proven to be 
incited by plant parasites (see section devoted to Infectious Diseases). 
1 Consult for consideration of ciliated and other cysts Hess, Ziegler's Beitr. zur. path. Anat., Bd. 
vii., p. 98, 1890: also Zahn, Virch. Arch., Bd. cxliii., p. 170, 1896. For later general bibliography of 
cysts see Aschoff, Lubarsch and Ostertag's " Ergebnisse," Jahrg. ii. for 1895, p. 456. 362 
TUMORS 
Technique of Fixation and Hardening. 
In general, tumors, like all tissues for microscopical study, should be cut into 
small pieces before immersing them in the preservative fluids, and the sooner they 
can be placed in these after removal the better will be the preservation. For study of 
the finer details with Zenker or other special fixatives the material must be preserved 
within an hour after removal at operation. In some cases much may be learned from 
large sections of tumors together with their surrounding tissues. In this case the 
suitable portion of the tumor must be preserved whole, and is best fixed in 5-per-cent. 
formaldehyde followed by alcohol. 
It is often important in the study of tumors to examine not only the fully devel- 
oped or mature tumor structures, but also those portions in which the new growth is 
forming and in which it is encroaching on adjacent parts. 
So that in selecting portions of tumors for preservation and study, it is not wise to 
snip off a small piece at random, but a careful selection should be made, liberal por- 
tions being saved from the centre, from the periphery, and from such surrounding 
tissues as are available. For the ordinary routine hardening of tumors, Orth's or 
Zenker's fluid followed by alcohol may be recommended. 
Special Forms of Tumors. 
FIBROMA. 
I he fibromata are composed of fibrillar connective tissue, which, as 
in the physiological type, is sometimes dense and firm, Fibroma durum, 
and sometimes loose in texture and soft, Fibroma molle. They are usu- 
ally sharply circumscribed and are frequently encapsulated, but they 
may be diffuse and merge imperceptibly into the surrounding tissue. 
They are frequently small and insignificant, but occasionally grow to an 
enormous size. Some fibromata consist almost 
entirely of intercellular substance, containing 
but few flattened or spindle-shaped cells (Fig. 
197); others contain very many variously 
shaped cells (Fig. 198). The cells are often 
more abundant in one part of the tumor than 
in another. The denser varieties usually con- 
tain but few blood-vessels, although they are 
occasionally quite vascular. Many of the 
softer varieties are very vascular. Nerves 
are occasionally present.1 The course and 
arrangement of the fibres in these tumors 
are usually irregular; they often cross and 
interlace in a most complex manner. The 
fibromata are usually of slow growth, but ex- 
ceptionally they grow rapidly. They are benign tumors, but by pressure 
on important organs, by ulceration, or by changing into other varieties 
of tissue they may become of serious import. Pure fibromata do not 
form metastases, but they are often multiple, and when so are frequently 
congenital. They may recur when not fully removed. 
It seems probable that in the multiple fibromata of the skin {Fibroma 
Fig. 197.-Dense Fibroma 
of Abdominal Wall-Fibroma 
Durum. 
Some of the bands of connec- 
tive-tissue fibres are cut across, 
others are cut lengthwise. 
1 For a study of elastic and reticular tissue in tumors see Baldwin, " Vaughan Anniversary Contri- 
butions," 1903, p. 495. For fibroglia fibrils see Mallory, Jour. Med. Res., vol. xiii., p. 113, 1905. 363 
TUMORS 
moZZwscwm) the new growths occur in some special form of connective 
tissue, as that of the nerves, blood-vessels, or glands. Some of them are 
The stroma is oedematous, and in gross appearance the tumor resembled myxoma. 
Fig. 198.-Fibroma Molle; from the Subcutaneous Tissue. 
Fig. 199.-Small Papilloma of the Skin. 
congenital. There is often a growth of very cellular tissue just beneath 
the epithelium. Such tumors resemble sarcoma.1 
While the fibromata are commonly nodular in form, when they 
1 See Gilchrist, Johns Hopkins Hosp. Rep., vol. i., p. 349, 1896. 364 
TUMORS 
develop on the skin or mucous membranes they frequently form papillary 
outgrowths covered more or less thickly with epithelium, and are then 
called papillomata (Fig. 199). Common warts of the skin are papillomata 
with excessive production of surface epithelium. To the papillomata 
also belong some of the so-called condylomata. 
The so-called cheloid, composed of very dense fibrous tissue with few 
cells, often develops rapidly in old cicatrices, or elsewhere, in the skin, 
forming flat or slightly lobulated tumors. It is not in all cases clear 
whether cheloids should be regarded as tumors or as inflammatory new 
formations. 
Fibromata are frequently combined with other kinds of tissue to form 
complex tumors. The looser, softer varieties not infrequently become 
The section shows the epithelial covering of the new growth, as well as its numerous blood-vessels and a 
few mucous glands. 
Fig. 200.-Mucous Polyp of the Nose. 
oedematous, when they may closely resemble myxomata (Fig. 198). 
Fibromata are liable to calcification and to fatty and mucous degenera- 
tion. By metaplasia they may partially change to form fibro-chondroma, 
fibro-lipoma, fibro-sarcoma, or fibro-osteoma. The latter transforma- 
tion frequently occurs when they form in the periosteum. 
Developing, as they do, in the connective tissue, fibromata occur in 
the various parts of the body: in the skin and subcutaneous tissue; in 
intermuscular tissue and fasciae; in periosteum; in the nerve sheaths and 
intrafascicular connective tissue; in the dura mater; the interstitial tissue 
of organs; and in the mucous membranes. Some of the so-called polypi 
of the mucous membranes (see Fig. 200) and some psammomata are 
forms of fibroma; the former are often soft and oedematous. A type of TUMORS 
365 
hard encapsulated fibroma occurring in the abdominal wall has received 
the clinical name of desmoid. 
Occasionally, in the ducts of glands, fibrous polypi grow to an enor- 
mous extent, their epithelial covering keeping pace in growth with their 
development, until they form very large, irregular, loose-textured tumors, 
which often finally ulcerate. Such forms are seen in the mammary 
gland, where they are sometimes mistaken for carcinomata. They are 
called intracanalicular fibromata, or perhaps more correctly fibro-adeno- 
mata (see Fig. 587, p. 847). 
It is often very difficult to distinguish between genuine fibromata and 
inflammatory or other connective-tissue hyperplasias, such as elephant 
tiasis; and perhaps the fuller knowledge of the future will show that the 
distinctions are not as definite as our classifications indicate. 
MYXOMA. 
Mucous tissue is essentially an embryonic tissue, for in the normal 
adult it is present only in a very imperfect and atypical form in the 
vitreous of the eye, and perhaps exceptionally in small amount about 
the heart, kidneys, and medulla of bone. 
Fig. 201.-Myxoma of the Larynx. 
Showing the diffuse staining of the mucin-containing stroma with haematoxylin. 
The myxomata are thus essentially embryonic-tissue tumors. These 
tumors consist, in their most typical forms, of a homogeneous or finely 
fibrillated, soft, gelatinous basement substance, in which are embedded 
a variable number of spheroidal, fusiform, branching, and often anas- 
tomosing cells (Fig. 201). They may contain few or many blood-vessels 
and sometimes nerves. By the addition of acetic acid, mucin may be 
precipitated from the basement substance. In sections it is usually 
stained with haematoxylin. The very soft forms which contain compara- 
tively few cells and much translucent basement substance are called 
Myxoma gelatinosum or M. molle. The presence of many cells renders 366 
TUMORS 
them more consistent and gives them a whiter and more opaque appear- 
ance; such forms are called M. medullare. 
Pure myoxomata are very rare. The myxomata are very apt to be 
combined with fibrillar connective tissue as fibro-myxoma; or with fat 
tissue, lipo-myxoma; or take part in the formation of very complex 
tumors. Most of the tumors regarded as myxomata are really of a 
sarcomatous nature, but such structure may only be evident in small 
areas of the tumor and therefore is frequently overlooked. The myxo- 
mata may be diffuse or encapsulated with fibrillar connective tissue; they 
are frequently very large, and may be multiple. Owing to the character 
of the basement substance, the blood-vessels not infrequently rupture, 
giving rise to larger or smaller haemorrhages within the tumor, or to the 
formation of cysts. The cells are liable to undergo fatty degeneration. 
In the fibrous tissue of many tumors, in chronic inflammation of the mucous mem- 
branes, variously shaped small cells occur whose bodies contain few or many well- 
defined basophile granules which are not infrequently mistaken for cocci. Such cells, 
called "clasmatocytes," occur in various parts of the normal body and resemble in 
some aspects the "mast" or basophile cells of the circulating blood but they are prob- 
ably not identical. The nature of the granules has not been definitely determined. 
Eosinophile and plasma cells are also very frequent in the mucous tissue of nasa. 
polypi. 
Composed, as they are, of a type of tissue from which fat tissue is 
developed in the embryo, the relations of myxomata to fat tissue are 
very intimate. They are most frequently developed in, and probably 
directly from, fat tissue. They are also found in the subcutaneous, sub- 
mucous, and subserous tissue, in the marrow and periosteum; in the 
brain and cord; in the sheaths and intrafascicular tissue of peripheral 
nerves; in intermuscular septa; and in the interstitial tissue of glands, 
such as the mamma and parotid. 
The pure.myxomata are in general benign; yet they are very prone, 
especially the lipomatous forms, to local recurrence. They sometimes 
grow very rapidly, and sometimes, though very rarely, form metastases. 
In the very frequent combination with sarcoma they may exhibit the 
most marked malignancy. Some of the polypi of mucous membranes 
are apparently myxomata or fibro-myxomata. On the other hand, many 
of the so-called mucous polyps, those of the nose for example, are simply 
oedematous hyperplasia of the mucosa.1 
(Edematous, loose, and cellular forms of fibrillar connective tissue 
so closely resemble some of the forms of mucous tissue that certain 
observers consider them identical. So prone are many tumors to 
undergo mucous degeneration, and so frequent are the combinations of 
the myxomata with other forms of tumors, that it is often difficult, some- 
times impossible, to say whether the mucous tissue in a given composite 
tumor is primary or secondary. 
SARCOMA. 
These tumors are formed on the type of connective tissue, but they 
are, as a rule, largely composed of cells with well developed cytoplasm; 
1 See reference to Wright, p. 580. TUMORS 
367 
the basement substance, though a constant and important factor, being 
much less conspicuous than in adult connective tissue. They more 
closely resemble, in general, the developing connective tissue of the 
embryo or the granulation tissue of inflammation. 
The cells of the sarcomata are most varied in size and shape. They 
may be flat, fusiform, spheroidal, or branched, and even cuboidal or 
cylindrical; they may be multinuclear and very large, or they may be 
very small and spheroidal, resembling leucocytes. The fibrillar base- 
ment substance may be present in such small quantity as entirely to 
escape a superficial observation, covered as it may be by the abundant 
cells; or it may be so abundant as to give the tumor the general appear- 
ance of a fibroma. It may be intimately intermingled with the cells in 
Fig. 202.-Large Spindle-Celled Sarcoma. 
fascicles, or it may be in large open-meshed networks, giving to the 
tumor an alveolar appearance. The cells, however, always stand in an 
intimate relationship to the basement substance, which they sometimes 
reveal by fibrillar processes continuous with it. Blood-vessels also form 
a constant and important structural element in these tumors, being in 
some of them so predominating a factor that they give structural out- 
line and general character to the growth. They, too, as in the normal 
connective tissue, are intimately associated with the basement substance 
and with the tumor cells. 
Sarcomata are most frequently found in the skin, subcutaneous 
tissue, fasciae, subserous connective tissue, the marrow or periosteum, 
and in the choroid. They may also occur; though more rarely, in the 
dura mater; brain and cord; lymph-nodes; in the adventitia of blood- 
vessels, and in nerve sheaths; in submucous tissue; in the uterus and 368 
TUMORS 
ovary, and in the kidney. In the liver, pancreas, lungs, and heart they 
may occur, but usually by metastasis. 
They are most common early in life. The cellular character, the 
rapid growth, the vascularity and succulence of many forms, the marked 
tendency to local recurrence, and the formation of metastases, stamp the 
sarcomata as malignant tumors. But in this they vary greatly; while 
some of the forms belong in every sense to the most malignant of tumors, 
others grow slowly, are very dense, and may remain localized and harm- 
less for years. Their tendencies in this respect will be mentioned under 
the special forms. 
Intimately related as they are to the blood-vessels, metastasis is more 
apt to occur through the blood than through the lymph channels, and 
consequently adjacent lymph-nodes are much less apt to be involved 
than in some other forms of tumor, notably the carcinomata. The 
richly cellular and vascular forms of sarcoma are especially prone to 
haemorrhages, degeneration, and ulceration. 
Showing abundant cell growth near a blood-vessel. 
Fig. 203.-Spindle-celled Sarcoma. 
A single form of cells is often so predominant as to furnish a suit- 
able qualifying name for the tumor, but in many cases the cell form 
varies greatly in the same growth. It may be said, in general, that there 
is a tendency to reproduce in these tumors some of the special charac- 
teristics of the tissues in which they originate. Thus, sarcomata of the 
bones are apt to be osteo-sarcomata; those of pigmented tissue, like the 
choroid, are apt to be pigmented sarcomata. It will be more convenient 
for our present purpose to describe briefly the more common forms one 
after another than to attempt any systematic classification of them. 
It should be remembered, however, that the various forms are not 
sharply defined, but are apt to merge into one another and to inter- 
mingle in various ways. 
Spindle-celled Sarcoma.-The cells in these tumors may be large- 
large spindle-celled S. (Figs. 202 and 203); or they may be small-small 
spindle-celled S. (Fig. 204). They may consist largely of cells, or may 
contain so much intercellular fibrous tissue as to be appropriately called 
fibro-sarcoma. The cells are frequently arranged in fascicles, which 
surround the blood-vessels, and these fascicles may cross and interlace, TUMORS 
369 
while great variations may also occur in the relative proportions 
between cells and intercellular tissue in different parts of the same tumor. 
The spindle-celled sarcomata, especially the small-celled forms, are, as a 
rule, denser and firmer and less malignant than other forms of sarcoma, 
but to this there are many exceptions. They may be encapsulated or 
infiltrating. To this class belong the growths formerly described as 
Fig. 204.-Small Spindle-celled Sarcoma of Forearm. 
fibro-plastic tumors and recurrent fibroids. They most frequently occur 
in the periosteum, subcutaneous tissue, and muscle; but are also seen 
in the uterus, and in various glands, notably in the mamma, testicle, 
thyroid, etc. These forms are among the most frequent of the sarcomata. 
Round-celled Sarcoma.-Of these there are two classes-1, small 
round-celled sarcomata and, 2, large round-celled sarcomata. 
1. The small round-celled sarcomata consist of cells of about the size 
and appearance of mononuclear leucocytes (Fig. 205), and may have 
Fig. 205.-Small Round-celled Sarcoma. 
From a metastatic tumor in the lungs. 
Fig. 206.-Large Round-celled Sarcoma. 
A tumor of the mamma. Mitotic figures 
in some of the cells. 
much or little intercellular substance, which may be irregularly dis- 
posed or arranged in large meshes resembling alveoli. In many cases, 
so small is the quantity of intercellular substance that it is difficult of 
detection without special modes of preparation. These tumors often 
contain many blood-vessels, and may be very soft and succulent. Their 
growth is sometimes rapid and they are often very malignant. 370 
TUMORS 
They most frequently occur in the connective tissue of the muscles 
and fasciae, in bone, and in lymph-nodes lymphosarcoma or lympho- 
cytoma [Ribbert].1 They also occur in the internal organs, not infre- 
quently in the brain and retina, associated with cells of the glia type. 
Whether all the small round cells are glia cells or whether there is a 
Fig. 207.-Melano-sarcoma. 
Tumor from foot. 
mixture of cells is not yet fully determined. Such tumors are generally 
designated glio-sarcoma (see p. 388). 
2. In the large round-celled sarcomata (Fig. 206) the cells vary in 
size, but are usually very much larger than in the last variety. Their 
nuclei are usually large and contain prominent nucleoli. They, too, are 
A small nodule showing local extension is seen in the subcutaneous tissue beneath. 
Fig. 208.-Melano-sarcoma of the Skin, Fungoid in Shape. 
often very vascular, and contain a variable quantity of basement sub- 
stance. They are occasionally alveolar in character. They are, as a 
rule, less soft and malignant than the small-celled varieties. 
Melano-sarcoma.-These tumors consist most frequently of poly- 
hedral cells of various sizes. They are characterized by the presence in 
1 For a study of so-called infectious lympho-sarcoma of dogs see Beebe and Ewing, Jour. Med. Res. 
vol. xv., p. 209,1906. TUMORS 
371 
Fig. 209.-Giant-celled Sarcoma of Finger. 
Periosteal type 
Fig. 210.-Giant-celled Sarcoma of Superior Maxilla. 
Fifth recurrence. Mitosis in giant cell. 372 
TUMORS 
the cells, and less frequently in the intercellular substance, of larger and 
smaller particles of brown or black pigment (Fig. 207). The pigment 
is usually quite irregularly distributed in patches or streaks. They arise 
most frequently in the skin (Fig. 208) and in the choroid. Pigmented 
moles of the skin often form their starting-points.1 They belong to the 
most malignant of tumors. They very readily form metastatic tumors 
in various parts of the body, which are, like the parent tumor, pigmented.2 
Various forms of tumors may contain brownish or yellowish pigment deposited 
in them by the degeneration of the haemoglobin from extravasated blood; these should 
not be mistaken for melanotic sarcomata. The blood pigment is not as a rule so 
dark as that of the tumors and is generally included in phagocytic cells lying in the 
stroma of the tumor. Careful search will usually reveal cystal or needle forms, and 
occasionally an iron reaction can be obtained by heating sections with acid and potas- 
sium ferrocyanide. 
Fig. 211.-Osteo-sarcoma of the Leg. 
Myeloid or Giant-celled Sarcoma.-Tumors of this class are usually 
formed chiefly of spheroidal or fusiform cells of variable size, but their 
characteristic feature is the presence of larger and smaller multinuclear 
cells, called giant cells. These are closely intermingled with the other 
cells, and may be very abundant or very few in number (Fig. 209). 
Giant cells may occasionally occur in other tumors, but are most abun- 
dant and characteristic in these. Mitotic figures may occasionally be 
seen in the nuclei of giant cells from the more rapidly growing and 
recurrent forms (Fig. 210). These tumors are chiefly formed in connec- 
tion with bone, and may originate in the marrow or in the periosteum. 
They are sometimes very soft and vascular, and subject to interstitial 
haemorrhages. Some of these vascular sarcomata were formerly classed 
1For bibl. of multiple melano-sarcomata of the skin see Wilson and Kalteyer, Amer. Jour. Med., 
Sci., vol. cxxvi., 1903, p. 751. 
2 On the occurrence of melanuria in cases of melano-sarcoma consult Thacher, Trans. New York 
Path. Soc., 1893, p. 105. TUMORS 
373 
together with other kinds of vascular tumors as fungus hsematodes. 
Some of the forms of epulis are giant-celled sarcomata (Fig. 212). 
When these tumors originate in the marrow of the long bones, which 
is a favorite place for them, they are apt to cause resorption of the bone; 
and although the tumor may be for a long time enclosed by a shell of 
new-formed bone, which enlarges with the enlarging tumor, it usually, 
sooner or later, breaks through this and infiltrates adjacent tissues. 
They may form metastases and frequently grow to a very great size, 
though relatively much more benign in nature than the other types of 
sarcoma. The giant celled sarcomata arising in the maxillary borders 
Fig. 212.-Epulis of the Gum. 
Showing the Langhans' type of giant cell as seen in these growths. Also the spongy soft connective 
tissue in which the cells lie. Numerous leucocytes and red blood cells are seen in the section. 
(epulis) are generally quite innocuous if carefully removed. In one series 
only two recurrences were noted in seventy cases. If the excision is 
imperfect, repeated local recurrences may take place without metastases 
forming elsewhere in the body. The periosteal forms are apt to be 
firmer in texture, and are prone to the development of irregular masses 
of new bone within them, thus forming one of the varieties of osteo- 
sarcoma. 
Osteo-sarcoma.-These are spindle- or round-celled tumors, usually, 
but not always, connected with bone, in which irregular masses of bone 
tissue are present. The bone is usually of irregular atypical structure, 
the regular lamellation and typical Haversian canals being usually 
absent (Fig. 211). Not infrequently calcification is very imperfect or 374 
TUMORS 
absent. The osteo-sarcomata are prone to form metastases, especially 
in the lungs, in which are present all the characters of the original growth. 
Angio-sarcoma.-In many of the sarcomata in various parts of the 
body the blood-vessels form so prominent and important a feature as 
to give special character to the growth, not alone by their size and 
Fig. 213.-Angio-sarcoma. 
Tumor from the arm. Sometimes called perithelial sarcoma. 
general prominence (Fig. 213), but sometimes by the peculiar arrange- 
ment which their presence gives to the cells. While in most of the 
sarcomata the blood-vessels have a very important influence in determin- 
ing the topography of the tumor, in most of the denser and in many of 
the softer varieties this influence is not easily traced. In many forms, 
however, particularly those which are soft and very cellular, the cells 
are closely grouped around the vessels, developing in their adventitiae 
Fig. 214.-Angio-sarcoma. 
Fig. 215.-Angio-sarcoma. Endothelioma? 
One of the blood-vessels with its cellular sheath 
from the tumor shown in Fig. 213. 
Tumor of lymph-node. 
and forming sheaths around them (Figs. 213 and 214). The masses of 
cells thus formed, with a blood-vessel for a centre, may be closely packed 
together in long strings with more or less frequent anastomoses or they 
may be arranged in rounded groups, giving to the tumor an alveolar 
appearance (Fig. 215). Such tumors are called angio-sarcomata. TUMORS 
375 
Simple vascularity, although this be extreme, does not make of a tumor 
an angio-sarcoma. 
Alveolar Sarcoma.-Sometimes, as above stated, the basement sub- 
stance of the sarcomata, particularly in some of the round-celled varieties, 
is quite abundant and arranged in a wide-meshed net, in the meshes of 
which the cells lie. These spaces are called alveoli, and this variety 
of structure has acquired importance from the general resemblance 
which these tumors have to the well-defined and characteristic alveolar 
structure which many of the carcinomata exhibit. It is true that 
occasionally the resemblance is very close indeed, but usually the sar- 
comata present a more or less intimate relation between the cells and 
basement substance. The cells usually do not simply lie in the cavities, 
but are often attached to the intercellular substance, which not seldom 
sends finer trabeculse into the alveoli between the cells. A careful study 
of sections especially prepared to show the finer connective-tissue fibrils, 
by silver impregnation for example, may be required and sometimes a 
careful shaking of sections in water is necessary to reveal the characters 
Fig. 216.-Myxo-sarcoma of the Parotid. 
of the reticulum. The cells, moreover, are usually, though not always, 
distinctive in character. This form of tumor is, in some cases at least, 
determined, as above stated, by the new formation and peculiar arrange- 
ment of the blood-vessels. Tumors of this kind are not common, but 
may occur in the skin, lymph-nodes, bone, and pia mater. They are 
usually very malignant. Many of these tumors are doubtless more 
properly classed among the endotheliomata, while some, especially those 
from the skin and from the lymph-nodes of the neck are not improbably 
derived from epithelium left during embryonic development. 
Mixed Forms of Sarcoma.-In addition to the above more or less well- 
defined forms of sarcoma, there exist various modifications which have 
received special names. The sarcomata in which cysts form, either by 
the softening of tissue by degeneration, or by the dilatation of gland 
ducts by pressure, or by the new formation of tissue in gland ducts or 
alveoli which dilate with the growth of the tumor, have received the 
name of cystosarcomata. 376 
TUMORS 
Mucous degeneration is frequent in the various forms of sarcoma. A 
combination of myxoma and sarcoma-myxosarcoma-is common (see 
Fig. 216). 
Combinations of sarcoma with fat tissue, liposarcoma; with glandu- 
lar structure, adenosarcoma (Fig. 217); with cartilage, chondrosarcoma; 
with muscle tissue, myosarcoma; and with various other tissues, are of 
frequent occurrence. Usually these accessory forms of connective or 
epithelial tissue structures play a subsidiary part in the metastatic 
activities of the growth, but in rare instances muscle fibres seem to obtain 
some of the powers of indefinite multiplication generally observed only 
in the less specialized forms of connective tissue, and tumors made up 
Fig. 217.-Adeno-sarcoma of Parotid. 
almost wholly of such fibres have been reported. This form of new 
growth is sometimes termed a malignant myoma but generally is classi- 
fied as a myo-sarcoma. 
Some forms of psammoma, or " brain-sand/' found chiefly in the dura 
mater, are fibrosarcomata or endotheliomata, which have undergone 
calcification, the lime being deposited in lamellated masses of various 
shapes within them. p 
Some of the soft papillomata and warts, and occasionally the polypi 
of the mucous membranes, belong to the type of sarcoma or myxo- 
sarcoma. 
The so-called chloroma is a small round-celled growth characterized by 
its greenish color; it occurs with especial frequency in bone and is often 
multiple. The nature of the coloring material is uncertain (see p. 478).1 
A special type of sarcoma is one arising from the cells of the bone 
marrow, known as myeloma. The growth is usually multiple, occurring 
1 For a discussion of the relationship of chloroma to blood pictures simulating certain types of 
leukaemia see Dock, Amer. Jour. Med. Sci., vol. cvi., p. 152, 1893, bibl., Sternberg, Lubarsch and 
Ostertag's "Ergebnisse d. allg. Path.," Jahrg. 9, Abth. 1903, p. 360; and Lehndorff, Ergebnisse d. 
inner. Med., 1910, Bd. vi., p. 221. TUMORS 
377 
most frequently in the skull, vertebral column, and thorax, and leads to 
absorption of the bone. As a rule, in contrast to chloroma, no marked 
changes are seen in the circulating blood. For further details see p. 902. 
ENDOTHELIOMA. 
An endothelioma is a tumor derived from endothelium. It most 
commonly originates in the endothelium of the blood- or lymph-vessels 
or the lymph-spaces. 
Tumors originating in the mesothelium of the great serous cavities, 
the pleural, pericardial, and peritoneal, are in many respects similar to 
those arising from the blood- and lymph-vessel endothelium, and we may 
therefore for the present group them among the endotheliomata, though 
it might, on some accounts, be better to call them mesotheliomata.1 A 
certain proportion of the gelatinous 
tumors covering the surface of the 
peritoneum have been shown to 
arise from small primary growths 
of the ovary, the mucous mem- 
brane of the gall-bladder, or the 
gastro-intestinal tract; it is there- 
fore important to exclude this 
particular group from the endo- 
theliomata. 
Endothelial cells are normally 
elongated and thin, forming a 
mosaic over the surfaces which 
they line. 'Under various ab- 
normal conditions, however, in 
hyperplasia, in inflammation, and 
in the reparative processes, these 
cells may become thicker 'than 
normal, evejn cuboidal in shape. 
So also in the endotheliomata, 
the cells seldom resemble the normal endothelium, but are cuboidal, 
polyhedral, or even cylindrical in shape, or on pressure may assume 
elongated, fusiform, or other bizarre forms. The cells in endotheliomata 
may form more or less distinct tubular structures, recalling their original 
function as lining cells, but they may be piled in several layers over one 
another with an open lumen here and there, or finally they may form 
solid reticular masses, scarcely to be distinguished on morphological 
grounds, with our present knowledge, from certain forms of epithelial- 
cell tumors-carcinoma. 
The cell masses in endothelioma are enclosed by a varying amount 
of fibrous tissue, either old or new-formed. This stroma is often vascu- 
lar and sometimes appears in places to consist almost wholly of vessels 
Fig. 218.-Endothelioma of the Thyroid 
Gland. 
Showing an early phase of cell proliferation in 
the lymph-spaces. 
1 For a study of the relationship between endothelium and mesothelium see Minot, Science, Mar. 29, 
1901. 378 
TUMORS 
around which the tumor cells are packed, the whole resembling some of 
the forms of angio-sarcoma. 
These tumors developing from the endothelium of the vessels or 
Fig. 219.-Endothelioma (Endothelial Sarcoma) of Dura Mater. 
lymph-spaces sometimes exhibit a structure closely simulating that of 
tubular glands lined with more or less cuboidal epithelium (Fig. 218). 
When originating in the blood-vessels these tumors are called hcemangio- 
Fig. 220.-Endothelioma of Dura Mater. 
Psammomatous form. 
endotheliomata; when derived from the lymph-vessels they are called 
lymphangio-endotheliomata. 
Sometimes the cells of the endotheliomata are packed together in 
dense concentric masses, which may have a glistening appearance, and TUMORS 
379 
such tumors are sometimes called cholesteatomata.1 Although, for the 
most part, the peculiar glistening appearance of these tumors is due to 
the closely packed thin cells which compose them, they not infrequently 
contain crystals of cholesterin, which may share in producing this char- 
acteristic appearance. But the cholesterin may be absent, or present 
in small amount. 
In the dura mater endotheliomata are formed of densely packed 
masses of flattened cells (Fig. 219); or the cells, often polyhedral or 
cuboidal in shape, are grouped around blood-vessels (Fig. 227); or, finally, 
they develop in closely packed concentric masses forming one of the 
types of psammoma (Figs. 220 and 221). . 
Fig. 221.-Endothelioma of Duba Mateb. 
Psammomatous form. 
The stroma of the endotheliomata may undergo various forms of 
alteration, developing hyaline, myxomatous, or cartilaginous, or very 
dense fibrous characters (Fig. 222); or it may atrophy, leaving the pro- 
liferated endothelium and the blood-vessels as the chief structural 
elements. On the other hand, hyaline and mucous degeneration of the 
endothelial cells may occur (Fig. 223), and considerable collections of 
these materials, free from the cells but surrounded by the cell masses, 
may give a cystic character or lend a glandular appearance to the growth. 
Such tumors-in which homogeneous or striated cylinders of hyaline 
or mucoid material (Fig. 224), often closely surrounded by layers of 
cuboidal or flattened cells (Fig. 225) > form a striking feature-have 
1 It is believed by Bostroem, Ribbert, and others that the cholesteatomata are dermoid structures 
formed from displaced epidermal tissue. See Bostroem, Centbl. f. allg. Path., Bd. viii., p. 1, 1897; 
Ribbert, "Lehrb. d. allg. Path.," p. 560, 1905. 380 
TUMORS 
sometimes been called cylindromata. It is probable that some of the 
tumors included here belong more properly among the so-called basal- 
celled carcinomata (see p. 408). 
The stroma of the endothelioma may become sarcomatous and thus a 
mixed tumor-a sarcomatous endothelioma-may be formed. 
The endotheliomata may be single, nodular, and of considerable size; 
or they may be multiple, numerous small tumors being scattered over 
the surface of the part in which they grow. They may even form a 
thick or thin pellicle over surfaces, or cause adhesions between adjacent 
organs. They may form metastases. 
Showing dense connective tissue surrounding the blood-vessels between the reticular endothelial-cell 
masses. 
Fig. 222.-Endothelioma of Upper Jaw. 
They occur in the dura mater and pia mater, in the pleura and perit- 
oneum, and tumors thus named have been described as occurring in 
the skin, bone, gums, lymph-nodes, ovary, liver, brain, testicle, glandula 
carotica, and salivary glands.1 
It is probable, however, that a considerable number of these tumors, 
especially those of the salivary glands, should be grouped among epithe- 
lial growths arising in some congenital anomaly. See Tumors of the 
Salivary Glands, p. 700.2 
1 For a discussion of the endotheliomata consult: 
v. Volkmann, "Ueber endotheliale Geschwiilste," Deutsch. Zeits. f. Chir., Bd. xli., p. 1. Lubarsch, 
"Ergebnisse d. allg. Path.," Jahrg. i., Ab th. 2, p. 366; also "Endotheliom.," ibid., Jahrg. ii., p. 592. 
For embryological considerations bearing on the subject see: 
Glockner, Zeits. f. Heilkunde, Bd. xviii., p. 209, 1897; Marchand, Verh. der Deutsch, path. Gesell- 
sch., Bd. ii., p. 38, 1900. 
On the occurrence of giant cells and cells with very large nuclei in endothelioma see Glockner, 
Ziegler's Beitr., Bd. xxvi., p. 73, 1900. 
2 For a study of tumors of the salivary glands and their alleged nature see Wood, Annals of Surgery 
vol. xxxix., p. 57, 1904. The difficulty of diagnosis in certain of the endotheliomata depends 
upon the fact that the cells in the developed tumors assume forms so 
entirely different from the normal endothelium, and upon the impossi- 
bility in many cases of detecting the origin of the tumor.'°In many 
instances one is forced to rely in a measure upon the probabilities of 
origin as indicated by the seat of the tumor. 
TUMORS 
381 
Fig. 223.-Endothelioma of Pleura. 
Showing the formation of mucus within the endothelial-cell masses; the mucus is stained with haema- 
toxylin. 
The alleged transition forms of cells which may be found in the peri- 
phery of such tumors between the tumor cells and the endothelium 
of blood- or lymph-vessels must be accepted with caution as evidence, 
since we have reason to believe, as we have seen above (p. 337), that the 
characteristic cells of a tumor are the direct descendants of those in 
which the growth started and are not derived from a later growth of 
the cells of the part in which the tumor is situated. 
One may be able to differentiate between carcinoma and endothe- 
lioma by the discovery of definite epithelial characters in the cells, such 
as secretion products, spines, and corneous transformations. Or, on 382 
TUMORS 
the other hand, one may discover a more intimate relationship between 
the cells and the stroma which characterizes the endotheliomata as 
tumors of the connective-tissue type. Thus in some endotheliomata 
one may discover that the external layers even of cuboidal cells send 
processes out among the surrounding fibrils of the stroma. One may 
furthermore discover a small amount of fibrillar tissue among the cell 
masses in the endotheliomata which otherwise resemble epithelium. 
LIPOMA. 
Lipomata are tumors formed of fat tissue. The fat tissue (Fig. 228) 
occurs in lobules and is similar to normal fat, except that the cells and 
lobules are usually larger and less regularly arranged. Occasionally a 
Showing formation of mucus in the gland-like endothelial-cell masses. This form of tumor is often 
called "cylindroma." 
Fig. 224.-Endothelioma of Upper Jaw. 
considerable number of the cells resemble those of embryonic or rapidly 
growing fat tissue. There may be little connective tissue in the tumors, 
when they are very soft, almost fluctuating-lipoma molle-or there may 
be so much as to give the tumor considerable firmness-fibro-lipoma. 
They may be in part transformed into mucous tissue-myxo-lipoma. 
Cartilage not infrequently develops in them, or they may undergo par- 
tial calcification. 
Occasionally the blood-vessels are very abundant and dilated- 
angio-lipoma. They are usually sharply circumscribed, but may infil- 
trate surrounding tissues. They are not infrequently pedunculated. 
They sometimes grow to enormous size and may ulcerate. 
They are usually isolated, but may be multiple, and are occasionally TUMORS 
383 
symmetrically arranged in relation to the median dorso-ventral plane 
of the body. They are common tumors, occurring usually in the sub- 
cutaneous or other fat tissue. They may occur in the mucous membrane 
of the gastro-intestinal canal, in the peritoneum, more rarely in the dura 
mater, kidney, liver, and lungs. They are benign tumors, not forming 
metastases; but they may be deleterious by ulceration or gangrene, and 
when not fully removed may exhibit local recurrence. They may 
become sarcomatous. 
CHONDROMA. 
These tumors, composed of either of the forms of cartilage, are usually 
hard, but sometimes quite soft. The cells do not present the same 
uniformity in size, shape, number, and relative position that they do in 
Fig. 225.-Basal-celled Epithelioma of Antrum. 
This complex form of tumor is often considered as endothelial in nature. 
normal cartilage (Fig. 229). Sometimes they are very large, spheroidal, 
and grouped in masses, and again small and far apart. They are fre- 
quently fusiform or branching. Fibrillar connective tissue in varying 
quantity is usually present in the chondromata, either as a perichondrial 
capsule or running in bands between the nodules of cartilage, or passing 
in fascicles into them.1 
The cartilage may change to mucous tissue, forming myxo-chondroma, 
the cells may undergo fatty degeneration or they may calcify or ossify- 
osteo-chondroma. Chondromata frequently form a part of mixed and 
complex tumors. 
They may form in connection with bone or cartilage usually at an 
epiphyseal line or in subcutaneous connective tissue and fasciae. They 
1 For a study of the minute structure of cartilage tumors see Ernst, Ziegler's Beitr., Bd. xxxviii., 
p. 67, 1905. 384 
TUMORS 
may occur in soft parts where cartilage is not normally present, as in the 
parotid, testicle, mamma, and ovaries, where they are apt to be mixed 
with other tissue. Under these conditions they doubtless arise from 
developmental anomalies. They may form in the lungs in connection 
with the bronchial cartilages or from embryonal displacement of portions 
of these. 
Chondromata are in general benign tumors. Sometimes, however, 
they assume malignant characters, encroaching largely upon adjacent 
tissues, growing into and along the lumen of blood-vessels and forming 
metastases, especially in the lungs and heart.1 The malignant chondro- 
Fig. 226.-Sacrococcygeal Chordoma. 
mata are softer than others and may be even of gelatinous consistence. 
A critical re-examination of some of the reported metastases has shown 
that the phenomenon has occurred in the mixed types rather than in the 
pure chondromata in which recurrence is apt to be local only. 
Small hyperplastic growths on the surfaces of cartilages are called 
ecchondroses. 
CHORDOMA. 
The chorda dorsalis, an important structure in the embryo, persists 
in the adult only as a small remnant in the intervertebral discs. The 
tissue consists of large cells with swollen cell bodies lying in a homo- 
geneous, jelly-like stroma. The extremely rare tumors of this tissue 
are found most frequently at the base of the brain on the clivus just 
behind the sella turcica. They may, however, occur anywhere along 
1 For a study of metastases in chondroma see Ernst, Ziegler's Beitr., Bd. xxviii., p 255, 1900, bibl. TUMORS 
385 
the spinal cord or grow from the sacrum and coccyx. The small tumors 
occurring at the base of the brain are often quite benign, but a consider- 
able number are now on record in which the tumor developed into a large 
mass infiltrating the brain substance1 or grew into the roof of the pharynx.2 
Both benign and malignant growths have been described as derived 
from the sacrum.3 
Fig. 227.-Endothelioma of Humerus. 
Type resembling angio-sarcoma. 
In those tumors which reach a large size and show evidence of malig- 
nancy the cells vary considerably from the original type of the chorda 
tissue (Fig. 226). 
OSTEOMA. 
The formation of bone in the body in abnormal places occurs quite 
frequently and under a great variety of conditions. It is on this account 
not easy to define the term osteoma, and it is frequently difficult to 
decide whether or not a given mass of new-formed bone should be thus 
designated. Bone tissue often occurs in tumors of the connective-tissue 
group as a secondary or complicating structure-osteo-fibroma, osteo- 
chondroma, osteo-sarcoma, etc. It may occur in muscles or fascia as a 
result of the repeated trauma of certain exercises, or as a result of a 
1 Jelliffe and Larkin, Jour. Nerv. and Ment. Dis., 1912, xxxix, 1. 
2 Linck, Ziegler's Beitr., 1909, xlvi., 573. 
3 Feldmann, Ziegler's Beitr., 1910, Ixviii., 630. 
For a full bibliography see Ribbert, Geschwulstlehre, Bonn, 1904, p. 149; also Frenkel et Bassal, 
Arch, de med. exper., 1910, xxii., 703. 386 
TUMORS 
peculiar inflammatory process, Myositis ossificans, or it may occur in con- 
nection with chronic inflammation in a variety of tissues. A circum- 
scribed mass of abnormal bone, not of inflammatory origin, may be called 
an osteoma. Small masses of new-formed bone of various shape, pro- 
Fig. 228.-Lipoma. 
The section shows a small portion of the tumor near the surrounding fibrous tissue. 
jecting from a bony surface and frequently of inflammatory origin, are 
usually called osteophytes. Bony tumors projecting from the surface of 
bones are frequently called exostoses. 
An osteoma may be loose in texture, consisting of bone tissue similar 
to cancellous tissue; or it may be very hard and dense like ivory, so 
Fig. 229.-Chondroma of Femur. 
called ivory exostoses. The difference between these forms lies chiefly 
in the varying number and size of the vascular and medullary spaces 
which they contain. The growth of the osteomata is, as a rule, slow. 
They are benign tumors, and are not infrequently multiple. TUMORS 
387 
Osteomata may develop in connection with the bone or periosteum, 
which is most frequently the case, or, independently of bone, in soft parts. 
New-formed bone has been found in the soft parts of the body; in 
the brain substance, dura mater, and pia mater; in the pleura, diaphragm, 
and pericardium; in the skin, choroid, air passages, lungs, kidneys, aorta, 
and penis, and in other places. 
To what extent some of these 
bone formations may have been 
due to inflammatory action it is 
not possible to say, but it seems 
probable that in many of the 
cases cited above an inflamma- 
tory or degenerative process pre- 
ceded the bone formation. 
Odontoma.-Tumors are some- 
times formed from the pulp dur- 
ing the development of the teeth. 
When these contain dentin they 
are called odontomata. 
Fig. 230.-Glioma of Bkain. 
GLIOMA. 
The gliomata are developed from the characteristic framework of 
nerve tissue, the neuroglia, which in structure many, though usually not 
all, of its cells closely resemble. Small cells with inconspicuous bodies 
and numerous delicate branching processes are most characteristic; but 
in connection with these there is usually a greater or less number of 
small spheroidal cells with pro- 
portionally large nuclei (Fig. 
230). It is usually necessary to 
shake sections in water or care- 
fully tease fragments of the 
tumor in order to see the char- 
acteristic neuroglia or so-called 
"spider" cells (Fig. 231). bit is 
held by Weigert and others that 
the so-called branches of the 
neuroglia cells are rather fibrils 
lying close beside ,the cells than 
actual branches.1' Certain glio- 
mata are marked by an alveolar 
arrangement of their cells which 
resemble the ependymal cells and may line small cavities or present a 
rosette-like arrangement; one side of the cells being free, the others 
sending prolongations into the surrounding tissues. Such tumors most 
clearly reveal their ectodermal origin. 
Gliomata may contain very numerous and frequently dilated thin- 
Fig. 231.-Neuroglia or "Spider" Cells 
from Glioma of the Brain. 
Teased specimen. 
1 See ref. Mallory, foot-note, p. 388. 388 
TUMORS 
walled blood-vessels. They may be very soft or moderately hard; and, 
especially when occurring in the substance of the brain, are frequently 
not sharply outlined against the adjacent normal tissue. They usually 
occpr singly, and are comparatively slow in growth. 
( .They are frequently associated with other tumor tissue, forming 
glio-myxoma, glio-sarcoma, etc. Owing to the abundance of thin-walled 
blood-vessels and the softness of the growth, they are liable to inter- 
stitial haemorrhages, and may then, when occurring in the brain, readily 
be mistaken for ordinary apoplectic clots. They are liable to fatty 
degeneration. They usually occur in the brain, spinal cord, and in the 
optic and other cerebral nerves. Some of the so-called gliomata of the 
retina are apparently small spheroidal-celled sarcomata; others arising 
through embryonal defects from the external retinal layers are called 
neuro-epitheliomata. 
Pure gliomata are benign tumors, though in their most common 
combination with sarcoma they may be very malignant. Their usual 
situation, however, is such as to make them almost always significant, 
although technically they are benign tumors.1 
This is of the smooth-muscle type-leiomyoma-and shows one bundle of muscle cells cut lengthwise, 
others across. 
Fig. 232.-Myoma of the Uterus. 
MYOMA. 
Tumors composed of muscle tissue are of two kinds, following the 
two normal types of muscle, the non-striated and the striated. 
I. Leiomyoma, Myoma Levicellulare.-The characteristic elements of 
these tumors are fusiform, smooth muscle cells, with elongated or rod- 
shaped nuclei. These are packed closely together, frequently inter- 
lacing and running in various directions, and are intermingled with a 
variable quantity of more or less vascular fibrillar connective tissue 
(Fig. 232). When, as is not infrequently the case, the connective-tissue 
elements are present in large amount, the tumor is called a fibrous 
1 Our knowledge of the normal neuroglia is still too meagre to permit us to understand very thor- 
oughly this class of tumors, and to separate it as precisely as could be wished from certain of its allies 
among the abnormal connective-tissue growths. For a study of "neuroglia fibrils" and the classifica- 
tion of the gliomata see Mallory, Jour. Med. Res., vol. xiii., p. 113, 1905; Jour. Exp. Med., vol. x, 
p. 575, 1908. TUMORS 
389 
myoma. In such tumors it should be remembered that the muscle, not 
the connective tissue, is still the essential characteristic feature (Fig. 233). 
It is not always easy to distinguish leiomyomata from certain con- 
nective-tissue tumors, small spindle-celled sarcoma, cellular fibromata. 
In normal smooth muscle tissue the characteristic cell is spindle-shaped, 
sharply outlined with rod-shaped 
nuclei. The tapering cells are 
placed with overlapping ends, in 
clusters and bundles surrounded 
by more or less fibrillar connective 
tissue which bears the vessels and 
nerves. In addition to certain 
fibrils within the cells, the smooth 
muscle cells are furnished with 
delicate fibrils lying along the peri- 
phery of the cell parallel with its 
long axis, and extending along the 
overlapping cell columns. These 
are called myoglia fibrils. 
In leiomyomata the muscle cells 
as well as their nuclei vary con- 
siderably in shape. They both 
may be long and slender, or short 
and plump, the latter forms with 
mitotic figures prevailing especially 
in the more rapidly growing forms. 
The myoglia fibrils are present in 
the tumors also and may present 
considerable variations in size, arrangement, etc.1 
These tumors may become cedematous, and, owing to their density 
and lack of blood-vessels, they not infrequently degenerate; forming 
cysts or becoming gangrenous. They frequently undergo hyaline degen- 
eration and calcification. They may occur singly or be multiple, are 
usually of slow growth, may be large or small, and are, for the most 
part, benign. But, especially in the uterus, they may become large, 
and being often multiple may lead to serious disturbance. On the other 
hand, a few instances are recorded of myomata in the uterus and gastro- 
intestinal canal which have been rapidly growing, locally invasive, and 
have metastasized. These are called malignant leiomyomata. Leio- 
myomata may occur wherever smooth muscle tissue exists. They are 
most frequently found in the uterus, where they are often multiple. 
They may occur in the wall of the gastro-intestinal canal, and have been 
seen in the kidney, in the bladder, and in the skin. A certain proportion 
of the so-called hypertrophies of the prostate, so frequent in advanced 
life, are sometimes considered leiomyomata of the interstitial muscle 
tissue of that gland. For a description of glandular myomata of the 
uterus see p. 813. 
The muscle cells are crowded apart by dense 
fibrous tissue. 
Fig. 233.-Fibro-myoma of Uterus. 
1 See, for methods of staining myoglia fibrils, Mallory, Jour. Med. Res., vol. xiii., p. 124, 1905. 390 
TUMORS 
II. Myoma Striocellulare, or Rhabdomyoma.-In these rare tumors 
striated muscle fibres are the characteristic elements. They very rarely 
compose a great part of the tumor, but are intermingled with other 
elements, fibrillar connective tissue, spindle-shaped and spheroidal 
cells of various forms, which often appear to be incompletely developed 
muscle cells. They are not infrequently associated with sarcomatous tis- 
sue. Blood-vessels and sometimes nerves are also present. The muscle 
fibres differ, as a rule, from normal striated muscle fibres in their arrange- 
ment, which is usually quite irregular, and also in size, being in general 
smaller than normal fibers, although varying greatly. The sarcolemma 
is either absent or incompletely developed. These tumors are usually 
small or of moderate size, and are supposed to originate from inclusions 
of cells destined to form muscle tissue in places where they do not belong. 
In the heart and certain other muscular parts, small circumscribed 
masses of striated muscle tissue have been described, and are sometimes 
called homologous rhabdomyomata. But genuine heterologous rhabdomyo- 
mata are, in almost all cases thus far recorded, confined to the genito- 
urinary organs, kidney, ovary, and testicles. The writer has described 
an exceptional case of rhabdomyoma occurring in the parotid gland.1 
These tumors, when not associated with other and malignant tumors, 
are usually benign and are of greater theoretical than practical interest.2 
NEUROMA. 
A true neuroma is a tumor containing new-formed nerve tissue. Such 
tumors are comparatively rare. Tumors developed in the connective 
tissue of nerves and composed usually of fibrous or mucous tissue are 
common, and are frequently 
called neuromata, but they 
should be called fibromata or 
myomata, etc., of the nerves, 
or false neuromata. The true 
neuromata are of two kinds, 
ganglionic or cellular neuromata 
and fibrillar neuromata, depend- 
ing upon the character of nerve 
tissue which they contain. The 
ganglionic neuromata-neuro ma 
ganglioniforme-in which new- 
formed nerve cells are present 
(Fig. 234), are found associated 
with other structures in certain of the teratomata in the ovaries, testicles, 
and in the sacral region; they also occur in the gray matter of the brain. 
They have been found in the adrenals and may also contain sarcomatous 
elements. 
Fig. 234.-Neuroma Ganglioniforme. 
Section from a tumor of the adrenal. 
1 Prudden, Amer. Jour. Med. Sci., vol. Ixxxv., p. 438, 1883. For later bibl. consult Helbing, 
Centralbl. f. Path., Bd. ix., p. 433, 1898. 
2 For a study of malignant rhabdomyoma see Burgess, Jour. Med. Res., 1914, N. S. xix., 447 (bib!.). TUMORS 
391 
The fibrillar neuromata are, according to Virchow, of two kinds, 
myelinic and amyelinic, depending upon whether the nerve fibres which 
they contain are medullated or not. The neuroma myelinicum is the 
more common and the better understood. The medullated nerve fibres 
in these tumors are associated with fibrillar connective tissue, and are 
usually curled and intertwined in a most intricate manner. They are 
The fibrous tissue is loose in texture and in places oedematous, so that many of the nerve fibres 
pass through the tumor with little structural alteration. 
Fig. 235.-False Neuroma-Fibroma of Lumbar Nerve. 
either single or multiple on the peripheral nerves. They may occur in 
considerable numbers as nodular tumors on the branches of a single nerve 
trunk, or they may form an irregular, diffuse, nodulated enlargement 
of the nerve branches-plexiform neuroma. These neuromata may or 
may not be painful. They not infrequently form at the cut ends of the 
nerves in amputation stumps. They are benign tumors, never forming 
metastases. 
Fig. 236.-Multiple Fibromata (False Neuromata) of Pneumogastric Nerve. 
One-quarter natural size. 
From the same case as that from which the photographic reproduction of Fig. 237 is made. 
The false neuromata are myxomata, or fibromata (Fig. 235), or some- 
times myxo-sacromata of the nerve sheaths or intrafascicular connective 
tissue, and may be single or multiple. In the latter case they may affect 
the branches of a single nerve trunk (Fig. 236), or they may be found 
on nearly- all the cerebro-spinal peripheral nerves. The writer has 
described a case (Figs. 236 and 237), in which more than eleven hundred 392 
TUMORS 
Fig. 237.-Multiple Fibromata (False Neuromata) of the Peripheral Nerves of the Arm 
and Leg. 
A, Nerves of the right arm; B, the left sciatic with its branches; C, the left anterior crural with 
its branches. From the same case as Fig. 236. The nerves of the other extremities were similarly in- 
volved. TUMORS 
393 
and eighty-two distinct tumors were found distributed over nearly all 
the peripheral nerves of the body.1 
The nerve fibres in these tumors may be crowded apart by the new 
growth and considerably atrophied; or, in cases in which the tumor is 
composed of soft tissue, as in myxoma or the soft fibroma, they may 
pass through or around the tumor entirely unchanged. The multiple 
false neuromata are in many cases congenital.2 
ANGIOMA. 
Angiomata are tumors consisting in large part or entirely of new- 
formed blood- or lymph-vessels or cavities. In many tumors of various 
kinds the new-formed or the old blood- and lymph-vessels may be very 
abundant or prominent by reason of their dilatations; the vessels of 
otherwise normal tissues may also be largely dilated, thus simulating- 
vascular tumors. These are, however, not true angiomata, although 
sometimes reckoned among them, and in many cases closely allied to 
them. Such are the so-called arterial varix, or cirsoid aneurisms, and 
Fig. 238.-Angioma Telangiectoides from the Skin. 
This section is from a vascular naevus, "strawberry mark," of the skin. 
haemorrhoids, and various lymphectasiae. True angiomata are of two 
kinds-I. Haemangioma, and II. Lymphangioma. 
I. Haemangioma.-These tumors are of two types: 1. Those formed 
largely of capillary blood-vessels with either thin or thickened walls, 
embedded in a more or less abundant connective-tissue stroma. These 
are called simple angiomata or angioma telangiectoides (Fig. 238). The 
walls of the vessels in these tumors are frequently dilated or pouched, 
and usually form a tangle of curled and intertwined vessels. They 
1 Prudden, Amer. Jour. Med. Sei., vol. Ixxx., p. 134, 1880. Consult also Preble and Hektoen, 
Trans. Assn. Am. Phys., vol. xv., p. 470, 1900, bibl. 
2 For association of these tumors with sarcoma see Larkin, Jour. Med. Res., vol. ix., p. 217, 1903. 394 
TUMORS 
occur most frequently in the skin or subcutaneous tissues, usually about 
the face, and may project above the general surface or be on a level with 
it. Such are the so-called vascular ncevi, or strawberry marks, which are 
usually congenital. They are sometimes sharply circumscribed, and 
Fig. 239.-Angioma Cavernosum of Liver. 
This section shows the entire small tumor. 
sometimes merge imperceptibly into the surrounding skin. They some- 
times occur in the mucous membranes, in the mamma, bones, and brain. 
They are benign tumors, never forming metastases, but may be asso- 
ciated with sarcomata. 
2. The second form of haemangioma, called angioma cavernosum (Fig. 
Fig. 240.-Congenital Lymphangioma from Arm of Child. 
239), consists largely of a series of intercommunicating, irregular-shaped, 
larger and smaller blood-spaces lined with endothelium, and surrounded 
by a variable quantity of fibrillar connective tissue, which may contain 
smooth*muscle cells. They resemble the erectile tissue of the corpora TUMORS 
395 
cavernosa of the penis and clitoris. They are apparently formed by a 
dilatation of old and new-formed capillaries and veins. They are some- 
times erectile and sometimes pulsating, and are not infrequently multi- 
ple. They may be seated in the skin and subcutaneous tissue, forming 
the so-called projecting naevi, or in internal organs. They are often 
found in the liver and less frequently in bone, the brain, spleen, uterus, 
kidney, intestines, bladder, and muscles. They are usually of little 
significance, though they may give rise to haemorrhages. 
IL Lymphangioma.-These tumors consist of dilated lymph channels 
which either preserve approximately the general shape of the original 
lymph-vessels, or are distinctly cavernous in character (Fig. 240) or even 
cystic. They probably originate in part in new-formed, in part in old 
lymph channels. A strict distinction between tumors formed by a 
dilatation of pre-formed and new-formed lymph channels is not possible, 
owing to the very primitive character of some of the ultimate lymph- 
spaces and our lack of knowledge of their exact relations to adjacent 
parts. 
In the lymphangiomata there may be much or little connective tissue 
between the dilated channels, which are usually filled with a translucent 
or milky fluid resembling normal lymph. These tumors are usually 
congenital, but are sometimes acquired. They usually occur in the 
skin as soft, sometimes considerably, sometimes but slightly elevated 
growths, and may occur in the tongue-some forms of so-called macro- 
glossia. They are benign tumors, but may rupture, giving rise to serious 
lymphorrhoea. 
Tumors in Which Epithelial Cells are Predominant or Characteristic 
Elements-Epithelial Tumors. 
I. ADENOMA. II. CARCINOMA. 
General Considerations Regarding Epithelial-cell Tumors. 
While in the main, in the normal body, the general distinctions 
between epithelial and other tissues are fairly well marked, there are 
instances, especially those in which epithelial tissues are in process of 
physiological growth or rejuvenation, in which the distinctions are quite 
ill-defined. When we remember the rapid growth of many tumors, the 
tendency to incomplete formation of their cells, their diverse seats, and 
the various complicating conditions under w'hich they originate and 
develop, it does not seem strange that the exact limitations of this class 
of tumors are not easy to fix, nor that they seem sometimes to merge into 
one another and into tumor tissues belonging to other classes. If epi- 
thelial cells, under all circumstances, had a definite and characteristic 
structure, or if, on the other hand, we could always know whether a 
given cell group originated in epithelium or not, the matter of distin- 
guishing between tumors of this and other classes would be simple and 
easy enough. As it is, in some cases both morphological and histogenetic 396 
TUMORS 
criteria fail us, and the clinical history and gross appearance are not 
characteristic. Such instances-which are indeed rare-suggest the 
possibility that the facts at our command do not justify such definite 
distinctions between epithelial and certain other tumors as on both 
theoretical and practical grounds we should like to command. While 
these difficulties in special cases must be acknowledged, the distinctions 
are in the main definite enough, and very useful both for clinical and 
scientific purposes.1 
Epithelial tumors always contain, in addition to the more or less 
characteristic cellular elements, a connective-tissue stroma which gives 
them support and carries the vessels (Fig. 241). This stroma may be 
sparse or abundant, may contain few or many cells, is sometimes ar- 
ranged in irregular fascicles or bands, and very frequently forms the 
walls of well-defined, variously shaped spaces or cavities called alveoli, 
in which the epithelial cells lie. 
Fig. 241.-Carcinoma of the Stomach-Medullary Carcinoma or Carcinoma Molle. 
In tumors of the adenomatous type the epithelium and the connective 
tissue grow co-ordinately, producing structures in which the relative 
proportions of cell and stroma correspond approximately to those seen 
in the organ from which the tumor is derived. For this reason, Ribbert 
prefers to designate the adenomata as fibro-epithelial tumors, in distinc- 
tion to the carcinomata where the epithelium forms the real mass of the 
tumor. The epithelial cells, in most cases, lie along the walls of the 
alveoli without an intimate connection with them. They are, moreover, 
packed together without more intercellular substance than the usual 
cementing material common to epithelial-cell masses. In this lack of 
fibrillar intercellular substance within the alveoli, and in the loose 
relationship between the cells and the alveolar walls, lie in many cases 
the chief morphological distinctions between certain carcinomata and 
alveolar sarcomata. 
1 For a study of the relationships between epithelium, endothelium, and connective tissue see 
Krompecher, Ziegler's Beitr., Bd. xxxvii., p. 28, 1905. TUMORS 
397 
In certain of the epithelial tumors there is a reproduction of typical 
gland tissue of various kinds, depending upon the seat and conditions of 
growth of the tumor. Such tumors are called adenomata or fibro-adeno- 
Fig. 242.-Intracanalicular Fibro-adenoma of Breast. 
mata (Fig. 243). A simple hypertrophy of a gland, or an increase in its 
size by excessive growth of its interstitial tissue, does not constitute an 
adenoma. There must be an actual new formation of more or less typical 
Fig. 243.-Adenoma of the Mamma. 
gland tissue. This is not always or frequently of exactly the same char- 
acter as the gland tissue in which it originates, and always exhibits a 
certain lack of conformity to the type in structure and mode of growth. 398 
TUMORS 
The alveoli and ducts usually have a lumen and sometimes a membrana 
propria, but the cells may differ in shape from one another and from 
those of the gland from which they spring. Occasionally the connective 
tissue may quite outgrow the epithelium as in the so-called intracanalicular 
fibro-adenomata of the breast (see Fig. 242). 
Epithelial tumors in which there is no close conformity to a glandular 
type, but an independent and atypical growth of epithelial cells in 
the meshes of an old or new-formed connective-tissue stroma, are called 
carcinomata (Fig. 241). 
It will readily be seen that there must be a border region between 
the adenomata and carcinomata, where conformity to the glandular type 
merges into the lawlessness of growth characteristic of carcinomata. In 
this border region a certain degree of individual bias must be permitted 
in assigning a name to the new growth. In some cases a sharp distinc- 
tion cannot be made; or the tumor may share in the characteristics of 
both, and then we very properly make use of the term adeno-carcinoma 
or carcino-adenoma. 
I. ADENOMA. 
The structure of the cellular elements of these tumors, and their 
arrangement into acini and ducts, vary even more than do those of the 
Fig. 244.-Hyperplasia of Thyroid Tissue without the Formation of Colloid. Often called 
"Fcetal Adenoma of the Thyroid." 
normal glands whose types they follow. The acini usually have a more 
or less well-defined lumen and membrana propria (see Fig. 246). The 
adenomata sometimes merge into the surrounding tissue, or are con- 
tinuous with the gland tissue in which they originate; sometimes they TUMORS 
399 
are distinct in outline and encapsulated. The interstitial tissue is some- 
times abundant, sometimes sparse, and may contain few or many cells. 
The irregularities of their growth often lead to the stoppage of the 
lumina of their ducts and the formation of cysts. They may undergo 
mucous metamorphosis and may become sarcomatous. 
Adenomata occur in the mamma, ovary, liver, kidney, adrenal, 
thyroid (Fig. 244), salivary and lachrymal glands, and in the caruncle; in 
the mucous membrane of the nose, pharynx, stomach, intestine, and 
Fig. 245.-Sebaceous Adenoma from Skin of Forehead. 
uterus; and occasionally in the sebaceous and sweat glands1 of the skin 
(Fig. 245). The so-called multilocular cystomata of the ovary are 
among the most frequent of the adenomata, and not only have a great 
clinical importance but are also interesting because of their peculiar 
morphology, which has led some observers to consider them of a terato- 
logical origin, and their power to give rise to extensive transplantation 
metastases on the surface of the peritoneum. 
1 For a study of sweat-gland adenoma see Landsteiner, Ziegler's Beitr., Bd. xxxix., p. 316, 
1906, bibl. 400 
TUMORS 
There are numerous papillary and polypoid growths, in gland ducts 
and on mucous membranes, in which there is an actual new formation 
of gland epithelium; but this is usually secondary to a primary growth, 
beneath the epithelial layer, of some other tissue, such as fibrous or 
mucous tissue, and the new growth of gland epithelium simply keeps 
pace with the growth of the stroma which it covers. Such growths are 
sometimes classed among the adenomata, but do not, strictly speaking, 
belong there. 
Many of the adenomata are benign tumors, being slow of growth 
and localized, but there are very important exceptions. Some of the 
adenomata of the stomach and intestines belong to the most malignant 
Fig. 246.-Adenoma of Stomach. 
A form of tumor which is on the border line of carcinoma and might be called adeno-carcinoma. 
of tumors in rapidity of local extension, in the formation of metastases, 
and the development of cachexia. Certain of the adenomata of the 
uterus, mamma, and thyroid are also very malignant. It should be 
remarked, however, that, as a rule, the malignant adenomata are those 
which, in structure, lie close upon the border line between tumors of 
this class and carcinomata (see Fig. 246), and by such observers as incline 
to lay more stress upon clinical than upon morphological distinctions they 
are usually classed among the latter. 
II. CARCINOMA. 
The carcinomata are formed of variously shaped, usually elongated, 
and often anastomosing masses of cells derived from epithelium. These 
epithelial-cell masses which constitute the characteristic and more essen- 
tial feature of these tumors are surrounded by more or less fibrillar 
connective-tissue stroma which carries the blood-vessels and may form 
with the tumor or may be, in part at least, a remnant of the tissue in 
which the tumor is growing. TUMORS 
401 
The characteristic epithelial cells of the carcinomata are all the 
descendants of those in which the tumor started; and while they often 
resemble these in type, they usually differ considerably from them in 
appearance, owing to vicissitudes of pressure, nutrition, functional per- 
formance, reversion, etc. The reticular masses of epithelial cells are not 
intermingled with the fibrous stroma, but lie against it in the manner 
Fig. 247.-Cancer Cells Infiltrating the Tissue Spaces in the Vicinity of a Tumor of the 
Mamma. 
From carcinoma mammae. 
characteristic of epithelium in general. In sections of such tumors the 
elongated cell masses are cut across at various angles so that the cells 
frequently appear to be lying in more or less rounded spaces which have 
been called alveoli (Fig. 241). 
A great practical difficulty in the description, and, to beginners, in the recognition, 
of the carcinomata and their varieties lies in the great diversity in shape which their 
Such cell masses are liable to be detached and carried along the vessel, forming metastases. 
Fig. 248.-A Growth of Carcinoma Cells in a Lymph-vessel near a Tumor. 
cells .present. It should be always borne in mind that the shape of cells depends in 
part upon their inherited tendencies in growth, which we cannot see under the micro- 
scope; but to a greater degree upon the varying conditions of nutriment and pressure 
in which they are placed during life. In the normal body these conditions conform 
to a certain standard, so that cells of a given kind at a given stage of development 
are approximately similar. 
In tumors, however, the lawlessness and lack of fixed conditions in growth are 
such that we may have many young and atypical so-called indifferent forms of cells; 402 
TUMORS 
while even the adult forms may depart widely from normal shapes. Thus, in cylin- 
drical-celled carcinomata there are many fully developed cells which are never cylin- 
drical; there are many others not fully developed which are quite indifferent in form, 
looking just like many other young cells. Finally, there may be in such tumors 
inflammatory processes through which young connective-tissue cells are formed, not 
to be distinguished individually from the atypical forms of epithelium. Thus it is 
that there is no morphologically characteristic " cancer cell," as was formerly supposed. 
Some of them are typical and some not, and the more typical may resemble normal 
epithelial cells, and the atypical may look like young connective-tissue cells or even 
lymphocytes. It is in the topography, together with the general characters of the 
cells and the situation of the growth, that we must seek for the evidences of the 
nature of such tumors. 
The carcinomata are very prone to local extension, the advancing 
tumor cells in the periphery making their way through the lymph-spaces 
in solid or more or less tubular masses (Fig. 247). As the epithelial- 
The primary tumor was in the vagina. The section shows at the right a small "epithelial pearl." 
Fig. 249.-Metastatic Carcinoma (Epithelioma) in a Lymph-node. 
cell masses advance into the surrounding parts, the latter may suffer 
resorption and disappear, or the connective tissue may adapt itself to 
the encroaching tumor-cell masses, or new connective-tissue stroma 
may form. Metastasis is of frequent occurrence in some forms of car- 
cinoma, and takes place chiefly, though not exclusively, through the 
lymph-vessels. Masses of the new-formed epithelial cells may fill and 
distend the lymph-vessels (Fig. 248), or detached cells or cell clusters 
may be swept along the lymph-vessels to lodge in the next lymph-nodes 
where secondary tumors may develop (Fig. 249). Mitotic figures (Fig. 
250) are frequently abundant in carcinomata, but bear but little numer- 
ical relation to the rate of growth of the tumor as a whole. Numerous TUMORS 
403 
mitoses may occasionally be found in slow growing tumors. The reason 
for this seems to be that the actual number of mitoses in a tumor varies 
from day to day, so that it is not an infrequent experience to find an 
enormous number of mitoses in a fragment excised for diagnosis and 
Fig. 250.-Mitosis in Carcinoma. 
then to discover only a few in sections taken from the same portion of 
the tumor when removed even twenty-four hours after the diagnostic 
excision. The same phenomenon may be observed by close study of the 
rate of growth of a tumor so situated that its dimensions can be accurately 
determined. Periods of rapid increase alternate with stationary or even 
Fig. 251.-Metastatic Carcinoma in Lymph-vessels of the Pleura. 
The primary tumor was in the liver. The subpleural lymphatics are widely distended with thetumor- 
cell masses. 
regressive phases, a fact which has led to serious error in judging of the 
supposed therapeutic effects of so-called cancer cures. 
The growth of the tumor cells in the lymph-vessels, either in the 
immediate vicinity of the original tumor or following metastasis in a dis- 
tant part of the body, may distend these so that on free surfaces like 404 
TUMORS 
the pleura and peritoneum they form a whitish, elevated network. 
Transverse sections of such distended lymph-vessels are shown in Fig. 
251. Secondary tumors are in the main similar in general structure to 
the primary foci, but may differ from them in vascularity and the abun- 
dance of the stroma, or in the shape of the cells. The carcinomata are, 
as a rule, malignant tumors, but the different forms vary widely in this 
respect. 
Carcinomata are liable to fatty, gelatinous, mucous, and amyloid 
degeneration, and are especially prone to ulceration (see Fig. 252), to 
Thia tumor is of the epitheliomatous type and presents a large, rough, ulcerated surface. 
Fig. 252.-Carcinoma of the Hand. 
haemorrhage and inflammation (Fig. 253). They may become partially 
calcified, and are not infrequently combined with other forms of tissue 
in the mixed tumors. 
They are more frequent in the middle-aged and elderly than in the 
young, but they may occur at any age.1 Multiple primary carcinomata 
have been occasionally reported.2 
When carcinomata, either in the primary or the secondary growths, extend and 
encroach upon adjacent tissues, they bring about in greater or less degree the destruc- 
tion of these, as we have seen, either by pressure atrophy or through phagocytosis or 
1 For a statistical summary of carcinoma cases, with bibl., see Riechelmann, Berl. klin. Wochen- 
chr., pp. 728 and 758, 1902; see also ref. to Bashford and Murray, foot-note, p. 353. 
2 See Warthin, Jour. Amer. Med. Assn., vol. xxxii., p. 963, 1899, bibl. TUMORS 
405 
lysis. It frequently occurs that the tumor cells are closely apposed to or infiltrate 
epithelial structures similar to those in which the tumor originates, so that one may 
see Side by side tumor epithelium and tissue epithelium having an almost identical 
appearance. The adjacent tissue cells may also show evidence of proliferation in 
mitotic figures. These two features, contiguity and mitosis, have led many observers 
to the conclusion that the epithelium adjacent to a growing tumor may assume 
exalted power of proliferation and share in the growth of the tumor, of which it may 
Fig. 253.-Exudative Inflammation in Cabcinoma. 
Showing leucocytes in the stroma and in the epithelium. The epithelium is disintegrating, and 
in the small region shown in the cut the leucocytes are apparently acting as phagocytes in the soften- 
ing and removal of the disintegrating epithelium. 
become a part. This view is erroneous, and the student of tumors should constantly 
remember that the characteristic cells of a tumor are the direct descendants of those 
cells in which the growth starts. For example, one often sees, at the edges of an 
ulcerating epithelioma of the skin, tumor-cell masses infiltrating the subcutaneous 
tissue and in close apposition to the cells of the rete Malpighii, the latter often in a 
condition of hyperplasia. But, however close or however intermingled, in such cases 
tumor epithelium and skin epithelium are quite distinct in origin and potency. 
Forms of Carcinoma. 
In certain carcinomata of the skin and mucous membranes, the cells 
following the type of epithelium from which they arise, as they grow 
older are apt to become flattened or squamous; these tumors are called 
squamous or flat-celled carcinomata, or simply epitheliomata. In another 
class of tumors, such as frequently occur in the gastro-intestinal canal 
and uterus, the cells are more or less cylindrical in shape, forming a 
palisade-like lining to the irregular alveoli; such tumors are called 
cylindrical-celled or alveolar carcinomata, although many of the cells 
are not cylindrical at all, but may have a variety of forms. There 
is a third and very common form of tumor, often derived from cuboidal 406 
TUMORS 
epithelium, in which the tumor cells have no constant characteristic 
shape, but vary as much as do the cell forms in the various glands of the 
body. Such tumors are conveniently classed together as carcinoma 
simplex. 
In addition to these forms there are several others which depend for 
their characteristics upon various metamorphoses or degenerations, or 
upon the preponderance of one or other of the anatomical constituents 
of the growth, such as gelatinous carcinoma, melano-carcinoma, fibrous 
carcinoma, etc. It will be most convenient to give a brief description 
of these various kinds, one after another, with the understanding that 
they are not specific forms, but are simply varieties which it is convenient 
to recognize for clinical as well as anatomical purposes. 
Epithelioma.-These tumors occur in the skin and in the mucous 
membranes which are covered with squamous epithelium. The cells 
present all of the various forms which normally exist in these parts. 
Fig. 254.-Epithelioma of the Neck. 
Shows epithelial pearls, spined cells, and reticular masses of variously shaped epithelial cells. 
In order to understand the various appearances which epitheliomata 
present in microscopic sections, one should bear in mind the structural 
and functional characters of the normal squamous epithelium. The 
cells of the deeper layers, the rete Malpighii, are cuboidal and polyhedral; 
upon these are more or less flattened cells; while upon the surface the cells 
are thin and in the epidermis are also horny. Some of the cells are 
joined by the so-called "intercellular bridges"-"spinal cells," "prickle 
cells." This epithelium rests upon a fibrous basement substance from 
which its nutriment is derived. TUMORS 
407 
The various forms of the cell in squamous epithelium represent reg- 
ular phases of development as the younger, more succulent cells beneath 
are pressed outward and flatten and finally pass off upon the surface. 
In epitheliomata the cells have in a measure the same life history; but 
as they are no longer growing on free surfaces, but in enclosed, elongated 
spaces, they become packed in masses, the older cells being forced toward 
the centres. So that at length there are formed concentrically arranged 
cell masses, which when cut across present the dense whitish, lamellated 
rounded structures which have been called "epithelial pearls" (Figs. 254, 
255, and 256). These epithelial pearls are not confined to these tumors, 
since any lesion which involves the growth of squamous epithelium 
into limited spaces may lead to their formation. Nevertheless their 
Fig. 255.-Epithelioma of Axillary Lymph-node. 
Thi® metastatic tumor was secondary to a large epithelioma of the back of the'hand. The small 
cells with darkernuclei are the cells of the lymph-node. It shows the epithelial pearls.in various stages 
of formation. 
occurrence in doubtful cases, as well as the presence of the intercellular 
bridges and marks of cornification may afford valuable diagnostic evi- 
dence of the origin of a tumor in squamous epithelium. 
The new epithelial-cell groups in epithelioma may be large or small, 
may be separated by much or little stroma; they often form reticular 
masses (Fig. 257), and may infiltrate the tissues deeply or remain near 
the surface; or they may project above the surface, forming wart-like 
or papillary growths. These tumors frequently ulcerate on the surface 
(Fig. 252), and the skin about them is apt to become thickened (Fig. 
258). The actual thickening of the skin with hyperplasia of the papillae 
and of the overlying epithelium, as well as the raising of the skin at the 
edges of the ulcer by the tumor growth beneath, lend to such ulcerating 408 
TUMORS 
epitheliomata, especially of the mucous membrane, their characteristic 
appearance. 
Epitheliomata are most apt to occur in the skin, especially in those 
parts in which it becomes continuous with mucous membranes-lips, 
external nasal openings, eyelids, labia, and glans penis-and are frequent 
in the mouth, oesophagus, vagina, and about the cervix uteri. They 
may develop in congenital naevi of the skin, such as that shown in Fig. 
259. This occurrence illustrates a congenital local predisposition to 
tumor formation. Simple congenital naevi are sometimes mistaken 
for epitheliomata because of similarity in the gross appearance. 
Fig. 256.-Epithelioma of the Skin, Showing Masses of Epithelial Pearls. 
Reproduced from photograph. 
Krompecher and others have described tumors arising im the skin 
and in the mucous membranes formed of squamous epithelium, or in 
glands which open upon these, which differ both clinically and morpho- 
logically from the epitheliomata which are in part formed from corni- 
fied cells. These tumors are made up of cells which resemble those of 
the rete Malpighii, or certain glands with cuboidal epithelium, such as 
the sweat glands, mammary glands, etc.1 They have been called basal- 
celled epitheliomata (see Figs. 225 and 260). 
In this group are tumors of the face and nose (see Figs. 261 and 262), 
of the mamma, ovary, and prostate, and perhaps some of the complex 
1 See Ricker and Schwalb, Geschwiilste der Hautdrusen, Berlin,'1914. 409 
TUMORS 
tumors of the salivary glands which have been called endothelioma, 
cylindroma, plexiform sarcoma, myxo-sarcoma, etc. 
In these tumors the proliferated basal cells form sometimes solid 
Fig. 257.-Epithelioma of Skin. 
Showing reticular masses of epithelial cells with fibrous stroma. 
masses of varied shapes, sometimes gland-like or cystic structures lying 
in a connective-tissue stroma with which they sometimes appear to 
merge, and then resemble sarcoma. Various forms of degeneration of 
Fig. 258.-Epithelioma of Back of Hand. 
The flat tumor occupied nearly the entire back of the hand, and was ulcerating at the surface. 
The figure shows the edge of the tumor and a portion of the ulcer. The papillae of the skin over the 
edge of the growth are hypertrophied, and the tissue about is infiltrated with small spheroidal cells. 
Fig. 255 shows a section from a metastatic tumor of the axillary lymph-node in this case. This tumor 
presented the gross appearance shown in the photographic reproduction in Fig. 252. 410 
TUMORS 
the stroma occur, and this with metaplasia and the appearance of embryo- 
nal characters contribute to their complex character.1 
Giant-celled Epithelioma.-Sometimes certain of the cells in an epi- 
thelioma appear to coalesce, forming a large multinuclear mass. This 
variety of epithelioma is sometimes called giant-cell epithelioma.2 Two 
types of giant cells may be formed (Figs. 263 and 264). In one the 
nucleus divides without corresponding response from the cell cytoplasm, 
so that a large syncytial mass is formed. In the other a true Langhans' 
Fig. 259.-A Portion of a Congenital Naevus of the Skin. 
Such small naevi are sometimes mistaken for epitheliomata and occasionally afford a starting-point 
for the latter. 
giant cell is produced, probably by fusion of a number of smaller cells, 
making a large cell with peripherally arranged nuclei. Both of these 
phenomena are apt to occur chiefly in epitheliomata growing freely 
through soft tissue, such as a granulating cervix uteri or an ulcerating 
epithelioma of the tongue. 
Epitheliomata are apt to recur if not thoroughly removed, and may 
form metastases, but in general they are the least malignant of the car- 
cinomata. Some of the smaller forms, especially those of the basal-celled 
type, may exist for years with no evident tendency to growth (Figs. 261 
and 262). 
Certain tumors of the retina, often classed with glioma and appar- 
ently arising from the external layers of the retina, are of ectodermal 
origin and are called neuro-epitheliomata, though they show none of the 
morphological characteristics of squamous epithelium. 
Cylindrical-celled Carcinoma.-These tumors, closely allied to some 
forms of adenoma (see Fig. 246), occur in the stomach, intestines, and 
1 For further consideration of these tnmors see Krompecher, Ziegler's Beitr., Bd. xxxvii., p. 28, 
1905; also his monograph "Der Basalzellen Krebs," 1903; also ref. to Wood, p. 651. 
2 For a study of giant cells in carcinoma see Delamare and Lecene, Arch. d. m6d. exp., t. xviii., p. 
102, 1906. TUMORS 
411 
uterus. The cells may be only in part cylindrical, the remainder having 
various shapes, and all being loosely or closely packed in larger or smaller 
alveoli. They may have much or little stroma. They merge impercep- 
tibly into the next class, though rarely the two forms may exist simul- 
taneously in the same organ and form separate metastases in the neigh- 
boring lymph-nodes. 
Carcinoma Simplex.-These, which are by far the most frequent of 
the carcinomata of internal parts, are characterized by irregular anas- 
tomosing masses of epithelial cells, sometimes solid, sometimes with 
Fig. 260.-Basal Celled Epithelioma. Metastasis in the Muscle of Abdominal Wall. 
The stroma is extremely cedematous and contains very few cells. 
interior spaces recalling the lumina of glands; all enclosed by a more or 
less abundant fibrillar stroma. The epithelial cells have no uniform 
shape but may be cuboidal, polyhedral, spheroidal, or fusiform, and are 
often so merged that they resemble a nucleated mass of cytoplasm rather 
than an aggregate of cells (Fig. 265). They not infrequently undergo 
degeneration and softening, which, if on the surface, may lead to ex- 
tensive ulcers. The cells may or may not resemble the epithelium of 
the gland in which they originate. 
They are usually nodular tumors, and may be hard or soft. If the 
new-formed stroma is abundant and dense, and preponderates over the 
cellular elements, the tumor is usually hard and is called scirrhus or 
fibro-carcinoma (Fig. 266). 412 
TUMORS 
If, on the other hand, the cellular elements largely preponderate, 
the tumor is usually soft, and, if it do not contain too many blood-ves- 
sels, may have a general resemblance to brain tissue, and is then called 
encephaloid or medullary cancer; or, better, carcinoma molle (Fig. 241). 
These are among the most malignant of the carcinomata. 
The intercellular tissue in carcinomata may become so abundant 
as nearly to obliterate the cellular elements, but it is doubtful if they 
Fig. 261.-Small Epithelioma of the Skin of the Face. 
ever undergo spontaneous cure in this way. They may be hard in one 
portion and soft in another. They may contain many blood-vessels, 
C. telangiectoides. They occur as primary tumors especially in the 
mamma, gastro-intestinal tract, liver, kidney, pancreas, thyroid, and 
prostate glands, occasionally in the testicle and ovary, and very rarely 
in the salivary glands. 
Gelatinous Carcinoma.-The cells of certain carcinomata, especially 
of the gastro-intestinal canal and surface of the peritoneum, may develop 
Fig. 262.-Small Superficial Epithelioma of the Face. 
a translucent gelatinous material whose nature is not well understood, 
which accumulates within the cells.1 In some cases this accumulation 
is moderate when the protoplasm of the cells may be more or less en- 
croached upon by the translucent droplets of the gelatinous material; 
but in other cases, over large areas the cells are partially or entirely 
destroyed, and replaced by the new material, so that the alveoli of the 
1 These tumors are often called "colloid cancers," but the material which characterizes them is not 
true colloid. TUMORS 
413 
Fig. 263.-Giant Cells in Epithelioma. 
Fig. 264.-Giant-celled Epithelioma of the Cervix Uteri. 414 
TUMORS 
tumor are distended by it, and their walls appear very distinct in the 
midst of the gelatinous substance (Fig. 267). In such cases the alveolar 
structure of the tumor is sometimes very evident to the naked eye, and 
Fig. 265.-Carcinoma of the Breast. Showing Large Cells 
with Multiple Nuclei. 
these tumors are therefore often called alveolar carcinoma. Sometimes 
only a part of the tumor is affected in this way. 
Carcinoma Myxomatodes.-The cellular elements of carcinomata may 
suffer mucous softening, and thus larger and smaller cysts containing a 
Fig. 266.-Fibro-carcinoma or Carcinoma Durum (Scirrhous Carcinoma). 
mucous fluid are sometimes formed. To this type of metamorphosed 
tumor the above name is sometimes applied, but it more properly belongs 
to carcinomata in which the stroma is composed of mucous tissue (Fig. TUMORS 
415 
268). Such tumors are most frequently found in the gastro-intestinal 
canal and mamma. 
Melano-carcinoma.-Tumors of this class are rare, and are charac- 
terized by the presence of a variable quantity of black or brown pigment 
particles either in the stroma or in the cells. They are usually soft and 
malignant, and most frequently occur in the skin. 
Fig. 267.-Carcinoma Gelatinosvm-"Colloid Cancer." 
From a tumor of the stomach. 
Molluscum contagiosum is the designation of small soft multiple growths of the 
skin, most frequent on the face, arms, and chest, and on the external genital organs. 
They are lobulated and contain cells similar to those of the rete Malpighii. Within 
the cells and crowding the nucleus to one side, or free among the cells, are rounded or 
ovoid bodies which are believed by many to be protozoan parasites. 
Adamantinoma (Cystadenoma adamantinum; Epithelioma adamantinum).- 
This group of tumors is of occasional occurrence in the jaws either on the surface 
beneath the mucous membrane, or in the depth of the bone. They appear to be 
Fig. 268.-Carcinoma Myxomatodes. 
From a tumor of the mamma. 
derived from the enamel organs of developing teeth. They are frequently cystic 
from the softening and absorption of their tissues, and, while in general benign, may 
infiltrate the jaw, inducing its atrophy. They are most apt to form during the period 
of development of the teeth. They consist in general of a fibrillar connective-tissue 
stroma in which ramify irregular and complex masses of epithelial cells (see Fig. 269). 
These epithelial-cell masses are made up of rows of cylindrical cells or of superimposed 
layers of cylindrical, polyhedral, and flattened cells. Frequently these lamellae of 
epithelial cells enclose a central mass of branching cells. The situation of these 416 
TUMORS 
tumors, their period of formation, and the resemblance of the structure to that in 
various phases of the evolution of the enamel organ, indicate their origin in some 
abnormality in the development of the teeth. There is frequently a recurrence after 
the removal of these tumors, and the growth may become sarcomatous.1 
Fig. 269.-Adamantinoma. 
Bibliography of Tumors. 
An extensive and important work on tumors, containing a vast store of informa- 
tion, is that of Rudolph Virchow, " Die krankhaften Geschwiilste." It is not com- 
pleted and is old, but is still invaluable as a work of reference. A valuable bibliogra- 
phy and digest of recent observations on tumors will be found in Ziegler's " Lehrbuch 
der path. Anat.," Bd. i., last edition. An important resume on the malignant tumors 
in childhood, by Stern, may be found in the Deutsche med. Wochenschrift, June 2d, 
1892, p. 494. "An Introduction to General Pathology," by Sutton, contains many 
suggestive facts about tumors, drawn from comparative pathology. Current addi- 
tions to the subject may be found in the files of Lubarsch and Ostertag's "Ergebnisse," 
see particularly Lubarsch, Jahrg. 1, p. 289, for a comprehensive summary; also for 
newer bibliography to 1899, Aschoff, Jahrg. 5, for 1898, p. 73 and Herxheimer and 
Reinke, Jahrg. 16, for., 1912. Borst's "Lehre v. d. Geschwiilsten," 1902, is a valu- 
able work with many excellent illustrations and bibliography; as is also Ribbert's 
" Geschwulstlehre," 2d edition, 1914. 
1 See for a rtsum# and bibl. of these tumors Chibret, Arch, de med. exp., t. vi., 1894, p. 278; also 
Borst, Die Lehr von den Geschwiilsten, 1902, p. 605. CHAPTER XII. 
THE LESIONS INDUCED BY POISONS. 
Forms of Poisons. 
A poison has been commonly considered to be a substance which 
when introduced into the body from without is capable of inducing, by 
means other than mechanical, pathological alterations of function or 
structure, or both. But this conception of poisons as extraneous pre- 
formed substances has recently been greatly modified. For it has been 
learned that poisons may be formed within the body, either through the 
action of micro-organisms upon its organic constituents or through the 
metabolism of the body-cells themselves. 
It is thus convenient in considering the lesions induced in the body 
by poisons-toxic lesions-to place in one group those due to preformed 
extraneous poisons-exogenous poisons-and in another group those due 
to substances formed within the body-endogenous poisons. 
It has furthermore been found convenient to make three classes of 
the endogenous poisons: First, those which are formed under the influ- 
ence of micro-organisms in the course of the acute infectious diseases 
and whose effects are most appropriately studied in that connection; 
these may be called endogenous poisons of infectious origin; second, those 
which are formed under the influence of micro-organisms in the gastro- 
intestinal canal or elsewhere and absorbed into the body fluids; third, 
those which are formed by the metabolism of the body-cells themselves. 
To endogenous poisoning induced by either of the latter two classes 
of agents the term auto-intoxication has been most commonly and most 
appropriately applied. 
As we have already studied the toxic lesions of the infectious diseases, 
we have only to consider here: 
First, the lesions induced by preformed or extraneous poison- 
exogenous poisons; and second, those due to the endogenous poisons which 
are concerned in the so-called auto-intoxication.1 
The Lesions Induced by Exogenous Poisons.2 
Sulphuric Acid. 
The effects of this poison vary with the amount taken and with its strength 
Death usually occurs in from two to twenty-four hours after the ingestion of the con- 
1 The limitation of the term auto-intoxication as it is here used is adopted from Martius, who has 
written most clearly and suggestively upon the subject. See Martius, "Pathogenese innerer Krank- 
heiten," Hefte i. and ii., 1899-1900. 
2 For special precautions to be taken in the post-mortem examination in cases of suspected poison- 
ing see p. 1022. 
417 418 
THE LESIONS INDUCED BY POISONS 
centrated acid. A case of death within an hour is recorded. When the poison is less 
concentrated or its effects are less intense, the patient may survive for months. 
The skin of the face about the mouth may be blackened and charred by the acid. 
The mouth and pharynx are of a grayish or blackish color, or are covered with a 
whitish layer, while the deeper tissues are reddened. Sometimes these regions escape 
the action of the poison. 
The larynx, trachea, and lungs are sometimes softened and blackened by the acciden- 
tal passage of the acid into them. This may take place even when the acid does not 
pass into the oesophagus. 
The (esophagus seldom escapes. It is colored grayish or blackish, softened, and 
the mucous membrane comes off in shreds. If life is prolonged, cicatrices and stric- 
tures are formed. The stomach may contain a blackish, pulpy fluid, due to the action 
of the acid on mucus, blood, etc. It is coated on its internal surface with a black, 
sticky layer, beneath which the mucous membrane is reddened. The mucous mem- 
brane may be blackened in patches or stripes. The organ may be contracted and the 
mucous membrane corrugated. Sometimes perforation takes place and the acid 
blackens and softens the adjoining viscera. In protracted cases cicatrices are formed 
and the organ is contracted. If the poison is dilute there may be only the lesions of 
chronic gastritis. 
The blood is sometimes thickened, syrupy, acid, and may form thrombi in the 
vessels. 
Fatty degeneration of the renal epithelium is mentioned by some authors. 
The body may be partially preserved from decomposition, owing to the action of 
the acid upon the tissues. 
The solution of indigo in sulphuric acid, commonly known as sulphate of indigo, 
produces the same lesions as sulphuric acid, and also stains the tissues with which it 
comes in contact a dark-blue color. It is stated that an indigo-blue tint is often 
found in the mucous membranes after poisoning by pure sulphuric acid. 
Nitric Acid. 
Death may occur very soon after the taking of the poison, but is not usual until 
the lapse of several hours, and may not ensue for several days or weeks. 
The surface of the mucous membrane of the mouth, pharynx, and (esophagus is 
covered with yellow eschars wherever the acid has touched it. Beneath and around 
the eschars the tissues are congested and red. The stomach contains a viscous, san- 
guinolent, yellow or greenish fluid. The mucous membrane is congested, red, swollen, 
softened, and ecchymotic. It is rarely perforated. The duodenum may be inflamed, 
and the inflammation extend to its peritoneal coat. The rest of the intestines usually 
escapes the action of the acid. The larynx is very frequently acted on by the acid. 
There are yellow eschars, congestion and swelling of the mucous membrane, sometimes 
oedema of the glottis. The trachea may be inflamed and the lungs congested. If the 
patient survive the first effects of the poison, chronic inflammation, cicatrization, and 
contraction may occur. If the fumes resulting from the action of the strong acid on 
organic material are inhaled, a subacute or chronic pneumonia may be caused, which 
is very often fatal.1 
In fatal cases death occurs on the average in about twenty-four hours. The lesions 
are in general similar to those produced by sulphuric and nitric acids, except that the 
eschars are usually of a whitish color at first, becoming, after a time, discolored and 
disintegrated. It is also more common to find false membranes on the inflamed 
surfaces. 
Hydrochloric Acid. 
Oxalic Acid. 
In fatal cases death may occur within ten minutes (in one case it occurred in three 
minutes) or it may be delayed for two or three weeks. The period of death does not 
depend, as do in general the symptoms, upon the amount and concentration of the 
poison. 
1 See Wood, Poisoning by Nitric Oxide Fumes, Arch. Int. Med., 1912, x., 478, bibl. THE LESIONS INDUCED BY POISONS 
419 
The mucous membrane of the mouth, pharynx, and oesophagus is usually white and 
shrivelled, and easily peeled off, and may be covered with brownish vomit from the 
stomach. The cesophagus may be much contracted. The stomach is usually contracted 
and contains a dark-brown, acid, mucous fluid. The mucous membrane of the 
stomach may be pale, soft, and easily detached, sometimes looking as if it had been 
boiled in water. Sometimes it is red and congested; sometimes blackened and gan- 
grenous; sometimes peeled off in patches. Perforation is of rare occurrence. If life 
be prolonged the whitened condition of the mucous membrane is succeeded by con- 
gestion and inflammation. The small intestines may be inflamed. Inflammation of 
the pleura and peritoneum, and congestion of the lungs are of occasional occurrence. 
In some cases of death from oxalic acid there are no well-marked lesions. 
Potassium oxalate produces the same lesions as oxalic acid. 
Tartaric Acid. 
This acid is seldom used as a poison, but in large doses may prove fatal. The 
lesions in the cases observed were redness and inflammation of the mucous membrane 
of the gastro-intestinal canal. 
Potash, Soda, and their Carbonates. 
These substances are not commonly used as poisons with suicidal or homicidal 
intent, but may be taken by mistake. They may cause death in a few hours, or life 
may be prolonged for several weeks. 
The mucous membrane of the mouth, pharynx, oesophagus, and stomach is softened, 
swollen, congested, and inflamed, or may be peeled off. It may be blackened from 
local changes in the blood. The mucous membrane of the larynx and trachea may also 
be swollen and inflamed. 
If life is prolonged for some time, cicatrices and strictures of the oesophagus and 
stomach are apt to be produced as a result of the reparative inflammation. 
Ammonia. 
The vapor of strong ammonia may cause death from inflammation of the larynx 
and air passages. The strong solution of ammonia produces lesions similar to those of 
potash and soda. The larynx, trachea, and bronchi are frequently inflamed, and may 
be covered with false membranes. Fatal inflammation of the rectum and colon has 
been produced by an enema of strong solution of ammonia. 
Potassium Nitrate. 
Accidental poisoning sometimes occurs from large doses of this salt. In the 
observed cases there were intense congestion and inflammation of the stomach and 
intestines, and in one case a small perforation of the stomach existed. 
For the effects of several infrequently employed salts of the alkalies and alkaline 
earths, which for the most part produce simple inflammation of the gastro-intestinal 
canal, we refer to special works on toxicology. 
Phosphorus. 
Poisoning by phosphorus is much more common in France and Germany than in 
this country. Some of the forms of rat poison, of which this is a frequent ingredient, 
and the ends of matches, are common media for its administration. It is more often 
used with suicidal than with homicidal intent. 
The post-mortem appearances vary according to the length of time which elapses 
before death, which may be from a few hours to several months. 
If death takes place in a few hours the only lesions may be those produced by the 
direct local action of the poison. The mouth, pharynx, and oesophagus usually 
escape. The stomach may be only slightly reddened, or there may be patches of 
inflammation and erosion. The contents of the stomach are often mixed with blood 420 
THE LESIONS INDUCED BY POISONS 
and may have the peculiar smell of phosphorus. There may be little bits of wood 
present when the poison has been taken from the heads of lucifer matches. It is 
said that the mucous membrane of the stomach may emit a phosphorescent light in 
the dark. 
If death does not ensue until after several days the lesions are more marked. The 
body is usually jaundiced. There may be ecchymoses beneath the pericardium, 
pleura, and peritoneum, in the lungs, the kidneys, the bladder, the uterus, the muscles, 
and the subcutaneous connective tissue, and bloody fluid in the visceral cavities. 
Chromatolysis of the ganglion cells may occur. 
The heart and voluntary muscles, the walls of the blood-vessels, and the epithelium 
of the pulmonary air vesicles may be in the condition of fatty degeneration. The 
blood is usually dark and fluid. 
The stomach sometimes presents no very striking changes. There may be small 
circumscribed spots of inflammation, erosion, or gangrene, and occasionally perfora- 
tion. The most constant change is albuminous and fatty degeneration of the cells 
which line the gastric follicles. In consequence of this the mucous membranes appear 
thickened, opaque, of white, gray, or yellow color. The small intestine appears normal 
or is congested. 
The liver is found in different degrees of albuminous and fatty degeneration, and is 
often stained yellow from the jaundice. It is usually increased in size and of a gray- 
ish-yellow or light-yellow color, unless stained by the bile. Less frequently the centres 
of the acini are congested, or the entire liver is congested, or there are small haemor- 
rhages in the liver tissue. The liver may be soft, flabby, and smaller than normal. 
In the interstitial tissue of the liver and along the branches of the portal vein there 
may be marked infiltration with small spheroidal cells. 
The kidneys often present albuminous and fatty degeneration of the epithelium. 
The mesenteric lymph-nodes may be soft and swollen from hyperplasia. 
Arsenic. 
This poison is very frequently employed with suicidal intent. Death may occur 
in a longer or shorter time from the direct irritative effects of the poison upon the 
gastro-intestinal canal, with the symptoms which usually accompany the ingestion of 
irritant poisons; or it may occur with symptoms of collapse, or coma, or shock; or the 
symptoms may resemble those of cholera. The average time of death in acute fatal 
cases is about twenty hours, but death has occurred in twenty minutes and has been 
postponed for two or three weeks. 
The mouth, pharynx, and oesophagus may be inflamed, but are more frequently 
unaltered. The stomach may be empty or contain mucus mixed with blood. *The 
arsenic, in substance, may be found adherent to the mucous membrane or mixed with 
the contents of the organ. It has, in rare cases, been found encysted in the stomach 
in considerable quantity. When invisible to the naked eye a microscopical examina- 
tion of the stomach contents will not infrequently reveal characteristic crystals of 
arsenious acid or some of its compounds. The stomach may be contracted and its 
mucous membrane corrugated. The entire inner surface may be red and inflamed,or 
there may be patches or streaks of inflammation or deep congestion. The inflamed 
and congested patches may be thickened and covered with false membrane mixed 
with larger and smaller particles or masses of the poison. Ulceration, perforation, and 
gangrene are rare. Blood may be extravasated into the mucosa and submucosa, and 
with the congestion give the mucous membrane a very dark-red or brown appearance. 
Frequently the mucous membrane is studded with small petechiae. Sometimes the 
arsenic is converted in the stomach into the yellow sulphid. There may be acute 
gastritis, even when the poison is absorbed by the skin or otherwise and not introduced 
into the stomach. The epithelium of the gastric glands may undergo granular and 
fatty degeneration. 
The entire length of the intestine may be congested and inflamed, but the action of 
the poison does not usually extend beyond the duodenum. In some cases the solitary 
lymph-nodules, Peyer's patches, and the mesenteric nodes are swollen. Inflammation of 
the bladder and peritoneum, and congestion and oedema of the brain, have been ob- THE LESIONS INDUCED BY POISONS 
421 
served, but are neither frequent nor in any way characteristic. Fatty degeneration 
of the muscles, liver, kidneys, blood-vessels, and vesicular epithelium of the lungs and 
chromatolysis of the ganglion cells may follow arsenical poisoning. 
Alterations in the spinal cord indicative of acute myelitis have been described by 
Popon1 as occurring in dogs poisoned with arsenious acid. 
The walls of the stomach and intestines and other parts of the body may be pre- 
served from decomposition for a long time after death by arsenical poisoning. 
It should always be borne in mind, in examining cases of suspected arsenical 
poisoning, that death may be produced by arsenic and its compounds without any 
appreciable lesions. While in general it may be said that in the cases in which no 
lesions are discovered death has probably occurred soon after the ingestion of the 
poison, it should be remembered that death without lesions may exceptionally take 
place long after the usual time at which inflammatory changes commence. 
Compounds of arsenic, such as the chlorid and sulphid, and the arsenite (Scheele's 
green, Paris green), are sometimes used for suicidal purposes, and produce lesions 
similar to those of arsenious acid. Paris green is a favorite article in New York, par- 
ticularly among Germans, for suicidal purposes. It is usually taken in considerable 
quantities, and is often found in the stomach after death.2 
Corrosive Sublimate. 
The mucous membrane of the mouth and throat may be swollen, inflamed, or have 
a grayish white appearance. The (esophagus may be swollen and white, or congested, 
or unaltered. The mucous membrane of the stomach is usually congested or inflamed, 
or there may be patches of softening, ulceration, or gangrene. Perforation is of rare 
occurrence. Small ecchymoses in the mucosa are not uncommon. Sometimes there 
is little or no change in the stomach. Sometimes the mucous membrane of the stom- 
ach is slate-colored from the deposition of metallic mercury from the decomposed 
salt. The intestines may appear normal, or there may be patches of congestion and 
ecchymosis. The larynx and trachea may be congested. 
The kidneys are congested, there is albuminous and fatty degeneration and necro- 
sis of the epithelium, especially of Henle's loops and the convoluted tubules. The 
epithelium may desquamate and block the tubules. The glomeruli are not obviously 
involved. Calcification may follow the degeneration and necrosis of epithelium3 
(Fig- 30). 
Lead. 
The different preparations of lead may prove fatal either from the immediate 
effect of large doses or from the gradual effects of repeated small doses. Although 
there may be marked symptoms during life, the post-mortem lesions are few and 
variable. 
There may be chromatolysis of the ganglion cells. 
Large doses may produce acute gastritis, and sometimes a whitening of the mucous 
membrane. The intestines are generally contracted, and there may be fatty degene- 
ration of the renal epithelium; very frequently there are no appreciable lesions. 
In chronic lead poisoning the intestines may be contracted, the voluntary muscles 
flabby and light-colored, or partially replaced by connective tissue, and there may be 
chronic meningitis. 
1 Popon, "Ueber die Veranderungen im Ruckenmarke nach Vergiftung mit Arsen," etc., Virch. 
Arch., Bd. xciii., p. 351. 
2 It is advisable, in cases of suspected arsenic poisoning, particularly if the body has lain for some 
time, as in exhumations, to preserve not only all of the internal organs entire for the chemist, but also 
portions of the muscles (back, thigh, arm, and abdomen), and also one of the long bones, preferably 
the femur, since arsenious acid and its compounds are quite diffusible, and may be present in proportion- 
ately larger quantity in other parts than in the gastro-intestinal canal. It is desirable to save the whole 
of the internal organs, and to weigh the muscle and bones as well as the whole body at the autopsy, 
in order that the calculations of the chemist, in case arsenic be found, may rest upon a definite basis, 
and be as little as possible dependent upon estimates, whose value may be questioned by lawyers should 
the case come into the courts. 
An interesting article on arsenic as a poison, with various collateral data by Pellew, will be found in 
Hamilton's "System of Legal Medicine," vol. i., p. 349. 
3 For studies on the action of sublimate on the kidneys see ref. footnote, to Neuberger and to Elbe, 
p. 753. See also Mouisset and Mouriquand, Jour, de phys. et path, gen., t. viii., p. 292, 1906. 422 
THE LESIONS INDUCED BY POISONS 
Copper. 
Acute poisoning by salts of copper is not very common, but it is of occasional 
accidental occurrence, and the salts are infrequently used with suicidal intent. The 
sulphate and acetate are the most important salts in this respect. Soluble salts of 
copper may be formed in the use of copper cooking utensils, and accidents most fre- 
quently occur in this way. 
The post-mortem appearances are somewhat variable. The pharynx and oesopha- 
gus may be somewhat inflamed or unchanged. The mucous membrane of the stomach 
and intestines may be inflamed, ulcerated, or gangrenous, and perforation and perit- 
onitis may occur. The mucous membrane may have a diffuse greenish color, or par- 
ticles of the salt may be found adhering to it. 
Tartar Emetic. 
This preparation of antimony may prove fatal when administered in a single large 
dose or in repeated small doses. The post-mortem lesions are not constant. In cases 
of chronic poisoning there are usually no appreciable lesions. 
In cases of acute poisoning there may be evidence of acute inflammation of the 
oesophagus, stomach, intestines, and peritoneum. Sometimes the stomach exhibits no 
lesions, while the intestine is involved. The larynx and lungs may be deeply congested. 
Vegetable Irritants. 
Aloes, colocynth, gamboge, jalap, scammony, savin, croton oil, colchicum, veratria, 
hellebore, elaterium, and turpentine. 
All these drugs may produce poisonous effects. The post-mortem lesions are con- 
gestion, inflammation, and sometimes ulceration of the gastro-intestinal mucous 
membrane; but these lesions are sometimes present and sometimes absent. 
Cantharides. 
This substance may be given in powder or tincture. The entire length or only a 
portion of the alimentary canal may be congested or inflamed. There may be patches 
of gangrene of the mucous membrane of the stomach. When the poison has been 
taken in substance a microscopical examination of the contents of the alimentary 
canal or of the mucous membrane may reveal the glistening green and gold particles 
of the fly. 
The kidneys, ureters, and bladder may be congested and inflamed. There is some- 
times congestion of the brain and its membranes. 
The post-mortem appearances in persons who have died from opium or morphin 
poisoning are inconstant and not characteristic. Congestion of the brain and its 
membranes, with serous effusion in the membranes and ventricles, and congestion of 
the lungs, are changes occasionally seen, but they are frequently entirely absent, and 
when present are not characteristic of death from this poison. 
Opium and Morphin. 
Poisonous Fungi. 
The action of these substances varies greatly, and the post-mortem appearances 
are inconstant and not characteristic. In general, when any lesions are present they 
are those of gastro-intestinal irritation or of venous congestion, or both. 
Microscopical examination may reveal characteristic fragments of fungi in the 
contents of the alimentary canal. 
Hydrocyanic Acid. 
This poison in fatal doses may destroy life in a very short time. The post-mortem 
appearances are inconstant and not characteristic. The skin may be livid and the THE LESIONS INDUCED BY POISONS 
423 
muscles contracted. The stomach may be congested or normal. The most frequent 
internal appearances are those of general venous congestion. Under favorable condi- 
tions the odor of prussic acid may be detected in the stomach or blood or brain, or 
other parts of the body. It may be absent in the stomach and present in other parts 
of the body. If the patient have lived for some time the odor may be absent altogether. 
Cyanide of potassium may produce the same lesions as hydrocyanic acid, and there 
is the same inconstancy in their occurrence. 
Nitrobenzol.-This substance produces general venous congestion, and the odor of 
the oil of bitter almonds may be more or less well marked in the body after death. 
Carbolic Acid. 
When this poison in concentrated form is taken into the stomach the mucous 
membrane of the mouth, oesophagus, and stomach may be white, corrugated, and par- 
tially developed in patches, and the edges of the affected parts may be hyperaemic or 
there may be patches of extravasation. Brownish, shrunken patches may be present 
about the mouth. The brain and meninges may be congested. There may be conges- 
tion and oedema of the lungs, and congestion of the liver and spleen. The blood is 
usually dark and fluid. The urine is commonly of a dark or greenish color. The 
odor of the poison may be evident in the body and in the urine. 
In cases which are not at once fatal the affected mucous membrane may slough, 
and healing follow with contraction of the stomach. Death from innutrition may 
follow temporary recovery after a considerable interval. If diluted carbolic acid be 
taken the white appearance of the mucous membrane may be absent but death may 
ensue with marks of necrosis, hyperaemia, and inflammation of the oesophagus and 
stomach. 
Alcohol. 
The different preparations of alcohol, when taken in concentrated form or in large 
quantities, sometimes produce sudden coma and death in from half an hour to several 
hours. In acute poisoning, if death have followed soon after the ingestion of the 
poison, the body may resist decomposition for an unusual length of time. The stom- 
ach and tissues may even have a more or less well-marked alcoholic odor. The 
stomach, and even the oesophagus and duodenum, may be of a deep-red color. There 
may be punctiform ecchymoses in the gastric mucous membrane. In many cases the 
stomach is apparently quite normal. There is apt to be venous congestion in some of 
the internal organs, but this is not constant. There are frequently congestion, and 
sometimes extravasation of blood in the brain and its membranes, and oedema of the 
membranes or of the brain substance, or both. There may be a serous effusion in the 
ventricles of the brain, also chromatolysis of the ganglion cells. 
In chronic alcohol poisoning death may ensue from some other disease, or after a 
debauch. In the latter case there may be delirium tremens, or the patient dies ex- 
hausted and comatose. Chronic alcoholism is not infrequently mistaken clinically for 
meningitis. The post-mortem lesions are sometimes marked, sometimes absent. 
There may be chronic pachymeningitis, resulting in thickening of the dura mater and 
its close adherence to the skull. The pia mater may be thickened and cedematous. 
The brain may be normal or cedematous or atrophied and show chromatolysis of the 
ganglion cells. The lungs are frequently congested. The heart may be thickly 
covered with fat, and its walls may be flabby and fatty. The stomach frequently 
presents the lesions of chronic gastritis. The liver may be cirrhotic, with or without 
fatty infiltration. The kidneys may present the lesions of albuminous or fatty degene- 
ration or of chronic diffuse nephritis. 
It should always be remembered, however, that all or a part of the above lesions 
may be absent in the bodies of drunkards, and, furthermore, that the same lesions 
may be due to other causes. 
Chloroform may cause death when it is taken in fluid form into the stomach or 
when inhaled. Death from swallowing liquid chloroform is rare, and its immediate 
Chloroform. 424 
THE LESIONS INDUCED BY POISONS 
cause is usually uncertain. The post-mortem changes are variable; sometimes there 
are no lesions. In some cases there is simple reddening of the gastric mucous mem- 
brane; occasionally there is acute gastritis or ulceration of the mucous membrane. 
The odor of chloroform may or may not be evident. Discoloration and softening of 
the mucous membrane of the pharynx, oesophagus, and duodenum have been observed. 
There may be general venous congestion; the heart may be flabby. Bubbles of gas 
have been frequently seen in the blood, but this is not characteristic. Degeneration 
and necrosis of the liver cells may follow chloroform administration (see page 716). 
Death from inhalation of chloroform is a not infrequent accident in surgical 
practice. After death from inhalation the results of the examination are usually 
quite negative, and in no case are there lesions which in themselves enable the exam- 
iner to declare death to have been due to chloroform poisoning. 
Ether. 
The inhalation of ether occasionally causes death. The post-mortem examina- 
tion is negative. The ingestion of fluid ether may induce inflammation of the stom- 
ach. The odor of ether may be perceptible if the autopsy is made soon after death. 
Chloral Hydrate. 
There are no characteristic post-mortem appearances after death by chloral. 
Hypersemia of the brain, and the odor of the drug, have been noticed. 
The post-mortem appearances after poisoning by these drugs are not characteristic 
and are inconstant. The body is usually relaxed at the time of death, but the rigor 
mortis, as a rule, comes on early and remains long. There may be congestion of the 
brain and spinal cord, and sometimes of the lungs and stomach. Chromatolysis of the 
ganglion cells is recorded. 
Strychnin-Nux Vomica. 
Animal Venom, Etc. 
The poisons which may be introduced into the body through the bites of venomous 
snakes and reptiles and the bites of insects cannot be considered in detail here.1 
The action of the venom of snakes, scorpions, etc., upon the animal body, is in 
many respects similar to that of certain bacterial toxins and cytolytic substances. 
By gradual adaptation of the lower animals to these venoms, antitoxins, i.e. antivenins, 
may be secured. 
Our knowledge of snake venom and especially of cobra venom is the most extensive. 
Snake venom contains toxins of several kinds, haemolytic, neurolytic, nephrolytic, 
etc.2 Some of these toxins seem to require the presence of complement to secure their 
haemolytic action upon the red blood cells. Furthermore this complement may, as 
it would appear, be furthered by the red blood cells themselves-endocomplement. 
It is conjectured that in this case the lecithin of the red cells may act as complement.3 
Abrin and ricin are examples of poisonous substances which induce in the body 
lesions similar to those in certain infectious diseases (see p. 203). 
This is one of the gases generated in the burning of charcoal, and forms one of the 
ingredients of illuminating gas. A most characteristic post-mortem appearance is 
the cherry-red color of the blood, and of the tissues and viscera which contain blood. 
The presence of carbonic acid in the gas may obscure the bright red of the carbonic 
oxide by the dark color which it induces in the blood, so that spectroscopic or other 
tests are sometimes necessary for its detection. 
Carbonic Oxide. 
U* 1 Consult Langmann, "Poisonous Snakes and Snake Poison," Medical Record, vol. Iviii., p. 401, 
1900; also Brown, "Twentieth Century Practice," vol. xx„ bibl. 
2 Flexner and Noguchi, Jour. Exp. Med., vi., 278, 1901-1905. 
3 Keyes, Berl. klin. Wochenschr, xxxix, 886, 1902. THE LESIONS INDUCED BY POISONS 
425 
There may be oedema and hyperaemia with haemorrhage in the brain and meninges. 
There may be haemorrhages, often symmetrical, in the basal ganglia and in the internal 
capsule. Or there may be areas of softening in the brain and cord. In some cases 
there appear to be hyaline thrombi formed of red blood cells in the vessels of the cen- 
tral nervous system as well as in the other viscera, to which, in part at least, the 
haemorrhages and softening may be attributed.1 Some of them may, however, be 
due to direct action of the poison. 
Recovery from carbonic-oxide poisoning in cases not immediately fatal is often 
slow, and various serious disturbances of the nervous system may accompany it. 
Any apparent speedy recovery may be folio-wed by the development of nerve lesions 
which in a longer or a shorter time may prove fatal. In cases in which death follows 
several weeks after the poisoning the areas of softening, often especially marked in or 
near the internal capsule,2 may show secondary changes due to absorption of degener- 
ated material, growth of connective tissue, etc. 
The lesions are essentially those of asphyxia, but the brain is said to be more fre- 
quently congested than in asphyxia by simple obstruction of respiration. 
Conium, Aconite, Lobelia Inflata, Digitalis, Stramonium. 
These vegetable poisons are administered in their natural form of leaves, berries, 
and roots, or in tinctures, infusions, and extracts, or in the form of their active alka- 
loid principles. 
If the leaves, berries, or seeds are given they may be detected in the contents of 
the alimentary canal by microscopical examination. Otherwise the results of autop- 
sies are not characteristic. 
The brain and its membranes, and the lungs, may be congested. The stomach 
may present patches of congestion, inflammation, and extravasation, or its entire 
mucous coat may be inflamed, or it may appear normal. 
Ptomains and Other Putrefactive Products. 
Poisonous substances of various kinds are often developed in the putrefaction of 
organic substances, and certain alkaloidal substances called ptomains form in the 
decomposition of proteids without putrefaction. Thus in sausages, some kinds of 
cheese, ice-cream, decayed fish and mussels, such substances have caused serious and 
even fatal poisoning. There are no characteristic post-mortem changes in poisoning 
by these substances. But the lesions of gastro-intestinal inflammation or toxaemia 
may be present. 
These alkaloidal substances may be of extreme importance in certain cases of 
death from obscure causes on account of the medico-legal questions which may arise.3 
For a more detailed consideration of poisons, their effects, modes of detection, etc., 
consult the great work of Kobert, "Lehrbuch der Intoxikationen," or the following: 
Taylor on Poisons; Maschka's "Handbuch der gerichtlichen Medicin," Bd. ii.; Wood- 
man and Tidy, "Forensic Medicine";Hoffmann's "Lehrbuch d. gerichtlichen Medicin." 
Wormley's "Micro-chemistry of Poisons" contains a series of good plates of the micro- 
scopical appearance of various forms of crystals of poisonous substances. Peterson 
and Haines's "Textbook of Legal Medicine and Toxicology," 1904, is good; and 
Kunkel, "Handbuch der Toxikologie," Jena, 1901, is very valuable. 
Lesser's "Atlas der gerichtlichen Medicin" contains a series of colored plates 
showing the appearance of the stomach after the action of various poisons. The work 
of Guy and Ferrier on "Forensic Medicine," 7th ed., revised by Smith, contains in very 
Bibliography of Poisons. 
1 See Schmidtmann, "Gerichtl. Med.," 9th ed., Casper-Liman., Bd. i., p. 872, 1905. 
2 For a consideration of the reasons for the localization of secondary lesions of CO poisoning 
in the basal ganglia see Hoffmann's "Gerichtl. Med.," 9th ed., p. 739, 1903. 
For a study of the blood supply of the basal ganglia see Kolisko. Wiener klin. Wochenschr., 1893, 
No. 11. 
3 For chemical aspects of this subject consult Vaughn in Hamilton's "System of Legal Medicine," 
vol. i., p. 475, and Vaughn and Novy, "Cellular Toxins"; also Vaughn in "Twentieth Century Practice," 
vol. xiii. 426 
THE LESIONS INDUCED BY POISONS 
compact and reliable form much information on the general subjects treated in the 
foregoing section. Lewin's " Lehrbuch der Toxicologie" contains many valuable and 
suggestive general considerations on the action of poisons. Schmidtmann's " Hand- 
buch d. gerichtlichen Medicin," 1905, is the last and 9th edition of the standard work 
of Casper-Liman and contains much valuable lore. 
Lesions Induced by Endogenous Poisons-Auto-Intoxications. 
As we turn now from poisons formed outside of the body to those 
formed within it-the endogenous poisons-we encounter two classes: 
I. Those poisons which arise from the metabolism of micro-organisms. 
II. Those which arise from the normal or aberrant metabolism of the 
body-cells themselves. 
I. ENDOGENOUS POISONS FORMED LARGELY UNDER THE INFLUENCE OF 
MICRO-ORGANISMS.1 
1. Those which are formed in infectious diseases (see Chapter IX., 
Part I., on Infectious Diseases). 
2. Those formed in the body without infection. 
The most common and important metabolic poisons of this class 
are those which are formed in the gastro-intestinal canal through the 
action of micro-organisms, mostly bacteria, upon the organic constituents 
of the intestinal contents and secretions. The new chemical substances 
thus formed become deleterious when absorbed into the body fluids, and 
this may occur either when they are produced in unusual quantity or 
when their elimination with the excreta is interfered with. When 
absorbed, some of these poisons may be demonstrable in the urine, and 
they may give rise to a variety of symptoms which cannot be considered 
here.2 Such are dizziness, headache, some forms of tetany, gastro- 
enteritis, etc. 
Endogenous poisons analogous in origin with these may be formed in 
the bladder, in putrid abscesses, or in necrotic tissues in various parts 
of the body. Structural lesions, if such there be, occurring under these 
conditions, are as yet but little known. 
II. ENDOGENOUS POISONS FORMED BY THE BODY-CELLS-HISTOGENIC 
POISONS. 
It is only within the past few years that the studies on cell metabo- 
lism have led to the belief that the body-cells may not only under occa- 
sional abnormal conditions form poisonous chemical compounds, but that 
even in the normal processes some of the intermediary metabolic prod- 
ucts may be inimical to the welfare of the body, if they be not constantly 
1 Consult in connection with this and the following section Herter, "Chemical Pathology," also 
Wells, "Chemical Pathology," 2d. edition, and Taylor on "Auto-intoxication," in Osler's Modern 
Medicine. 
2 It is the opinion of some pathologists that the term auto-intoxication should be strictly limited to 
the effects of those substances which are actually derived from the cells of the body; that these alone 
are truly endogenous: that intoxication by bacterial products is not auto-intoxication; and, especially, 
that it is improper to use this term in connection with the intestinal bacterial decomposition, since the 
digestive canal is, strictly speaking, exterior to the body tissues and cavities. THE LESIONS INDUCED BY POISONS 
427 
rendered inert. This may be affected either by excretion or, as now 
seems probable, in part at least through the influence of what have been 
called the 11 internal secretions" of such glands as the thyroid, pancreas, 
adrenals, hypophysis, etc., or possibly in ways as yet wholly unknown. 
Thus there is a group of auto-intoxications due to the accumulation 
in the body of the products of normal metabolism through defects in the 
excretory apparatus; for example, uraemia in renal insufficiency or reten- 
tion of urine; cholaemia in retention of bile; acidosis due to beta-oxy- 
butyric acid; carbonic-acid poisoning in various forms and grades of 
asphyxia. Possibly some of the serious symptoms following extensive 
burns of the skin and occurring in sunstroke and eclampsia are of similar 
origin. This may be called auto-intoxication through retention. 
On the other hand, there is a group of auto-intoxications which it is 
assumed may in part at least be due to a failure of the organs concerned 
with the internal secretions to furnish the necessary link in the chain of 
intermediary metabolic products. In this group may be placed cachexia 
strumipriva and myxcedema, pancreatic diabetes, Addison's disease, and 
possibly some forms of acute yellow atrophy of the liver. 
While the nature and action of the recently discovered internal 
secretions are still obscure, they do exist and are of extreme importance 
in the subtle adjustments of individual cell metabolism to the welfare of 
the organism as a w'hole, and there is abundant reason to believe that, 
when this adjustment is disturbed, forms of histogenic auto-intoxication 
may arise. 
At any rate the hypotheses which have been formed in the new light 
have contributed largely to our understanding of a series of important 
general diseases. These diseases, whether involving or not internal 
secretions in accordance with our present conceptions, may be considered 
as dyscrasic auto-intoxications.1 
Whether gout, oxaluria, and some forms of simple diabetes should 
be considered as auto-intoxications may be questioned. Possibly Base- 
dow's disease and some forms of puerperal eclampsia (see p. 717) should 
be regarded as in part involving the foi mation and retention of histogenic 
poisons. 
Of course this grouping of diverse forms of disease should be consid- 
ered as only tentative and suggestive. And it may well be doubted 
whether analogy may not be often overstrained in regarding as the 
effect of poisons what may, after all, be metabolic aberrancies of far more 
subtle character than the word auto-intoxication would imply. 
It should be borne in mind that in but a very small proportion of 
the abnormal processes which are considered auto-intoxications have the 
assumed poisons been actually demonstrated. The assumption rests 
largely upon symptoms which are regarded as analogous with those 
incited by known exogenous poisons. It is wise to remember also that 
even in poisoning by well-defined agents whose general effects have long 
been known we are almost totally ignorant, except in the case of the 
1 For a discussion of internal secretions, see Starling, Harvey Lectures, 1907-8. Vincent, Internal 
Secretions, 1912; and Biedl, Innere Sekretion, 2d edition, Berlin, 1913. 428 
THE LESIONS INDUCED BY POISONS 
so-called destructive or corrosive poisons, of the exact ways in which they 
act. A few induce changes in the blood; many appear to act upon the 
nerve cells; but the nature of this action is still unknown.1 
Without insisting upon the advantages of such a grouping as has been 
outlined above, and with the full recognition of its incompleteness, the 
more important of the so-called "general diseases," some of which may 
be regarded as auto-intoxications, will be considered in the next chapter. 
1 For convenience of reference, the grouping of poisons briefly set forth above may be tabulated as 
follows: 
I. Exogenous poisons Inorganic and organic. 
II. Endogenous poisons-concerned 
in autochthonous or endogenic 
poisoning-auto-intoxication. 
Endogeneous poisons 
formed largely by 
micro-organisms. 
A. In infectious diseases. 
B. Without infection, largely 
enterogenic. 
Endogenous poisons formed under the influence of or by the 
body-cells-histogenic poisons-inducing auto-intoxication in 
the more limited sense. CHAPTER XIII. 
GENERAL DISEASES. 
In the so-called general diseases, various parts of the body are structurally or 
functionally involved, but there is usually a primary lesion in some special organ. 
The grouping of certain diseases under this heading is rather for convenience than 
because these diseases are fundamentally different in their relations to the body as a 
whole from many others, such as infections, intoxications, etc. Fever, which is so 
often one of the manifestations of toxaemia, has been grouped with the general dis- 
eases, because in some respects it presents important analogies with them. 
CACHEXIA STRUMIPRIVA-MYXOEDEMA. 
The thyroid is one of the so-called ductless glands which furnishes 
internal secretions essential to normal metabolism in the body. 
Removal or destructive lesions of this gland, both in man and the 
lower animals,1 may be followed by serious and fatal disease character- 
ized as cachexia strumipriva. In man the more common manifestation 
of this disease is called Myxoedema. It occurs most frequently in middle- 
aged women. 
The skin of the face is apt to be swollen and waxy, giving a peculiar 
and rather characteristic appearance to the features, (Fig. 270). The 
skin of the body is apt to be dry and rough, and the hair may fall out 
Perspiration is, as a rule, diminished. The mental condition is dull, and 
loss of memory and insanity may occur. Bodily movement arid speech 
are apt to be impaired. The fat tissues may be atrophic, and the sub- 
cutaneous tissue has been shown in some, though not all, of the cases to 
contain an unusual amount of mucin. In some cases the fibres of the 
upper layers of the corium are crowded apart by fluid. 
The most marked and constant lesion in this disease is an atrophic 
condition of the thyroid gland. The parenchyma of the gland is more 
or less completely replaced by fibrillar connective tissue, and by new- 
formed reticular tissue resembling the lymphatic tissue of the lymph- 
nodes. The general appearance of the atrophied thyroid gland is shown 
in Fig. 272. 
In addition to the lesion of the thyroid there are apt to be chronic 
endarteritis and chronic diffuse nephritis. In some cases there is an 
accumulation of small spheroidal cells about the smaller blood-vessels in 
various parts of the body, and also petechial haemorrhages. 
If the thyroid be completely removed in young animals there is 
deficient development of the osseous system, while in man the frequent 
1 For an extensive critical and experimental study of this subject see Cunningham, "Experimental 
Thyroidism," Jour. Exp. Med., vol. iii., p. 147, 1898, bibliography. For a study of the transplantation 
of the thyroid see Payr, Arch. f. klin. Chirurgie, Bd. Ixxx., 1906. 
429 430 
GENERAL DISEASES 
association of cretinism with goitre or other thyroid lesions indicates in 
another way the close relationship between the thyroid and cell metab- 
olism.1 
Cretinism is a congenital condition in which development is retarded 
and faulty. An adult in years is often infantile or childish in stature 
and mental capacity, ill formed and uncouth (see Fig. 271). 
Fig. 270.-Myxcedema. 
Showing "puffy" skin of face and falling of the hair-case of Dr. Henry Hun. 
The nature of the substances composing the internal secretions 
of the thyroid is little understood, but the wonderful therapeutic effects 
of the administration of the extract of the gland in cases of myxoedema 
and in cretins, in which they are deficient, make clear their great import- 
ance. Whether directly toxic substances are formed in the thyroid or 
not, it seems proper to consider the cachexia strumipriva as due directly 
or indirectly to auto-intoxication. 
1 Consult Osler, "Sporadic Cretinism in America," Trans, of the Congress of American Physicians 
and Surgeons, vol. iv., p. 169, 1897. GENERAL DISEASES 
431 
About twenty years of age 
Fig. 271.-A Cretin. 432 
GENERAL DISEASES 
EXOPHTHALMIC GOITRE. (Basedow's Disease, Graves' Disease.) 
The lesions of this disease are unilateral or bilateral enlargement of the thyroid 
gland and protrusion of the eyeballs-exophthalmos. Associated with these is 
enlargement of the lymphatic system, which is especially marked in the thymus, 
spleen, and lymph nodes. Correlated with this lymphoid hyperplasia is a relative or 
absolute increase in the lymphoid elements of the blood, and, in addition, there are 
certain characteristic disturbances, among them rapid heart action-tachycardia- 
and muscular tremor. The pathological changes found in the thyroid are extremely 
complex. In cases in w'hich the clinical syndrome of exophthalmic goitre is present 
there may be found normal thyroid tissue; this probably represents an early stage of 
exophthalmic goitre in which the hyperplasia has not yet begun or has been inhibited 
Fig. 272.-Section of the Atrophied Thyroid Gland in Myxcedema. 
a. Interstitial tissue; &, atrophied lobules with small spheroidal-celled or lymphatic tissue in their 
peripheries. 
by the administration of iodine. Secondly, there may be an active hyperplasia of the 
glandular epithelium with atrophy of the colloid material and alteration in its 
staining qualities, the colloid no longer taking a bright red color with eosin. The gland 
also may show the lesions of colloid goitre-large alveoli filled with normal staining 
material and lymphoid tissue in the stroma. This condition is also induced in hyper- 
plastic glands by the administration of iodine for therapeutic purposes. Thirdly, 
adenomata of the thyroid, of either the fetal or the tumor type, may be present in 
exophthalmic goitre, though probably simply coincident with the disease and not 
directly related to it. Finally, the changes in the gland may be highly complex, when 
the condition develops in old colloidal goitres, the hyperplastic structures being com- 
mingled with cysts, haemorrhagic areas, calcification, and adenoma nodules. There is, 
therefore, no specific lesion connected with exophthalmic goitre, but the majority of 
the glands show more or less cellular hyperplasia with diminished colloid. This may 
be considered as the most frequent lesion. In all cases lymphoid collections are 
apt to be found in various portions of the gland distributed throughout the con- 
nective tissue. The connective tissue also undergoes hyperplasia, both the trabec- 
ulae and the substance of the gland and the capsule. The vascularity of the organ is 
often greatly increased, the arteries and the veins being dilated, and this congestion 
may account for a very large portion of the increase in size always noted in exophthal- 
mic goitre, though it is generally held that there is a definite increase in cellular volume 
also. Some of the symptoms of myxoedema are frequently shown by patients suffering 
from exophthalmic goitre and the terminal stage of the untreated hyperplastic process Plate A 
Exophthalmic Goitre 
Colloid Goitre 
Fcetal Adenoma of Thyroid GENERAL DISEASES 
433 
is often an atrophy of the glandular structures with the ultimate production of myxce- 
dema. The heart usually shows a considerable hypertrophy of the left ventricle which 
is simply due to the extra labor falling on that organ owing to the extreme rapidity of 
the pulse. The iodine content of the gland varies inversely with the amount of hyper- 
plasia, normal thyroids and colloidal goitres containing the most iodine, while ex- 
tremely hyperplastic glands contain the least. This is in relationship with the amount 
of colloidal substance microscopically noted as present in the structures, the specific 
protein of the thyroid containing a large amount of iodine. 
Four theories are current in explanation of this condition, the first is that it is due to 
a hyperthyreosis or excessive secretion of the thyroid gland. This is based upon the 
fact that overdoses of thyroid extract produce some of the symptoms of exophthalmic 
goitre and that removal of a portion of the gland or ligature of some of its vessels is 
often beneficial in checking the disease. The second theory is that the condition is due 
to perverted secretion-dysthyreosis; but experimental researches have not adduced 
definite confirmation of this theory. The third view is that the disease is a general dis- 
turbance of the chemistry of the body, the thyroid undergoing a compensatory 
hyperplasia in endeavoring to overcome the toxic effects of some poison in the system. 
The fourth theory is that an abnormal nervous system stimulates the thyroid and is in 
turn excited by the thyroid secretion, thus inciting a vicious cycle. Although the 
majority of observers believe in the hyperthyroidism theory, the whole question is still 
under discussion and cannot be regarded as finally settled.1 
ADDISON'S DISEASE. 
This name is applied to a disease especially characterized morpholog- 
ically by a peculiar pigmentation of the skin and by certain changes, 
morphological or functional, in the adrenals. The patients suffer from 
cerebral symptoms, great prostration, syncope, and derangements of 
the functions of the stomach and intestines. 
The pigmentation of the skin is the symptom which has especially 
attracted attention. The change in color usually begins and becomes 
most marked in those parts of the skin which are not covered by the 
clothing or are naturally of darker color. The rest of the skin afterward 
changes color, but not uniformly, white patches being left. The color 
is at first a light yellow or brown; this becomes darker until it is of a 
dark greenish, grayish, or blackish brown. The mucous membrane of 
the tongue, lips, and gums may be similarly pigmented. 
Under the name of Addison's disease different observers have 
described cases in which the symptoms and bronzed skin existed without 
disease of the adrenals; cases in which the bronzed skin was the only 
lesion; and cases in which the adrenals were diseased without symptoms 
or bronzed skin. 
The Skin.-The discoloration of the skin is due to a deposit of yellow- 
ish brown pigment in the deeper layers of the epidermis, especially in the 
layer covering the papilke, and less constantly in the connective tissue 
of the cutis. 
1 For studies on the lesions of the thyroid gland and exophthalmic goitre see Ewing, Trans. Assn. Am. 
Phys., 1906, xxi., 567; and MacCallum, Jour. Am. Med. Assn., 1907, xlix., 1158; and the numerous papers 
by Marine and Lenhart, Arch. Int. Med., 1909, iv., 440;ibid., 1911, vii.,506; ibid., 1911, viii., 265. For 
the study of adenomata of the thyroid gland, some of the cases exhibiting a few of the symptoms of 
exophthalmic goitre see Bloodgood, Surg. Gynec. andObstet., 1906, ii., 121. For a presentation of the 
dysthyreosis theory see Klose, Beitr. f. klin. Chir., 1912, Ixxvii., 601. For a study of the relation between 
the nervous system and the thyroid see Oswald, Cor.-Bl. f. schweiz. Aerzte, 1912, xlii,, 1130. 434 
GENERAL DISEASES 
The Brain.-Pigmentation of the gray matter, acute meningitis, 
chronic meningitis, and distention of the ventricles with serum have been 
observed. 
The sympathetic nerves, especially those which are in contact with 
the adrenals, may show a variety of changes apparently due to chronic 
inflammation. Various changes in the nerve cells of the semilunar gan- 
glia have been described. 
There may be fatty degeneration of the heart muscles and hyperplasia 
of the intestinal lymph-nodules and spleen. 
The Adrenals.-The most common lesion of these bodies is a tubercu- 
lous inflammation, and this or some other lesion has been found in nearly 
one-half of the cases. On the other hand, it should be remembered that 
similar lesions of the adrenals often occur without other indications of 
Addison's disease. Tuberculous adrenals may be large, hard, and nodu- 
lar; less frequently of normal size or smaller than normal. On section 
they may contain cheesy masses surrounded by zones of gray, semitrans- 
lucent tissue. Later the cheesy masses may become calcified or they may 
soften and break down. The grayish zones are composed of tubercle 
tissue or denser connective tissue.1 
Other cases have been described in which the adrenals were the seat 
of carcinoma or of fatty or waxy degeneration. But these lesions, 
especially carcinoma of the adrenals, may occur without the manifesta- 
tions of Addison's disease. The adrenals may be atrophied. They may, 
however, be normal, and in some such cases lesions of the semilunar and 
other sympathetic ganglia have been found. 
On the whole, the clinical, morphological, and experimental data now 
available seem to point to lesions of both the sympathetic system and 
the adrenals as of probable significance in determining this disease. 
The hypothesis which is most in favor at present assumes that the 
adrenals furnish an internal secretion without which normal metabolism 
cannot be effected, and that lesions of the adrenals or of the sympathetic 
ganglia and vessels about them, by altering or diminishing this secretion, 
may lead to the functional and structural changes characterizing the 
disease.2 This active principle, which is present in the medullary and 
chromaffin portion of the adrenal in about one-tenth of one per cent., 
has recently been produced synthetically and found to be a base, chem- 
ically designated as methylamino-acetocatechol. The relationship 
between the medulla of the adrenals and the sympathetic is apparently 
intimate but is as yet obscure. Complete removal of the adrenals 
is rapidly fatal. Injection of the extracts after removal of the organs 
fails to maintain life. The action of extracts of the adrenals or the pure 
base upon the muscle fibres of arteries leads to an increase in blood 
pressure. 
1 For a study of experimental tuberculosis of the adrenals and its relations to Addison's disease see 
de Vecchi, Cent. f. allg. Path., Bd. xii., p. 577, 1901. 
2 For the effects of removal of suprarenal body and the nature of its " active principle," consult Abd, 
'Vaughan Anniversary Contributions," 1903, p. 139, bibl. Also Barger, Natural Bases, New York, 
1914, and Biedl, Innere Sekretion, 2d edition, 1913. GENERAL DISEASES 
435 
DIABETES MELLITUS. 
This disease involves such defects in nutrition as lead to an abnormal 
accumulation of sugar in the blood and its discharge by the urine (glyco- 
suria), which is increased in amount.1 
A great variety of lesions have been found in the body after death 
from diabetes, but few of them, aside from those of the pancreas, appear 
Fig. 272a.-Fibrous Replace- 
ment with Hypertrophy of Re- 
maining Cells in Island of 
Langerhans in Case of Dia- 
betes. 
Fig. 272b.-Hyaline Degen- 
eration in Island of Langer- 
hans in Case of Diabetes. 
to be of well-defined significance in this special relationship. The general 
condition of malnutrition and debility, so often marked in this disease, 
renders diabetics especially vulnerable to slight injuries or infections, 
furunculosis, carbuncle, eczema, etc.; gangrene is liable to occur either 
with or without marked injury in cases of diabetes.2 
The nervous system may be normal. Peripheral neuritis with or 
without lesions in the gray matter of the anterior horns is frequent. A ter- 
minal pneumonia is not uncommon. The liver may be cirrhotic or fatty. 
The kidneys may show diffuse nephritis and often a glycogenic infiltra- 
tion of the epithelium of Henle's loop. A moderate amount of fat is 
often present in the blood and fat emboli in the lungs have been described. 
The lesions in the pancreas are variable; there may be a general atro- 
phy with fat replacement and an increase of interstitial tissue. Hyaline 
degeneration and fibrosis of the islands of Langerhans are present in a 
large proportion of the cases.3 An adenoma-like hypertrophy of the 
islands is occasionally noted. Tumors, cysts, and calculi in the pancreatic 
duct have also been found. In about ten-per-cent, of the cases no altera- 
tions are found in the pancreas, though functional lesions may be present 
without corresponding anatomical change. Excision of the pancreas in 
man or animals causes diabetes. (See also section on the Pancreas, 
pages 701 to 707.) 
1 For a resume of metabolism in diabetes, see Lusk, Harvey Lectures, 1908-9, bibl. 
2 For bibliography of diabetic gangrene consult Davis, Jour. Amer. Med. Assn., July 16th, 1898. 
3 For the relationship of diabetes to lesions of the pancreas, and particularly to lesions of the is- 
lands of Langerhans, see Opie, "Disease of the Pancreas," 1903; also Cecil, Jour. Exp. Med., 1911, xi., 
266. 436 
GENERAL DISEASES 
Diabetes mellitus may be associated with haemachromatosis and 
cirrhosis of the liver-so-called "bronzed diabetes."1 
h- Under the influence of the doctrine of internal secretions it is now 
commonly assumed that the pancreas, in addition to its intestinal secre- 
tion, furnishes some other substance to the body which is essential in the 
metabolic changes to which the carbohydrates and proteids must be 
subjected in securing normal nutrition.2 Interference with this internal 
secretion of the pancreas is thus assumed to be accountable for the 
faulty metabolism.3 
Fig. 273.-Lesions of Gout in the Hands. 
Some of the smaller tophi at the finger tips are ulcerating. 
GOUT. 
The characteristic lesion of gout is the presence of an abnormal 
amount of uric acid in the blood and the deposit of urate of sodium in 
the articular cartilages, the ligaments of the joints, the ears, and the 
eyelids. Inflammatory changes may be associated with the deposits 
in the joints. There appears to be an hereditary predisposition to the 
disease.4 
The most frequent situation of the gouty deposit is the metatarso- 
phalangeal joint of the great toe. The cartilage may be infiltrated or 
1 See Opie, loc. cit., p. 54. 
2 Internal secretions which, formed in one organ, are necessary or useful in correlating the functions 
of the organ of origin with those of other organs of the body are called hormones, see Starling, Harvey 
Lecture, 1907-8. 
3 Other forms of glycosuria are known which are to be otherwise accounted for. They may be 
associated with lesions of the nervous system or induced by the action of certain poisons, phloridzin- 
diabetes for example, or may occur under other conditions. 
4 For study of gout see Minkowski, Die Gicht, Vienna, 1903. GENERAL DISEASES 
437 
encrusted with the deposit. These masses of urates, often called ''chalk- 
stones" or "tophi," may appear upon the surface by the ulceration of 
the skin (Fig. 273). 
A very important feature of gout is that patients with the gouty di- 
athesis are especially liable to derangements of digestion and to certain 
chronic inflammations, such as chronic inflammation of the arteries, the 
bronchi, and the kidneys. Cardiac hypertrophy may be associated with 
the arterio-sclerosis. The interstitial tissue, especially in the pyramids 
of the kidney, may be infiltrated with the urates. 
The nature of the disturbances of nitrogenous metabolism underlying 
the manifestations of gout is not yet clear, nor are we able to estimate 
the influences upon accumulations of uric acid in the body of faulty 
elimination or local tissue alterations. Nor is the relationship plain of 
local inflammatory processes to the gouty deposits. 
SUNSTROKE. (Insolation; Heat Exhaustion.) 
Persons exposed, while at work or when exhausted, to the sun or to 
high temperatures are liable, especially if of intemperate habits, to sud- 
den prostration, often associated with cardiac failure, asphyxia, convul- 
sions, and coma. Death in many cases soon ensues. 
After death, decomposition sets in early and progresses rapidly. The 
blood usually remains fluid. 
The brain and its membranes are in some cases congested, in others 
not. There may be an increased amount of serum beneath the pia mater, 
or small and thin extravasations of blood beneath the pia mater and 
between the pia and dura mater. Chromatolysis of the ganglion cells has 
been described by Van Gieson1 and others. The thoracic and abdominal 
viscera may be congested; albuminous degeneration may be evident 
in the liver and kidneys. 
In the cases in which cerebral symptoms are protracted for a number 
of days the lesions of meningitis have been found after death. 
According to Cramer,2 persons surviving for some time the first severe 
effects of the heat may suffer important alterations in certain nerve fibres 
of the brain. 
SCORBUTUS. (Scurvy.) 
This disease appears to result from imperfect nutrition under condi- 
tions which cannot be considered in detail here, but which is usually 
attributed to insufficient or inappropriate diet. The lesions are variable, 
the most common being anaemia; extravasation of blood in the skin, 
subcutaneous tissue, and muscles; swelling and ulceration and bleeding 
of the gums. Small and sometimes extensive haemorrhages are apt to 
occur in the mucous membranes and on serous surfaces. Small ulcers 
may form in the mucous membranes. Fatty degeneration of the heart, 
liver, and kidneys is not uncommon. The spleen may be large and soft. 
1 Van Gieson, "Toxic Basis of Neural Diseases, " N. Y. State Hospital Bulletin, vol. i., p/407, 
1896; also Lambert, Medical News, July 24th, 1897. 
2 Cramer, Centralblatt fur allg. Path., etc., Bd. i., p. 185, 1890. 438 
GENERAL DISEASES 
No constant characteristic changes have been discovered, either in the 
blood-vessels or the blood, which would satisfactorily account for the 
extravasations and other lesions. 
The body is apt to decompose early. The skin may be mottled with 
small and large purple, blue, brown, or blackish spots produced by 
degenerative changes in the extravasated blood in the cutis. Sometimes 
ulcers are produced by the perforation of effused blood on to the surface. 
The joints may be inflamed, may contain serum or blood. Rarely the 
haemorrhages are followed by destruction of the cartilages and ends of 
the bones. Very rarely there is haemorrhage between the periosteum 
and bone, and in the bone itself, producing softening and destruction of 
the bone, and separation of the epiphyses. The sternal ends of the ribs 
are the most frequent seat of this change. Albuminous degeneration of 
the heart, liver, or kidneys, and enlargement of the spleen, are common. 
Infantile Scorbutus.-Infants (under two years) may develop similar 
anaemia and tendency to haemorrhages. The most common location of 
the haemorrhages is beneath the periosteum of the bones of the lower 
extremities, especially of the femora, with separation of the lower epiphy- 
ses. There may be haemorrhages in the skin and subcutaneous tissues, 
the eyelids, and orbit, and in the internal organs. Haemorrhagic inflam- 
mation and ulceration of the gums are usually limited to infants having 
teeth and to portions of the jaw in which teeth are apparent or just 
about to come into view.1 
That some forms or phases of scorbutus are of infectious nature is 
not improbable, but definite data in this direction are wanting. 
This rare disease is especially marked by an overgrowth of the ter- 
minal portions of the extremities, and of the bones of the face.2 But 
there may be a general involvement of the skeleton-gigantism. This 
excessive growth is in the diameter rather than in the length of the bones, 
and is accompanied by local exostoses. Equally important and common 
is a general hyperplasia of the connective tissue of the body. The thymus 
may be persistent; there may be fibrous-tissue formation in the walls of 
the vessels and in the sympathetic ganglia. The skin is often pigmented. 
The most constant lesion which appears to bear upon the etiology of acro- 
megalia is that of the hypophysis. This in many cases has been found to 
be the seat of lesions, most frequently a hyperplasia or adenomatous 
growth in the prehypophysis. While endothelioma and sarcoma of the 
hypophysis have been described in acromegaly, it seems not unlikely that 
hyperplasia has, in most cases at least, been mistaken for these tumors. 
The complete removal of the hypophysis or of its anterior portion is 
ACROMEGALIA. 
1 For a study of scorbutus in infants, " Barlow's Disease," which was first recognized in the United 
States by Northrup, consult Northrup and Crandall, N. Y. Med. Jour., May 26th, 1894. See also The 
American Pediatric Society's "Collective Investigation on Infantile Scurvy in North America," Trans. 
Amer. Ped. Soc., vol. x., 1898, p. 5. For a study of histological changes consult Jacobsthal, Ziegler's 
Beitr. z. path. Anat., Bd. xxvii., p. 173, 1900. 
2 Several cases have been described in which there was enlargement of the hands and feet and lower 
ends of the long bones, without involvement of the bones of the face. While this condition may follow 
syphilitic infection, its frequent association with pulmonary lesions has led to the designation hyper- 
trophic pulmonary arthropathy. See Janeway, Am. Jour. Med. Sci., vol. cxxvi., 1903, p. 563. GENERAL DISEASES 
439 
invariably fatal. It is believed that the hyperplastic hypophysis is in 
some way concerned in inducing the nutritional abnormalities leading to 
the general overgrowth of connective tissue and bone,1 probably through 
interference with its internal secretion. An extract of the fresh gland 
from animals-pituitrin-induces muscular contraction and has been 
widely employed in stimulating peristalsis of the bowels and contraction 
of the uterus during delivery. 
This name is applied to a variety of conditions in which extravasa- 
tions of blood are present in the skin or the mucous and serous mem- 
branes. 
Haemorrhages, particularly from the mucous membranes, may be 
severe and even fatal. This condition is often called purpura 
heemorrhagica. 
The ecchymoses characteristic of purpura may occur as a result of 
poisoning with certain drugs, and with snake venom; in various cachectic 
conditions; in diseases,of the nervous system; in rheumatism; in gastro- 
intestinal disorders, especially of children. The local ecchymoses in 
pyaemia are sometimes classed as a form of purpura; and in these, bac- 
teria, especially the pyogenic forms, may be demonstrable.2 
Either from the direct action of poisons; or through degeneration of 
the endothelium of the smaller vessels; or as the result of capillary 
embolisms, extravasation of blood may take place.3 
PURPURA. (Purpura Haemorrhagica.) 
LYMPHATIC CONSTITUTION. (Constitutio Lymphatica: Status Lymphaticus.) 
Sudden death after the administration of ether or after slight trauma 
is frequently correlated with a pathological condition in which the chief 
lesion is a hyperplasia of the lymph tissue of the body with hypoplasia of 
the heart and aorta. The thymus is often enormously enlarged and may 
reach such a size as to compress the bronchi and large vessels of the upper 
mediastinum. (See Figs. 275 and 276, and section on the Thymus, page 
511.) The pharyngeal, thoracic, and abdominal lymph nodes are most 
frequently involved in the hyperplasia, the process infiltrating the sur- 
rounding connective tissue. The spleen shows hyperplasia of the follicles 
but is usually not enlarged. 
Clinically, as Norris has shown, a diagnosis can be made in male adults 
if with lymphoid enlargement there is connected a feminine type of body 
outline, with scanty hair on the face, axilla, and sternum, and a feminine 
distribution of the pubic hair, a slender thorax, a rounded contour of the 
upper arms and thighs with arching of the latter, and hypoplasia of the 
external genitals. In women the hair on the body may be scanty, though 
1 For an excellent r^sumi of acromegalia, with cases and bibl., see Brooks, Archives of Neurology 
and Psychopathology, vol. i., p. 485, 1898; also Lewis, Bull. J. H. Hosp., vol. xvi., 157, 1905. For 
physiology and pathology of the hypophysis see Biedl, Internal Secretory Organs, New York, 1913, and 
Cushing, The Pituitary Body and its Disorders, Philadelphia, 1912. 
2 For a more detailed consideration, in the light of recent studies, of cases often grouped under the 
name " Haemorrhagic Infections," consult Honl, Lubarsch and Ostertag's " Ergebnisse der allg. Aetiolo- 
gie," Jahrg. i., Ab. I, p. 793, bibl. 
3 Duke, Arch. Int. Med., 1912, x., 445; and Osler, Brit. Med. Jour., 1914, p. 517. 440 
GENERAL DISEASES 
usually there is more than normal on the face; there is also hypoplasia 
of the genital apparatus and slender thorax and extremities. In children 
the diagnosis is difficult, but may occasionally be made by x-ray demon- 
stration of an enlarged thymus. Such children are usually pale and 
feeble and show general lymphatic enlargement. Rickets, tuberculosis, 
and syphilis are common accompaniments of the disease.1 
Fig. 274.-Hyperplasia of Lymphoid Tissue of the Intestine in the'Status 
Lymphaticus. 
Lymph-N odes and -Nodules.-The pharyngeal, thoracic, and abdom- 
inal lymph-nodes are most frequently involved in hyperplasia, the new 
cells often infiltrating the surrounding tissue. There may be hyper- 
plasia of the tonsils, of the cervical, mediastinal, axillary, and abdominal 
lymph-nodes, as well as of the lymphatic tissue of the gastro-intestinal 
canal (Fig. 274). 
The thymus may be congested and large and soft from hyperplasia. 
It sometimes evidently exerts such pressure on the adjacent bronchi and 
large vessels as to lead to death. 
The spleen may be moderately enlarged from hyperplasia, especially 
of the lymphoid tissue of the Malpighian bodies, and it maybe congested. 
FEVER. (Pyrexia.) 
The heat of the body is derived from tissue metabolism. The heart, 
the muscles, the liver, and other abdominal organs are the great sources 
of heat production. The temperature of the body under normal con- 
ditions is maintained within narrow limits by the heat-regulating mech- 
anism which preserves the balance between heat production and heat 
loss effected largely through the skin and respiratory surfaces. 
1 For a study of the lymphatic constitution and its relationship to sudden death, Ewing, N. Y. Med. 
Jour., 1897, July 10; Bartel and Bauer, Status Thymico-Lymphaticus u. Status-Hypoplasticus, Leipzig, 
1912; v. Neusser, Zur Diagnose des Status Lymphaticus, Wien, 1191 (conta ns reference to work of Nor- 
ris, page 228); Paltauf, Wien, klin. V chnschr., 1889, No. 46, and 1890, No. 9; and Emerson Arch. Int. 
Med., 1914, xiii., 169. GENERAL DISEASES 
441 
Fever may be defined as a general disturbance of metabolism usually 
due to infection or various forms of intoxication which leads to a rise of 
the temperature within the body. 
The rise of temperature in fever depends primarily upon an increase 
in the metabolic combustion. Oxygen is used in larger amount than is 
usual, while the combustion products, carbonic acid, and the nitrogenous 
substances, urea, uric acid, etc., are excreted in greater abundance. 
This increased combustion is usually associated with disturbances of 
digestion and assimilation of food, so that the abnormal heat production 
is effected largely at the expense of the body proteids of the various 
tissues and organs concerned in metabolism. 
But with the increased heat production there usually occur, in the 
earlier periods of fever, such disturbances in the vasomotor control of 
the cutaneous blood-vessels as lead to their contraction. Thus, heat 
elimination is retarded. In later periods the vessels of the skin may 
dilate so that, in spite of its persistent dryness and lack of the cooling 
effect of sweat evaporation, there is an excessive loss of heat from this 
source. This is not sufficient, however, to balance the excessive heat 
production. We need not consider here the various subjective and 
objective phenomena characteristic of the febrile condition. The height 
of temperature varies in fever, seldom exceeding 42° C. (107.6° F.), and 
is usually much less than this. Even this temperature, if it last for a few 
hours, may induce coagulation of the cell protein and thus cause death. 
In the great majority of cases fever is due to the presence in the body 
of deleterious substances, either introduced from without, or, more com- 
monly, produced within the body. These are most often formed in 
infections, and arise either from the growth in the tissues of pathogenic 
micro-organisms or from the disintegration of their bodies; that is, they 
are toxins or endotoxins. But there is abundant evidence that fever is 
not infrequently due to perverted metabolism of the tissue cells, leading 
to the formation of toxic substances. Such self-engendered substances 
are called autotoxins. The pyrexia of sunstroke is believed to be an 
example of this phase of auto-intoxication. 
Similarly it is known that certain drugs-cocain, caffeine, purin bases, 
phosphorus, various bacterial toxins, and organic substances-proteids, 
leucocytic proteases, ferments, etc.-introduced from without may induce 
fever.1 
Exactly how these various substances act in the incitement of fever 
is unknown. But one assumes that the cell metabolism is disturbed 
by the poison, while the heat-regulating mechanism is so modified that 
the normal balance is overthrown. That the nervous system may play 
an important role in these disturbances is indicated by the fact that more 
or less persistent elevations of temperature may follow puncture or 
haemorrhage in the corpus striatum or lesions of the bulb or certain other 
affections of the nervous system.2 
1 See Vaughan, Protein Split Products, Philadelphia, 1913. 
2 For a study of fever and allied conditions see Chantemesse and Podwyssotsky, "Les Processes 
Generaux," 1901; see also Krehl, "Clinical Pathology," Tran, by Hewlett. 
For metabolism in fever see MacCallum, Harvey Lectures, 1908-9. CHAPTER XIV. 
THE LESIONS IN CERTAIN FORMS OF DEATH FROM VIOLENCE: 
SUDDEN DEATH. 
The Lesions in Certain Forms of Death from Violence. 
SUFFOCATION ASPHYXIA. 
By suffocation is meant that condition in which, without direct 
pressure on the larynx or trachea, air is prevented from penetrating into 
the lungs. The interruption of the function of respiration which is thus 
brought about induces the condition known as asphyxia. In this way 
many deaths from drowning and strangulation take place. 
The ways in which the supply of air may be cut off from the lungs 
are various. The mouth and nose may be closed by the hand, by plas- 
ters and cloths, by wrapping up the head in cloths, by covering the face 
with earth, hay, grain, etc. Foreign bodies may be introduced into the 
mouth, pharynx, and larynx. Blood may pass into the trachea from an 
aneurism or from a wound. The glottis may be closed by inflammatory 
swelling. Vomited material may lodge in the larynx. 
On the other hand, injury or disease of the medulla oblongata, or 
paralysis or spasm of the muscles of respiration from drugs, tumors 
pressing upon the air passages, or diseases of the lungs themselves, or 
irrespirable gases which exclude oxygen from the lungs, may induce 
asphyxia. 
External Inspection.-The body should be examined for marks of violence, 
the cavities of the mouth and nose for foreign substances. 
The face may be livid and swollen or present a natural appearance. The conjunc- 
tiva may be congested and ecchymotic. There may be small ecchymoses on the face, 
neck, and chest. The mouth often contains frothy blood and mucus. The tongue 
may be protruded. 
Internal Examination.-The brain and its membranes may be congested, or 
ansemic and cedematous, or unchanged. The blood throughout the body is usually 
dark-colored and fluid. 
The larynx may contain foreign bodies which have induced the suffocation. The 
mucous membrane of the larynx, trachea, and bronchi may be congested and some- 
times ecchymotic: these passages contain frothy blood and mucus. The lungs are 
usually congested and cedematous, but sometimes do not differ from their ordinary 
appearance. There may be small patches of emphysema near the surface of the lungs. 
Sometimes, especially in infants, small ecchymoses are found in the costal and pul- 
monary pleura. 
The heart usually presents its right cavities full of blood, its left cavities empty; 
but to this there are frequent exceptions. 
The abdominal viscera are usually congested. 
442 THE LESIONS IN CERTAIN FORMS OF DEATH 
443 
DEATH FROM STRANGULATION-HANGING. 
Strangulation is effected by the weight of the body in hanging, by 
pressure on the neck with the hands or by some other object, or by con- 
striction of the neck with a cord or ligature of some kind. Death usually 
occurs by asphyxia, or by asphyxia combined with the effect of the 
cutting-off of the blood supply to the brain by pressure on the large 
vessels of the neck. In some cases of hanging, death ensues as a result 
of fracture or dislocation of the cervical vertebrae. 
External Inspection.-The face may be livid and swollen, the eyes prominent, 
the lips swollen, and the tongue protruded. These appearances are, however, often 
absent. Erection of the penis, ejaculation of semen, and evacuation of feces and 
urine are frequently observed. 
In many cases marks are left upon the neck by the objects which have directly 
produced the strangulation. In cases of hanging, the mark about the neck varies con- 
siderably in position, direction, and general characters, depending upon the kind of 
ligature employed, the time of suspension, period after death at which the observation 
is made, etc. The most common mark left by a cord about the neck is a dry, dense, 
brownish furrow, whose breadth corresponds but in a very general way with the diam- 
eter of the cord. In some cases, according to Tidy and others, there may be no mark 
at all if the hanging be quickly accomplished with a soft ligature and the body cut 
down immediately after death. There may be abrasions and ecchymoses of the skin 
at the seat of ligature. 
In cases of strangulation by the fingers the mark on the neck may correspond in a 
general way to the shape of the fingers. 
The application of the same forces immediately after death may produce the same 
marks as when death is induced by them. 
Internal Examination.-The brain and its membranes may be congested, or 
there may be extravasation of blood, or there may be no abnormal appearances. 
The Neck.-In some cases there is effusion of blood beneath the ligature, rup- 
ture of the cervical muscles, fracture of the os hyoides and cartilages of the larynx, 
fracture and dislocation of the cervical vertebrae, rupture of the internal vertebral 
ligaments and of the inner and middle coats of the carotid arteries. Similar changes 
may be produced in the dead body by the use of great violence. 
If death occur from asphyxia, the internal lesions are similar to those described 
above. In some cases-for example, where death has occurred from fright or shock- 
the results of post-mortem examination are entirely negative. 
DEATH FROM DROWNING. 
In examining the bodies of persons who are supposed to have been 
drowned, it is necessary to bear in mind a number of questions which 
may arise: Whether the person came into the water alive or dead? 
How long a time has elapsed since death? Whether the person has com- 
mitted suicide, or was drowned by accident, or was murdered? These 
questions are to be solved sometimes certainly, sometimes with prob- 
ability, sometimes not at all, by the post-mortem examination. Pre- 
sons dying in the water, to which condition the term drowning is com- 
monly applied, may die from asphyxia, from exhaustion, from fright 
or syncope, from disease of the heart, apoplexy, injuries, etc. While 
in the majority of cases asphyxia is a predominant or important factor 
in death by drowning, the conditions under which death occurs are so 
apt to be complex that in the minority of cases only are the lesions of 444 
THE LESIONS IN CERTAIN FORMS OF DEATH 
pure asphyxia found after death, while in most cases the bodies present 
the more or less well-marked lesions of asphyxia together with those 
indicative of complicating conditions. There are no post-mortem con- 
ditions which alone are absolutely characteristic of drowning, and it is 
only by considering all the facts elicited by the autopsy together that 
any just conclusion can be arrived at. It should always be borne in 
mind, moreover, that even the most characteristic of the evidences 
of drowning are apt to be modified or to disappear as decomposition 
goes on. 
External Inspection.-Post-mortem rigidity usually sets in early, sometimes 
immediately after death. Decomposition progresses, especially in summer, with 
unusual rapidity in bodies which have been removed from the water. Frequently, 
but by no means constantly, the peculiar roughening of the skin, known as goose-skin 
(cutis anserina), is found, but this may occur after death from other causes. A light, 
lathery froth, either white or blood-stained, is frequently seen about the mouth and 
nostrils within twelve to twenty-four hours after removal of the body from the water, 
but it may be absent, and may be seen after death from other causes. After the body 
has lain for several hours in the water (twelve to twenty-four) the thick skin of the 
palms of the hands and soles of the feet may become macerated and thrown into 
coarse wrinkles, just as it may after prolonged soaking during life, or in a dead body 
thrown into the water. The penis and nipples may be retracted, and the scrotum 
shrunken, but this is not constant nor characteristic. 
If the person has struggled in the water and clutched at objects within his reach, 
there may be evidences of this in excoriation of the fingers or in the presence of sand, 
weeds, etc., under the nails or grasped in the hands. 
External marks of injury, bruises, etc., should be sought for, since persons in dying, 
or on being thrown into the water with homicidal intent, may have died from the 
violence, and not, strictly speaking, from drowning. It should also be borne in mind 
in such complex cases that injuries, not in themselves fatal, may, when the body is in 
the water, prove so on account of the inability of the person to rescue himself or gain 
time for recovery from the injury, and that then the struggle for breath may be but 
slight, and the more prominent signs of drowning but little marked. 
Internal Examination.-The Brain.-Congestion of the brain and its mem- 
branes is found only in a small proportion of cases. 
The hlood, when death occurs from asphyxia, is usually fluid throughout the body 
and of a dark color, as in asphyxia from other causes. 
The Air Passages.-In persons who die from asphyxia the mucous membrane of 
the larynx, trachea, and bronchi is usually congested, and the air passages contain a 
variable quantity of bloody or mucous froth. In persons dying in the water from 
other causes than asphyxia, these appearances are absent. Foreign substances from 
the water, such as sand, weeds, etc., or materials regurgitated from the stomach, may 
find their way into the air passages during the act of drowning or as a post-mortem 
occurrence. Thus, in bodies washed about the bottom, sand or mud may get into the 
air passages for a certain distance, from the mechanical action of the water. 
The lungs in typical cases are distended so that they fill the thorax and cover 
the heart. The increased size is due partly to congestion, partly to the presence of the 
fluid in which the person was drowned, which is often inspired during the act of drown- 
ing, and partly to the distention of the air vesicles with air. In cases of drowning in 
which there is a struggle and water is breathed in, the lungs may contain considerable 
fluid; but, as a result of decomposition, this may find its way in greater or less quantity 
into the pleural cavities by transudation, leaving the lungs comparatively empty. 
It should be remembered, however, that a considerable quantity of reddish fluid may 
collect in the pleural cavities under other conditions than drowning, through a post- 
mortem change, by transudation from the blood-vessels and other adjacent tissue. 
The Heart.-In those who die from asphyxia the right cavities are usually filled THE LESIONS IN CERTAIN FORMS OF DEATH 
445 
with fluid blood, while the left cavities are empty. But when death is due to com- 
plex causes this may not be the case. 
The abdominal viscera may be congested in persons who die from asphyxia. 
Fig. 275.-Enlarged Thymus. 
The Stomach.-The fluid in which the person was drowned, sometimes mixed 
with sand, weeds, etc., may be swallowed during the act of drowning. Sand may 
wash for a short distance into the oesophagus after death, in bodies washing about the 
bottom. 
Case of sudden death in child of twelve years. 446 
THE LESIONS IN CERTAIN FORMS OF DEATH 
In persons dying in the water from syncope, shock, etc., we may find no lesions. 
When the death is partly due to asphyxia and partly to other causes, the lesions may 
vary in numerous ways, which need not be described here. 
In important cases of doubtful drowning it is desirable carefully to collect and 
save some of the fluid from the lungs and stomach for micro-chemical examination, 
since the identification of these fluids with those in which the person was presumably 
drowned will often give certainty to an otherwise doubtful case. 
For the detailed consideration of the anatomical diagnosis of drowning, the changes 
which bodies dead from drowning undergo from decomposition, and the factors 
bearing on the question of suicide, homicide, etc., we refer to works on medical 
jurisprudence. 
Sudden Death. 
Some forms of sudden death from violence have been already consid- 
ered. Aside from these, by sudden death, in the ordinary sense, is usu- 
Showing enlarged lymph nodules at the base of the tongue and in the walls of the pharynx. 
Fig. 276.-Enlarged Thymus-Sudden Death. Child Twelve Years of Age. 
ally meant "the rapid and unforeseen termination of a latent acute or 
chronic disease." We shall not consider here sudden death either from 
violence or poisoning or in well-defined and evident acute or chronic 
diseases: it will be practicable only to enumerate some of the more com- 
mon conditions under which sudden death may occur-and first in the 
adult. THE LESIONS IN CERTAIN FORMS OF DEATH 
447 
Circulatory System.-Heart-fatty degeneration, chronic myocarditis, 
abscess of the myocardium, rupture, lesions of the coronary arteries, 
endocarditis, and pericarditis. Blood-vessels-arterio-sclerosis, aneu- 
risms-especially intracranial, intrapericardial, abdominal, and pulmo- 
nary; rupture of the aorta, congenital narrowness of the aorta, thrombosis 
and embolism of the pulmonary or cerebral arteries. 
Fig. 277.-Suffocation from the Lodgment of a Large Piece of Meat in the Larynx. 
This individual died within a few seconds after bolting this mass of meat. 
Brain-haemorrhage, meningitis, abscesses, and tumors. Very slight 
injuries of various parts of the body have been followed by sudden 
death, probably through inhibition. Syncope or shock may terminate 
in death. 
Respiratory System.-Foreign bodies lodging at the entrance to the 448 
THE LESIONS IN CERTAIN FORMS OF DEATH 
larynx are not infrequently followed by immediate death without evi- 
dence of asphyxia (Fig. 277). CEdema of the glottis, oedema of the lungs, 
hypertrophy of the thyroid, mediastinal tumors, pleurisy, and pneumo- 
thorax may lead to sudden death. 
Abdominal Viscera.-Rupture of visceral abscesses; perforation of 
ulcers of the gastro-intestinal canal; rupture of the spleen, especially 
if the latter be enlarged as in malaria; extra-uterine gestation, retro- 
uterine haematocele, and rupture of the uterus, are among the lesions not 
infrequently leading to sudden death. 
Sudden death is frequent in diabetes, in various forms of kidney 
lesion and in alcoholism, and in association with the so-called lymphatic 
constitution.1 
Sudden death in young children is most often associated with disorders 
of the respiratory system, thus differing from adults, in whom lesions of 
the circulatory system are of the greatest significance. Brouardel attrib- 
utes sudden death in children usually to one of five principal causes- 
syncope, convulsions, asphyxia, pulmonary congestion, and intestinal 
disorders. A large thymus (Figs. 275 and 276) with the lymphatic con- 
stitution is frequent in cases of sudden death in young children.2 
1 See Ewing, New York Med. Jour., vol. Ixvi., p. 37, 1897, bibl. 
2 For further details on sudden death consult Brouardel, "Death and Sudden Death," English 
translation, 1897; also Ewing, in Peterson and Haines' "Text-book of Legal Medicine," 1903. PART II. 
SPECIAL PATHOLOGY. SPECIAL PATHOLOGY. 
General Considerations. 
We have now completed the study of those fundamental processes 
and structural alterations which are embraced in general pathology. 
These have been considered without reference to special regions or 
organs of the body. We now enter upon the study of these pathological 
processes and their associated lesions as they are modified by the special 
conditions and characteristic structures of one and another of the tissues 
or organs or regions of the body. It is clear that both the disease proc- 
esses and the structural alterations with which these are associated 
may be modified by the functional and structural peculiarities of the 
affected organ. Thus while degeneration, regeneration, inflammation, 
etc., may be fundamentally similar, for example, in liver, kidney, and 
nerve, they may present sufficient variation in one or another of these 
parts to require a separate consideration and even a special nomen- 
clature. We shall have occasion to call attention now and then to those 
functional and structural characteristics of the organs which often throw 
much light upon their mode of response to the various excitants of 
disease. 
It is well, on the other hand, to remember that there are in all the 
organs and in most parts of the body certain elementary structures, such 
as connective tissue, blood- and lymph-vessels, and nerves, whose lesions 
are quite similar wherever they may be. So that many forms'of lesion 
involving these structures, while of varying significance to the organism, 
differ in the various parts of the body chiefly in distribution or topography. 
451 CHAPTER I. 
THE BLOOD AND THE BLOOD-FORMING ORGANS. 
Changes in the Composition and Structure of the Blood.1 
The Coagulability of the Blood and the characters of the resulting 
clot vary widely, depending partly upon the composition of the blood 
and partly upon the conditions under which the coagulation occurs. 
There may be very little coagulation of the blood in death from suffoca- 
tion, or from conditions which interfere with the aeration of the blood 
and permit the accumulation of carbonic acid within it. Thus, in death 
from strangulation, high-voltage electric currents, drowning, many 
chronic diseases, or scurvy, and under many conditions which we do not 
understand, the blood may remain fluid, or nearly so, after death. On 
the other hand, in a variety of infectious diseases, such as rheumatism, 
pneumonia, etc., very voluminous clots may be formed, although this is 
by no means constantly the case. The fact that large clots form after 
death is not conclusive evidence that an undue amount of fibrin-forming 
elements was present in the blood, nor does the absence of marked coagu- 
lation prove a diminution in the blood of fibrin-forming elements. 
The composition of the clot varies with the rapidity of its formation 
and with the specific gravity of the plasma. Clots very rapidly formed 
in plasma of high specific gravity, or in still slowly circulating blood, 
are apt to be dark red, from admixture of red cells and fibrin. After 
complete failure of circulation, especially in plasma of low specific grav- 
ity, the red cells tend to settle to dependent vessels. Yellowish white 
succulent clots then form in the clear supernatant plasma, while soft 
black clots result from the excess of red cells collected in the dependent 
vessels. 
The current theory of coagulation of the blood is that four factors 
are necessary for the production of fibrin: fibrinogen, prothrombin, 
thrombokinase, and calcium salts. By the interaction of the latter three, 
thrombin is produced; and this substance acting on fibrinogen causes 
the formation of fibrin, or clotting. The fibrinogen is in solution in the 
plasma. By the action of thrombin upon it, it is split into a soluble 
serum globulin and fibrin. Prothrombin is present in the circulating 
blood and of itself has no action on fibrinogen, but in the presence of 
thrombokinase and a calcium salt, a new body, thrombin, is formed, 
which acts upon fibrinogen. Thrombokinase is not found in the plasma 
of the circulating blood, but is present in the tissues and in the leuco- 
1 A full discussion of the subjects in this chapter can be found in Ewing, "Clinical Pathology of the 
Blood," 1903: DaCosta, Clinical Hematology, 1905; and Naegeli, Blutkrankheiten und Blutdiag- 
nostik, Leipzig, 1912. 
452 THE BLOOD AND THE BLOOD-FORMING ORGANS 
453 
cytes and blood platelets of the blood. Howell1 has proposed a new view 
which postulates an antithrombin inhibiting the conversion of the pro- 
thrombin into thrombin. When the blood is shed the platelets furnish a 
thromboplastin which combines with the antithrombin, thus freeing the 
prothrombin; the latter, activated by calcium, then acts on the fibrinogen. 
The time of coagulation of the blood in healthy persons is fairly con- 
stant when determined by satisfactory methods. In disease, consider- 
able variations have been noted in the coagulation time. In cases of 
hereditary haemophilia the blood may require 60 to 70 minutes to coagulate 
instead of the normal 7 to 10 minutes. In jaundice the coagulability of 
the blood may be impaired. Some of the severe anaemias and purpuras 
may also show moderate slowing of coagulation. Repeated haemorrhages 
shorten the time of coagulation. It has been stated that the injection 
of gelatine into the vessels and the ingestion of calcium chloride or lactate 
also shorten the coagulation time. The facts concerning calcium chlo- 
ride are fairly well established, but the influence of gelatine is still open 
to question. The difficulty lies largely in our inability to obtain a satis- 
factory quantitative method by which the amount of thrombokinase 
can be accurately determined, and the influence of accidental mechanical 
factors can be eliminated. 
Reaction of the Blood.-Owing to the general use of litmus as m 
indicator the reaction of the blood has long been considered to be alkaline. 
This substance, however, does not afford reliable determinations of the 
actual reaction, and it has lately been shown by physico-chemical 
methods that the blood may be considered as approximately a neutral 
fluid; that is, that the proportion between the hydrogen and the hydroxyl 
ions is nearly the same as in distilled water. The reason for the apparent 
alkalinity to litmus and the real neutrality of the blood is that there are 
present in this fluid substances which when dissociated act both as acids 
and as alkalies. The acids are represented by the carbon dioxide dis- 
solved in the plasma and phosphoric acid present as a monosodium 
salt. The alkalies are represented by sodium bicarbonate and disodium 
phosphate which are alkaline in reaction. The proteids of the blood 
also act both as bases and as acids. Litmus not being sensitive to carbon 
dioxide is turned blue by the excess of basic ion present. If, however, 
a more sensitive indicator is used, such as phenolphthalein, no alteration 
in the color is produced; in other words, the blood is actually acid to 
that substance. 
All the older observations based upon litmus as an indicator must be 
revised, and there are at present but few reliable determinations avail- 
able. These show that even in diabetes with a high content of beta- 
oxybutyric and aceto-acetic acids in the blood there is but very slight 
alteration in the reaction towards the acid side. The maximum change 
observed in such cases does not render the blood over three times as acid 
as distilled water, and so great is the binding power of the proteids and 
so large an amount of free alkali is available for neutralization that the 
1 Howell, Amer. Jour. Physiol., 1911, xxix., 187. 454 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
conclusion must be drawn that there is no real acid intoxication as 
indicated by marked changes in the blood reaction. 
Anhydraemia-the condition in which the blood contains an excessive 
proportion of albumin, cells, and other solid elements-occurs in 
diseases associated with excessive serous discharges from the intestines. 
It is extreme in some cases of cholera, and has been noted in a lesser 
degree in other infectious diseases, as pneumonia and diphtheria. 
After removal of large quantities of fluid from the peritoneal or 
pleural cavities a passing concentration of the blood even to the doubling 
of the number of red corpuscles present may be observed. This is due to 
the rapid transudation of serum from the blood to take the place of that 
withdrawn from the serous cavity. When the balance is again estab- 
lished the anhydraemia quickly gives place to the opposite condition, 
hydraemia. 
Hydraemia is that condition in which the blood contains a large 
amount of water in proportion to the solid ingredients. It occurs in a 
variety of diseases of the heart, lungs, liver, and kidneys, and character- 
izes all forms of anaemia. 
Haemoglobinaemia.-Owing to the destruction of red blood cells in 
some forms of poisoning, burning, etc., the blood plasma may contain 
free haemoglobin, by which it is discolored (hcemoglobinoemid), or it may 
be stained from the absorption of bile pigment. 
A similar destruction of the red cells with solution of the haemo- 
globin is occasionally observed following direct transfusion in persons 
suffering from severe anaemia, especially of the pernicious type. 
Anaemia.-In general, anaemia means a diminished quantity of blood 
or of red blood cells in the vessels of the whole or any part of the body. 
With one exception-mild chlorosis-it is invariably characterized by a 
reduction in number and change in form of the red cells (oligocythaemia), 
and by diminished alkalinity and coagulability. It is always associated 
with a reduction in specific gravity, in haemoglobin, and in solid elements. 
Hydraemia and an increased tendency toward osmosis are equally con- 
stant features of this condition. The albumens remaining in the serum 
after coagulation are very slightly diminished in anaemia. 
Generally speaking, anaemia is produced by excessive haematolysis, 
or by defective haematogenesis, or by actual loss of blood, in bulk (haem- 
orrhage) , or in its fluid ingredients (transudation). 
Anaemia may be secondary to haemorrhage, to exudative processes, 
to prolonged malnutrition, to chronic organic diseases of many kinds, 
to the action of poisons, to congenital hypoplasia of heart and arteries, 
to functional disturbances of an unknown nature in the blood-forming 
organs, and to wholly unknown causes. Simple atrophic changes in 
many tissues, hypertrophy of the red marrow, lymph-nodes, spleen, liver, 
and thymus, fatty degeneration of the liver, kidneys, heart, and blood- 
vessels, with capillary haemorrhages and .transudations, are frequent 
accompaniments of severe anaemia. 
Polycythaemia.-By polycythaemia in its proper usage is meant an 
increase in the number of corpuscles in the blood without necessarily an THE BLOOD AND THE BLOOD-FORMING ORGANS 
455 
increase in the total volume. This condition is frequently noticed in 
chronic dyspnoea from either congenital or acquired heart disease, in 
certain chronic diseases of the lungs accompanied by cyanosis, and after 
poisoning by illuminating gas. What may be termed a physiological 
polycythaemia has been observed in persons living at high altitudes. 
This has been attributed to the stimulating effect of the diminished 
oxygen partial pressure on the blood-forming organs, which causes them 
to produce an excessive number of red cells, and to the rapid evaporation 
from the skin which takes place, thus concentrating the blood by the 
transfer of plasma from the blood to the tissues. The question can not, 
however, be regarded as finally settled.1 
The other type of polycythsemia, seen in diseases in which the circula- 
tion is interfered with, is probably entirely a local phenomenon, the 
increase in the number of corpuscles being due in all probability to the 
concentration of the blood-vessels in the peripheral capillaries. This is 
induced by the increased viscosity of the blood incident upon the in- 
creased carbon dioxide content following the imperfect aeration in the 
lungs. The polycythsemia disappears in such cases very promptly on 
inhalation of oxygen, and at the same time the viscosity falls. As soon, 
however, as the oxygen treatment is terminated the peripheral stasis 
reappears. In cases of chronic cardiac disease with broken compensa- 
tion the disappearance of the polycythsemia is noted as soon as the heart 
lesion improves. While the polycythsemia is usually a general phenom- 
enon, that is, the blood concentration exists in all the peripheral vessels, 
it may occasionally be local. The most striking example of such local 
concentration of the formed elements of the blood is seen in cases of 
intrathoracic tumor with a compression of the superior vena cava and 
azygos veins. Under these circumstances intense congestion of the upper 
extremity may be induced, and blood taken from the finger may show a 
million more red cells to the cubic millimeter than that taken from 
the toe.2 
Plethora.-The existence of a true plethora, that is, an increase in 
the volume of the blood accompanied by a co-ordinate increase in cor- 
puscles, has long been debated; but recently cases have been reported, 
occurring chiefly in persons suffering from a disease of unknown etiology, 
generally accompanied by hyperplasia of the spleen or bone marrow, high 
blood pressure, and cyanosis, and designated clinically as polycythaemia 
or erythraemia. The number of red and white cells and the amount of 
haemoglobin are greatly increased. The condition of plethora may be 
suggested at autopsy by the very great distention of all the vessels and 
the overfilling of the organs with blood.3 The only accurate method, 
however, is to determine the total amount of blood in the body during 
life by the relatively simple procedure of Haldane,4 by which the patient 
inspires a measured quantity of carbon monoxide. A sample of the 
1 For a very full discussion of the work of previous observers and many important personal observa- 
tions, see Zuntz, Lowy, Muller, u. Caspari, Hohenklima u. Bergwanderungen, Berlin, 1906. 
2 For study of polycythsemia, with bibl., see Ducas, Arch. Int. Med., 1912, x., 597; Senator, Polyzy- 
thamie und Plethora, Berlin, 1911; and Hirschfeld, Polyzythamie und Plethora, Halle, 1912. 
3 Westenhoefer, Ein Beitrag zur pathologischen Anatomie der plethora vera, Deutsch, med. Wchn- 
schr., 1907, xxxiii., 1446. 
4 Haldane and Smith, Jour, of Physiol., 1897, xxii., 231; 1900, xxv., 331. 456 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
blood is then taken and analyzed to determine what percentage of haemo- 
globin has been altered into carbon monoxide haemoglobin.1 
These may be diminished in number and may undergo various 
changes in shape and size and structure. 
THE RED BLOOD CELLS. 
Alteration in Number of the Red Blood Cells. 
Oligocythaemia is that condition of the blood in which the number of 
the red cells is reduced. This reduction in number may be temporary, 
as after haemorrhage, or it may be persistent, as in some forms of anaemia. 
The number of red blood cells may in extreme cases of anaemia be reduced 
to one-tenth of the normal, or even less; that is, from the normal num- 
ber, which is between four and five millions, there may be a reduction to 
half a million or less. 
A persistent diminution in the number of red cells may be effected 
either by increased destruction (hcematolysis) or by defective formation 
(hoematogenesis) of these elements, but the relation of the two factors in 
the production of the chronic anaemias is as yet imperfectly determined. 
Excessive hcematolysis occurs after burns, is the result of poison- 
ing by arsenic, phosphorus, and chlorates, phenylhydrazin, nitrobenzol, 
acetanilid, etc., and may occur in infectious diseases through the action 
of bacterial toxins. All stages of a peculiar destruction of red blood 
cells may readily be followed in the blood in malaria. In chronic infec- 
tious diseases, prolonged suppuration, and in the cachexia attending 
malignant new growths, destruction of red cells is probably effected, 
in part, by toxic agents circulating in the blood. In pernicious anaemia 
the condition of the blood may, with considerable certainty, be referred 
largely to a destruction of red cells by some unidentified toxic material 
in the blood. 
In the destruction of the red cells, especially if rapid, haemoglobin 
may separate from the cells, dissolve in the plasma (haemoglobinaemia), 
and may then be excreted unchanged in the urine (haemoglobinuria). 
Such destruction occasionally follows chilling of the extremities after 
exposure to cold in persons suffering from a disease known as paroxys- 
mal haemoglobinuria.2 
The gradual and more common form of destruction of red cells is 
attended with an alteration of the haemoglobin, effected chiefly in the 
liver, and with its deposit in the endothelial and glandular cells of vari- 
ous organs, especially in the liver, spleen, kidneys, bone marrow, and 
secondarily in any of the tissues. 
A part of the altered haemoglobin is to be found in the form of pig- 
ment granules, or as a diffuse deposit, in the cells of the above-named 
organs, where its content of iron may or may not be demonstrable by 
1 For a full review of the subject of polycytheemia, erythraemia, and plethora, see paper by F. P. 
Weber, Quart. Jour. Med., 1908, ii., 85. 
2 For an interesting study of the conditions underlying the haemolysis which occurs in paroxysmal 
haemoglobinuria see Donath and Landsteiner, Zeit. f. klin. Med., Bd. Iviii., 1906, p. 173. THE BLOOD AND THE BLOOD-FORMING ORGANS 
457 
microchemical tests (hamosideriri). Another product of the haemoglo- 
bin, not containing iron, may be found in the same situations, in the 
forms of granules or crystals {hcematoidin). Finally, the derivatives of 
haemoglobin are excreted largely in the form of normal or pathological 
urinary pigment. The remaining fragments and stroma of the red cells 
are soon removed from the circulation largely by leucocytes, and partly 
by endothelial cells and giant cells, in the liver, spleen, and marrow. 
Defective h^matogenesis must be regarded as an important factor 
in the production of such anaemias as are associated with pathological 
changes in the bone marrow (pernicious anaemia), and in the lymph-nodes 
spleen, and liver (leukaemia). This, too, is probably the chief cause of the 
persistence of an anaemia following prolonged malnutrition (secondary 
anaemia). The pathological changes in the blood-producing organs may 
sometimes arise as primary diseases of these organs, or similar changes 
may be secondary to excessive demands for the regeneration of the blood. 
In mild grades of anaemia the regeneration of the blood is attended with 
an hyperplasia of the red marrow, which replaces the yellow marrow of 
the long bones. The chief defect in the production of red cells may then 
be a deficiency in haemoglobin (chlorosis). In severe and prolonged 
anaemia, under the influence of toxic agents in the blood, the reproduction 
of cells may be insufficient, and these new cells may be more susceptible 
to the action of the toxic agent, which is itself the cause of their structural 
defects. In such cases the normoblasts of the marrow may be produced 
in very large numbers and form red cells of normal or slightly diminished 
size, or they may be replaced by very large nucleated red cells {megalo- 
blasts) ; from these are developed very large red cells which are compara- 
tively incapable of the functions of the normal cell. The megaloblastic 
form of regeneration is confined to the anaemia of a pernicious type, with 
the exception of the form due to the Bothriocephalus latus or that 
following the prolonged action of certain organic poisons such as nitro- 
benzol. 
Alterations in Morphology of the Red Blood Cells. 
In mild forms of ancemia the red cells are deficient in haemoglobin, the 
blood may be pale or watery in appearance, and the cells appear in the 
fresh condition as very pale discs or as slightly refractive rings enclosing 
a nearly colorless central mass. In dry preparations stained with eosin, 
such cells may show only a narrow red ring surrounding a central por- 
tion which is entirely devoid of hsemoglobin. In this grade of anaemia 
there may be noted moderate differences in size and irregularities in 
shape of the red cells. In severe anaemia and under a variety of con- 
ditions, as after certain forms of poisoning, extensive burns, etc., varying 
numbers of very small red cells are seen, called microcytes. They are 
spheroidal or irregular in shape, may be excessively minute, and their 
haemoglobin is either increased, or normal, or diminished. Under similar 
conditions, a variety of bizarre forms of red cells are found, called poiki- 
locytes. In certain forms of anaemia very large red cells occur in consider- 458 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
able numbers. These cells, called megalocytes, are derived from the large 
nucleated red cells of the marrow, and their appearance in the blood 
indicates the early onset or actual establishment of some form of pro- 
gressive pernicious anaemia (see Plate II., Fig. 4). 
Amoeboid movement of megalocytes has been observed in specimens 
from the blood of pernicious anaemia examined on a warm stage. The 
tendency of the red cells to form rouleaux is much diminished or absent 
in very grave anaemia. 
Not infrequently a loss of haemoglobin is associated with a change in 
the stroma of the cell, so that the mass stains slightly with methylene 
blue. To this change the name of anaemic or polychromatophilic degen- 
eration has been given, and it is thought to show a more or less com- 
plete coagulation necrosis by which change the protoplasm of the red cell 
becomes more basophilic1 in its staining reaction, though recent investi- 
gations have shown that similar cells are present in normal bone marrow 
and in the blood of the foetus. It is therefore probable that our staining 
methods do not differentiate between a degenerative change in the body 
of the cell and a condition expressive of physiological youth. Normally, 
perhaps, such cells are retained in the marrow until fully developed and 
only appear in the blood when excessive demands are made upon the 
blood-forming organs. 
Instead of a uniform absorption of the dye some parts of the cell may 
be condensed in the form of small granules or rings occupying the cell 
body and staining more deeply with methylene blue than do normal 
cells (granular degeneration). 
It should be remembered that during the manipulations required in 
making dried specimens the red cells may suffer a variety of artificial 
changes, many of which are very confusing. 
Nucleated red blood cells are found in the blood in all forms of anaemia, 
and their appearance indicates regenerative activity on the part of the 
blood-producing organs. Their presence in the blood in large numbers, 
though at all periods of extra-uterine life abnormal, has been regarded 
as of favorable import in disease. Within a few hours after severe 
haemorrhage nucleated red cells may be noted in considerable numbers.2 
During the regeneration of the blood in anaemia, the occurrence of nucle- 
ated red cells is nearly constant, but subject to rather sudden periodical 
variations sometimes called " blood crises." In favorable cases of anaemia 
nucleated red cells of normal size only {normoblasts) (Plate II., Figs. 
2 and 3) are seen, whose compact, darkly staining nuclei may be found 
either in the centre of the cell or slightly protruding from the periphery; 
or, nuclei apparently quite extruded from the cell may be found free in 
the plasma. 
In severe anaemia attended with an abnormal type of blood formation, 
1 It is convenient to classify the dyes used in staining into the acid, the neutral, and the basic, and 
to designate cells, in accordance with the relative persistency with which they hold these dyes, as acido- 
phile, neutrophile, or basophile. 
2 The appearance of nucleated red cells and abnormal forms has been frequently noted in those who 
have recently arrived in mountainous regions, the probable explanation being that the lowered oxy- 
gen tension of the rarefied air demands a larger amount of haemoglobin to supply the wants of the tissues, 
with the result that for a short time immature red cells are set free from the bone-marrow. THE BLOOD AND THE BLOOD-FORMING ORGANS 
459 
very large nucleated red cells (megaloblasts) (Plate II., Fig. 4) appear 
in varying numbers. The protoplasm of these cells often shows an 
excess of haemoglobin, but frequently the purple stain produced by a 
combination of the eosin and methylene blue indicates an altered form 
of haemoglobin, or very fine basophile granules may be demonstrated 
by treatment with methylene blue. The nuclei of the megaloblasts 
may be single and compact, or a single large nucleus may show stages of 
direct division, or in extremely large cells (gigantoblasts) the nuclei may 
present phases of mitosis. 
THE WHITE BLOOD CELLS. 
The Leucocytes of Normal Blood. 
The leucocytes of normal blood may be classified according to their 
place of origin, or by the character of their nuclei, or by the reaction 
of the granules in their protoplasm to certain dyes. The most service- 
able classification is that based both upon the character of the nucleus 
and upon the reaction of the protoplasm to dyes, according to which we 
may distinguish in normal blood the following forms (see Plate II., Fig. 1): 
1. Lymphocytes, small leucocytes of about the size of red cells or 
larger, with a single, compact, deeply staining nucleus, surrounded by a 
thin rim of homogeneous protoplasm. The cell body usually possesses 
a stronger basophilic reaction than the nucleus, so that in staining with 
methylene blue the nucleus shows as a pale spot in the centre of the dark 
ring of the cell body. This ring is often ragged in its outline and may 
show distinct projections which are sometimes cast off into the circu- 
lating blood. Large and small lymphocytes may be distinguished 
(Plate II., Fig. 5). 
When deeply stained with a methylene azure-eosin mixture, the 
bodies of a certain number of the lymphocytes show moderate numbers 
of so-called azure granules. These granules are usually not found in the 
lymphocytes from normal blood. They have been variously interpreted 
(a) as granules of the same specific quality as those in other leucocytes, 
(b) as secretory products of the cell protoplasm occurring during degen- 
erative changes, and, finally, (c) as very small nuclear fragments set free 
in the protoplasm of the cell. The last view is strongly suggested by 
morphological appearances in the cells. 
2. Large mononuclear leucocytes, with a single, compact or vesicular, 
rather faintly staining nucleus, and a relatively large amount of proto- 
plasm which stains much less strongly than the nucleus. According to 
Ehrlich, these cells represent a type different from the lymphocytes; but 
it is often difficult to make such a distinction on a morphological basis. 
At the present time they are usually classed as belonging to the group of 
large lymphocytes, though some observers consider them as precursors 
of the myelocytes. They may contain azure granules. 
3. Transitional leucocytes, of the same size as many of the large 
mononuclear leucocytes, with a compact or vesicular, irregular or Description of Plate II. 
All the Specimens are Stained with Eosin and Methylene-azure. 
Fig. 1. Normal Blood.-The red cells are nearly uniform in size and shape. The haemoglobin 
is fairly evenly distributed, but is slightly more dense near the periphery than at the centre, especially 
in those cells which have dried slowly. In rapidly dried red cells the stain is even throughout. To 
the left is a lymphocyte with reddish, deeply stained nucleus and a pale bluish cell body, which is 
narrow in proportion to the size of the nucleus. To the right is a small lymphocyte, smaller than the 
red cells which surround it, with a deeply stained nucleus and a narrow cell body from which projects 
a small mass of protoplasm. At the upper portion of the figure is a large oval cell w'hich corresponds 
to the large mononuclear cell of Ehrlich, but considered by mapy equivalent to a large lymphocyte. 
In the centre of the drawing is a cell with a lobed nucleus and purplish granules by which this basophile 
cell is distinguished from the neutrophile just below it and from the eosinophile in the right lower 
quadrant. Two neutrophile cells are shown, one with abundant fine granules, the other showing a 
smaller number; both types being abundantly present in normal blood. To the right is a small cluster 
of blood-plates, some of which show darker staining masses near the centre which are presumed by 
some observers to be nuclear remains, by others to be fragments of haemoglobin. The eosinophile 
cell in the lower right-hand quadrant is distinguished from the neutrophile by the coarseness of its 
granules, which are shot-like and quite regular in form, though not all the granules are of the same size. 
They often take a much more brilliant red color than the neutrophiles. 
Fig. 2. Chlorosis.-The blood was obtained from a young woman of twenty-two years, who 
had 3,000,000 red cells and 30 per cent, of haemoglobin. The red cells are about of the same size 
as those in normal blood, but show a greatly diminished amount of haemoglobin to the individual 
cell, as evidenced by the much fainter staining of a number of cells in the plate which appear merely 
as remnants. Some of the cells have assumed irregular shapes and are known as poikilocytes. In 
the left upper quadrant are three forms which may be considered as pathological in circulating blood. 
Below, to the left, is a purplish red cell rather deeply stained, showing polychromatophilia. To 
the right of this cell and separated from it by a nucleated red cell of normoblastic type is a cell showing 
granular degeneration. 
Fig. 3. Secondary Anaemia.-The blood was obtained from a case of carcinoma of the stomach 
in which the red cells were reduced to 1,500,000; the haemoglobin was 25 per cent.; the leucocytes, 
30,000. The changes in the red cells are much the same as those noted in the chlorotic plate. There 
is marked diminution of the haemoglobin of the red cells with poikilocytosis and also granular degenera- 
tion and polychromatophilia. Two nucleated red cells are present, one in the upper right, the other 
in the lower left-hand quadrant. Both show degenerative changes in the nuclei, which should not be 
mistaken for mitotic figures. In secondary anaemia of this type the polynuclear neutrophiles are nota- 
bly increased. 
Fig. 4. Pernicious Anaemia.-The blood was obtained from a case showing 400,000 red cells, 10 
per cent, of haemoglobin, and 3,000 leucocytes. The striking features of the blood in this disease are 
the marked alterations in size, shape, and staining properties of the red cells. The leucocytes are 
usually diminished in number and show no characteristic changes, with the exception of a relative 
increase in the lymphocytes. The various types of deformation of the red cells are very well noted in 
the various poikilocytes in the sketch, some of which contain large quantities of haemoglobin, others 
a diminished amount. In the red cells approachng more nearly to the normal form it will be imme- 
diately noted that the amount of haemoglobin present as evidenced by the depth of stain is relatively 
large. The cell in the centre of the field, for example, stains a great deal more deeply than any normal 
cell. These deeply staining cells are also very large and often of peculiar oval and irregular form. 
The so-called megaloblasts are abundantly present in the blood of pernicious anaemia, in contrast 
to the microcytic type of cell usually found in the secondary anaemias and in chlorosis. It is this 
macrocvtosis with the consequent increase in the haemoglobin content of each cell that gives rise to 
the high relative haemoglobin index of the blood of pernicious anaemia. A normal-sized cell showing 
marked polychromatophilia is seen above; a macrocyte with granular degeneration is seen below it, 
and a normal-sized red cell with nucleus, or normoblast. In the lower left quadrant is a large erythro- 
cyte with a large nucleus with fine chromatin network. The cell body takes on a combination of the 
blue and pink of the stain; in other words is polychromatophilic. Below it is a normal lymphocyte. 
In the lower right quadrant are two other megaloblasts showing a slightly different morphology and 
with an orthochromatic protoplasm: that is, the cell body takes the eosin alone. The upper cell shows 
a dense nucleus with thick strands of chromatin forming a network. In the lower the chromatin shows 
no structure. 
Fig. 5. Chronic Lymphatic Leukaemia.-The blood of this case showed 3,500,000 red cells, 
160,000 leucocytes, and 50 per cent, of haemoglobin. Of the leucocytes 95 per cent, were lymphocytes. 
It will be noted from the drawing that the red cells are practically normal in size and shape. The 
abundance and variety of the lymphocytes will be noted immediately. In the upper right quadrant 
is a single normoblast; in the lower right quadrant of the upper part is a washed-out cell with irregu- 
lar outline which is a degenerated lymphocyte. In the acute forms of lymphatic leukaemia these cells 
become exceedingly abundant. 
Fig. 6. Myelogenous Leukaemia.-The blood of this case showed 1,000,000 red cells, 20 per 
cent, haemoglobin, and 1,200,000 leucocytes, the exact proportions of which could not be determined 
on account of the large number of irregular and degenerated forms, but myelocytes and basophiles were 
very abundant. In the upper left quadrant can be seen an eosinophile myelocyte with a single oval 
nucleus and large shot-like granules. Below it are a normoblast with granular degeneration of the 
protoplasm and a polymorphonuclear neutrophile with fine granules. In the lower left quadrant can 
be seen a large degenerated neutrophile mvelocyte in which the granules have become scattered over 
the slide in the process of spreading the blood. To the right and below the centre are a normoblast 
with clover-leaf nucleus, a polymorphonuclear neutrophile and a lymphocyte, and above an eosinophile 
mvelocyte. In the upper right quadrant, beginning at the left, can be seen a small basophile cell with 
faintly staining nucleus, to the right two myelocytes, one with deeply staining nucleus, the other 
somewhat fainter, both containing neutrophile granules. To the right a normoblast with pyknotic 
nucleus, and still farther to the right a so-called basket-cell or degenerated leucocyte. Pathology-Delafield and Prudden. 
Plate II. 
Fig. 1. Normal Blood. 
Fig. 2. Chlorosis. 
Fig. 3. Secondary Anaemia. 
Fig. 4. Pernicious Anaemia. 
Fig. 5. Chronic lymphatic Leukaemia. 
Fig. 6. Myelogenous Leukaemia. 
Changes in the Morphology of the Blood. 
Drawn by Francis Carter Wood. 
(Magnified pOO Diameters) THE BLOOD AND THE BLOOD-FORMING ORGANS 
461 
incurved nucleus, and a considerable mass of protoplasm, in which fine 
neutrophile granules can occasionally be demonstrated. 
4. Polynuclear neutrophile leucocytes, of the same size as the trans- 
itional leucocytes, with a partially or completely divided nucleus, of 
which the separate portions are either compact or vesicular, deeply or 
faintly staining, and with considerable protoplasm in which distinct 
granules may be demonstrated by the neutral dyes. 
5. Eosinophile cells, of the same characters as the ordinary poly- 
nuclear leucocytes, but containing in their bodies large refractive gran- 
ules, which stain deeply with so-called acid dyes such as eosin. 
6. Basophile cells, of about the same size as the polynuclear cells, 
but containing coarse granulations stained only by basic dyes such as 
methylene blue. The nucleus is small, stains feebly, and is usually 
lobular. It is often covered very largely by the granulations. 
These various forms of leucocytes occur in normal blood in the fol- 
lowing proportions, which represent averages only and are subject to 
considerable variations: 
Polynuclear neutrophile leucocytes 60 to 72 per cent. 
Large mononuclear and transition forms 2 to 4 per cent. 
Lymphocytes 22 to 35 per cent. 
Eosinophiles 2 to 4 per cent. 
Basophile cells less than 0.5 per cent. 
In the normal blood of young children the relative proportion of 
mononuclear cells is considerably greater than in that of adults.1 
The numbers and proportions of the polynuclear leucocytes are in 
disease subject to very wide variations, and abnormal forms of the 
white cells frequently make their appearance in the blood. 
The Leucocytes of Abnormal Blood. 
1. Myelocytes.'-In many diseases, especially the leukaemias but also in 
acute infections, large mononuclear cells make their appearance in the 
blood. They measure from 15 to 20 in diameter. (Plate II., Fig. 6.) 
Three types may be differentiated by the tinctorial relations of their gran- 
ules: neutrophilic, eosinophilic, and basophilic. The nucleus is usually 
pale, and oval or round, and lies to one side of the cell. The protoplasm 
is generally fairly abundant. The neutrophile myelocytes contain large 
numbers of fine neutrophile granules which, however, often show a baso- 
philic habit when compared with the neutrophile granules of normal 
blood. 
Eosinophile myelocytes are of much the same type, but are easily 
differentiated by the large size of the granules. The cells are very easily 
destroyed in the process of making smears, and the granules may be 
scattered to a considerable distance from the nucleus. 
Basophile myelocytes are quite rare, are usually smaller than the 
other two types, and contain large numbers of irregularly shaped baso- 
phile granules. 
1 See for recent study, Schloss, Archives of Int. Med., 1911, vi., 638. 462 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
All these types of cells arise normally from the bone marrow and can 
be found in smears from this organ. In advanced leukaemias it is probable 
that the liver and spleen assume to a certain extent their embryonic 
function and act as centres for the production of these cells. 
Myelocytes are found in the blood chiefly in leukaemias, but the neutro- 
phile form occasionally appears in severe infectious diseases and in 
primary or secondary tumors of the bone marrow. Eosinophile myelo- 
cytes have been very rarely seen in high eosinophilia due to the presence 
of parasites in the body. 
2. Large Lymphocytes.-While cells of a lymphocytic type appear in 
normal blood in moderate numbers, a very large cell giving the same 
staining reactions also occurs in acute lymphatic leukaemia. Until 
recently these cells were considered as unquestionably large types of 
lymphocytes; but the demonstration of proteolytic and lipolytic fer- 
ments by Longcope1 and of oxidases by Schultze2 suggests that the cells 
belong to the bone-marrow group, and not to the true lymphocytes which 
do not give these reactions. A further discussion of this question will be 
found under acute lymphatic leukaemia (p. 465). 
3. Plasma Cells.-In severe anaemias and leukaemias and in certain 
of the infectious diseases, large cells measuring 6 to 15 /j., with a single 
pale nucleus and a cell body staining very deeply with methylene blue, 
appear in the circulation. The cell body shows a definite spongy struc- 
ture. These were named by Turk3 " irritation forms." It has been 
shown that these cells have many tinctorial relations with the cells seen 
in large numbers in chronic inflammations occurring in connective tissue, 
and though there are slight morphological differences between the two 
forms yet these blood cells are usually considered as of the plasma-cell 
group. 
4. Myeloblasts.-In myelogenous leukaemia and also in typhoid fever, 
large cells resembling myelocytes appear in the circulation, but they 
contain no characteristic granules stainable either with the Jenner or 
with one of the azure stains. They can be differentiated from the large 
mononuclears by the fact that the nucleus is very rich in chromatin and 
shows large nucleoli. The protoplasm also is more basophilic than that 
of the large lymphocytes. These cells have been named myeloblasts by 
Naegeli. 
Leucocytosis is that condition of the blood in which the leucocytes 
are temporarily or persistently increased in number. When several 
forms of leucocytes are increased in number and the usual proportions 
are but partially disturbed, we speak of mixed leucocytosis. Such a con- 
dition is seen in some forms of anaemia. When the polynuclear neutro- 
phile leucocytes alone are increased, the condition is termed polynuclear 
leucocytosis, or simply leucocytosis. If the mononuclear cells are chiefly 
Leucocytosis. 
1 Longcope and Donhauser, Jour. Exper. Med., 1908, x., 618. 
2 Schultze, Munchen, med. Wchnschr., 1909, Ivi., 167. 
3 Turk, Vorlesungen uber klinische Hamatologie., Wien, 1904. THE BLOOD AND THE BLOOD-FORMING ORGANS 
463 
affected, the condition may be denoted as lymphocytosis. The eosino- 
phile cells alone may be increased. 
Polynuclear leucocytosis may be either physiological or pathological. 
Physiological polynuclear leucocytosis is seen during normal digestion, 
in the later months of pregnancy, and in the first days of infancy, and 
is usually of moderate grade. 
Pathological polynuclear leucocytosis occurs in many inflammatory 
and infectious diseases, and accompanies the various cachexias. Of the 
infectious diseases attended with leucocytosis may be mentioned pneu- 
monia, diphtheria, scarlet fever, erysipelas, rheumatism, suppurative 
cerebro-spinal meningitis, and any disease associated with a pronounced 
exudative or suppurative lesion. On the other hand, leucocytosis is 
absent in uncomplicated typhoid fever, typhus, malaria, measles, and 
tuberculosis. 
The origin and significance of the leucocytosis of infectious diseases 
are imperfectly understood, but may be partially explained by the princi- 
ples of chemotaxis and phagocytosis. From experimental evidence and 
clinical observation it is known that during the onset of some infectious 
diseases the entrance of bacteria or their products into the blood is fol- 
lowed by a disappearance from the circulation of many polynuclear leu- 
cocytes, which are removed from the larger vessels and lodged in the 
capillaries, principally in the lungs and liver. This condition of the 
blood, called hypoleucocytosis, may be attended with a transient reduc- 
tion in temperature and weakening of the heart's action, and is usually 
succeeded shortly by the reappearance of polynuclear leucocytes in 
large numbers, and by a rise of temperature. These leucocytes are apt 
to gather in regions in which micro-organisms are abundant, and are 
believed to take up and destroy micro-organisms (phagocytosis), and to 
prevent their further entrance, and possibly the entrance of their prod- 
ucts also, into the circulation. Of the place and method of origin of 
these new leucocytes very little is definitely known. 
In many very severe cases of infectious disease, such as pneumonia, 
diphtheria, and peritonitis, the initial hypoleucocytosis persists, in which 
event the disease usually runs an asthenic and fatal course, with a ten- 
dency to low temperature and feeble pulse. 
When leucocytosis is established, the grade varies frequently with the 
extent of the local lesion and the height of the fever associated with 
the infectious process, and disappears with, or soon after, the decline of 
the disease. In general, according to our present knowledge, the leu- 
cocytosis of infectious diseases may be regarded as the effort of the 
blood-producing organs to protect the blood and tissues by means of 
leucocytes against the invasion of micro-organisms and against the action 
of toxins present in the circulation. 
The blood in typhoid fever presents a peculiar variation from that in 
most infectious diseases. In the first weeks of the disease there is usu- 
ally a reduction in the number of leucocytes, especially of the polynu- 
clear forms. In the later weeks the lymphocytes may form 80 per 
cent, of the leucocytes present in the blood. Each relapse is attended 464 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
with an increase of the lymphocytosis, while an increase of polynuclear 
leucocytes usually occurs with complications only. 
In the various forms of tuberculosis there is no leucocytosis unless 
the lesion is markedly exudative in character, as in tuberculous menin- 
gitis, or is complicated by suppuration or chronic anaemia. In pulmonary 
tuberculosis with secondary infection by pyogenic cocci, leucocytosis 
is apt to develop. 
Cachectic leucocytosis is a feature of altered conditions of the blood, 
such as are associated, with the growth of malignant tumors, and with 
many diseases producing secondary anaemia. This increase of poly- 
nuclear leucocytes may serve to distinguish many forms of secondary 
from primary anaemia. The inflammation and toxaemia accompanying 
many new growths afford a sufficient reason for the appearance of 
cachectic leucocytosis, but under many other circumstances its direct 
cause is less apparent.1 
Hypoleucocytosis occurs not only in infectious diseases, when the 
polynuclear cells alone are reduced in numbers, but also from shock, 
reduction of body temperature, and exhaustion, when all forms of leuco- 
cytes may be diminished. It is a fairly constant feature of primary 
pernicious anaemia.2 
Polynuclear Eosinophile Leucocytosis is found in a number of unre- 
lated conditions. In bronchial asthma the eosinophile cells are con- 
siderably increased, often forming 10 to 20 per cent, of the total 
white cells. A considerable increase is seen in scarlatina. In acute 
and chronic diseases of the skin, such as pemphigus, prurigo, and psori- 
asis, the eosinophiles are often increased to a marked degree, but the 
condition is not constant. In trichinosis and helminthiasis the increase 
is so constant that it becomes of diagnostic value in these conditions. 
A post-febrile eosinophilia is frequently observed. 
Lymphocytosis, frequently seen in the anaemias, in pertussis, and the 
acute intestinal disorders of childhood, has also been noted in some 
forms of secondary anaemia (syphilis), and in an extreme degree as the 
chief characteristic of the blood of lymphatic leukaemia. It is also quite 
frequent in exophthalmic goitre. 
Degenerative Changes in the Leucocytes are usually indicated by 
variations in the percentage of normal and abnormal varieties, rather 
than by alterations in the individual cells, for degenerating leucocytes 
are usually quickly removed from the circulation. Occasionally, how- 
ever, there may be seen in normal blood a cell in which the nuclear 
chromatin has entirely lost its power to take the stain; and these degener- 
ating or basket cells are sometimes very abundant in the leukaemias. 
Staining reactions of the various granules, by which degenerative changes 
may be recognized, have not yet been devised. In leukaemia, pernicious 
anaemia, and diphtheria, a diminished reaction to nuclear dyes has been 
observed. In leukaemia, and in the severe infectious diseases, the 
1 For further data concerning leucocytosis consult Rieder, "Bietrage zur Kenntniss d. Leukocytose," 
Leipsic, 1892; Turk, "Klin. Utersuchungen u. d. Verhalten d. Blutes," etc., Wien, 1898. 
2 For hypoleucocytosis consult Lowit, " Studien uber Physiol, und Pathol, d. Blutes u. d. Lymphe," 
Jena, 1892; Ewing, "Toxic Hypoleucocytosis," New York Medical Journal, vol. Ixi., p. 257, 1895. THE BLOOD AND THE BLOOD-FORMING ORGANS 
465 
leucocytes may be extremely cohesive, and it is believed that a large 
quantity of bacteria or toxins in the circulation may even effect a com- 
plete solution and destruction of leucocytes (leucocytolysis). Fatty 
and glycogenic degeneration of leucocytes has been demonstrated. 
Blood Plates.-These are small spherical or oval transparent bodies 
which appear in the blood plasma in large numbers. They measure 
from 2 to 3.5 y in diameter, though occasionally in pneumonia and 
suppurative conditions very large plates may be found measuring up to 
5 or 6 Structurally they are composed of a peripheral hyaline trans- 
parent layer with a granular central mass which is not sharply outlined. 
This granular mass takes a faint color with the ordinary chromatin stains; 
the periphery is clear. In stained specimens it is occasionally possible 
Fig. 278.-Megakaryocytes from Bone Marrow. Showing Formation of Blood Platelets. 
From preparation of Dr. J. H. Wright. 
to find long curved protoplasmic processes, simulating cilia, given off 
from the periphery of the blood plate. Under suitable conditions the 
blood plates show ameboid motion. 
Their number in the blood varies, the average number is considered 
as approximately 200,000 to 250,000. The number of blood plates is 
increased in many anemias, both primary and secondary, and especially 
in carcinoma. In pneumonia, septic processes, and leukemia there,'is 
also an increased number of blood plates. A diminution of the plates is 
noted chiefly in cases of purpura and pernicious anaemia. 
The blood plates are closely connected with the formation of thrombi, 
and some of the small, so-called white thrombi are entirely composed of 466 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
these bodies. They are also thought to carry the blood-coagulating 
ferment, thrombokinase. 
There are a number of theories concerning the origin of blood plates. 
Hayem considered them predecessors of the red blood cells. Others 
regard them as individual cells, and not as fragments of leucocytes or 
red cells as has also been frequently suggested. The theory that they are 
formed by the extrusion of the nuclear substance of the red cells has had 
many adherents. Wright1 has recently offered very strong evidence that 
blood plates are formed from the megakaryocytes of the bone marrow. 
These cells frequently show budding masses of the same structure as 
the blood plates (see Figs. 278 and 279). The hyaline peripheral zone 
Fig. 279.-Megakaryocytes from Bone Marrow. Showing Formation of Blood Platelets. 
From preparation of Dr. J. H. Wright. 
of the giant cell has the power of amoeboid motion and can be observed 
on the warm stage to give out protoplasmic processes. In addition the 
blood plates are found only in such mammalia as have megakaryocytes 
in the bone marrow, and it has also been noted that blood plates appear 
only in embryonal mammalian blood at the time when the giant cells 
are present in the blood-forming organs. 
METHODS OF EXAMINATION OF THE BLOOD. 
The blood may be examined fresh on the warm stage without the addition of any 
fixative, simply surrounding the cover with oil or vaselin to prevent evaporation. 
This method is especially useful in the examination of blood for the plasmodia malariae. 
For most purposes, however, the cells should be treated the instant the blood leaves 
the vessels in such a way as to retain their normal form. This fixation may be accom- 
plished by the use of chemical agents (wet method) or by quick drying on the cover- 
glass or slide (dry method). 
1 Wright, Jour, of Morphology, 1910, xxi., 2. Also Ogata, Ziegler's Beit., 1912, lii., 192. THE BLOOD AND THE BLOOD-FORMING ORGANS 
467 
Wet Method.-Among the chemical fixative agents are osmic acid and a solution 
of corrosive sublimate. Osmic acid: Five c.c. of a 1-per-cent. solution of osmic acid 
are mixed with 10 drops of glacial acetic acid in a Petri dish. Short pieces of glass 
tubing are placed in the dish to support the slide which is exposed to the vapor of the 
acids for two minutes. The finger is then punctured and the blood spread in a thin 
film upon the surface of the slide which has been exposed to the vapor. The slide is 
then again exposed to the vapor for one minute. It is allowed to dry, passed three 
times through a film, washed for one minute in a dilute solution of potassium perman- 
ganate (extemporized from a concentrated solution by diluting until the fluid is a 
deep pink), washed in water, dried, and stained by any of the ordinary methods. If 
it is not desirable to dry the slide it may be transferred into a very dilute alcohol and 
carried up by stages of 10 per cent, until thoroughly fixed.1 
Sublimate may be used in the form of Hayem's solution, consisting of 
Chlorid of sodium 1 gm. 
Sulphate of sodium 5 gm. 
Corrosive sublimate 0.5 gm. 
Water, distilled 200 gm. 
The blood is received directly into this solution, in which it is studied. The wet 
method of fixation is especially to be recommended for studies on the minute structure 
of blood cells. 
Another solution which is highly recommended2 is made up as follows: 
Muller's fluid 9 parts. 
Formaldehyde, 40 per cent 1 part. 
Distilled water lOparts. 
The solution should always be made up fresh and warmed to about 40° C. The 
fixed blood is washed in distilled water until all the chrome salts are removed, passed 
through graded alcohols to absolute, transferred to absolute alcohol and carbon 
bisulphid equal parts, and then to pure carbon bisulphid, carbon bisulphid and 
paraffin, and finally embedded in paraffin. Thin sections can be cut, which often 
demonstrate interesting phases of mitosis and other phenomena in the cells. 
None of these methods of fixation in bulk, however, is as satisfactory as the 
Weidenreich or the dry smear methods. 
Dry Method.-It has been found that if the freshly drawn blood from a finger 
prick be immediately dried on a glass in a very thin layer, the cell forms are quite well 
preserved and may be exposed to the action of staining agents. 
For this purpose square cover-glasses of medium size should be cleaned in strong 
nitric acid, rinsed in alcohol and ether, carefully dried, and kept free from dust. 
A drop of blood may be expressed by very light pressure only from the finger tip, previ- 
ously cleansed with alcohol and ether, and for the best results the drop must be 
spheroidal and about one-sixteenth of an inch in diameter. One cover-glass should 
be held in the forceps, or between the fingers if thoroughly dry, and its central point 
touched to the drop of blood. After contact with the blood this cover-glass should be 
instantly laid upon a second glass so as to cover all but an eighth of an inch along one 
side; and as soon as the blood has spread to the edges, the cover-glasses should be 
quickly separated by sliding without pressure and dried in the air. If, instead of 
drying in the air, the specimens are rapidly dried high over an alcohol flame, the 
fixation will be more successful, and many artificial changes in the red cells will be 
avoided. 
Another method, more successful in many hands, consists in touching the drop 
with the smooth edge of a glass slide, applying this edge with its adherent blood 
obliquely to a slide, and, when the blood has spread along the edge of the slide, draw- 
ing it rapidly across the surface of the second slide. 
For the permanent fixation of the cells and to prevent their solution by strong dyes, 
one of two methods may be recommended: 
1 Weidenreich, Folia haematologica, 1906, iii., 1. 
2 Schridde u. Naegeli, Hamatologische Technik, Jena, 1910. 468 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
1. Heat Fixation.-The specimens are heated in a hot-air bath or on a copper 
plate, for from five minutes to two hours at a temperature of 110° C. to 120° C. 
2. Chemical Fixation.-1The specimens are placed for from one to thirty minutes in 
strong methyl alcohol. 
Various staining agents are to be employed according to the object in view. The 
triacid mixture of Ehrlich1 gives an excellent stain for the neutrophile and eosinophile 
granules, but fails to show basophile granules or parasites, for which reason it is being 
supplanted for general work by combinations of methylene blue and eosin. The com- 
position of the Ehrlich stain is as follows: 
Saturated aqueous solutions of 
Orange G 13 to 14 c.c. 
Acid fuchsin 6 to 7 c.c. 
Methyl green 12.5 c.c. 
To the mixture of these add 
Water ; 15 c.c. 
Absolute alcohol 25 c.c. 
Glycerin 10 c.c. 
The specimen should be stained in this fluid for three to five minutes, washed in dis- 
tilled water, dried, and mounted in dammar dissolved in xylol. 
The red cells are then found stained orange-yellow, the nuclei dark green or blue, 
the neutrophile and eosinophile granules dark red. The mast-cell granules are not 
stained. 
For general purposes a stain which has been devised by Jenner bids fair to supplant 
the older methods on account of its simplicity, rapidity, and ease of application. It 
consists of a half-per-cent, solution in methyl alcohol of a compound made by mix- 
ing a 1.2-per-cent. aqueous eosin and a 1-per-cent. aqueous methylene-blue solution. 
The precipitate which forms is filtered off, washed with distilled water, dried, and 
dissolved in the methyl alcohol. The blood smears are fixed and stained by this 
solution in from one to three minutes. The red cells are of a terra-cotta color, the 
nuclei blue, the neutrophile and eosinophile granules red, the mast-cell granules 
purple; bacteria, malarial organisms, and blood plaques blue. 
An extremely satisfactory stain which not only demonstrates the important 
morphological details of the red and white cells, but also gives a characteristic chro- 
matin stain to the malarial parasite is the following:2 
Five gm. of sodium bicarbonate, 10 gm. of methylene blue (B. X. or "medicinally 
pure ") and 1,000 c.c. of water are heated in a steam sterilizer at 100° C. for a full hour. 
The mixture should be contained in a flask of such size as to allow it to form a layer 
not over 6 cm. deep. After cooling it is filtered to remove the precipitate. When 
cold it should be of a deep purple-red-color when viewed in a thin layer by transmitted 
yellowish light. 
To each 100 c.c. of the filtered mixture, 500 c.c. of a 0.1-per-cent aqueous solution 
of Griibler's "yellowish, water-soluble" eosin are added and mixed thoroughly. The 
precipitate which appears immediately is collected on a filter and when dry dissolved 
in methylic alcohol (Merck's reagent) in the proportion of 0.1 gm. to 60 c.c. of alcohol, 
rubbing them together in a porcelain dish or mortar to facilitate solution. This forms 
the staining fluid. It should be kept in a well-stoppered bottle, and if it becomes too 
concentrated by evaporation, may be thinned by the addition of the proper amount 
of methylic alcohol. The method of staining is as follows: 
1. Cover the film with a noted quantity of the stain with a medicine dropper. 
2. After one minute add to the staining fluid on the film an equal quantity of 
distilled water by means of the dropper, and allow the mixture to remain for two or 
three minutes according to the intensity of the stain desired. Too long staining may 
1 Great care must be used in selecting these dyes. Those made by Griibler, of Leipsic, are reliable. 
It is far better to purchase the solution already mixed as sold by Griibler under the name of "triacid 
mixture for neutrophile granules," 
2 Wright, Jour. Am. Med. Assn., 1910, lv., 1979. THE BLOOD AND THE BLOOD-FORMING ORGANS 
469 
produce a precipitate. Eosinophilic granules are best brought out by a short staining 
period. 
3. Wash the preparation in water for thirty seconds, or until the thinner portions 
of the film become yellow or pink. 
4. Dry and mount in xylol-dammar. 
Films more than a few hours old do not stain as well as fresh ones.1 
For the demonstration of fat in blood from a finger prick, cover-glass preparations 
dried in the air should be fixed in formalin vapor and stained with Sudan III (see 
p. 44). To avoid numerous sources of error, a control preparation should be previously 
placed in chloroform for twenty-four hours to dissolve the fat, and two specimens, 
carried together through the stain. In the one, red fat droplets will be seen, which 
should be entirely absent in the other. 
FOREIGN BODIES IN THE BLOOD. 
Various bodies which do not belong there, aside from those above 
mentioned, may find access to the vessels and mingle with the blood. 
Pus cells may get into the blood from the opening of an abscess into a 
vessel or from some inflammatory change in its walls. Desquamated 
endothelial cells from the vessel walls, either in a condition of fatty 
degeneration or in various stages of proliferation, may be mingled with 
the normal blood elements; also tumor cells of various kinds, fragments 
of disintegrated thrombi, portions of heart valves, etc. Crystals of 
bilirubin have been found in the blood in icterus, and Charcot-Leyden 
crystals have been seen post mortem in the blood and bone marrow of 
cases of leukeemia. 
Fat, in a moderate amount, is a normal ingredient of the blood, 
during digestion and in lactation it is increased. Under pathological 
conditions it may occur in larger and smaller droplets. This lipoemia 
occurs in diabetes, in drunkards, in acute phosphorous poisoning, and in 
some cases of dyspnoea from various causes. The droplets are small 
and liable to escape observation, but if the blood is kept a white layer of 
fat collects on the surface of the serum as it separates. 
In many cases of injury, particularly in crushing fractures pf the 
bone, the fat of the marrow finds its way into the blood, and it may col- 
lect in large drops in the vessels of the lungs, forming the so-called fat 
emboli (Fig. 9, p. 30); or it may pass the lungs and form emboli in other 
parts, as the brain, kidneys, etc. Fat embolism in eclampsia is of 
occasional occurrence. 
The fat may be absorbed from the vessels, having produced little or 
no disturbance; or in some cases it may produce serious results by the 
stoppage of a large series of vessels in the lungs, brain, or other parts of 
the body.2 
Tissues and organs whose blood-vessels are suspected to contain fat droplets should 
be fixed in Muller-formol or 4 per cent, formaldehyde and thoroughly washed in 
water. Frozen sections are then treated w'ith a mixture of equal volumes of Muller's 
fluid and 2 per cent, osmic acid, or stained with Sudan III (see p. 44). The sections 
should then be stained with haematoxylin and mounted in glycerin. v q, 
1 For other blood stains see under Malaria, page 316. 
2 For resume of this subject, with bibliography, consult Welch in article on Embolism in Allbutt's 
"System of Medicine," vol. vi., p. 258. 470 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
Air, as a result of an opening in the veins, is of occasional occurrence. 
If the amount of air be small, it appears to be readily absorbed, and does 
little or no harm. If, on the other hand, a large quantity is admitted to 
the veins at once, it collects on the right side of the heart, from which 
the contractions of the organ are unable to force it in any considerable 
quantity, and, the supply of blood being thus cut off from the lungs, 
death very quickly ensues. The blocking of the smaller pulmonary ves- 
sels and of the vessels of the heart with air bubbles may also hasten 
death. It is especially from wounds of the veins of the neck and thorax 
that the accident is most apt to occur. But it may be due to the intro- 
duction of air into the uterine veins in intra-uterine injection, or in the 
removal of tumors.1 One should remember in this connection that 
infection with Bacillus aerogenes gives rise to gas bubbles in the blood- 
vessels, as well as in other tissues (see p. 289) and that gas may form in 
the blood in caisson disease (see p. 11). 
Parasites and other Foreign Bodies in the Blood.-The occurrence 
of animal and vegetable parasites is considered more in detail in parts of 
this book devoted to these organisms. It will suffice to mention here 
that the more important of the parasites found in the blood are: The 
Plasmodium malariae, Trypanosomata, Filaria sanguinis hominis, the 
embryo of Trichina spiralis, the Spirillum Obermeieri, and the Spirochaeta 
pallida. 
The various forms of bacteria which may be found in the blood will 
be considered in parts of this book in which these organisms are treated 
in detail.2 Parenchyma-cell emboli are considered on page 29. 
Melanaemia.-In this condition the blood contains larger and smaller 
irregular-shaped particles or masses of brown or black pigment. This 
condition is most frequently the result of intermittent and remittent 
fever, particularly the severer forms. It may be accompanied by anae- 
mia and leucocytosis. It does not occur in all cases of the above-named 
affections. In may be transient in character. The pigment may be 
free, or, more usually, enclosed in leucocytes. Under the same con- 
ditions pigment may be deposited in the liver, spleen, lymph-nodes, 
bone-marrow, and blood-vessels. Owing to the deposit of pigment in 
the organs they may assume a gray or slate color. The pigment devel- 
oped in malaria originates in the decomposition of the haemoglobin under 
the influence of the plasmodium. Pigment which has been taken into 
the lungs from the air, such as coal dust, etc., may find its way into the 
blood either before or after deposition in the bronchial or other lymph- 
nodes, and may be afterward deposited in the spleen and liver.3 
1 Welch, ibid., Allbutt's "System of Medicine," vol. vi, p. 254. 
2 For methods and results of bacterial studies of the blood, with bibliography, consult Kiihnau, 
Zeit. f. Hyg., Bd. xxv., p. 492, 1897; Rosenberger, Am. Jour. Med. Sci., vol. cxxvi., 1903, p. 234; Canon, 
"Die Bakteriologie des Blutes," Jena, 1905; Lenhartz, "Die Septischen Erkrankungen," Wien, 1903. 
For method of demonstrating animal parasites see Staubli, Munch, med. Woch., 1908, No. 50. 
3 For further details concerning changes in the blood consult Simon, "Clinical Diagnosis," 4th ed.; 
Ewing, "Clinical Pathology of the Blood," 1903; Cabot, "Clinical Examination of the Blood," 1904; 
or Wood, "Chemical and Microscopical Diagnosis," 3d ed., 1911. THE BLOOD AND THE BLOOD-FORMING ORGANS 
471 
General Diseases Involving the Blood and Blood-Forming Organs.1 
There is a group of diseases in which the most striking lesion seems 
to be an alteration in the composition of the blood, although in some 
members of the group other lesions are also present. This group em- 
braces chlorosis, secondary and pernicious anaemia, leukaemia, and certain 
closely related, but still obscure conditions. 
CHLOROSIS. 
Chlorosis is a disease of the blood seen in women only and attended 
with a diminution in the haemoglobin, and usually in the number of the 
red blood cells. 
Of the essential element in the incitement of this disease and of the 
exact method of its origin we are ignorant. The condition has been 
attributed to congenital hypoplasia of the heart and blood-vessels, to 
prolonged malnutrition, to intestinal intoxication, and to functional 
disturbance of an unknown nature in the blood-producing organs. 
In the mildest grade of chlorosis the only change to be observed is a 
slight diminution of haemoglobin. In severer forms may be added a 
diminution in number and moderate variations in size and shape of the 
red cells. In very severe and relapsing cases the haemoglobin may be 
excessively decreased, the color index falling even as low as 0.4; the red 
cells may number less than two millions per cubic millimetre, and the 
average size of the cells be less than normal. The leucocytes are not 
increased in number. There may be a slight relative increase of the 
lymphocytes; megalocytes, microcytes, and poikilocytes may appear (see 
Plate II., Fig. 2). Polychromatophilia is frequent. 
The specific gravity of the blood is diminished in proportion to the 
fall in hsemoglobin; the total quantity is greatly increased. The time of 
coagulation is often very short, a change undoubtedly correlated with 
the not infrequent thrombosis seen in chlorosis. Even in cases of 
considerable severity the degenerative changes in the viscera character- 
izing other forms of ansemia have been found wanting, although degen- 
erative changes in the red cells may occur in accordance with the severity 
of the disease. The liver does not contain an excess of iron, and the 
urine is free from pathological urinary pigments. 
The regeneration of the blood in chlorosis under rest and treatment 
with iron may usually be rather promptly effected by increased activity 
of the red marrow, which is probably hyperplastic. This regenerative 
process may be indicated in the blood by the periodical appearance of 
considerable numbers of normoblasts. The appearance of these nucle- 
ated red cells may be accompanied by a moderate increase of leucocytes, 
both mononuclear and polynuclear. Myelocytes also may rarely be 
seen. 
1 For a full discussion of the subjects treated in this chapter the reader is referred to von Noorden. 
" Bleichsucht," Nothnagel's "Spec. Path. u. Therap."; Ehrlich and Lazarus, "Die Anaemie," 
Nothnagel's " Spec. Path. u. Therap."; Helly, ibid., "Die Hamatopoetischen Organe;" and Naegeli, 
" Blutkrankheiten und Blutdiagnostik," Leipzig, 1912. 472 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
SECONDARY AN2EMIA. 
While chlorosis may be considered usually a disease of adolescence, 
and while its occurrence is confined to the female sex, there is another 
type of blood change which seems best classified under the heading of 
secondary anaemia, and which is independent of sex or age. The deter- 
mining agents are either of a general nature, such as poor food and bad 
air, or they are actual diseases, or they may be intestinal parasites, or, 
finally, chronic poisoning. Among those diseases which are likely to 
induce a well-defined anaemia we may mention prolonged suppuration, 
mycotic endocarditis, diseases of the stomach and intestines, malaria, 
syphilis, and malignant tumors. The intestinal parasites are chiefly the 
Ankylostoma duodenale and the Bothriocephalus latus. The poisons 
Fig. 280.-Bone Marrow from Shaft of Femur from Case of Secondary Anaemia due to Re- 
current Carcinoma. 
The normal fat tissue is to a certain extent replaced by an cedematous reticular connective tissue 
containing islands of nucleated red cells and myelocytes. The hyperplasia is not so extensive as that 
seen in leukaemia or pernicious ansemia, in which often all of the fat is replaced by the new growth of 
cells. 
are lead and, more rarely, arsenic. The alterations which are apparent 
on examining the blood are very variable, depending upon the agent. 
The haemoglobin is regularly diminished to a greater per cent, than the 
red cells; it may fall as low as 15-20 per cent.; the red cells rarely fall 
below one million. Nucleated red cells of the normoblastic type are 
frequent in the severe cases; megaloblasts are not found except in 
advanced cases of Bothriocephalus anaemia. As a rule the average 
diameter of the red cells is slightly below normal, with a moderate 
poikilocytosis. Granular degeneration is present to a variable extent 
in the red cells except in malaria and lead poisoning, when it is the rule. 
In the anaemias produced by the Bothriocephalus the blood picture may THE BLOOD AND THE BLOOD-FORMING ORGANS 
473 
be that of pernicious anaemia, with a great increase in the size of the cells 
and the appearance in the blood of numerous megaloblasts, thus forming 
an exception to the general rule that the blood of secondary anaemia is 
normoblastic in type. In the anaemia due to the Ankylostoma or the 
Uncinaria the blood shows the picture of a chlorotic anaemia often accom- 
panied by a considerable eosinophilia, which is not usually seen in the 
Bothriocephalus variety. The leucocytes are increased in anaemia due 
to suppuration and in about 50 per cent, of the tumor cases; in other 
forms there is usually but little change in the number, though it is im- 
possible to formulate a general rule (Plate II., Fig. 3). When, however, 
a tumor invades the bone marrow an extensive hyperplasia of this tissue 
may occur with consequent flooding of the blood current with large 
numbers of immature leucocytes so that the blood simulates that of 
myelogenous leukaemia (Fig. 280). 
PERNICIOUS ANEMIA. 
Pernicious anaemia is a disease of the blood and blood-forming organs, 
characterized by excessive destruction associated with defective produc- 
tion of red cells. 
The exact relation of the factors concerned in the causation of the 
disease has not been determined. It may be said, however, that while 
very rapid cases of pernicious anaemia have been observed unaccom- 
panied by the usual lesions in the bone marrow associated with defec- 
tive haematogenesis, the disease seems not to exist without excessive 
haematolysis. 
Pernicious anaemia may probably originate as a primary disease of 
the blood or bone marrow, but many cases apparently primary have 
been shown at autopsy to be secondary to such conditions as cancer, 
nephritis, tuberculosis, atrophy of the gastric mucosa, or the presence of 
parasites in the blood or intestine. The studies of Hunter indicate that 
the destruction of the blood may in some cases result principally in the 
portal circulation and particularly in the spleen from the action of toxic 
substances absorbed from the intestines, and Herter has shown that the 
toxic products arising from anaerobic putrefaction of the proteins by 
certain bacteria may play an important part in the induction of haematoly- 
sis. Whatever its origin, the distinguishing feature of pernicious anaemia 
is the fact that the anaemia is entirely disproportionate to any apparent 
cause, and when once established tends to progress to a fatal issue. 
The essential lesion is an extreme and progressive diminution in 
number and very great variation in size and form of the red blood cells 
(as shown in Plate II., Fig. 4). Nearly constant is a widely distributed 
lesion of the bone marrow, in which the normal nucleated red cells are 
partly replaced by an excessive number of larger nucleated corpuscles or 
megaloblasts, with atrophy of fat cells. The destruction of haemoglobin 
is followed by a considerable deposit of iron in the liver, spleen, marrow, 
and other organs, and by the appearance of abnormal pigment in the 
urine. The prolonged anaemia may be accompanied by fatty degenera- 474 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
tion in the viscera, especially of the liver, kidneys, and heart muscle. 
As a combined result of fatty changes in the arterial walls and of the 
diminution in albuminous ingredients and in the coagulability of the 
blood, haemorrhages in various parts of the body, especially the retina, 
are of frequent occurrence. Disseminated areas of sclerosis in the spinal 
cord have been described and regarded as the result of minute haemor- 
rhages in this region. 
In the blood the red cells are usually reduced to less than two millions 
and occasionally to half a million per cubic millimetre. Of the remaining 
Cells a considerable percentage may be abnormally large (megalocytes), 
or very small (microcytes). Cells of very irregular shape are often 
present in abundance (poikilocytes) (Plate II., Fig. 4). The quantity of 
haemoglobin in the majority of the cells is usually increased, but may be 
diminished in a certain proportion of cells, which then resemble those 
found in chlorosis. The "haemoglobin index"-that is, the relation of 
the total percentage of haemoglobin to the total number of cells-may be 
normal when a deficiency of haemoglobin in one cell is counterbalanced 
by a proportionate excess in another, but in general it is greater than 
unity. 
A variety of degenerative changes in the red cells are commonly 
present, including especially those alterations in the staining reactions of 
the protoplasm known as polychromatophilia and granular degeneration. 
In the first the cell stains a more or less uniform blue with methylene 
blue; in the second the cells contain granules which give a strong baso- 
philic staining reaction. 
Nucleated red cells of normal size (normoblasts) are of frequent occur- 
rence in the blood of well-established pernicious anaemia. Abnormally 
large nucleated red cells (megaloblasts) are a nearly constant element at 
some stage of the disease and are of great diagnostic importance, as they 
indicate the presence of a grave lesion in the bone marrow. They are 
more abundant than the normoblasts in well-developed cases. 
Megalocytes and megaloblasts usually show an excess of haemoglobin, 
may exhibit amoeboid movement, and have no tendency toward the 
formation of rouleaux. Extremely large nucleated red cells (giganto- 
blasts) are frequently found in advanced cases, and in these cells as well 
as in the megaloblasts the nuclei may be rarely seen in various stages of 
normal or pathological mitosis. "Blood crises," by which is indicated 
the appearance of large numbers of normo- or megaloblasts in the circu- 
lation, may occur in pernicious anaemia, but it must be remembered that 
the blood picture in any severe anaemia varies much from day to day 
without any marked alteration in the general condition of the patient. 
In the absence of complications producing leucocytosis in pernicious 
anaemia, the leucocytes are usually diminished in number. There is a 
relative increase in the number of lymphocytes, and usually a few myelo- 
cytes may be found. 
Aplastic Anaemia.-A very rare variety of a rapidly fatal form of 
anaemia has been described in which the number of red cells is diminished 
without the blood showing the changes characteristic of pernicious THE BLOOD AND THE BLOOD-FORMING ORGANS 
475 
anaemia. The bone marrow in these cases has been found to be fatty 
instead of hyperplastic as in the typical marrow of pernicious anaemia. 
It has been suggested that the bone marrow for some unknown reason 
had not responded to the call made upon it by the rapid haematolysis 
taking place in the disease, and therefore did not undergo the megalo- 
blastic changes so characteristic of the bone-marrow in well-marked 
cases of pernicious anaemia.1 
LEUKEMIA (LEUCOCYTRSMIA). 
Leukaemia is a disease in which the characteristic changes are an alter- 
ation in the relative proportions of the different leucocytes of the blood, 
with usually an increase in their number, and the appearance of certain 
forms not seen in the circulation under normal conditions. The red cells 
are diminished in number, and abnormal forms appear in the blood. 
Accompanying these alterations in the circulating blood are changes in 
the bone marrow, less often in the spleen and in the lymph-nodes. Its 
inciting factors are still unknown. Leukaemia may be classed in four 
types, which are fairly well defined clinically and morphologically, but 
between these there exist many transitional forms, especially from the 
point of view of the morphology of the blood. These four types are the 
acute and chronic lymphatic leukaemia and the acute and chronic myel- 
ogenous leukaemia (spleno-myelogenous). 
Acute Lymphatic Leukaemia is a disease resembling clinically an 
acute infection, with a rapidly increasing anaemia, enlargement of the 
lymph-nodes, as a rule, and a moderate increase in the size of the spleen 
and liver. Cases are on record, however, in which there was no enlarge- 
ment of the spleen or lymph-nodes.2 The blood changes are very 
characteristic. The red cells diminish rapidly in numbers, normoblasts 
and occasionally megaloblasts are present, and the leucocytes are 
increased, though usually below 100,000. The forms present are chiefly 
lymphocytes, either large or small, the large, as a rule, predominating. 
While the staining reactions of the large lymphocytes in this disease 
correspond with those of the cells of normal blood, yet Longcope3 has 
shown that they contain a proteolytic and lipolytic ferment character- 
istic of the granular types of cells from the bone marrow. This has been 
confirmed4 by the discovery that in the large lymphocytes it is possible 
to demonstrate an oxidase, a ferment heretofore considered to be con- 
fined to the granular types. These findings indicate that the cells in 
question should be considered rather as myeloblasts than as large lympho- 
cytes. The bone marrow is altered to a tissue showing large numbers 
of lymphocytes, the so-called lymphoid hyperplasia, which often extends 
to the lymphoid tissue in the viscera. 
Chronic Lymphatic Leukaemia.-The blood shows a severe anaemia 
with great increase in the lymphocytes. The small forms of the lympho- 
1 For a study of a series of such cases see Lavenson, Am. Jour. Med. Sei., 1907, vol. cxxxiii., p. 100. 
2 See Kelly, Univ. Penn. Med. Bull., 1903, p. 270. 
3 Longcope and Donhauser, Jour. Exper. Med., 1908, x., 618. 
4 See Schultze, Munchen, med. Wchnschr., 1909, Ivi., 167, and Peters, ibid, 1478. 476 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
cytes are most abundant, in contradistinction to the acute type of the 
disease, in which the large forms are usually in excess. The lymph-nodes 
and spleen are usually enlarged; the bone marrow is in a condition of 
lymphoid hyperplasia, and there are lymphoid infiltrations in the various 
organs (see Figs. 281 and 282 and Plate II., Fig. 5). 
Acute Myelogenous Leukaemia.-A few cases of leukaemia of the 
myelogenous type have been reported in which the clinical course was 
very acute, with a rapidly increasing anaemia and the occasional appear- 
ance of nucleated red cells. In some of the cases the blood was not 
characteristic and the diagnosis could be made only after death by a 
Fig. 281.-Leukemic Infiltration of Kidney in Case of Lymphatic Leukemia. 
study of the changes in the bone marrow; in others the blood picture 
resembled that of a chronic myelogenous leukaemia with the usual large 
percentage of myelocytes. Some of the cases diagnosed as acute myelog- 
enous leukaemia were undoubtedly of the type of disease known as 
chloroma, while others were presumably acute infections with a high 
leukocytosis and the appearance of a few myelocytes in the blood with 
a marked hyperplasia of the bone marrow due to the prolonged septic 
condition. The difficulties in the diagnosis of acute myelogenous leu- 
kaemia are complicated by the fact that the lymphocytes in acute lym- 
phatic leukaemia may be greatly diminished toward the end of the disease, THE BLOOD AND THE BLOOD-FORMING ORGANS 
477 
and a few myelocytes may appear under these conditions, thus render- 
ing a differentiation impossible.1 
Chronic Myelogenous Leukaemia.-The blood shows a severe anaemia, 
rarely of a pernicious type, with marked quantitative and qualitative 
changes in the leucocytes. The increase in number of white cells may 
be to more than one million per cubic millimetre. Myelocytes, both 
neutrophilic and eosinophilic, are quite constantly present in consider- 
able numbers. They may form a large proportion of the leucocytes 
Showing infiltration of the organ with leucocytes. The large collections are in Glisson's capsules, 
but small numbers are seen between the liver cells. 
Fig. 282.-Liver from a Case of Lymphatic Leukaemia. 
present. Basophile cells are very abundant in cases of long duration, 
especially the type with polymorphic nuclei, myelocytes with baso- 
philic granulations being rare. In rapidly advancing cases mitoses may 
be rarely seen in the red cells and in the leucocytes (see Plate II., Fig. 5). 
The pathological forms of leucocytes in myelogenous and lymphatic 
leukaemias have little or no amoeboid motion. This explains the inter- 
esting fact that the pus from an abscess in a leukaemic subject contains 
only the polynuclear neutrophile cells found in such exudates in persons 
with a normal blood condition. In acute infections and after treatment 
with the Rbntgen rays, the number of myelocytes present in the circu- 
1 Billings and Capps, "Acute Myelogenic Leuk®mia," Amer. Jour. Med. Sci., vol. cxxvi., p. 375, 
1903. 478 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
lation may be greatly reduced and the blood may even lose the cell forms 
characteristic of leukaemia, the myelocytes being replaced by lymphocytes 
or the ordinary polynuclear leucocytes of normal type. 
The same condition may be seen in mild cases, which may under treat- 
ment reach a point in which it is difficult to make a diagnosis from the 
blood alone. 
In this connection it must be remembered that the blood picture in 
pernicious anaemia and the leukaemias is a very variable one. As a rule, 
more than one examination is necessary for a certain diagnosis, and it 
must not be forgotten that occasionally a case, apparently of pernicious 
anaemia, may go on to a typical lymphatic or myelogenous leukaemia. 
In myelogenous leukaemia there is hyperplasia of the bone marrow, 
which usually fills the shafts of the long bones with a firm, pink mass 
composed largely of myelocytes. This hyperplasia may involve the 
whole bone marrow of all the long bones, or it may be confined to irreg- 
ular, scattered areas, so that one should be critical in accepting reports 
of cases of leukaemia without bone-marrow changes. The other organs 
show hyperplasia of lymphoid tissue, often especially well marked in the 
gastro-intestinal tract, while scattered through the spleen are often seen 
numerous small areas containing myelocytes. 
There is some reason to think that in the spleen, for instance, some 
multiplication of the cells goes on in the so-called " marrow' cell or mye- 
loid metastases." The same change may rarely be seen in the liver and 
lymph-nodes. In the blood, spleen, and marrow, after death, elongated 
octahedral crystals (called Charcdt-Leyden crystals) are occasionally 
found. Haemorrhages into the serous and mucous membranes and the 
retina are quite frequent, especially the latter, and fatty degeneration 
of the viscera is a quite constant expression of the impoverished condi- 
tion of the blood. For more detail concerning the lesions of the organs 
see chapters on spleen, lymph-nodes, bones, etc. 
CHLOROMA. 
Under this name, which means merely "a green tumor," are grouped 
a number of forms of a disease which shows many points of resemblance to 
both malignant tumors and the leukaemias. It is now generally con- 
sidered to belong to the group of primary diseases of the haematogenetic 
organs, its closest relationships being with the leukaemias. The impor- 
tant lesions are the presence of new growths of a greenish color in the 
osseous system, accompanied in many cases by alterations in the circu- 
lating blood. The tumors are frequently observed in the bones of the 
skull, but may involve any of the organs of the body. Nothing is known 
as to the chemical relationships of the coloring matter. 
Two chief types of tumors can be distinguished histologically, the 
lymphoid and the myeloid. In the lymphoid form the tumor and its 
metastases are composed of cells resembling lymphocytes, generally of 
the large variety. Diffuse infiltration of the other organs may also 
occur, resembling that seen in the leukaemias. In the myeloid type THE BLOOD AND THE BLOOD-FORMING ORGANS 
479 
the tumor is characterized by the presence of large cells resembling the 
myelocytes or myeloblasts of the bone marrow. In this form widespread 
involvement of the bone marrow and spleen is apt to occur, and extension 
to other organs generally takes place in the form of small nodules of 
myeloid tissue. 
The blood pictures may be conveniently divided into four types: 
One with small lymphocytes; one with large lymphocytes, which is the 
most frequent type; one with atypical large mononuclear cells resembling 
myeloblasts; and one in which the myelocytes are the cells most abun- 
dantly present. The red corpuscles also show the changes due to an 
ansemia. 
Unless definite superficial tumors are present it is often impossible to 
differentiate the blood picture from that of a leuksemia, and many of the 
cases have been diagnosticated only after death by the finding of greenish 
tumors scattered throughout the organs.1 
PSEUDO-LEUKEMIA. (" Hodgkin's Disease," "Adenie.") 
For a consideration of pseudo-leukaemia and Hodgkin's disease see 
page 489. 
This is a somewhat peculiar form of anaemia occurring in children, 
and characterized by progressive anaemia, by a considerable increase of 
leucocytes, by enlargement of the spleen and liver, and often by hyper- 
plasia of the lymph-nodes. A large number of nucleated red cells are 
present in well-marked cases. Myelocytes are found, but rarely form 
more than 10 per .cent, of the white cells. 
By some authorities it is regarded as an early stage of leukaemia or 
as a type of leukanaemia, by others as a form of secondary anaemia fol- 
lowing rachitis, tuberculosis, or syphilis. 
The histological changes in the blood-forming organs are, so far as is 
known, very similar to, but less pronounced than, those of leukaemia.2 
ANAEMIA INFANTUM PSEUDO-LEUKEMIC A. (Von Jaksch.) 
A very chronic form of anaemia with enlargement of the spleen was 
first described by Banti.3 The course of the disease may be divided 
into three stages; one in which there is marked anaemia with increase in 
the size of the spleen and irregular attacks of fever, the white cells re- 
maining normal in number and proportion. This period is usually from 
three to five years, but may be much longer. Then follows an interval 
of a few months in which there are jaundice and gastro-intestinal dis- 
turbances, passing into the final stage with fever, jaundice, ascites, 
diminished leucocytes, extreme anaemia, and often severe haemorrhages 
from the gastro-intestinal tract. The chief lesions are a very much 
SPLENIC ANAEMIA. 
1 Dock, Amer. Jour. Med. Sci., 1893, cvi., 152; Dock and Warthin, Med. News, 1904, Ixxxv., 971; 
Lehndorff (Ergeb. d. inn. Med., 1910, vi., 221) gives a very complete discussion of all the published cases, 
now amounting to about ninety, and a copious bibliography; see also Burgess, Jour. Med. Research, 1912, 
N. S. xxii., 133. 
2 Consult Monti and Berggrun, "Die chronische Anaemie d. Kindesalters," Leipsic, 1892. 
3 Banti, Ziegler's Beitr., 1898, xxiv., 21; Lossen, Mitt. a.d. Grenzgeb., 1904, xiii., 753. Fora very 
careful study of the remarkable improvement in the blood following splenectomy see Bierring and 
Egdahl, Jour. Am. Med. Assn., 1906, xlvii., 1149 (bibliography). 480 
THE BLOOD AND THE BLOOD-FORMING ORGANS 
enlarged spleen with induration of the splenic pulp, atrophy of the 
Malpighian bodies, and frequently, though not always, an extreme 
sclerosis of the portal and splenic vessels. The sinuses are often dilated 
and may contain large cells filled with phagocyted red corpuscles. A 
moderate interlobular cirrhosis of the liver is usually present, but is not 
of a high grade. In the earlier stages no cirrhosis can be made out. 
Changes have not been observed in either the lymph-nodes or the bone 
marrow. 
Originally the condition was considered merely an abnormal cirrhosis 
of the liver with enlargement of the spleen, but study of many cases in 
recent years, together with the striking improvement noticed after 
splenectomy, has forced the conclusion that the splenic lesion is the most 
important and that the cirrhosis is largely a secondary phenomenon. 
Umber1 has described an extremely interesting case in which there 
was apparently an extensive toxic destruction of the proteid material in 
the body. After excision of the spleen this destruction was checked and 
the proteid balance became positive. 
In the type of splenomegaly described by Gaucher, there is often 
extreme anaemia. The blood may contain very large numbers of nucle- 
ated red cells, with a high leucocytosis and a small percentage of myelo- 
cytes. This is not constant, however, and is apparently due to the pres- 
ence of metastases in the bone marrow from the splenic tumor. (For a 
description of the lesions of the spleen, see page 499.) 
Splenomegaly accompanied by anaemia is occasionally seen in adults, 
and in some of the cases there seems to be an actual limitation of the 
disease to this organ, but there is no reason to consider the condition as 
worthy of a separate classification. Many of the cases -ultimately prove 
to be obscure forms of lymphatic leukaemia in which the characteristic 
blood pictures appear only a few days or weeks before death. Other 
forms are due to a splenic tuberculosis or syphilis. In children, rickets, 
syphilis, and chronic gastro-intestinal lesions are the chief causes of 
splenic enlargement with anaemia. 
A separate class of splenic anaemias heretofore included in this group 
has been shown to be due to a parasite of the genus Leishmania. This 
type of splenic anaemia in adults is seen chiefly in India and the Soudan. 
Minute organisms, the Leishmania donovani, are found in the splenic 
pulp, chiefly inclosed in the mononuclear cells. The disease is also 
known as kala-azar. The organisms can be grown on artificial culture 
media and develop into a flagellate form resembling trypanosomes. 
The splenic anaemia frequently occurring in children in Southern 
Italy and Northern Africa has been shown by Nicolle to be due to a 
similar parasite, the Leishmania infantum. 
A marked relative lymphocytosis characterizes the blood of both of 
these conditions. The parasites can be found in the blood in about a 
half of the adult cases, but in children they are very scanty. In blood 
obtained by splenic puncture the parasites can, how'ever, be easily found 
in both forms. 
1 Umber, Ztschr. f. klin. Med., 1904, lv., 289. CHAPTER H. 
THE LYMPH-NODES. 
General Characteristics of the Lymph-Nodes. 
It is well, in studying the lesions of the lymph-nodes, to remember that they are 
structures so placed in the course of the lymph-vessels that the lymph, in flowing 
toward the larger central trunks, passes through them, undergoing a sort of filtration 
as it percolates through the trabecute of the lymph sinuses. If this fact be borne in 
mind the lesions of the lymph-nodes, which are in the majority of cases secondary, are 
much more readily understood. Particles of pigment, cells from malignant tumors, 
fragments of dead or disintegrating cells either free or within phagocytes, red blood 
cells, bacteria, etc., which in any way get into the lymph-vessels, are carried along 
until a lymph-node is reached, and here they are, in part at least, deposited among the 
trabeculae of the sinuses, or are taken up by phagocytic cells, while the lymph passes on 
and out of the efferent vessels. Soluble toxic substances also are carried into the 
lymph-nodes, often inciting marked and significant alterations.1 
The lymph-nodes as blood-forming organs stand in close relationship to many 
abnormal processes in the body. 
What is called lymphatic tissue embraces not only the so-called lymph-glands and 
the less complex but still well-defined structures found in the stomach, intestines, ton- 
sils, and elsewhere, and called lymph follicles, but also the less well-defined, irregular 
masses of tissue resembling that of lymph follicles, which, as Arnold has shown (Vir- 
chow's Archiv, Bd. Ixxx., p. 315; Bd. Ixxxii., p. 394; Bd. Ixxxiii., p. 289; Bd. Ixxxvii., 
p. 114), are widely disseminated in variable amounts in different parts of the body; in 
the lungs, beneath the pleura, in the interlobular septa, and elsewhere; in the liver, 
kidneys, etc. Although the exact nature of these more diffuse masses of lymphatic 
tissue is too h'ttle understood, as indeed is that of the lymph follicles and glands them- 
selves, there is reason to believe that they are analogous structures and prone to be 
affected by similar deleterious agencies. It seems better, in view of the fact that the 
so-called lymph-glands are not glands at all, in the ordinary sense of the word, to call 
them lymph-nodes, and the smaller masses of lymphatic tissue scattered through 
various parts of the body lymph-nodules instead of "lymph-follicles." 2 
There is considerable variation in the situation, number, and size of lymph-nodes 
in special regions of the body, and they vary in size with age. It may be said that 
the lymph-nodes are most fully developed in the adult, and undergo fatty degenera- 
tion and involution in old age.3 
Finally the lymph-nodes are built up of cells many of which have not achieved a 
high degree of differentiation and thus are prone to undergo mitosis and rapid pro- 
liferation, when, from infective or destructive processes in regions to which they 
minister, deleterious agents gather in their recesses. 
Atrophy is a very regular occurrence in old age. In this condition 
the nodes are small, hard, and, unless pigmented, light in color. Micro- 
scopical examination shows a marked diminution in the number of par- 
ATROPHY. 
1 For a study of bacteria in normal lymph-nodes see Kulble, Munch, med. Wochenschr., 1899, 
p. 622. 
2 For a study of the structure of lymph-nodes see Weidenreich, Arch. f. mik. Anat., Bd., Ixv. 
p. 1, 1905. 
3 For a study of regeneration of lymph-nodes and vessels see Meyer, Johns Hopkins Hosp. Bull., 
vol. xvii., p. 185, 1906, bibl. 
481 482 
THE LYMPH-NODES 
enchyma cells, while the reticulum and the capsule and trabeculae may 
be thickened. There may be an accumulation of fat around the node 
in senile atrophy. 
(EDEMA. 
(Edema of the lymph-nodes may be associated with a blocking of the 
associated lymph-vessels. Under these conditions the lymph sinuses 
may be widely distended (Fig. 283). 
DEGENERATION. 
Amyloid Degeneration of the blood-vessels and reticulum of the 
lymph-nodes occurs under the conditions which favor this change in 
general. It may occur in connection with amyloid degeneration of other 
parts of the body, or by itself. It may occur in nodes otherwise normal, 
Fig. 283.-(Edema of a Lymph-node-Typhoid Fever. 
The perifollicular lymph sinuses are widely distended with clear fluid. The lymph follicles 
and lymph cords are flattened from pressure of the fluid. 
or in those which are the seat of other lesions-thus in simple chronic or 
tuberculous inflammation. It is frequently found in the mesenteric 
lymph-nodes, in connection with waxy degeneration of the intestinal 
mucous membrane. 
Hyaline degeneration of the external layers of the smaller arteries and 
the capillaries and reticulum of the lymph-nodes occurs occasionally in 
old age or in connection with wasting diseases. THE LYMPH-NODES 
483 
The pigment which is very frequently found in lymph-nodes may be 
derived from the haemoglobin of the blood, either in the nodes themselves 
or in remote parts, or it may be formed of various materials introduced 
into the body from without, such as the pigments used in tattooing, 
respired dust particles of various kinds-coal, stone, iron, etc. (Fig. 284). 
The pigment particles, which usually lodge first in the lymph sinuses, 
may collect here in large quantities, either in the reticulum or the cells 
lying in its meshes; they may penetrate the follicles and cords and find 
permanent lodgment there. They usually induce a greater or less degree 
of chronic inflammation, so that in extreme cases, such as are frequently 
seen in the bronchial lymph-nodes, nothing is finally left of the node, but 
a more or less deeply pigmented mass of dense connective tissue. The 
PIGMENTATION. 
The pigment is largely in the lymph sinuses and enclosed in cells. A, Capsule of node; B, lymph 
follicles-nodule; C, perifollicular lymph sinuses. 
Fig. 284.-Pigmentation of Bronchial Lymph-node. 
function of the node may be, of course, in this way partially or entirely 
destroyed. The pigment in these cases appears to reach the node, in 
part by being carried along free in the lymph current, in part through 
transportation by leucocytes in which the particles have become enclosed. 
Pigmentation of the nodes is most marked in those about the root of the 
lungs, which are frequently of a mottled gray or a black color, but it 
may occur in the mesenteric and other nodes. Under similar conditions 
the diffuse lymphatic structure in the lungs and liver may be pigmented. 
INFLAMMATION. 
Acute inflammation of the lymph-nodes is commonly due to the pres- 
ence of pathogenic micro-organisms or of toxic substances, usually 
bacterial in origin, which may be formed in the node or brought to it in 
the lymph current from the tributary region of the body. Under these 484 
THE LYMPH-NODES 
conditions the nodes are usually swollen, reddened, and softer than 
normal, and are often the seat of small haemorrhages. One or all of the 
nodes of a cluster may be affected. 
Two forms of the acute inflammatory process may conveniently be 
recognized, a hyperplastic and an exudative. 
In the hyperplastic form a microscopical examination shows the 
lesion to be largely due, in addition to the hyperaemia and haemorrhage, 
to a proliferation of the cells of the node, the spheroidal mononuclear 
cells of the nodules ("follicles") and cords, and especially the endothe- 
lial cells of the lymph-spaces (Fig. 285), which may increase in number 
and exfoliate to such an extent as to fill and largely distend the lymph 
Fig. 285.-Acute Hyperplastic Inflammation of Lymph-node in Typhoid Fever. 
Showing a portion of one of the mesenteric nodes. A, Capsule; B, perifollicular space or lymph 
sinus, containing in its meshes many large cells; C, portion of one of the follicles, with large and small 
cells in the meshes of its reticulum. 
sinuses. These endothelial cells often contain red blood cells, leuco- 
cytes, and fragments of other cells (Fig. 286). In diphtheria, scarlatina, 
and typhoid fever, as well as in many other infectious diseases, necrosis 
of the hyperplastic tissue is common. The necrosis is usually in circum- 
scribed areas-focal necrosis-and often involves especially the ger- 
minal centres of the nodules. 
After simple hyperplasia of the lymph-nodes, resolution readily 
occurs. But if necrosis have taken place, such areas may be replaced 
by fibrous tissue. 
This form of lesion of the lymph-nodes is common. It may occur in 
the cervical nodes with many forms of angina; in the inguinal nodes in 
connection with acute infectious processes in the external genital organs; 
in the axilla with infectious processes in the hand, arm, or breast; in THE LYMPH-NODES 
485 
the mesenteric nodes with infection or intoxication of intestinal or other 
origin. Similar lesions occur in the solitary lymph-nodules and Peyer's 
patches of the intestine (Fig. 287). 
In exudative or suppurative forms of inflammation of the lymph- 
nodes, in addition to the simple hyperplastic changes just described, 
there are emigration and collec- 
tion of leucocytes, with the 
formation of more or less fibrin 
in the lymph sinuses as well as 
in the interstices of the nodules. 
The capsule of the nodes may 
be infiltrated with exudate. 
With these changes there may 
be necrosis and softening of the 
tissue of the nodes and the de- 
velopment of abscesses. Small 
abscesses may coalesce, and thus 
a considerable part of the node 
is converted into a suppurating 
necrotic mass-bubo. Such a 
bubo may open externally or into the surrounding tissue and heal by 
granulation tissue and cicatricial tissue; its contents may be absorbed 
or become dry and dense and calcified, and surrounded by fibrous tissue. 
Suppurative inflammation of the lymph-nodes often occurs in connection 
with suppurative processes elsewhere, in pyaemia, venereal infection, etc. 
The lymph-nodes of children are, as a rule, more readily involved in 
infectious processes of 
other parts than are 
those of adults. 
Chronic Inflamma- 
tion.-This is charac- 
terized by the increase 
of the connective-tissue 
elements of the node, 
with a gradual and 
commensurate disap- 
pearance of the lym- 
phoid cells. The ret- 
iculum of the follicles 
and sinuses becomes 
thickened and fibrous, 
and in the trabeculae 
and capsule new connective tissue is formed, until, in advanced cases, 
the entire node may be more or less extensively converted into a mass of 
fibrous tissue. This condition is very frequently seen in the lower tracheal 
and in the bronchial nodes, apparently as a result of the lodgment in them 
of respired pigment particles; but it may occur in any nodes, either as a 
result of repeated moderate degrees of inflammation or from causes 
Fig. 286.-Endothelial Cells in Hyperplasia 
of the Lymph-nodes. 
The exfoliated cells contain red blood cells, fat 
droplets, and masses of blood pigment. 
Fig. 287.-Hyperplasia of Peyer's Patch in Typhoid 
Fever. 
Showing new-formed endothelial cells in the meshes of the 
reticular tissue between the blood-vessels. 486 
THE LYMPH-NODES 
which we do not know. In some cases the nodes are greatly enlarged 
and the new tissue contains many large cells, while in other cases the 
connective tissue is dense and contains but few cells (Fig. 288).1 
Tuberculous inflammation may be local, confined to the nodes, or it 
may occur in connection with general acute miliary tuberculosis, or with 
tuberculous inflammation of single organs. It may occur in single nodes, 
or in several nodes of the same group, or in groups situated in different 
parts of the body. In its simple and acute form there may be no evi- 
dent change to the naked eye in the appearance of the nodes, or they may 
Fig. 288.-Chronic Inflammation of Bronchial Lymph-node. 
Showing obliteration of the lymph sinuses and atrophy of the lymph-nodules by the new-formed 
connective tissue. 
be besprinkled with small, grayish white, translucent spots. Under 
these conditions the nodes may be reddened and soft, or swollen and 
denser than normal. In more advanced forms of the lesion the tubercles 
coalesce and undergo a greater or less degree of cheesy degeneration. 
Under these conditions the cheesy areas are evident to the naked eye as 
more or less sharply circumscribed, opaque, w'hitish or yellowish areas, 
frequently surrounded by an irregular, more translucent, grayish zone 
of tubercle tissue which merges insensibly into the adjacent tissue. 
The entire node may become involved, and more or less completely con- 
verted into a cheesy mass, in the periphery of which a zone of tubercle 
tissue may or may not be evident. 
Microscopically the small nodules or miliary tubercles are seen to 
consist of more or less circumscribed collections of small spheroidal, or 
more frequently larger polyhedral cells, with or without well-defined 
giant cells. They usually commence to form in the follicles and lymph 
cords of the nodes, and from these may spread and involve the entire 
1 Consult Ribbert, "Ueber Regeneration und Entziindung der Lymphdriisen," Ziegler's Beitrage 
zur path. Anat., Bd. vi., p. 187, 1889. THE LYMPH-NODES 
487 
surrounding tissue. The cheesy degeneration, which here as elsewhere is 
apt first to involve the central portions of the tubercles, presents the 
usual appearances. Tubercle bacilli may be found in the edges of the 
cheesy areas or in the tubercle tissue about them. 
Simple inflammatory changes regularly occur in the periphery of the 
tubercles. There is an increase of cells in the lymph sinuses and follicles, 
and a more or less marked swelling, and apparently a proliferation of the 
cells of the reticular tissue of the node. In cases in which the process is 
chronic there is often marked increase of the connective tissue of the 
nodes, the reticular tissue becomes dense and fibrous, and the trabeculae 
and capsule are thickened. The tubercles themselves, instead of under- 
going cheesy degeneration, may become fibrous or be converted into a 
hyaline material. 
The cheesy material may dry and shrink, and become enclosed by a 
capsule of dense connective tissue and become calcified; or it may soften, 
and thus cavities be formed in the nodes, filled with grumous material; 
or inflammatory changes may be induced in the vicinity of the nodes, 
leading to abscesses. On the other hand, hyperplastic inflammation in 
the periphery of the affected nodes may result in their becoming bound 
together into a dense nodular mass. 
The formation of bone in lymph-nodes has been described in con- 
nection with tuberculous inflammation, carcinoma, and other lesions.1 
Scrofula.-Tuberculous inflammation of the lymph-nodes, espe- 
cially in those of the cervical,2 bronchial (Plates HI. and IX.), and 
mesenteric groups, often occurs in children, particularly in those who are 
ill-nourished. Northrup and Bovaird found in an analysis of 200 cases 
of tuberculosis in children that the lungs and bronchial lymph-nodes 
were involved in 148.3 Such persons, in addition to the lesion of the 
lymph-nodes, are very liable to suffer from chronic tuberculous and 
other inflammations of the mucous membranes, skin, periosteum, joints, 
and the subcutaneous and other connective tissues. This general con- 
dition is known as scrofula, and the lesion of the nodes is sometimes 
called scrofulous inflammation. 
While in many cases the portal of entry of the tubercle bacilli is not 
evident, and the lesions often present the appearance of hyperplasia of 
the lymphoid tissue with cheesy degeneration and the formation of more 
or less dense fibrous tissue rather than the typical characters of tubercu- 
lous tissue, nevertheless, miliary and other forms of tuberculous inflam- 
mation are often present in so-called scrofula, and tubercle bacilli, while 
sometimes absent, are often present and virulent.4 
The necrotic portions of such cheesy lymph-nodes in scrofula may 
1 See Merkel, Munch, med. Woch., 1905, p. 1238. 
2 For bibliography of cervical tuberculous lymph-nodes see Dowd, Annals of Surgery, May, 1899. 
3 For a study of tuberculous bronchial lymph-nodes in children consult Northrup, N. Y. Med. 
Jour., vol. liii., p. 203, 1891; also Bovaird, ibid., vol. Ixx., p. 1, 1899. See further, reference to Marfan, 
p. 543. For later study of tuberculosis of lymph-nodes, especially in childhood, see Harbitz, Jour. Inf 
Dis., vol. ii., p. 143, 1905. 
4 In the examination of lymph-nodes for tubercles and tubercle bacilli it should be remembered 
that not infrequently, though one fails to find either morphological tubercles or stained bacilli, the 
inoculation of portions of the fresh tissue into guinea-pigs will show that living and virulent bacilli 
were present. 488 
THE LYMPH-NODES 
soften and break down, and by the establishment of purulent and necrotic 
inflammation about them abscesses may form which may open externally. 
These abscesses may heal; but usually the healing is difficult and slow, 
and long-continued suppurations, frequently with the development of 
fistuke, are very common. Instead of softening, the cheesy material in 
the nodes may become dry and hard and undergo calcification. 
Generalized Tuberculous Lymphadenitis.-Several cases have 
been recorded of extensive tuberculous hyperplasia of the lymph-nodes 
in various parts of the body, the lesion resembling in its gross characters 
that of pseudo-leuksemia. While in some of these cases the morphology 
of the lesions is characteristic of tuberculosis, in others the new tissue is 
diffuse and consists largely of new-formed, small, spheroidal and poly- 
hedral cells with large multinuclear cells, and of fibrous tissue. The 
new-formed cells may undergo necrosis. Thus the tuberculous nature of 
the lesion is not always plain, even on microscopic examination. Animal 
inoculations are often necessary for the establishment of the nature of 
such cases.1 
Syphilitic Inflammation.-The lesions of the lymph-nodes which occur 
in connection with syphilis vary greatly, depending upon the stage of the 
disease. In the primary stage the nodes in the region of the seat of 
infection are apt to present the lesions of an ordinary acute inflammation 
frequently with suppuration. 
In the secondary stage of the disease the nodes of other regions, neck, 
elbow, axilla, etc., are often swollen and hard. On microscopic exam- 
ination, there may be an increase of connective tissue in the capsule and 
trabeculae, but the chief change is in the accumulation in the follicles and 
lymph sinuses of larger and smaller spheroidal and polyhedral cells. 
The reticular tissue may be thickened and the walls of the blood-vessels 
infiltrated with cells. In this condition the nodes may remain for a long 
time, not tending to form abscess; or they may undergo resolution through 
degeneration and absorption of the cells. 
In the tertiary stage of the disease the nodes may be the seat of 
chronic inflammation characterized by the formation of gummata. 
Under these conditions they may form large, firm nodular masses from 
the growing together by new connective tissue of several altered nodes. 
The gross and microscopical characters of gummata of the lymph-nodes 
are, in the main, similar to those in other parts of the body. 
HYPERPLASIA OF THE LYMPH-NODES. (Lymphoma.) 
In addition to the considerable enlargements of the lymph-nodes in 
inflammation which have been described above, they become enlarged 
under a variety of conditions which we do not understand. This lack 
of knowledge of the etiology, together with our ignorance of certain 
functions of the lymph-nodes, and the morphological similarity, or even 
identity, which these enlarged nodes present under various conditions, 
1 For a study of this form of tuberculosis consult Crowder, N. Y. Med. Jour., vol. Ixxii., pp. 443 
and 490, 1900, bibl. THE LYMPH-NODES 
489 
render it very difficult to decide upon the exact nature of the change, 
and in many cases to distinguish one form of enlargement from another. 
In the first place, there is a class of cases in which, sometimes slowly, 
sometimes with great rapidity, the lymph-nodes of certain regions, 
especially the abdominal, axillary, cervical, and inguinal, enlarge, not 
infrequently to an enormous extent. They may be either hard or soft, 
even almost fluctuating; the individual nodes may be distinct or merged 
into one another. Sometimes the nodes in nearly all parts of the body 
are affected. Microscopic examination shows, in the soft varieties, a 
large increase of small spheroidal and polyhedral cells and a growth of 
the reticular tissue. It is a new formation of lymphatic tissue, but the 
normal relations of follicles, cords, and lymph sinuses are not preserved. 
In the harder varieties there is a thickening of the reticular tissue in 
addition to an increase of cells. In rare cases portions of the nodes 
become necrotic. Sometimes larger and smaller haemorrhages occur in 
the nodes, especially in the softer forms. In addition to these changes 
in the lymph-nodes there is, in a considerable proportion of cases, a new 
formation of lymphatic tissue in greater or less quantity, in other parts 
of the body, in the spleen, in the gastro-intestinal canal, in the marrow 
of bones, in the liver, kidneys, etc., and the number of lymphocytes in 
the blood and in other parts of the body is increased. This general 
condition is known as leukemia and has been considered above, under 
" Diseases of the Blood and Blood-forming Organs." The enlarged 
lymph-nodes in this disease may be called, for convenience, leukcemic 
lymphomata, 
There is occasionally a moderate enlargement of the lymph-nodes in 
the myeloid form of leukemia, though the increase in size is rarely so great 
as that seen in the lymphatic type. The nodes remain discrete, though 
the capsule is frequently infiltrated with cells resembling lymphocytes 
or myelocytes. Microscopically there is a growth of mononuclear cells 
of the granular types ordinarily found in the bone marrow. As these 
areas of myelocytes increase in size the lymph follicles gradually dis- 
appear and finally the whole lymphoid tissue of the node may be replaced 
by myeloid structures. Usually such nodes are soft and do not undergo 
fibrous changes. The blood changes of a myelogenous leukaemia also help 
to differentiate this type of lesion from the purely lymphatic enlargement. 
PSEUDO -LEUKEMIA. 
There are two forms of disease resembling leukaemia in many respects, 
but usually accompanied with a less marked involvement of the spleen 
and no increase in the number of leucocytes in the blood. These may be 
called pseudo-leukaemia and Hodgkin's disease. While the gross appear- 
ances of the lymph-nodes in both of these diseases are quite similar, there 
are differences in the microscopical structure which warrant the separa- 
tion of the two conditions. In the true pseudo-leukaemia there is a pro- 
gressive hyperplastic growth of lymph-nodes, and often in addition a 
diffuse hyperplasia of the lymphoid tissue normally present in such 490 
THE LYMPH-NODES 
organs as the liver or kidney. It is not impossible that transitions 
between this disease and leukaemia may occur, or that many of the cases 
included under this head may have been forms of chronic lymphatic 
leukaemia without blood changes sufficiently marked to compel their 
consideration as true leukaemias. 
The changes may involve individual nodes, or, what is more usual, 
the^nodes of a definite region may enlarge simultaneously. When sec- 
Fig. 289.-Lymph-node from Case of Chronic Lymphatic Leukemia. 
Compare with lymph-nodes in Hodgkin's disease. 
tioned the tumors are soft and grayish red. They usually do not show 
necrotic areas. 
Microscopically the nodes resemble those seen in lymphatic leukaemia, 
there being a loss of the typical structure and replacement by a diffuse 
growth of lymphocytes and fine reticular connective tissue (Fig. 289). 
Rarely large or even multinucleated cells may be found. The anaemia 
in*these cases is no greater than that due to interference by similarly 
extensive malignant growths affecting any other tissue. 
The second type, or Hodgkin's disease, shows microscopically 
changes in the lymph-nodes which are entirely different from those just THE LYMPH-NODES 
491 
described. The nodular lesions in some cases which have until recently 
been classified as Hodgkin's disease resemble tubercle tissue, and the 
changes are unquestionably due to a diffuse tuberculosis of the lymphoid 
system,1 though the bacilli can usually be demonstrated only by animal 
inoculations. 
This group should be sharply differentiated from the other form, 
which has been designated by Pappenheim 11 granulomatous pseudo- 
leukaemia" and is the type to which Hodgkin's name is now generally 
Fig. 290.-Bone Marrow in Hodgkin's Disease. 
Showing eosinophile cells in great abundance. 
attached. True tubercles are not present except as an accidental super 
imposed lesion, but the nodes undergo peculiar changes which are quite 
characteristic even in an early stage. The alterations characteristic of 
Hodgkin's disease may involve the superficial nodes of the neck, axilla, 
inguinal, or cubital regions, or the lesion may be confined entirely to the 
bronchial or retroperitoneal nodes. In some cases the spleen is very 
slightly affected; in others extensive necroses with fibrous-tissue replace- 
ment may occur. The bone marrow shows a moderate hyperplasia 
1 Sternberg (Ztschr. f. Heilk., 1898, xix., 21) has made a careful study of cases of this type. 492 
THE LYMPH-NODES 
(Fig. 290). In advanced cases the liver may show a few of the charac- 
teristic nodules (Fig. 291). The gross appearance of the nodes is con- 
siderably altered from the normal. They may be lobulated, soft or hard, 
and white, gray, or red, and often show areas of necrosis. They are 
usually entirely discrete, and there is no infiltration of the capsule or 
perinodular fat with lymphocytes as is the case in the forms of enlarge- 
ment due to leukaemia or lymphosarcoma. At first the only lesion, 
Fig. 291.-Hodgkin's Disease. Nodule in Liver. 
The abdominal and bronchial lymph nodes alone were involved in this case. The hyperplasia in the 
liver is of the same type as that in the nodes; with the formation of connective tissue and large irregu- 
lar multinucleated cells. 
besides a moderate hyperplasia, may be the development of areas con- 
taining a considerable number of large cells with a faintly staining cell 
body and a single large nuclei, sometimes showing mitosis (Figs. 292 and 
293). In this early stage these cells correspond closely in morphology 
with the large cells of the germinal centres; they are not the same as 
the multinucleated cells of the later development of the disease. Not 
all the enlarged nodes show these changes equally well. Such alterations 
in the structure can scarcely be considered as specific, since they may be THE LYMPH-NODES 
493 
Fig. 292.-Hodgkin's Disease. Lymph-node with Lymphoid Tissue still Preponderating 
but the Large Endothelial Cells Show Hyperplasia. 
There is only a moderate connective tissue replacement. 
Fig. 293.-Hodgkin's Disease. Lymph-node Showing Extensive Hyperplasia of Large Cells. 494 
THE LYMPH-NODES 
found in nodes undergoing chronic hyperplasia in response to the irrita- 
tion of a neighboring malignant epithelial growth. 
In the second stage, however, the diagnosis is usually possible from 
an individual node, for there are present not only the large cells before 
mentioned, but necrotic areas surrounded by cells of the epithelioid 
(Fig. 294) type and more or less numerous large cells with polymorphic 
nuclei or with two or more small oval nuclei lying in the centre of the 
cell body. True giant cells of the Langhans' type (see Fig. 264, p. 413) 
with peripherally arranged nuclei are rare in comparison with the other 
Fig. 294.-Hodgkin's Disease. Lymph-node in which the Lymphoid Tissue Still Pbedominates 
but the Large Endothelial Cells show Hyperplasia. 
There is a beginning connective tissue replacement. 
form (Fig. 295). This group of cells is probably produced by hyperplasia 
of the reticular endothelial cells. Necrosis in the nodes and spleen in 
these cases may be very extensive. There is usually a beginning re- 
placement hyperplasia of the fibrous tissue of the reticulum. 
In the third stage the nodes may be smaller than the previous types, 
and are composed very largely of dense anastomosing bands of fibrous 
tissue which occasionally undergo hyaline degeneration (Fig. 296). 
Thrombosis or extensive obliterative endarteritis of the vessels is not 
uncommon, and the lymphoid tissue may project under the epithelium 
so as nearly to close the lumen. The lymphoid tissue is occasionally THE LYMPH-NODES 
495 
reduced to a few scattered areas surrounded by dense connective tissue 
(Fig- 297). 
Eosinophile cells may be abundant in the nodular substance, and 
sometimes an increase in eosinophiles is seen in the circulating blood; but 
neither condition is constant. Plasma cells also may be found in the tis- 
sues in large or small numbers. Lymphoid infiltration in the organs, 
such as is seen in leukaemia, is not usually found. In fact, an important 
Fig. 295.-Hodgkin's Disease. Lymph-node showing Large Cells. 
characteristic of Hodgkin's disease is that the lesions have a tendency 
to remain in nodular form and not to destroy the organ involved com- 
pletely, if we except the lymph-nodes. There is always a severe pro- 
gressive secondary anaemia with occasionally a high leucocyte count, 
though usually the alterations in number and proportions of the white 
cells from the normal are slight.1 
Le Count has recently described a benign tumor-lymphoma-in the 
1 Important papers on the histology of Hodgkin's disease, with bibliography, are those by 
Langcope, Bull. Ayer Clin. Laboratory, 1903, No. 1; Reed, Johns Hopkins Hosp. Rep., 1902, x., 133, 
Simmons, Jour. Med. Res., 1903, ix., 378 and K. Ziegler, Die Hodgkinsche Krankheit, Jena, 1911, bibl. 496 
THE LYMPH-NODES 
Fig. 296.-Lymph-node in Hodgkin's Disease. 
The trabeculae have undergone hyaline degeneration. A considerable number of lymphoid cells 
still remain lying between the connective tissue bands, together with some large cells. 
Fig. 297.-Lymph-node in Hodgkin's Disease, Densely Fibrous. 
The lymphoid structures have been almost entirely replaced by connective tissue- THE LYMPH-NODES 
497 
groin having the structure of a lymph-node.1 A form of generalized 
tuberculous lymphadenitis which may be mistaken for Hodgkin's dis- 
ease is described above. 
It is now generally acknowledged that the tubercle bacillus can be 
demonstrated in only about ten per cent, of the cases of typical Hodgkin's 
disease, and repeated efforts to isolate the specific organism, stimulated 
by the finding by Fraenkel and Much of granular rods resembling bacilli 
in the antiformin centrifugate obtained from nodes, have recently led to 
the isolation by Negri and Mieremet2 of a diphtheroid organism which 
they call Corynebacterium granulomatis maligni. These findings have 
Fig. 297a.-Endothelioma of Lymph-node. 
been confirmed.3 By the injection of cultures of this bacillus Bunting 
and Yates have been able to produce in the Macacus rhesus a lymphoid 
hyperplasia with proliferation of the stroma and eosinophilic infiltration, 
and Billings and Rosenow4 have noted certain therapeutic improvements 
following the use of a vaccine made from the organism. The fact that 
similar diphtheroid pleomorphic bacteria have been found in carcinomata 
and isolated from the blood in various diseases render necessary most 
1 Le Count, Jour. Exp. Med., vol. iv., p. 559, 1899, bibliography of lymphoma. 
2 Negri and Mieremet, Centralbl. f. Bakt., I. Abt. Orig., 1913, Ixviii., 292. 
3 Bunting and Yates, Arch. Int. Med., 1913, xii., 236, and Jour. Amer. Med. Assn., 1913, Ixi., 1803; 
Verploegh, Kehrer, and v. Hoogenhuyze, Munchen, med. Wchnschr., 1914, Ixi., 1158. 
* Billings and Rosenow, Jour. Amer. Med. Assn., 1913, Ixi., 2122. 498 
THE LYMPH-NODES 
critical studies of the relationships between the newly found organism 
and Hodgkin's disease, in order to affirm its etiological importance. 
TUMORS. 
Sarcoma occurs in the lymph-nodes as a primary and secondary 
tumor, and may be of various forms: spindle-celled, large and small 
round-celled, and angio-sarcoma. It is not easy in many cases to dis- 
tinguish morphologically between the small round-celled sarcomata and 
the above-described lymphomata, but in general the leukaemic and 
pseudo-leukaemic lymphomata remain circumscribed, while the sarco- 
mata tend to break through the node capsule and invade the surround- 
ing tissues. Fibroma, myxoma, and chondroma occur in the lymph- 
nodes, but are rare. Endotheliomata are described, but are not common.1 
Secondary carcinomata of metastatic origin are of frequent occurrence, 
the form of the cells and the nature of their growth depending upon the 
seat and character of the primary tumors. 
When the cells of malignant tumors are detached in lymph channels 
and are carried away in the lymph currents, they are usually sooner or 
later caught in the meshes of the perifollicular lymph sinuses of the 
nodes. Here they may grow, encroaching upon the lymphoid tissue of 
the node, which they may finally largely or wholly replace. The node 
is then markedly enlarged and harder than normal. After a time the 
proliferating tumor cells may overcome the retarding action of the lymph- 
node filter, and pass beyond them into the veins, whence they may be 
widely distributed. 
PARASITES. 
Aside from the various forms of bacteria which are not infrequently 
found in the lymph-nodes in infectious diseases, among the animal para- 
sites filaria, trichina, and pentastomum have been described. 
HAEMOLYMPH -NODES. 
Numerous observers have described the occurrence in man and certain of the lower 
animals, under normal as well as pathological conditions, of structures which resemble 
lymph-nodes, but are usually smaller and are red or mottled red and white. In man 
they are found especially in the prevertebral fat, in the deep cervical region, in the 
retroperitoneal region, near the renal vessels, and about the rim of the pelvis. They 
are normally present, but they may be more conspicuous under certain pathologi- 
cal conditions-pernicious anaemia, acute infections, intoxications, etc. Their color is 
due to the presence of blood in the sinuses of the nodes. There are numerous transi- 
tional forms between nodes containing lymph sinuses only and those which more 
nearly resemble the spleen in character. They become more prominent and are 
increased in number after splenectomy in animals.2 These structures do not appear 
to be lymph-nodes in which blood has accumulated from hyperaemia or haemorrhage. 
1 See Ewing, Jour. Med. Res., 1913, N. S. xxiii., 1. 
2 See Warthin, Jour. Med. Res., vi., 3, 1901, and ''Vaughan Anniversary Contribution to Medical 
Research," 1903, p. 216. For a full and excellent summary of this subject, with bibliography, con- 
sult Warthin, Trans Chicago Path. Soc., vol. v., p. 151, 1902. For a study of the development of 
haemolymph-nodes in adipose tissue see Proc. Path. Soc. of Phila., vol. vi., p. 229, 1903. Dayton, Am. 
Jour. Med. Sci., vol. cxxvii., p. 448, 1904. CHAPTER III. 
THE SPLEEN AND THYMUS. 
The Spleen. 
General Characteristics of the Spleen. 
In studying the lesions of the spleen it is important to bear in mind the peculiar 
relations in which this organ stands to the blood-vessels and to the circulation. After 
passing through the various branches of the splenic artery and the limited systems of 
capillaries which are associated with it, the blood is not received at once into venous 
trunks, as in other parts of the body, but is poured directly into the pulp tissue. In 
this it circulates, under conditions which render it liable to stagnation and undue accu- 
mulation, before it is taken again into well-defined vessels through the open walls of 
the cavernous veins. Moreover, these conditions, naturally unfavorable to undisturbed 
and vigorous circulation, are reinforced by the association of the splenic with the 
sluggish and often interrupted portal circulation. Bearing these considerations in 
mind, it is in a measure plain why, as is in fact the case, the spleen should be more 
liable to alterations in size than any other organ in the body, and why, serving as it 
does as a sort of blood filter, it should be especially susceptible to the influence of 
deleterious materials of various kinds which in one way or another gain access to the 
blood. The relationship between the lymph-vessels and the spleen is also intimate. 
Finally, the spleen as a blood-cell forming and blood-cell destroying organ bears an 
important relationship to many abnormal conditions in the body. 
Malformations and Displacements. 
The spleen may be absent in acephalous monsters, and with defective development 
of other abdominal viscera. Absence of the spleen in otherwise normally developed 
individuals has been recorded. There may in this condition be a compensatory hyper- 
plasia of the lymphatic tissues of the body.1 Small accessory spleens, from the size of 
a hazlenut to that of a walnut, are not infrequent. They usually lie close to the spleen, 
but may be at a considerable distance from it; thus they have been found embedded in 
the head of the pancreas.2 Two spleens of about equal size have been observed. The 
spleen may be made up of several distinct lobes. It may be displaced congenitally or 
as the result of disease. It may be on the right side in transposition of the viscera. 
As the result of congenital defects in the diaphragm the spleen may be found in the 
thorax; or in deficient closure of the abdominal wall it may, together with other 
abdominal viscera, be found outside of the body. 
The spleen may be pressed downward by any increase in the contents of the thorax, 
It may be bound by adhesions to the concave surface of the diaphragm, so that its 
long axis is nearly horizontal instead of vertical. It may be displaced by changes in 
the contents of the abdominal cavity. If the organ be increased in size it frequently 
becomes tilted, so that its lower border reaches the right iliac region. If the ligaments 
be too long congenitally, or if they are lengthened by traction, and if the organ is at 
the same time increased in weight, it may become very movable. It may sink down- 
ward, with its hilus turned upward; or it may be rotated on its axis, and, owing to 
torsion of the vessels thus produced, the organ may atrophy; or the pressure of the 
ligaments and vessels across the duodenum may cause occlusion of the gut. 
1 See Hodenpyl, Med. Rec., vol. liv., p. 695, 1898, bibl. For a study of the effect of splenectomy 
in animals on the haemolymph-nodes see Warthin, " Vaughan Anniversary Contributions," 1903, p. 216. 
For certain pathological relations of the spleen see Eppinyer, Berl. klin. Wchnsch., 1913, lii., 1509. 
2 Haemolymph-nodes may be mistaken for accessory spleens. 
499 500 
THE SPLEEN AND THYMUS 
Wounds of the spleen are usually accompanied by extensive haemor- 
rhage and are commonly fatal. Death usually occurs as the result of 
this haemorrhage, but it may be due to secondary inflammatory changes. 
Healing and recovery may, however, occur. 
Rupture of the spleen may be traumatic or spontaneous. In the 
former case it may be due to direct violence in the region of the organ 
or to injury to the thorax, falls, etc. In certain diseased conditions the 
spleen is more liable to rupture than when it is normal. The rupture 
usually involves not only the capsule, but a more or less considerable 
portion of the parenchyma, and of course leads to haemorrhage. Spon- 
taneous rupture is rare, but may occur in excessive enlargement of the 
organ, as in typhoid fever, malaria, etc.-see below-or as the result of 
abscess. 
Haemorrhage.-Aside from the extensive haemorrhages from injury 
and rupture, the spleen may be the seat of small circumscribed haemor- 
rhages in various infectious diseases, although, owing to the peculiar 
distribution of the blood, it is often very difficult to distinguish between 
a moderate interstitial haemorrhage and hyperaemia. Sacculated aneu- 
rism of the splenic artery has been reported. 
WOUNDS, RUPTURE, AND HEMORRHAGE. 
ATROPHY. 
Atrophy of the spleen may occur in old age; as a result of prolonged 
cachexiae, and in connection with profound and persistent anaemia; or, 
more rarely, from unknown causes. The capsule may be wrinkled and 
thickened, the color pale, the trabeculae prominent, the consistence in- 
creased. The change is largely in the pulp, whose parenchyma cells 
are decreased in number. 
DEGENERATION. 
Amyloid Degeneration.-This may affect the glomeruli or the pulp 
tissue, or both together. When confined to the glomeruli the spleen may 
or may not be enlarged, and the cut surface is more or less abundantly 
sprinkled with round or elongated, translucent bodies resembling consid- 
erably in general appearance the grains of boiled sago. These are the 
waxy glomeruli. Such a spleen is often called "sago spleen" (Fig. 298). 
Microscopical examination shows that the degeneration is confined to the 
walls of the arteries, capillaries, and reticulum of the glomeruli, with 
atrophy and often finally total disappearance of the lymphoid cells. 
In other cases, either with or without involvement of the glomeruli, 
there is waxy degeneration of the blood-vessels and reticulum of the 
pulp, which may occur in patches or be general and more or less exces- 
sive. If the alteration is general and considerable, the spleen is enlarged, 
its edges are rounded, its consistence is increased. On section it appears 
translucent, and the distribution of the degenerated areas may be readily 
seen by holding a thin slice up to the light. The spleen alone may be 
affected, or there may be similar degenerations in other organs. THE SPLEEN AND THYMUS 
501 
PIGMENTATION. 
This may occur as the result of the decomposition of haemoglobin in 
the organ or elsewhere, under a great variety of conditions: thus after 
haemorrhagic infarctions, small multiple haemorrhages, acute hyper- 
plastic splenitis, and in haemochromatosis, etc. Or the pigment may be 
anthracotic and be brought to the organs from the lungs or bronchial 
nodes; bile pigment may also be deposited in the spleen in jaundice. 
The pigment may lie in the walls of the smaller arteries, in the cells and 
reticulum of the pulp, or free in the latter tissue, or in the follicles. It is 
Fig. 298.-Amyloid Degeneration of the Glomeruli of the Spleen-"Sago Spleen." 
The waxy portions are stained. 
usually quite unevenly distributed. The pigment may be red, brown, 
or black. Anthracotic pigment is deposited especially along the adven- 
titial sheaths of the arteries. It may be sometimes seen with the naked 
eye in the periphery of the glomeruli as dark crescents. This pigment, 
derived from the lungs, has gained access to the blood-vessels, through 
which it is brought to the spleen. 
DISTURBANCES OF THE CIRCULATION. 
Anaemia.-This may be associated with general anaemia, but it is not 
always present in this condition. When marked and unassociated with 
other lesions the spleen is apt to be diminished in size, the capsule more 
or less wrinkled, the cut surface dry and lighter in color than normal, 
the trabeculae unduly prominent. 
In this, as in other alterations simply of the blood content of the 
spleen, neither the gross nor microscopical appearances are constant, 502 
THE SPLEEN AND THYMUS 
because of the redistribution of blood which is apt to occur in the viscera 
after death. 
Hyperaemia.-Passive hyperemia may occur in obstruction to the 
portal circulation, most frequently in cirrhosis of the liver, but also 
with certain valvular lesions of the heart, emphysema, etc. The spleen 
is enlarged, but usually only to a moderate degree. The capsule is apt 
to be tense, and on section the pulp is dark red and may be soft or firm. 
The cavernous veins are dilated (Fig. 299). Usually, when the lesion 
has existed for some time, there is a thickening of the trabeculae and 
A " 
I 
c 
b 
Fig. 299.-Hyperemia-Congestion-of the Spleen. 
b, Dilated cavernous veins; c, trabeculae of pulp tissue compressed between dilated cavernous veins; 
d, glomerulus. 
reticular framework of the spleen, so that these are prominent on section. 
In other words, there is a chronic interstitial splenitis following the 
chronic congestion. 
Active hyper^emia of the spleen, which in most cases is scarcely 
to be differentiated from some forms of acute inflammation, and prob- 
ably in many cases is associated with it, very frequently occurs in a great 
variety of acute and infectious diseases, such as typhoid fever, pneu- 
monia, diphtheria, pyaemia, the exanthemata, etc. The spleen is 
enlarged, the capsule tense; on section the pulp is soft, dark red in color, 
often swelling out from the cut surface and concealing the glomeruli and 
trabeculae. Under these conditions the cavernous veins are distended 
with blood and the interstices of the pulp infiltrated with a variable, 
sometimes large quantity of red and white blood cells. Or, in addition 
to this, there may be hyperplasia (see below). 
Embolism and Infarction of the Spleen.-Embolic infarcts of the spleen 
are of frequent occurrence. They may be single or multiple, small or 
very large, sometimes occupying half of the organ. They usually arise 
from the detachment of thrombi from the aorta or the heart valves. THE SPLEEN AND THYMUS 
503 
They are in general approximately wedge-shaped, corresponding to the 
area of tissue supplied by the occluded artery (Fig. 10, p. 30). They 
may be haemorrhagic, i.e., red, or they may be white. Infarctions, 
originally red, may become white after a time from changes in the blood 
pigment (Fig. 300). They may usually be seen as dark red, reddish 
white, or white, hard, sometimes slightly projecting areas on the sur- 
face of, the organ. Not infrequently the centre of the infarction is light 
in color, while the peripheral zone is dark red. A layer of fresh fibrin 
is sometimes seen over the surface of the infarction. The general as 
well as the microscopical appearances which they present depend largely 
upon the age of the infarctions. In the earlier stages the haemorrhagic 
infarctions present little more under the microscope than a compact 
mass of red blood cells, among which may be seen the compressed paren- 
chyma. The white infarction may show at first an outline of the splenic 
Embolus from heart valve in chronic endocarditis. 
Fig. 300.-Infarction of the Spleen. 
structure, but the entire tissue is in a condition of coagulation necrosis. 
The tissue may disintegrate and soften, and be more or less completely 
absorbed, with or without fatty degeneration. A zone of inflammatory 
tissue may appear around the infarction and upon the capsule, and this 
tissue, becoming denser, assume the characters of a cicatrix and con 
tract around the unabsorbed remnant of the infarction, so that finally 
nothing may be left but a dense mass of fibrous tissue, which frequently 
draws in the surface, causing more or less distortion of the organ. This 
cicatrix may be pigmented or white. 
If the embolus be infective, in addition to its mechanical effects there 
may be suppuration, gangrene, and the formation of abscess. There 
may be perforation of the capsule and fatal peritonitis. Infarctions of 
the spleen may follow thrombosis of the splenic vein. 
Thrombosis of the splenic vein is rare as a primary lesion, but it 
may be of secondary occurrence in connection with portal or mesenteric 
thrombosis, with other lesions of the spleen, or with acute inflammation 504 
THE SPLEEN AND THYMUS 
of the pancreas. Thrombosis of the splenic vein has been reported 
following typhoid fever. 
INFLAMMATION. 
Inflammatory Hyperplasia (Acute Hyperplastic Splenitis, Acute Splenic 
Tumor).-The conditions under which hyperplasia and acute inflamma- 
tion of the spleen occur have already been mentioned under "Active 
Hypersemia," with which it is usually associated. It is a frequent though 
not a constant accompaniment of the acute infectious diseases. The 
spleen is enlarged, sometimes to two or three times its normal size. On 
section the pulp is soft, often almost diffluent, and projects upon the cut 
surface. The color is sometimes dark red, sometimes grayish red, or 
mottled red and gray. The trabeculae and glomeruli are usually con- 
cealed by the swollen and softened pulp, but the glomeruli are sometimes 
unusually prominent. 
Microscopical examination shows the marked increase in size to be 
due in part to the hyperaemia; in part to a swelling and increase in the 
number of cells, sometimes of the pulp, sometimes of the glomeruli, or 
of both. There are multinuclear cells; cells resembling the ovoid and 
polyhedral cells of the pulp, but larger and with evident division of the 
nuclei. Cells resembling leucocytes may be present in large numbers, 
and larger and smaller cells in a condition of fatty degeneration, or con- 
taining pigment, are often seen. The elongated cells lining the cavernous 
veins may be swollen or increased in number. Not infrequently the 
larger and smaller cells contain red blood cells or their fragments. In 
some cases, particularly in scarlatina, hyperplasia of the glomeruli is a 
prominent feature; in other cases, particularly in typhus and recurrent 
fevers, the cells of the glomeruli undergo marked degenerative changes, 
so that they may form small softened areas looking like little abscesses. 
Focal necroses and areas of small-celled accumulation or cell prolifera- 
tion are common in typhoid fever and other infectious diseases (see 
p. 203). As the primary disease runs its course the swelling of the 
spleen subsides, the capsule appears wrinkled, the color becomes lighter, 
and sometimes the organ remains for a long time, or permanently, small 
and soft. 
The lesions of the spleen are in many cases due to the presence of 
micro-organisms which are usually present in the spleen in septicaemia, 
or they may be due to soluble toxic substances in the blood.1 
Suppurative Splenitis (Splenic Abscess).-Small abscesses may be 
found in the spleen as the result of minute infectious emboli, and these 
may coalesce to form larger abscesses. Sometimes the entire paren- 
chyma is converted into a soft, necrotic, purulent mass surrounded by 
the capsule. It is rare for simple infarctions to result in abscess. Ab- 
scess of the spleen may occur from the propagation of a suppurative 
inflammation to the organ from adjacent parts; from perinephritic 
1 For a study of the r61e of the spleen in infections see Courmont and Duffau, Arch, de med. exp., 
x., p. 431, 1898, bibl. THE SPLEEN AND THYMUS 
505 
abscesses, ulcer and carcinoma of the stomach, etc. They may open 
into the peritoneal cavity, inducing fatal peritonitis, or, owing to an 
adhesive inflammation, the opening may occur into the post-peritoneal 
tissue, into the pleural cavity, lung, stomach, intestines, or they may 
open on the surface. On the other hand, the contents of the abscess may 
dry, shrink, and become encapsulated and calcified. Abscesses may 
occur in ulcerative endocarditis, pyaemia, typhoid fever, and, more rarely, 
in intermittent fever, and under a variety of other conditions. 
Chronic Indurative Splenitis {Chronic Splenic Tumor).-There may be, 
as we have already seen, a new formation of connective tissue in the 
spleen as a result of chronic congestion or infarctions, or about abscesses. 
But there is a more diffuse formation of connective tissue, usually in the 
nature of a hyperplasia, which occurs under a variety of conditions, 
and is now marked and extensive, and again comparatively ill-defined. 
It is always associated with more or less extensive changes in the paren- 
chyma. In its most marked form it is found in chronic malarial poison- 
ing; and under these conditions it may be found not only in persons who 
have suffered from repeated attacks of intermittent fever, but also in 
those who have not thus suffered but have resided in malarial regions. 
The enlarged spleen is often called "ague cake." Similar conditions, 
though usually less marked, may occur in congenital and acquired 
syphilis, from prolonged typhoid fever, and as a result of acute hyper- 
plastic splenitis from various causes, and also in leukaemia and pseudo- 
leukaemia. 
The gross appearance of the spleen in chronic indurative splenitis 
varies greatly, both in the size of the organ and in the appearance of the 
section. The spleen may be enormously 
enlarged or it may be of about normal size. 
It is usually, however, enlarged. The cap- 
sule is commonly more or less thickened, 
frequently unevenly so. The consistence 
is as a rule considerably increased, but this 
is not always the case. The color and ap- 
pearance of the cut surface present much 
variation. It may be nearly normal or it 
may be grayish, or dark brown, or nearly 
black. The color may be uniform or the 
surface may be mottled. The glomeruli 
may be scarcely visible or very prominent; 
the trabeculae are in some cases nearly con- 
cealed by the pulp; in others they are large, 
prominent, and abundant, so that the sur- 
face is crossed in all directions by an interlacing network of broader and 
narrower irregular bands, between which the red or brown or blackish 
pulp lies. 
Not less varied are the microscopical appearances of the spleen under 
these conditions. In one class of cases there is more or less uniform 
hyperplasia of both pulp and interstitial tissue. The parenchyma cells 
Fig. 301.-Chronic Indurative 
Splenitis. 
Showing swelling and proliferation 
of the lining cells of the cavernous 
veins. 506 
THE SPLEEN AND THYMUS 
are increased in size and number; there may be swelling and prolifera- 
tion of the lining cells of the cavernous veins (see F g. 301). The retic- 
ulum of the pulp, as well as that of the glomeruli, and also the trabeculae, 
are thickened. In another class of cases the thickening of the reticular 
a 
c 
d 
£ 
a, Thickened capsule; b, thickened trabeculae; c, dilated cavernous veins; d, dense pulp tissue 
with obliterated cavernous veins. 
Fig. 302.-Chronic Interstitial Splenitis. 
and trabecular tissue, either uniformly or in patches, is the prominent 
feature (Fig. 302), while the changes in the pulp are rather secondary 
and atrophic. In both forms irregular pigmentation is frequent, the 
pigment particles being deposited either in the cells of the pulp or glom- 
eruli, or in the new-formed interstitial tissue 
(Fig. 303). Finally, there are all intermediate 
forms of induration between those described, 
and the changes are by no means uniform in 
the same organ. When these spleens are large 
they are liable to displacement. 
Syphilitic Splenitis.-This lesion may pre- 
sent itself as an indurative process due to the 
formation of new connective tissue, and 
present no distinct morphological character- 
istics. In rare cases, however, gummata may 
be present in connection with the new 
fibrous tissue; then the nature of the lesion is 
evident. 
Tuberculous Splenitis.-This lesion is usually secondary to tuberculous 
inflammation in some other part of the body, or is the result of the gen- 
eral infection in acute general miliary tuberculosis. The tubercles may 
be very numerous and still invisible to the naked eye, or they may be 
Fig. 303.-Malarial Spleen. 
Showing thickening of the 
trabecular network of the pulp, 
with pigmentation of the pulp 
cells. THE SPLEEN AND THYMUS 
507 
just visible, or as large as a pin's head, and very thickly strewn through 
the organ or sparsely scattered. In other cases the tubercles are larger, 
sometimes as large as a pea (Fig. 304), and they are then ordinarily not 
numerous. Microscopically they present the usual variety of structure, 
sometimes as simple tubercle granula, sometimes as conglomerate tuber- 
cles; they may consist simply of a collection of small spheroidal cells, 
or there may be larger polyhedral cells and giant cells with a well-defined 
reticulum. Cheesy degeneration occurs under the usual conditions. 
Tubercle bacilli are commonly present, particularly in the more acute 
forms, sometimes in small, sometimes in enormous numbers. They seem 
to be especially abundant in acute general miliary tuberculosis of chil- 
The tubercles are large and irregular in shape and distribution, and are in places confluent. 
Fig. 304.--Tuberculosis of the Spleen. 
dren. These tubercles may be formed in the glomeruli, in the walls 
of the smaller arteries, in the pulp tissue, and in the trabeculae and cap- 
sule. Owing to the peculiar character of the spleen tissue the earlier 
stages are not readily recognized, since simple collections of small sphe- 
roidal cells are not distinctly outlined against the normal tissue. There 
is frequently a moderate swelling of the spleen, owing to hypersemia and 
hyperplasia of the parenchyma.1 
Perisplenitis.-Acute inflammation of the capsule of the spleen 
may occur as a part of a general or localized peritonitis, or as a result 
of lesions of the spleen itself, such as infarctions, abscesses, and acute 
hyperplastic inflammation. Under these conditions a fibrinous pellicle, 
with more or less pus, may be formed on the surface of the organ. 
Chronic inflammation, resulting in the production of new connective 
tissue, either in patches or as a more or less general thickening of the 
capsule, is of frequent occurrence. It may follow acute inflammation of 
the capsule, or be a part of general or localized chronic peritonitis. It 
1 For study of tuberculosis of spleen, with bibl., see Winternitz. Arch. Int. Med., 1912, ix., 680. 508 
THE SPLEEN AND THYMUS 
is common in connection with chronic indurative splenitis, and it may 
occur from unknown causes. Sometimes the capsule is three or four 
millimetres in thickness over a considerable area; sometimes very small 
nodular thickenings or papillary projections occur. As a result of this 
process, adhesions, sometimes very extensive, may form between the 
spleen and adjacent parts. The thickened capsule is sometimes more 
or less extensively calcified. 
CHRONIC ENDOTHELIAL HYPERPLASIA OF THE SPLEEN. ("Primary 
Splenomegaly.") 
Bovaird has recently described a slowly progressive lesion developing 
in early life in which the spleen was greatly enlarged and firm in tex- 
ture, presenting on section numerous irregular white or yellowish areas, 
extending from the capsule into the substance of the organ. The splenic 
Showing increase in number and exfoliation of the endothelium of the cavernous veins. 
Fig. 305.-Chronic Endothelial Hyperplasia of the Spleen. 
and mesenteric lymph-nodes and the liver were enlarged. On micro- 
scopic examination the spleen lesion was found to consist largely of an 
excessive proliferation of the endothelial cells of the pulp (Fig. 305), in 
part alone, in part associated with fibrous hyperplasia. Similar endo- 
thelial hyperplasia occurred in the splenic and mesenteric lymph-nodes 
and in the connective tissue of the liver. There was marked pigmenta- 
tion of the involved lymph-nodes and in the liver lesion. This condition 
has apparently been several times described, but has been usually regarded 
as tumor rather than endothelial hyperplasia.1 
1 For details of this lesion see Bovaird, Am. Jour. Med. Sci., vol. cxx., p. 377, 1900; Brill, Mandle- 
baum, and Libman, ibid., vol. cxxix., p. 491, 1905; Mandlebaum, Jour. Exper. Med., 1912, xvi., 979; and 
Brill and Mandlebaum, Am. Jour. Med. Sci., 1913, cxlvi., 863. THE SPLEEN AND THYMUS 
509 
ALTERATIONS OF THE SPLEEN IN LEUKAEMIA AND PSEUDO-LEUKAEMIA. 
The lesions of the spleen are essentially similar in both of these con- 
ditions. They consist, in general, of a hyperplasia, sometimes most 
marked in one, sometimes in another, of the structural elements of the 
organ, but they usually all participate in the alterations. The changes 
which occur in the earlier stages are but little known (Fig. 306). The 
gross appearances of the spleen vary. It is, as a rule, enlarged and some- 
times is ten or fifteen times the normal size. It is commonly hard, but 
Fig. 306.-Hodgkin's Disease. Showing Labge Cell Hyperplasia in Spleen. 
is sometimes of the ordinary consistence, or softer, and the capsule is gen- 
erally thickened and rough (Fig. 307). The section of the spleen may be 
of a uniform dark red color, but it is more frequently mottled red and 
gray. Sometimes the glomeruli are inconspicuous, but they are very 
often enlarged and prominent. They may be two to four millimetres in 
diameter, and, owing to an infiltration of the arterial sheaths with lymph 
cells, may appear to the naked eye as grayish, round or elongated bodies, 
arranged along branching, interrupted, grayish streaks. The trabeculae 510 
THE SPLEEN AND THYMUS 
may be greatly thickened, as also the reticulum of the pulp, so as to be 
evident to the naked eye. Brown or black pigment may be collected 
around the glomeruli or in the pulp. Haemorrhagic infarctions or cir- 
cumscribed extravasations of blood may further complicate the picture. 
Microscopically the appearances are essentially the same as those 
above described in acute hyperplasia and in chronic interstitial splenitis, 
depending upon the stage and variety of the disease. Owing to the great 
Fig. 307.-Subendothelial Infiltration of Splenic Sinuses by Lymphoid Cells in a Case of 
Lymphatic Leukemia. 
A similar lesion occurs in Hodgkin's disease. 
size which some such spleens attain they are liable to displacement, 
and they may interfere by pressure with the functions of neighboring 
organs. 
Primary tumors of the spleen are rare. Small fibromata, sarcomata, 
and cavernous angiomata sometimes occur. Sarcoma and carcinoma 
may occur in the spleen secondarily either as metastatic tumors or by 
extension from some adjacent part, as the stomach. Dermoid cysts 
are described, but are rare. Other larger and smaller cysts, whose mode 
of origin is in most cases obscure, not infrequently occur; some of these 
may be lymphangiomata.1 
TUMORS. 
1 For cysts of spleen see Otto, Arbeiten path. anat. Inst. Tubingen, Bd. v., p. 13, 1904. THE SPLEEN AND THYMUS 
511 
PARASITES. 
Pentastomum denticulatum is not infrequently found in the spleen, 
usually encapsulated and calcified. Cysticercus is rare. Echinococcus 
is occasionally found, and, if the cysts are large or numerous, may cause 
more or less extensive atrophy of the organ. 
Various forms of bacteria have been found in the spleen. The pyo- 
genic cocci have been found in pyaemia, smallpox, ulcerative endocar- 
ditis, diphtheria, and under other conditions. The Bacillus anthracis 
occurs here in anthrax; the Bacillus tuberculosis in tuberculous inflam- 
mation; and typhoid bacilli in typhoid fever. Spirochae te Obermeieri may 
be present in relapsing fever. 
The Thymus. 
Small accessory thymus glands are occasionally found near the thyroid. 
It is usual for the development of the thymus to reach its height in the early years 
of life. It then undergoes involution or atrophy, losing its epithelial characters and 
becoming largely composed of lymphoid cells. It is finally represented in old age by a 
small mass of fat tissue. Occasionally, however, the thymus persists until youth or 
middle age 1 (Fig. 275). Furthermore, it may become enlarged-so-called hypertrophy 
of the thymus. The enlargement is, however, due to a hyperplasia rather than hyper- 
trophy: the new-formed tissue may present a more or less marked lobulated or 
glandular appearance. This new-formed tissue, according to the studies of Sultan 
and Lochte, may be largely composed of lymphoid cells, or of larger polyhedral cells, 
so-called "epithelioid" cells.2 Focal necroses have been recorded in diphtheria. 
MALFORMATION AND HYPERTROPHY. 
HAEMORRHAGE. 
Small, and sometimes large, haemorrhages are occasionally seen in the 
thymus of young children as the result of venous congestion in asphyxia, 
poisoning, etc. They may also occur in the haemorrhagic diathesis.3 
INFLAMMATION. 
Suppurative inflammation of the thymus is of occasional occurrence, 
and is usually secondary to a similar inflammatory process in some other 
part of the body. Tuberculous and syphilitic lesions of the thymus are 
described, but are rare. 
TUMORS. 
Sarcoma of the spheroidal-cell form is the most common tumor; 
Angioma, Endothelioma, and Dermoid Tumors are recorded. 
1 For the significance of a persistent thymus in certain cases of sudden death see Norton, Phila. 
Med. Jour., vol. i., p. 249, 1898, bibl.; also ref. to Ewing, p. 1. On the relationship of hyperplasia in a 
persistent thymus to Hodgkin's disease consult Brigidi and Piccoli, Ziegler's Beitr. z. path. Anat., 
etc., Bd. xvi., p. 388, 1894. For a study of the weight of the thymus in infancy see Bovaird and 
Nicoll, Arch, of Pediatrics, Sept., 1906. For a thorough and admirable study of the normal and path- 
ological histology of the thymus see Pa/ppenheimer, Jour. Med. Res., xxii., 1, 1910. 
2 See Lochte, Centbl. f. allg. Path. u. path. Anat., Bd. x., p. 1, 1899, bibl. 
3 For a study of "Apoplexy" of the thymus see Mendelsohn, Arch. f. Kinderheilkunde, Bd. xliv., 
p. 1. 1906. CHAPTER IV. 
THE THYROID AND ADRENALS. 
The Thyroid. 
Malformations. 
The thyroid gland is sometimes very small, either as the result of atrophy or 
as a congenital deficiency. For the relationship of this condition to cretinism and 
myxoedema see page 429. 
The thyroid may be irregularly lobulated. There may be small accessory glands 
situated at some distance from the normal position, as in the mediastinum or pleura.1 
Colloid degeneration of the epithelial cells of the gland, and the filling 
of the alveoli with colloid material, are of common occurrence, and when 
in moderate degree may be regarded as normal, since a certain amount of 
this change is found in many otherwise apparently normal glands. It 
may occur, however, to such an extent as to constitute an important 
lesion (see below). 
Amyloid degeneration, particularly of the blood-vessels, is of infre- 
quent occurrence. 
Hyaline degeneration of the stroma of the thyroid may occur. 
DEGENERATION. 
DISTURBANCES OF CIRCULATION. 
Hyperaemia of the thyroid gland, often accompanied by considerable 
enlargement of the organ, may be the result of valvular disease of the 
heart; it occurs in Basedow's disease; it may be temporary or perma- 
nent, and in the latter case may be associated with the formation of new 
connective tissue. Haemorrhages may occur, leading to cysts and to 
pigmentation of the organ. 
INFLAMMATION. (Strumitis.) 
Inflammation of the thyroid gland is not very common and may occur 
under a variety of conditions, especially in infectious diseases, septi- 
caemia, typhoid fever, diphtheria, etc. It may result in the formation of 
larger and smaller abscesses or in the production of new connective 
tissue which may be associated with atrophy of the parenchyma. Tuber- 
culous inflammation, with the formation of miliary tubercles, is of infre- 
quent occurrence.2 Syphilitic inflammation, with the formation of 
gummata, has been described, but is rare.3 
1 For references to studies on removal and transplantation of the thyroid see foot-note, p. 78. 
2 See Roger and Garnier, Arch gen. de med., t. iii., p. 385, 1900, bibl. 
3 For a study of the normal and pathologic histology of the thyroid, with bibl., see Erdheim, 
Ziegler's Beitr., Bd. xxxiii., 1903, p. 159. For myxoedema and Basedow's disease see pp. 429 and 432. 
For relations of thyroid to pregnancy see Ward, Surgery, Gynecology, and Obstetrics, ix., 617, 1909. 
For relations of thyroid hyperplasia to various diseases and infections see Farrant, Brit. Med. Jour., 
1914, i., p. 470. 
512 THE THYROID AND ADRENALS 
513 
STRUMA. (Hyperplasia of the Thyroid; Goitre.) 
Among the most important of the lesions of the thyroid is the enlarge- 
ment of the organ commonly known as the goitre or struma. The 
enlargement of the gland may occur in several ways. Thus, a simple 
hyperaemia may, as above stated, lead to considerable enlargement of 
the organ, and this is sometimes called struma hyperoemica. The true goi- 
tre, however, consists in the enlargement of the old and the formation 
of new gland alveoli, while with these changes there is very frequently 
The colloid material filling the alveoli is stained red. 
Fig. 308.-Colloid Struma-Goitre. 
associated a greater or less amount of colloid degeneration. When there 
is new formation of gland tissue the growth has the character of an ade- 
noma. The hyperplasia may occur diffusely, so that the whole gland is 
more or less enlarged; or it may occur in the form of circumscribed nod- 
ules. When the colloid degeneration is prominent, so that the tumor 
has a gelatinous appearance, it is called colloid struma (Fig. 308).1 Accu- 
mulations of fluid, blood, colloid, etc., in the old or new-formed alveoli, 
may lead to dilatation and atrophy of the walls of the alveoli, so that 
cysts, sometimes of large size, are formed. Thus occurs the cystic struma. 
Again, the blood-vessels may undergo marked dilatation, so that we may 
have a telangiectatic struma; or cavernous angiomata may form within 
goitres. Very frequently all these varieties of lesions are present in the 
same goitre. The appearances may be rendered still more complex by 
the occurrence of haemorrhages and pigmentation, calcification, purulent 
1 For study of pathological anatomy of thyroid see Marine and Lenhart, Arch. Int. Med., 1911, vii., 
506. 514 
THE THYROID AND ADRENALS 
or indurative inflammation (strumitis), and by the not very infrequent 
association with carcinoma and sarcoma. The excitants of goitre are not 
well understood. The growth is, as a rule, slow, but occasionally a very 
rapid enlargement occurs as the result of a sudden increase of the col- 
loid degeneration. In many cases even very large goitres give rise to 
but moderate inconvenience, but they may assume great significance by 
encroaching upon neighboring parts. Thus death may be caused by 
pressure on the trachea, oesophagus, or on the large vessels. For lesions 
frequently observed in exophthalmic goitre see page 432. 
TUMORS. 
Some of the forms of goitre above described may be regarded as 
tumors or may be associated with tumors. Sarcoma and endothelioma 
are the most common tumors of the thyroid. 
Sarcoma, either spheroidal or spindle-celled, may occur as primary 
tumors in the thyroid, either in otherwise normal glands or in connec- 
tion with struma.1 Melano-sarcoma has been observed. Secondary 
sarcomata are rare. 
Primary carcinoma, both glandular and scirrhous, occurs in the thy- 
roid, and, particularly in the softer forms, may spread to adjacent parts 
and occasionally form distant metastases. Dermoid cysts are of occa- 
sional occurrence.2 Blood cysts are frequently found.3 
PARASITES. 
Echinococcus cysts have been found in the thyroid. 
PARATHYROID GLANDS. 
Closely connected with the thyroid, occasionally within, sometimes without its 
capsule, are four small gland-like bodies, usually two on each side. These are the 
parathyroids ("epithelial bodies") and are apparently in some way associated with 
the thyroid in function.4 There may be accessory parathyroids. 
The parathyroids appear to be of great importance in the metabolism of the body, 
since their complete removal apparently usually leads to fatal tetany. It has been 
shown by MacCallum and Voegtlin5 that the calcium salts of the body are rapidly 
excreted on the removal of the parathyroids in dogs, and that the symptoms of tetany 
following the removal cease on the administration of calcium salts. It is inferred 
from these observations that the parathyroids control the calcium metabolism of the 
body. Berkeley and Beebe' conclude from their experiments that the symptoms 
following removal of the thyroid are due to deranged metabolism giving rise to some 
active poison and not to the abnormal excretion of calcium. 
1 Consult for summary of observations on sarcoma of the thyroid, Morf, Jour. Am. Med. Ass'n, 
vol. xxxii., p. 911, 1899, bibl. 
2 For a risumi of mixed tumors of the thyroid see Leo Loeb, Am. Jour. Med. Sei., vol. cxxv., p. 
243, 1903. 
3 For a study of haemorrhagic cysts of the thyroid see Bradley, Jour. Exp. Med., vol. i., p. 401, 
1896. 
4 For a study of the parathyroids, with bibl., see Thompson, Jour. Med. Res., vol. xv., p 399, 
1906. 
6 MacCallum and Voegtlin, Johns Hopkins Hosp. Bull., xix., 91, 1908, and Jour. Exp. Med., xi., 
118, 1909. 
8 Berkeley and Beebe, Jour. Med. Res., xx., 149, 1909. THE THYROID AND ADRENALS 
515 
The parathyroids may be the seat of tumors.1 Other lesions have been described, 
but the nature and pathology of these organs are too little understood to permit of 
further consideration of them here.2 
The Adrenals. (Suprarenal Bodies, Suprarenal Capsules.) 
In acephalic and other monsters the adrenals may be atrophied or entirely absent. 
Sometimes in well-formed adults these organs cannot be discovered. There may be 
little rounded nodules loosely attached to the surface of the adrenals and having the 
same structure. Accessory and misplaced adrenals are not uncommon. A few cases 
have been reported of accessory adrenals in the broad ligament.3 They may be 
present in the liver.4 
If one kidney be absent or in an abnormal position its adrenal usually retains its 
proper position.5 
Malformations. 
ATROPHY AND DEGENERATION. 
Atrophy of the adrenals may be extreme. 
Fat Infiltration.-An accumulation of fat or of myelin droplets6 in 
the cortical portion is the rule in the adult. It sometimes occurs in 
Fig. 309.-Fatty Degeneration of the Adrenal. 
nodular areas (Fig. 309). In children under five years of age it is patho- 
logical. 
Amyloid degeneration may involve both the cortical and medullary 
portions. In the cortex it usually involves only the walls of the blood- 
vessels; in the medulla both the blood-vessels and the cells of the paren- 
1 See MacCallum, Johns Hopkins Hosp. Bull., vol. xvi., p. 87, 1905; also W eichselbaum, Verb. 
Deut. Path. Ges., Bd. x., p. 83, 1907. 
2 For transplantation of parathyroids see Thompson and Leighton, Jour. Med. Res., xxi., 135, 
1909. 
8 See Warthin, American Journal of Obstetrics, vol. xlii., 1900, bibl. 
4 See Noyes, Trans. New York Path. Soc., 1899-1900, p. 4; also Beer, Zeits. f. Heilkunde-Abth. 
path. Anat., Bd. xxv., p. 381, 1904. 
6 For consideration of relationship of the adrenals to the nervous system see A lexander, Ziegler's 
Beitr. z. path. Anat., Bd. xi., p. 145, 1892, bibl. 
"For a study of myelin substances in the adrenal see H errmann, Arbeiten a. d. path. Inst., Tubingen, 
Bd. v., p. 417, 1906. 516 
THE THYROID AND ADRENALS 
chyma may undergo this degeneration. The organs are usually firm 
and have a grayish, semitranslucent appearance. 
Pigmentation of the inner cortical zone is frequent in old persons. 
Focal necroses may occur in infections. 
THROMBOSIS AND HEMORRHAGE. 
Venous and capillary thrombosis may occur. 
In children, soon after birth, it is not very infrequent to find large 
haemorrhages in one of the adrenals, converting it into a cyst filled with 
blood (Fig. 310). This lesion has been observed in a few cases in adults.1 
INFLAMMATION. 
Suppurative inflammation, with the formation of abscesses, has been 
seen in a few cases. 
The most frequent lesion of the adrenals is tuberculous inflammation. 
They are usually increased in size; their surfaces are smooth or nodular. 
Fig. 310.-Hemorrhage into and about the Adrenal. (Infant.) 
The normal structure of the gland is more or less replaced by tubercle 
tissue, which usually undergoes cheesy degeneration and may soften. 
Fibrous tissue may form in considerable amount. For a consideration 
of the relationship of lesions of the adrenals to Addison's disease see page 
433.2 
Syphilitic inflammation, with and without the .development of gum- 
mata, is of occasional occurrence. 
1 For bibl. see Arnaud, Arch. gen. de med., t. iv., p. 5, 1900. 
2 For reference to nature of adrenal secretion, etc., see Abel, foot-note, p. 434. For a study of 
pathology of adrenals see Karakascheff, Ziegler's Beitr., Bd. xxxix., p. 373, 1906, bibl.; see also for 
recent risumi, Davis, N. Y. Med. Jour., vol. Ixxxiv., p. 263, 1906, bibl. THE THYROID AND ADRENALS 
517 
TUMORS. 
Sarcoma, glioma,1 and endothelioma occur in the adrenals. 
Neuroma.-Ganglionic neuromata have been described by Weichsel- 
baum and Freeman. 
Adenoma of the adrenals, resembling in type the structure of the 
cortex, may form as small encapsulated nodules or as large vascular 
tumors, often necrotic and haemorrhagic, which may invade the neigh- 
boring vessels and form metastases. This condition has been called 
stroma suprarenalis lipomatosa. The so-called fat droplets here, as in 
the normal suprarenal, are probably myelin. Some of the so-called 
adenomata of the kidney are adenomata of displaced accessory adrenals 
(see p. 777). 
Carcinoma is not common, but may be primary or secondary.2 
The Carotid Gland. 
This is a small ductless, encapsulated structure, five to seven milli- 
metres long, lying at the bifurcation of the carotid artery. It is com- 
posed of a connective-tissue framework and masses of polyhedral cells 
grouped with tufts of blood capillaries. It contains many nerves. It 
is believed to be analogous to the adrenals, hypophysis cerebri, and 
coccygeal gland. The carotid gland is occasionally the point of origin 
of lobulated tumors. These have been called angio-sarcoma, endo- 
thelioma, perithelioma.3 
1 For a study of glioma of sympathetic and adrenal, see Schilder, Frankfurter Zeitschr. f Path., 
hi., 317, 1909. 
2 For bibliography of primary malignant tumors of the adrenals see Ramsay, Johns Hopkins 
Hospital Bulletin, vol. x., p. 20, 1899. Davis, Arch. Int. Med., 1911, viii., 61. 
3 For a study of carotid tumors see Keen and Funke, Jour. Amer. Med. Assn., vol. xlvii., pp. 469 
and 566, 1906, bibl. CHAPTER V. 
THE CIRCULATORY SYSTEM. 
The Pericardium. 
INJURIES. 
The pericardium may be injured by penetrating weapons, by gunshot 
wounds, and by fragments of bone. It may be ruptured by severe con- 
tusions of the thorax, and by rapid extravasation of blood into the 
pericardial sac. Perforations may occur with empyema, mediastinal 
abscesses, abscesses of the chest wall and of the liver, or in connection 
with aneurisms of the aorta and suppurative inflammation of the peri- 
cardium. 
HAEMORRHAGE. (Haemopericardium.) 
Extravasations of blood into the cavity of the pericardium may follow 
wounds and rupture of the heart, rupture of the aorta and of aneurisms, 
and may occur with pericarditis from the rupture of new-formed blood- 
vessels. Small extravasations in the substance of the pericardium are 
found with scurvy, purpura, and in infectious diseases. 
At autopsies a few hours after death a few cubic centimetres of clear, 
light-yellow serum are usually present in the pericardial sac. If decom- 
position have commenced, this may be reddish, or it may be slightly 
turbid from the falling-off of the pericardial endothelium. 
Large accumulations of clear yellowish serum are often found as part 
of general dropsy from heart disease, kidney disease, etc. The amount 
is sometimes so great as to interfere writh the movement and nutrition of 
the heart. 
HYDROPERICARDIUM. (Dropsy.) 
Air or gas in the pericardium may be the result of post-mortem 
decomposition and there may then be drying of portions of the pericar- 
dium. Wounds or paracentesis of the pericardium; the perforation of 
ulcers of the stomach, cavities of the lungs, and ulcers of the oesophagus, 
or subdiaphragmatic abscess, may admit air into the pericardial cavity.1 
In purulent pericarditis with foul, decomposing exudate, gases may be 
evolved. 
PNEUMOPERICARDIUM. 
INFLAMMATION. (Pericarditis.) 
Pericarditis is rarely primary, but is usually secondary to infectious 
diseases, such as pneumonia, pleurisy, tuberculosis, typhoid fever, endo- 
1 See James, Am. Med., vol. viii., p. 23, 1904. 
518 THE CIRCULATORY SYSTEM 
519 
carditis, and pyaemia. It may follow injuries and is frequently associated 
with rheumatism or inflammation of the kidneys. It may be exudative 
or productive in character. 
Exudative Pericarditis.-It is convenient to distinguish in exudative 
pericarditis a fibrinous, a sero-fibrinous, and a purulent form. 
Fibrinous and Sero-fibrinous Pericarditis.-In the earlier 
stages or lighter forms of fibrinous pericarditis, the whole surface or 
portions of the pericardium may be dull or slightly roughened from a 
delicate fibrinous pellicle, more or less hyperaemic, and often studded with 
minute petechiae. Later, if the exudate accumulate, the entire surface 
Fig. 311.-Fibrinous Pericarditis. 
The pericardial sac is laid open and the part is seen covered with an irregular villous layer of fibrin. 
of the pericardium may be covered with a net-like layer of thick masses 
of fibrin. This may cover both the visceral and parietal surfaces and 
is often beset with irregular villosities (Fig. 311). Fibrinous adhesions 
may form between the two layers. There is usually some serous fluid 
as well as leucocytes mingled with the fibrin. 
Serum may accumulate in considerable quantity-sero-fibrinous peri- 
carditis. The pericardial sac may be greatly distended with this form of 
exudate so as to displace the heart and compress the larger air passages, 
the oesophagus, or the aorta. 520 
THE CIRCULATORY SYSTEM 
Purulent Pericarditis.-In this form of exudative pericarditis 
there are usually more or less serum and fibrin mingled with pus cells and 
often red blood cells. The process may start as a sero-fibrinous inflam- 
mation. It is apt to occur as an extension of an infectious process in the 
neighborhood or as a part of a general pyaemic process. Streptococcus 
pyogenes, Diplococcus pneumoniae, Staphylococcus pyogenes aureus, 
and the tubercle bacillus are the bacteria most commonly found in 
exudative pericarditis. 
Chronic Pericarditis.-In exudative pericarditis the mesothelium1 
(endothelium) in the early stages, and later this with the underlying 
connective-tissue cells contributes to the cellular elements in the exudate. 
In recovery the exudates degenerate and are gradually absorbed, while 
Fig. 312.-Adhesions of the Pericardium. 
The pericardial sac is opened so that the heart is viewed from the direction of the apex. There are 
two clusters of delicate fibrous bands joining the parietal and the visceral pericardium. 
from the blood-vessels and the connective-tissue cells of the pericardium 
more or less new fibrous tissue is formed, at first very cellular and vascular, 
later dense in character. There may finally be local or general thicken- 
ings of the pericardium. If a moderate amount of new fibrous tissue 
is formed this may appear as thin, white patches on the pericardium sur- 
face, the so-called maculae tendinea. The new fibrous tissue may extend 
between the subpericardial muscle fibres of the heart. Calcification of 
this new-formed fibrous tissue may occur. But more or less permanent 
adhesions may form between the visceral and parietal pericardium. 
These may be in the form of delicate fibrous strings (Fig. 312) or of 
larger areas of firm adhesion.2 
Obliteration of the Pericardial Sac.-As the result of the for- 
1 See reference to Minot, p. 377. 
2 For a study of such cases see Smith, Jour. Am. Med. Assn., 1913, Ixi., 739. THE CIRCULATORY SYSTEM 
521 
mation of vascular new connective tissue between the pericardial walls, 
the sac may be partially or wholly obliterated (Fig. 313). 
This may be the conclusion of an acute inflammatory process or it 
may result from the organization of a blood-clot following haemorrhage 
into the sac. It may occur as the result of the latter process early in life. 
Supra-arterial Epicardial Fibroid Nodules.-Small fibrous nod- 
ules are occasionally formed along the branches of the coronary arter- 
ies, especially on the surface of the ventricles. According to the studies 
of Knox1 they are frequently associated with lesions of the arteries, lead"- 
ing to the weakening of their walls at these situations. 
Tuberculous Pericarditis.-This lesion may occur by itself, but is apt 
to be associated with other tuberculous inflammation in the vicinity of 
Fig. 313.-Obliteration of the Pericardial Sac in a Child, Following Pericarditis. 
Showing blood-vessels growing from the visceral pericardium into the blood-clot filling the sac. 
Transverse section. A, Heart; B, pericardium; C, new-formed vascular tissue extending above to 
the unorganized clot. A similar layer of new vascular tissue was present over the parietal pericardium, 
and in places the two layers had coalesced, obliterating the sac. 
the heart. There may be miliary tubercles scattered diffusely, or limited 
to certain regions in the pericardium, which is otherwise little changed. 
Not infrequently, however, there is a considerable thickening of the peri- 
cardium, either visceral or parietal, or both. 
In such cases the new-formed tissue consists of fibrous tissue and of 
tubercle tissue which has undergone extensive cheesy degeneration (Fig. 
314). The thickened visceral and parietal layers of the pericardium are 
often more or less grown together, so that the pericardial sac may be 
partially or almost completely obliterated. An inflammatory exudate 
often accompanies the tuberculous process.2 
1 Knox, Jour, of Exp. Med., vol. iv., p. 245, 1899. 
2 For bibliography of tuberculous pericarditis see Norris, Bull. Univ. Penn., vol. xvii., p. 155 
1904. 522 
THE CIRCULATORY SYSTEM 
TUMORS. 
Fibromata are sometimes developed in the pericardium. They are 
often of polypoid form, and from atrophy of the pedicle may become 
free in the pericardial sac. Lipoma of the pericardium has been de- 
scribed. Endotheliomata are of occasional occurrence as primary tumors. 
Sarcomata and carcinomata occur as secondary growths either from 
continuous infiltration or as metastatic tumors. Primary sarcoma of the 
pericardium has been described.1 
The greatly thickened pericardium shows diffuse tissue with giant cells and irregular areas of 
cheesy degeneration. The free-upper-surface is covered with a layer of fresh fibrin. 
Fig. 314.-Tuberculous Pericarditis. 
Cysts of the visceral pericardium have been described. The writer 
has seen a pedunculated cyst, containing about 6 c.c. of clear fluid, hang- 
ing into the pericardial sac from its attachment near the pulmonary 
artery. The origin of such cysts is obscure. 
The Heart. 
Malformations and Malpositions. 
Malformations of the Heart.-The malformations of the heart are usually 
closely associated with malformations of the aorta and pulmonary artery. They 
depend on arrest of, or abnormal, development; on endocarditis, myocarditis, throm- 
bosis, or mechanical causes. 
I. The common arterial trunk is only partially, or not at all, separated into aorta 
and pulmonary artery. The divisions between the heart cavities are at the same time 
1 Williams, N. Y. Med. Jour., vol. Ixxi., p. 537, 1900, bibl. THE CIRCULATORY SYSTEM 
523 
defective, so that there may be one ventricle and no auricles; one ventricle and one 
auricle-reptilian heart (Fig. 315); or one ventricle and two auricles. 
II. The trunk of the pulmonary artery or of the aorta is stenosed or obliterated, 
and from the obstruction to the current of blood there is interference with the develop- 
ment of the septa between the heart cavities. 
1. The aorta, at its origin, or in the ascending portion of the arch, is stenosed or 
closed. The pulmonary artery gives off the descending aorta, and supplies the carotids 
and subclavians. The foramen ovale remains open, or there is no septum between 
the auricles. The ventricular septum is also usually defective. The right ventricle is 
hypertrophied. 
2. The pulmonary artery is stenosed or closed (Fig. 316). Its branches are sup- 
plied by the aorta, through the ductus arteriosus. The ventricular septum is defec- 
tive, the foramen ovale is open, or the auricular septum defective. 
Shows one auricle and one ventricle.1 
Fig. 315.-Reptilian Heart. 
III. The malformation affects the aorta and pulmonary artery after they are more 
fully developed. 
1. There is stenosis of the aorta between the left subclavian and ductus arteriosus, 
or just at the opening of the ductus arteriosus. The descending aorta is then a con- 
tinuation of the pulmonary artery. 
2. The aorta gives off all its branches from the arch, but the descending aorta is a 
continuation of the pulmonary artery; or the carotids may spring from the aorta, the 
subclavians from the pulmonary artery. 
3. The vessels are transposed; the pulmonary artery arises from the left, the aorta 
from the right ventricle; the pulmonary veins empty into the left, the venae cava? into 
the right auricle; or the veins also may be transposed. The septa are defective. 
1 For a description of this case see Northrup, Trans. N. Y. Path. Soc., 1888, p. 41. 524 
THE CIRCULATORY SYSTEM 
IV. The aorta and pulmonary artery are normal, but the cardiac septa are 
defective. 
1. The foramen ovale remains partly open. This condition may continue through 
life without ill effects. It has been found by some observers in about one-fifth of 
their autopsies. 
2. The ductus arteriosus may remain open for many years; this also may cause no 
disturbance. 
3. There is a small or large opening in the ventricular septum, usually in its upper 
part (Fig. 317). This may give rise to no symptoms, unless disease of the heart or 
lungs be superadded. 
V. Either of the auriculo-ventricular orifices may be entirely closed. The fora- 
men ovale remains open, and the ventricular septum is defective.1 
Fig. 316.-Stenosis of the Pulmonary Artery. 
The ductus arteriosus is open. 
VI. The valves of the different orifices of the heart may be absent or defective. 
The arteries or the ventricles are usually defective at the same time. 
The aortic and pulmonary valves may consist of two large or four small leaves, 
instead of the usual three. 
The edges of the semilunar valves may be fenestrated. This alteration is usually 
of no significance. It is frequent in the aortic and pulmonary valves. The valves 
may be thinner than normal, and near their free edges are small slits or openings (see 
Fig. 318). 
Generally speaking, the existence of openings between the two auricles or the two 
Consult for a study of rare forms of cardiac anomalies, Hektoen, Am. Jour. Med. Sci., vol. cxxi., 
p. 163, 1901, bibl. THE CIRCULATORY SYSTEM 
525 
ventricles, admitting some admixture of venous and arterial blood, produces no 
marked change in the circulation. If, however, the passage of the current of venous 
blood into the right heart is in any way interfered with, the consequences are very 
serious. Cyanosis is produced, the skin is of a bluish color, the small veins and capil- 
laries are dilated, exudation of serum and hypertrophy of connective tissue take place, 
especially in the fingers and toes. 
There may be absence of the heart; abnormal septa and chordae tendineae1 (Fig. 
319) in the heart cavities; abnormal shapes of the heart. Very rarely two more or 
less perfect hearts are found in the same thorax. 
Fig. 317.-Opening in the Ventricular Septum of the Heart-Interventricular Foramen. 
The opening is about 5 mm. in diameter, and its edges are formed by fibrous tissue. 
Malpositions of the Heart.-1. There is a smaller or larger defect in the 
walls of the thorax, so that the heart projects on the outside of the chest; the pericar- 
dium is usually absent. 
2. The diaphragm is absent, and the heart is in the abdominal cavity. 
3. The heart is in some part of the neck or head; this occurs only in foetuses very 
much malformed. 
4. The heart is transposed, being on the right side. 
Abnormal Size of the Heart.-1. The heart may be abnormally large in con- 
nection with obstructive anomalies of the great vessels. 
1 For a study of the origin of abnormal chordae tendineae in the heart see Tawara, Ziegler's Beitr., 
Bd. xxxix., p. 563, 1906. 526 
THE CIRCULATORY SYSTEM 
2. The heart may be abnormally small (hypoplasia). This abnormality is apt to 
be associated with the so-called status lymphaticus (see p. 439). 
Displacements of the Heart.-Changes in the position of the heart are con- 
genital or acquired. The congenital malpositions have already been mentioned. 
The acquired malpositions may be associated with: 
1. Hypertrophy of the heart; its long axis approaching the horizontal position. 
2. Changes in the thoracic viscera. Emphysema of both lungs may push the heart 
downward. Emphysema, pleurisy with effusion, or pneumothorax of one side pushes 
Fig. 318.-Fenestration of the Semilunar Valves. 
the heart to the other side. Pleurisy or chronic pneumonia, producing retraction of 
one side of the thorax, draws the heart to that side. New growths, aneurisms, and 
curvatures of the spine displace the heart in various directions. 
3. Changes in the abdomen. Accumulations of fluid and new growths in the 
abdomen, and tympanites, may push the heart upward. 
WOUNDS AND RUPTURES. 
Wounds of the heart are most frequently made by penetrating instru- 
ments, by bullets, and by fragments of bone. The right ventricle is the 
more frequently wounded (Fig. 320); next the left; rarely the auricles. 
The wound may penetrate into the cavities of the heart or pass only partly 
through its wall, or a bullet or the broken end of a weapon may be 
embedded in the wall. If the wound penetrate a cavity and be gaping, 
death may follow instantly and the pericardium be found filled with 
blood. If the wound be small and oblique, the blood may escape grad- 
ually and death may not ensue for several days. In rare cases adhesions 
are formed with the pericardium and the wound cicatrizes. Wounds 
which do not penetrate may cause death by the inflammation which they 
excite, or they may cicatrize. Bullets and foreign bodies may become 
encapsulated in the heart wall and remain so for years.1 
Rupture of the heart wall occurs in various ways: 
1 For a study of foreign bodies in the heart see Bailey, Arch. Int. Med., 1913, vii., 440. THE CIRCULATORY SYSTEM 
527 
1. Severe contusions of the thorax may produce rupture, usually of 
one of the auricles.1 
2. Spontaneous rupture occurs usually in advanced life. Rupture 
is most frequent in the left ventricle, and, in a considerable proportion of 
cases, near the apex. There is usually one rupture, but sometimes there 
are more. The rupture is usually oblique and larger internally than 
externally. The heart wall, near the seat of rupture, may be infiltrated 
These unite to form a slender band stretching across the cavity of the ventricle. 
Fig. 319.-Abnormal Chordae Tendine^e. 
with blood, or blood may infiltrate the subpericardial fat. The heart 
wall may be of normal thickness, or thin; it is usually soft and in a con- 
dition of fatty infiltration or degeneration. The rupture very frequently 
takes place when the patient is quiet. Death may be almost instan- 
taneous or may not ensue for several hours. 
Fatty degeneration leading to rupture of the heart may be general, or 
it is frequently circumscribed and due to obliterating endarteritis, ather- 
1 For bibliography see Newton, Med. Record, vol. lv., p. 864, 1899. Also Hamilton, Phila. Med. 
Jour., January 24th, 1903. 528 
THE CIRCULATORY SYSTEM 
oma, thrombosis, or embolus of one of the coronary arteries, whereby a 
portion of the heart wall is deprived of nourishment and degenerates. Or 
rupture of a branch of one of the coronary arteries may induce rupture 
of the heart wall. Acute and chronic myocarditis, with or without the 
Fig. 320.-Rupture of the Heart. 
From contusion. 
formation of abscess or cardiac aneurism, or the presence of tumors in 
the heart wall, or hydatids, may lead to rupture.1 
3. In rare cases rupture is associated with stenosis of the aorta and 
dilatation of the heart cavities. 
4. Rupture of the papillary muscles and tendons may be due to fatty 
degeneration or inflammatory or ulcerative processes. 
ATROPHY. 
Atrophy of the walls of the heart may be accompanied with no change 
in the size of its cavities; or with dilatation ("passive dilatation"); or, 
more frequently, with diminution in the size of the cavities. 
The atrophy involves most frequently all the cavities of the heart, 
but may be confined to one or more of them. 
1 Consult Councilman, "On Sudden Deaths due to the Heart," Boston Med. and Surg. Jour., 
Nov. 9th, 1893. THE CIRCULATORY SYSTEM 
529 
Ihe muscular tissue appears normal, or may be brown from the 
presence of little granules of pigment in the muscle fibres, which are some- 
times present in large numbers-brown atrophy; or the muscle fibres may 
undergo fatty degeneration; or there may be an abnormal accumulation 
of fat beneath the pericardium; 
or there may be a peculiar gela- 
tinous material beneath the peri-„, 
cardium-this consists of fat 
which has undergone mucous de- 
generation. The heart may be so 
much atrophied as to weigh only 
four ounces. 
Atrophy of the heart may be 
congenital; it may be associated 
with repeated haemorrhages or 
wasting diseases, or senility, with 
chronic pericarditis, with effusion, 
with obstructive lesions of the coro- 
nary arteries, with chronic myo- 
carditis, or with mitral stenosis. 
Atrophy of ths pericardial fat 
tissue not infrequently occurs in 
persons emaciated by chronic dis- 
ease, and then the usual situa- . i 
tions of the fat are occupied by a tissue resembling mucous tissue in its 
gross characters. Microscopical examination shows that in this atrophic 
fat the fat cells have largely lost their contents, and the whole tissue 
has undergone a partial reversion to its embryonic form (see Fig. 321). 
Fig. 321.-Atrophic Pericardial Fat Tissue. 
From a young person dead of Carcinoma of the 
stomach and peritoneum. Stained with osmic acid 
and teased. 
ANEURISM OF THE HEART AND VALVES. 
Aneurism of the Heart.-Sacs filled with blood, situated in the walls 
of the heart and communicating with its cavities, are formed in several 
different ways: • i 
1. In interstitial myocarditis a small or large portion of the wall may 
be replaced by fibrous tissue, and this, yielding to the pressure of the 
blood from within, may be pressed outward. Such a pouch may be a 
circumscribed sac communicating with the heart cavity by a small open- 
ing, or may be a simple dilatation of part of the ventricle. The wall of 
such an aneurism becomes thinner as the sac increases in size. It is com- 
posed of the endocardium, new fibrous tissue, visceral pericardium, and 
sometimes the adherent parietal pericardium. The walls may calcify, or 
rarely they become so thin as to rupture externally or into the right ven- 
tricle. The sacs may contain fluid blood or be filled with fibrin. 
Such aneurisms are usually situated in the wall of the left ventricle; 
rarely in that of the left auricle. If they are in the septum they may 
project into the right ventricle or auricle (Fig. 322). They are usually 
single, but sometimes two or three are found in the same heart. 530 
THE CIRCULATORY SYSTEM 
2. Fatty degeneration of the heart wall may reach such a degree that 
the wall yields and is pouched out into an aneurismal sac. 
3. Endocarditis and myocarditis, or fatty degeneration, may so soften 
a portion of the heart wall that the endocardium and part of the muscular 
tissue are ruptured and a ragged cavity is formed. This form of aneu- 
Fig. 322.-Aneurism of the Heart Opening from the Left Ventricle into the Right Auricle. 
Seen from behind. 
rism usually does not attain a large size, but soon ruptures externally 
and causes the death of the patient. 
Small aneurisms of the sinus of Valsalva are of occasional occurrence. 
Aneurisms of the Valves.-These are formed in two ways: 
1. They are the result of endocarditis. One of the lamellae of the 
leaf of a valve is destroyed, and the other lamella is converted into a sac 
filled with blood. These aneurisms are found in the aortic valve, pro- 
jecting into the ventricle, and in the mitral valve, projecting into the 
auricle. Not infrequently the wall of the aneurism gives way, so That 
there is a rupture entirely through the valve. 
2. The entire thickness of a leaf of a valve is pouched, forming a sac 
filled with blood. This occurs in the aortic, mitral, and tricuspid valves. THE CIRCULATORY SYSTEM 
531 
THROMBOSIS OF THE HEART. 
It is common to find after death, in the heart cavities, yellow, succu- 
lent, semitranslucent masses. They are most common and of firmest 
texture in persons who die of acute inflammatory diseases. They may 
adhere quite firmly to the walls of the heart and may extend in long, 
branching cords into the vessels. They are formed in the last hours 
of life and just after death. They are not of clinical or pathological 
importance. It is, however, often difficult to determine to what extent 
such clots have been formed during life, for these so-called "agonal" 
clots may be continuous with those formed some time before death as 
well as with those formed after life has become extinct. 
Fig. 323.-Polypoid Thrombus in the Left Auricle of the Heart. 
The thrombus was dark red in color, with smooth surface. 
Coagula of the fibrin of the blood in the heart form during life, and 
may exist for years. If the fibrin adheres to the valves in small masses 
these are called vegetations; if it coagulates in the heart cavities in larger 
bodies they are called thrombi or heart polypi. 
Such thrombi are found in all the heart cavities. They form flattened 
masses firmly adherent to the endocardium; or rounded bodies in the 
spaces between the trabeculae; or have a polypoid shape and are attached 
by a narrow pedicle (Figs. 323 and 324); or very rarely are globular and 
free in the cavity of the auricle (Fig. 325). Cardiac thrombi are most 
frequent in the auricular appendages and between the columnae carneae 
near the apices of the ventricles. (See Fig. 326.) 532 
THE CIRCULATORY SYSTEM 
They are usually found in connection with some valvular lesion (Fig. 
327), which involves a roughening of the surface, or prevents the free 
circulation of blood through the heart.1 
Old cardiac thrombi are firm, dry, and of a whitish color; they may 
soften and break down at their centres, so as to look like cysts filled 
with pus, or they may calcify. They are usually entirely unorganized, 
consisting simply of fibrin, but may become organized. 
Fig. 324.-Globular Thrombus in the Left Ventricle. 
This thrombus was softened at its centre. 
Cases are reported of organized thrombi in the auricles, the seat of 
tuberculous inflammation.2 
Sometimes sarcomatous and carcinomatous tumors in different parts 
of the body are accompanied by the formation of thrombi in the heart 
cavities, which are composed partly of coagulated blood, partly of tissue 
like that of the primary tumor. 
1 For a study of cardiac thrombosis see Martin and Rennie, Lancet, 1899, ii., p. 782. See also 
Welch in Allbutt's "System of Medicine," vol. vi., p. 182. 
2 Kotlar, Ref. Cbl. f. Bak., Bd. xv., p. 498, 1894; also Moser, I. c., 542. THE CIRCULATORY SYSTEM 
533 
DEGENERATION. 
Albuminous Degeneration. (Parenchymatous Degeneration.)-This 
lesion frequently occurs in diphtheria/ typhoid and typhus fever, pyaemia, 
erysipelas, and other infectious diseases, as a result of burns, and under 
a variety of other conditions. It is characterized by the presence in the 
muscle fibres of the heart of greater or less numbers of albuminous gran- 
ules of various sizes, most of them very small. They are not as refractile 
Fig. 325.-Labge Globular Thrombus in the Right Aubicle of the Heabt. 
as fat droplets, and are insoluble in ether, while swelling up and becom- 
ing almost invisible under the influence of acetic acid. Sometimes 
they are so abundant as to conceal the striations of the fibres. The 
degeneration is usually quite uniformly diffused through the heart, whose 
walls are softer than normal and of a grayish color. This lesion may be 
associated with or followed by fatty degeneration. 
1 See reference, p. 282. 534 
THE CIRCULATORY SYSTEM 
Fatty Degeneration of the Heart Muscle.-This consists in the trans- 
formation of portions of the muscle fibres of the heart into fat or closely 
allied substances/ which collect in the fibres in larger and smaller drop- 
lets, sometimes few in number, sometimes so abundant as almost entirely 
to replace or conceal the normal striations (Fig. 328). These droplets 
are soluble in ether, and remain unchanged on treatment with acetic 
acid. This degeneration is sometimes quite universal, but is more apt 
to occur in patches, giving the heart muscle a mottled appearance. 
Fig. 326.-Thrombi among the Trabecul.e of the Heart. 
This mottling may usually be best seen on the papillary muscles. The 
degenerated areas have a pale yellowish color, and the muscle tissue is 
soft and flabby; but when moderate or slight in degree the gross appear- 
ance may be little changed, and the microscopical examination be neces- 
sary for its determination. This degeneration may lead to thinning of 
1 See, in thia connection, p. 40. THE CIRCULATORY SYSTEM 
535 
the walls, or to rupture of the heart, or to inability to fulfil its functions. 
It is not infrequently the cause of sudden death. 
Fatty degeneration may be secondary to hypertrophy of the heart, to 
inflammation of the heart muscle, or to pericarditis; to disturbances of 
the circulation of the coronary arteries by inflammation, atheroma, etc. 
It may be due to deteriorated condi- 
tions of the blood in wasting dis- 
eases, excessive haemorrhages, ex- 
hausting fevers, leukaemia, etc., to 
poisoning with phosphorus and ar- 
senic, and to the toxins of microbic 
origin developed in infectious dis- 
eases, such as diphtheria, scarlatina, 
typhoid fever, etc.1 It may occur 
in otherwise apparently healthy 
persons. 
Fatty Degeneration of the Endo- 
cardium.-It is not uncommon to 
find, especially in elderly persons, 
fatty degeneration occurring in 
patches, especially on the valves, but 
also on the general endocardium. It 
may also occur in ill-nourished and anaemic individuals. Small, or even 
considerable, areas of fatty degeneration appear, as a rule, to be of little or 
no clinical significance. They are at least not inconsistent with perfect 
health. In these areas of fatty degeneration the connective-tissue cells 
are more or less completely filled with larger and smaller fat droplets. 
Amyloid degeneration of the endocardium or the walls of the blood- 
vessels and intermuscular con- 
nective-tissue septa is a not 
very infrequent, but usually not 
very important, lesion. 
Hyaline degeneration some- 
times occurs in the blood-vessels 
and in the muscle fibres. 
There may be calcification of 
the products of inflammation in 
pericarditis, or of connective- 
tissue membranes in chronic 
pericarditis; in the latter case 
the heart may be more or less 
enclosed by a calcareous shell. 
The muscle fibres of the heart wall may, though rarely, become densely 
infiltrated with salts of lime. 
Fatty Infiltration.-This lesion, which should be clearly distinguished 
Fig. 327.-Thrombus Formed over the 
Roughened Edge of the Mitral Valve. 
Fig. 328.-Fatty Degeneration of Heart Muscle. 
1 Consult Flexner, Johns Hopkins Hosp. Bull., vol. v., p. 26, 1894. For focal fatty degeneration of 
heart associated with Treponema pallidum see Warthin, Jour. Am. Med. Assn., 1912, Iviii., 409. 536 
THE CIRCULATORY SYSTEM 
from fatty degeneration, consists of an unusual accumulation of fat 
about the heart and between its muscle fibres. 
<■ .The subpericardial fat, which may be present in considerable quantity 
under normal conditions, may be so greatly increased in amount as to 
form a thick envelope enclosing nearly the entire organ. Sometimes the 
accumulation of fat extends into the walls of the heart, between the 
muscles, causing atrophy of the latter, frequently to a very great extent 
The lesion is excessive, the heart muscle being to a large extent atrophied. (The fat cells are repre- 
sented in the drawing, for the sake of clearness, of relatively too large size.) 
Fig. 329.-Fatty Infiltration of the Heart-Lipomatosis. 
(Fig. 329), so that the function of the heart is seriously interfered with. 
This occurs sometimes in general obesity, or as a result of chronic peri- 
carditis, or in drunkards, or in debilitated or old persons. 
SEGMENTATION AND FRAGMENTATION OF THE MYOCARDIUM. 
Attention'has been called by a number of observers to a condition of 
the heart muscle sometimes observed, it is said, in acute infectious dis- 
eases, in acute and chronic diseases of the central nervous system, and 
in sudden death from a variety of causes. The muscle tissue is soft, 
friable, opaque, and often yellowish. Examination shows a loosening of 
the muscle cells from one another, as if by some change in the cement 
substance-segmentation-or the fibres may be broken across-fragmen- 
tation. The significance of this alteration is not yet fully established, for 
though in some cases it is associated with degeneration and other changes 
in the heart muscle, in others these are not present and the alteration 
may be agonal, or it may in some instances be due to post-mortem 
changes.1 
'Consult Hektoen, Am. Jour. Med. Sci., vol. cxiv., p. 555, 1897, bibl.; MacCallum, Jour. Exp. 
Med., vol. iv., p. 409, 1899, bibl. THE CIRCULATORY SYSTEM 
537 
LESIONS OF THE CORONARY ARTERIES. 
Lesions of the Coronary Arteries in Acute Infections.-It has recently 
been shown that in acute infectious diseases, typhoid fever, diphtheria, 
influenza, scarlatina, pyaemia, and others, the media and the intima of 
the coronary arteries may be involved in necrotic and hyperplastic 
processes which are apparently of great significance in leading to certain 
forms of sclerosis of these vessels. 
The coronary arteries may show, on gross examination, in both larger 
and smaller trunks, circumscribed, yellowish white, elevated spots, from 
2 to 6 mm. in diameter, or small dull white depressions of the intima. 
These lesions seem to begin as a localized serous infiltration in the media 
which undergoes necrosis. At a later period, after recovery from the 
acute disease, fibrous tissue may form in the media and intima, some- 
times associated with calcification. Thus a patchy form of arterio- 
sclerosis may be developed.1 
Obliterating Endarteritis-Sclerosis-of the coronaries, which occurs 
frequently, is of great significance, since diminished nutrition of the heart 
wall may lead to local anaemia, degeneration of the muscle, fibrous 
hyperplasia or aneurism, etc.; but the formation of thrombi increases the 
gravity of the lesion. Thrombosis most commonly occurs in connection 
with degenerative or inflammatory processes in the coronary arteries. It 
may, however, be associated with occlusion of the coronary arteries at 
their orifices either through inflammation of the aorta in this region or by 
vegetations or clots on the aortic valves. 
The blocking of one main trunk of the coronary arteries by a throm- 
bus may cause death, but this is not always the case. 
When through obliterating endarteritis, thrombosis, or embolus of 
a branch of the coronary arteries,2 the blood supply is cut off from a 
circumscribed portion of the heart wall, the tissue in the affected area 
may undergo fatty degeneration, leading to rupture.3 Or, instead of 
extensive fatty degeneration, the cutting off of the blood supply from 
a limited region may result in necrosis-white infarction. These areas, 
grayish in color, often slightly projecting from the surface, are fre- 
quently surrounded by a red zone of hypersemia. The nuclei of muscle 
SCLEROSIS AND THROMBOSIS. 
1 For a study of this lesion of the coronary arteries see Wiesel, Wiener klin. Wochenschr., 1906, 
p. 723; and Zeits. f. Heilkunde, Abt. f. path. Anat., Bd. xxvii., p. 262, 1906; also Wiesner, Wien. klin. 
Woch., 1906, p. 725. 
2 According to Sternberg, the right coronary artery supplies the following regions of the heart: 
most of the right auricle; the posterior part and most of the anterior part of the right ventricle; most 
of the interauricular and interventricular septa; the posterior part of the left ventricle and the posterior 
papillary muscles. The remainder of the heart is supplied by the left coronary artery. 
While there are superficial anastomoses between the larger trunks of the coronary arteries, their 
branches do not communicate after they enter the heart muscle. For a study of coronary arteries 
see the monograph of Jamin and Merkel, "Die Koronararterien des menschl. Herzens," 1907. 
3 Through the Thebesian vessels sufficient nutriment may reach the myocardium to maintain 
the muscle for a time, even with considerable lesion of the coronary arteries. See Pratt, American 
Journal of Physiology, vol. i., p. 86, 1898. Also Baumgarten, ibid., vol. ii., p. 243, 1899. For a study 
of the results of occlusion of one or more of the coronary arteries see Porter, Jour, of Physiol., vol. xv., 
p. 121, 1898; also Jour. Exp. Med., vol. i., p. 46, 1896. 538 
THE CIRCULATORY SYSTEM 
and fibrous tissue fail to stain, the muscle cells become necrotic, lose 
their striation and degenerate, and may be absorbed or gradually 
replaced by fibrous tissue. When larger areas are involved, the muscle 
fibres may break down into a granular detritus and the connective tissue 
about them suffer degeneration or necrosis, so that the whole affected 
area may be soft and yellowish white or grayish in color. If, as not 
infrequently occurs, there is considerable extravasation of blood, the 
degenerated area may be of a dark red color.1 Under these conditions 
the heart wall may rupture, or acute inflammatory processes may occur, 
or the degenerated muscle tissue may be gradually absorbed and replaced 
by granulation tissue formed from the surrounding fibrous tissue and 
blood-vessels. This gradually grows dense, shrinks, and assumes the 
characters of cicatricial tissue. 
This may occur in any part of the heart wall or in the papillary 
muscles, but is most common in the region supplied by the left coro- 
nary artery; that is, in the interventricular septum and the anterior wall 
of the left ventricle near the apex. Thrombosis of the coronary arteries 
is more frequent than embolism and more commonly leads to infarction. 
When the heart wall is involved the new-formed connective tissue may 
yield to the blood pressure from within and aneurism of the heart be 
formed. 
Impaired nutrition of a portion of the heart wall as the result of 
narrowing or obliteration of the coronary arteries or their branches, 
whether it lead to such extreme lesions as those just described, or to 
fatty degeneration, or to atrophy of the muscle cells with a production of 
new connective tissue, is of great significance, and it may be the domi- 
nant factor in many cases of sudden death. 
Embolism of the coronary arteries is much less common than thrombo- 
sis and may be followed by similar lesions of the myocardium. Infective 
emboli are frequent excitants of suppurative lesions of the myocardium. 
INFLAMMATION. 
Myocarditis.-The inflammatory changes in the walls of the heart 
involve primarily the interstitial tissue and blood-vessels, the muscle 
fibres being secondarily affected by atrophic and degenerative changes. 
Interstitial myocarditis may be acute and suppurative, or chronic 
with the formation of new connective tissue. 
Acute suppurative myocarditis may be diffuse, infiltrating the wall of 
the heart with pus. This may occur as a complication of infectious 
diseases, such as scarlatina, diphtheria, typhoid fever, gonorrhoea,2 or 
may be associated with ulcerative endocarditis.3 
More frequently the suppurative inflammation is circumscribed, 
resulting in abscesses. These occur with pyaemia, mycotic ulcerative 
1 Thia condition of the heart is often called "myomalacia." 
2 For a consideration of gonorrhoeal myocarditis consult Councilman, Am. Jour. Med. Sci., vol. 
cvi., p. 277, 1893. 
3 For a study of experimental focalized myocarditis in relation to Aschoff nodules see Thalhimer and 
Rothschild, Jour. Exper. Med., 1914, xix., 429. THE CIRCULATORY SYSTEM 
539 
endocarditis, and other infectious diseases. They are of different sizes 
and either single or multiple. They are produced by the lodgment of 
infectious emboli in small vessels. There is at first necrosis of the muscle 
fibres near the bacterial mass (Fig. 330), followed by local suppuration 
and the formation of abscess. The contents of the abscesses consist 
of pus, broken-down muscle tissue, and bacteria. These abscesses may 
open into the pericardial sac and set up a purulent pericarditis; or into 
a heart cavity, giving rise to thrombi in the heart and infective emboli 
in different parts of the body; or the wall of the heart is weakened by the 
abscess so that it ruptures, or an aneurismal sac is formed; or an abscess 
in the interventricular septum may establish an opening between the 
ventricles; or the suppurative process may extend upward and form an 
Fig. 330.-Bacterial Embolus in Heart Muscle. 
The bacteria have multiplied since lodgment in the small vessel, so that the latter is widely dis- 
tended. The surrounding muscle is necrotic, s 
abscess in the connective tissue at the base of the heart. Streptococcus 
and Staphylococcus pyogenes are the most common excitants. 
In rare cases the patients recover, the contents of the abscesses 
become dry and hard and enclosed by a wall of fibrous tissue, or the con- 
tents may be absorbed and the whole replaced by fibrous tissue.1 
Chronic interstitial myocarditis may be associated with chronic peri- 
carditis or endocarditis; it may be secondary to damage to the muscle 
by bacterial or other toxins, but in a large proportion of cases it occurs in 
connection with lesions of the coronary arteries. 
Lesions of the coronary arteries which interfere with the blood supply 
of the heart muscle, such as obliterating endarteritis with or without 
thrombosis or embolism, may lead to degeneration or necrosis of the 
muscle and to a new formation of fibrous tissue which is in reality a 
replacement hyperplasia. Thus either in small foci or over more diffuse 
areas, patches of fibrous tissue may be formed as the muscle disappears 
(Figs. 330 and 331). 
If the occlusion of the coronaries has led to infarctions of the heart, 
1 For study of experimental myocarditis, Fleischer and Loeb, Arch. Int. Med. iii., 78, 1909. For a 
summary of conditions under which myocarditis occurs see Brooks, Am. Jour. Med. Sc., 1911, cxlii., 781. 540 
THE CIRCULATORY SYSTEM 
then also, as we have seen above, new fibrous tissue may form, replacing 
the muscle. 
Local degenerative processes and necrosis in the muscle tissue of the 
Fig. 331.-Chronic Interstitial Myocarditis (Fibrous Replacement Hyperplasia). 
heart may be associated with acute infectious diseases, especially with 
diphtheria, typhoid fever, and scarlatina. In such areas of damaged 
muscle new connective tissue may form. This is at first cellular, later 
Fig. 332.-Chronic Interstitial Myocarditis. 
Showing transverse section of a portion of a papillary muscle. The fibrous tissue is dense and the 
muscle fibres are atrophied. 
dense and cicatricial in character. As the result of this replacement 
hyperplasia, patches of fibrous tissue may be scattered through the 
myocardium. Similar lesions may be induced experimentally in animals THE CIRCULATORY SYSTEM 
541 
by the injection of bacterial toxins.1 Calcification of the muscle fibres 
has been observed in connection with the degenerative processes due to 
the action of toxins.2 
Chronic interstitial myocarditis, whether diffuse or focal, leads to a 
weakening of the heart wall. This may be slight or excessive. Hyper- 
trophy of the muscle may follow or be associated with it; degeneration 
of the remaining muscle may occur; or the heart wall may yield to the 
internal pressure and pouch, forming aneurism of the heart. Thrombi 
Showing cross section of a papillary muscle. The muscle tissue is least involved about the vessels 
and near the surface. 
Fig. 333.-Chronic Interstitial Myocarditis. 
may under these conditions form in the dilated cavities. Lack of 
rhythm in the heart-beats or cardiac pain-angina pectoris-may result 
from myocarditis. 
It is believed by most modern observers that the new connective 
tissue which develops in the heart in connection with atrophy of the 
muscle fibres, as a result of impaired nutrition due to a narrowing of the 
lumen of the coronary arteries or due to other causes, is not in the stricter 
sense inflammatory in its nature, but is rather a fibrous hyperplasia, 
the new-formed connective tissue forming secondarily, to replace the 
muscle fibres which have atrophied. Nevertheless we still for con- 
1 Flexner, Johns Hopkins Hosp. Rep., vol. vi., p. 259, 1897. 
Degeneration of muscle fibres and the formation of new connective tissue has been induced by 
Pearce in the hearts of rabbits by the injection of adrenalin into the ear vein. See Pearce, Jour. Exp. 
Med., vol. viii., p. 400, 1906. 
2 Cullen, Johns Hopkins Hosp. Bull., vol. xvii., p. 267, 1906. 542 
THE CIRCULATORY SYSTEM 
venience call the lesion myocarditis, thus implying inflammation. It 
is interesting in this connection to note that under these conditions 
the muscle fibres immediately beneath the endocardium and close 
around the blood-vessels where the nutritive supply is most abundant 
are often not atrophied, nor is the growth of connective tissue marked 
(Fig. 333). 
Tuberculous myocarditis is of occasional occurrence and may be asso- 
ciated with tuberculosis of the pericardium or endocardium.1 
Fig. 334.-Ulcerative Endocarditis. 
The valve and adjacent portion of the heart wall are ulcerated, and a ragged clot has formed upon 
the roughened surfaces. 
Syphilitic Myocarditis is accompanied by the growth of connective 
tissue or granulation tissue in the wall of the heart between the muscle 
fibres or in the walls of the blood-vessels. The pericardium and endo- 
cardium may also be thickened, and pericardial adhesions may be 
formed. Guinmata of the heart are of rare occurrence.2 
Endocarditis.-The endocardium is a connective-tissue membrane, 
containing but few blood-vessels, which lines the cavities of the heart and 
forms its valves. Its inner surface is covered with a layer of endothelial 
cells. The connective-tissue cells and basement substance are princi- 
pally concerned in the inflammatory processes. The new tissue thus 
produced is prone to degeneration and calcification. The roughening of 
'Consult Moser, "Tuberculosis of the Heart," Rep. of the Bost. City Hosp., 11th series, p. 194, 
1900. Also Anders, Jour. Am. Med. Assn., vol. xxxix., p. 1081, 1902. Also Raviart, Arch, de med. 
exp., t. xviii., p. 141, 1906, bibl. 
2 See Loomis, Am. Jour. Med. Sciences, vol. ex., p. 389, 1895, bibl. Also Adler, Trans. Assn. 
Am. Phys., vol. xiii., p. 73, 1898, bibl. THE CIRCULATORY SYSTEM 
543 
the endocardium due to the inflammation often leads to the formation 
of fibrin on the affected surface. 
The endocardium which forms the valves is that which is most fre- 
quently involved, but the other portions of it are by no means exempt. 
In adult life it is the endocardium of the left ventricle, and especially the 
aortic and mitral valves, which is most commonly affected. 
In foetal life it is the endocardium of the right heart which is usually 
affected. 
i. Simple Acute Endocarditis.-This is frequent with rheumatism, but 
may occur under other conditions. It may occur in a heart previously 
healthy, or in one already the seat of chronic endocarditis. 
In some cases the only lesion is a simple swelling of the valves. These 
Fig. 335.-Masses of Bacteria in Vegetation on the Heart Valve in Infective (Malignant) 
Endocarditis. 
are thick and succulent, but their surfaces remain smooth. The base- 
ment substance is swollen, and there is a moderate production of new 
connective-tissue cells. In other cases the growth of connective-tissue 
cells is more marked, the basement substance is split up, and little cellu- 
lar fungous masses of connective tissue, called "vegetations," project 
from the free surface of the endocardium. This is sometimes called 
verrucous endocarditis. On these roughened surfaces the fibrin of the 
blood may be deposited, and thus vegetations of considerable size may 
be formed (see Fig. 334). In still other cases the cell growth, while in 
some places forming vegetations, in other places degenerates, and thus 
portions of the valves are destroyed. This is simple acute ulcerative 
endocarditis. In some cases of this disease the patients recover and the 
valves seem to return to a normal condition; in other cases the valves 
are left permanently damaged; and in still others chronic endocarditis 
follows the acute form. 544 
THE CIRCULATORY SYSTEM 
2. Mycotic or Malignant Endocarditis (Malignant Ulcerative Endo- 
carditis).-The direct excitants of simple acute endocarditis of the forms 
described above are unknown, but in a considerable number of cases of 
acute endocarditis bacteria have been found in and about the vegeta- 
tions, and proved, by careful experiments, to stand in a causative relation 
to the lesion. 
Those cases of acute endocarditis in which the lesions are induced by 
the direct action of bacteria are called mycotic or malignant endocarditis; 
or, since the new-formed as well as the old tissue about the bacteria is 
Section showing thickening of the cusp of the aortic valve. 
Fig. 336.-Chronic Endocarditis. 
apt to become necrotic and thus lead to larger or smaller losses of sub- 
stance, the lesion is often called malignant ulcerative endocarditis. Cases 
of multiple aneurism in connection with mycotic endocarditis have been 
reported. Various species of bacteria may be excitants of malignant 
endocarditis (Fig. 335). 
It is most commonly induced by Staphylococcus pyogenes aureus and 
Streptococcus pyogenes. Diplococcus pneumoniae,1 B. typhosus, B. 
1 For a risumi of pneumococcus endocarditis see Preble, Am. Jour. Med. Sci., vol. cxxviii., p. 
782, 1904. THE CIRCULATORY SYSTEM 
545 
tuberculosis, B. anthracis, Micrococcus gonorrhoeae,1 and others have 
been occasionally found.2 - 
It has, furthermore, been found that a lesion or injury of the endo- 
cardium, either on the heart valves or elsewhere, predisposes to the lodg- 
Showing thickening and coalescence of two of the aortic cusps. 
Fig. 337.-Chronic Endocarditis. 
ment and growth upon it of pathogenic bacteria when once they have 
gained access to the circulating blood. 
Mycotic endocarditis is frequently a secondary complicating lesion, 
but may occur as a primary disease. It is most apt to be associated 
with the acute infectious diseases, and may be one of the local mani- 
festations of pyaemia.3 
In some cases there is a formation of new tissue in the form of organ- 
1 For ref. and bibl. of gonorrhoeal endocarditis see Lartigau, Am. Jour. Med. Sci., vol. cxxi., p. 
52, 1901. For later summary Kulbs, Wiener klin. Woch., Jan. 3, 1907, p. 11. 
2 For a general consideration of infective endocarditis see Washbourn and others, Brit. Med. Jour., 
Nov. 4th, p. 1269, 1899. For a study of the meningococcus in endocarditis see Warfield, Bull. Univ. 
Penna., vol. xvi., p. 180, 1903, and Cecil and Soper, Arch. Int. Med,, 1911, viii„ L 
* For a study of local predisposing factors in malignant endocarditis see Prudden, Am. Jour. Med. 
Sci., vol. xciii., p. 55, 1887; for experimental endocarditis see Posenow, Jour. Infect. Dis., 1912, xi.,210. 546 
THE CIRCULATORY SYSTEM 
ized vegetations on the valves or general endocardium; in other cases 
necrosis either of the new-formed or the old tissue is the most marked 
Fig. 338.-Vegetation on Aortic Valve in Endocarditis. 
Showing granular thrombus over the surface 
Showing fibrous "vegetation" on the mitral valve. With a large blood clot formed upon it. 
Fig. 339.-Chronic Endocarditis. 
feature. Thrombi are apt to form on the affected surfaces and often 
largely make up the so-called vegetations. The mitral and aortic valves 
are frequently the seat of the lesion, but it may occur elsewhere. THE CIRCULATORY SYSTEM 
547 
Detachment of bacteria containing fragments of the vegetations or 
clots may give rise to single or multiple infectious emboli and abscesses 
in various parts of the body, such as the spleen, kidneys, brain, skin, 
heart wall, etc. Bacteria similar to those in the heart lesion may be 
found in these secondary abscesses. 
It is probable that abscesses in ulcerative endocarditis do not always 
arise from cardiac emboli, but may precede the heart lesion.1 
3. Chronic endocarditis may succeed acute endocarditis, or the inflam- 
mation may be chronic from the outset. It affects most frequently the 
aortic and mitral valves, and the endocardium of the left auricle and 
ventricle, similar changes in the right side of the heart being much less 
frequent. 
The new papillary growths of connective tissue involve the mitral valve and obstruct the mitral orifice. 
Fig. 340.-Chronic Endocarditis (Verrucous Endocarditis). 
There are two main anatomical varieties of chronic endocarditis, which 
may occur separately or together: 
1. The endocardium is thick and dense, its surfaces are smooth or 
covered with small, hard vegetations or ridges (Figs. 336 and 337); it is 
often infiltrated with the salts of lime. 
2. There is a growth of connective-tissue cells in the endocardium, 
1 For a study of chronic infectious endocarditis, see Billings, Arch. Int. Med., iv., 409, 1909; for 
studies on bacteria in blood in "subacute" endocarditis, Libman, Am. Jour. Med. Sci., 1910, cxl., 516; 
and 1912, cxliv., 313. 548 
THE CIRCULATORY SYSTEM 
with a splitting-up of the basement substance. Some of the new cells 
continue to live, others degenerate. By the combination of such a cell 
growth and destruction the endocardium is in some places destroyed, in 
others changed into projecting vegetations (see Fig. 338). Fibrin is 
deposited on the roughened surfaces (Figs. 339 and 340). After a time 
the condition may be further complicated by the shrinkage and deposition 
of the salts of lime in the new tissue and in the endocardium (Fig. 338). 
All these changes may extend to the wall of the heart beneath the endo- 
cardium. As the result of the new formation of connective tissue the 
cusps of the valves may be shortened or grown together or adherent to 
the heart wall. The chordae tendineae may be shortened and the papillary 
muscle fibres shortened and distorted. 
The most important result of chronic endocarditis is its effect on 
the heart valves, producing insufficiency and stenosis (Figs. 341 and 342). 
Fig. 341.-Stenosis of the Aortic Valves. 
In chronic endocarditis. 
The changes in the valves are followed by changes in the walls and cav- 
ities of the heart, and disturbances of the circulation throughout the 
body (see p. 552). 
4. Chronic Ulcerative Endocarditis.-Large ulcers or perforations of 
the valves may be formed in chronic endocarditis, upon which clots 
may form, so that in gross appearance a great similarity exists between 
this and malignant ulcerative endocarditis, particularly if the latter 
have been engrafted upon an already chronically diseased endocardium. 
.The microscopical and biological examinations must usually be resorted 
to in order to determine the exact significance of the lesion. 
5. Tuberculous Endocarditis may occur in connection with tubercu- 
lous pericarditis or general miliary tuberculosis. The tubercles may be 
small and single, or grouped in masses, and show the usual degenerative 
changes.1 ' 
1 See reference, Moser, p. 542; also Etienne, Arch, de med. exp., vol. x., p. 146,'1898. THE CIRCULATORY SYSTEM 
549 
STOKES-ADAMS' DISEASE.1 
In this disease there is a slow pulse, sometimes accompanied by 
pulsation in the veins of the neck, which is more frequent than the beat 
of the ventricles. This is associated with attacks of syncope with a 
very slow pulse rate. This lack of rhythm in the beat of the auricles 
and ventricles is sometimes considerable, the former sometimes con- 
tracting three or four times as often as the latter. This condition, called 
"heart-block," is attributable to interference with the muscular connec- 
tion which has been shown to exist between the auricles and ventricles. 
Fig. 342.-Chronic Endocarditis with Calcification of the Thickened Valves.' 
It was formerly believed that the impulse which causes the walls of 
the chambers of the heart to contract arises in the automatic hehrt 
ganglia, and is conveyed to the muscle cells by nerves. The more 
modern view is that the impulse arises in the musculature of the great 
veins and is propagated to the walls of the heart chambers through their 
musculature.2 - ' i 
1 For a study of this condition see Erlanger, Jour. Exp. Med., vol. vii., p. 676, 1905; also ibid'., vol. 
viii., p. 8, 1906. : r 1/ 1 
2 For a summary with bibliography of the cause of the beat see Howell, " Harvey Lectures," 1905- 
1906; and[Erlanger, Arch. Int. Med., 1913, xi., 334. I 550 
THE CIRCULATORY SYSTEM 
His has shown that in mammals there is a narrow band of muscle 
joining the septa of the auricles and ventricles. This is called the 
" auriculo-ventricular bundle of His,"1 and it is important in regulating 
the heart beats. 
In many cases of Stokes-Adams ' disease, autopsy has failed to reveal 
lesions directly involving the region of the His bundle, but in others 
lesions have been found. In one case a small mural tumor was dis- 
covered; in another a gumma;2 in another3 there was a patch of sclerosis 
and atheroma involving the bundle; in still other cases lesions have been 
found.4 The experiments on animals in which heart-block has been 
induced by injuries of the wall near or involving the His bundle, together 
with the observed local lesion, show the importance of careful examina- 
tion of this region in such cases. 
Other forms of irregular heart action, palpitation, arrhythmia, tachy- 
cardia (rapid heart), brachycardia (slow heart) are so frequently unasso- 
ciated with obvious lesions that we refer for their consideration to trea- 
tises on clinical pathology.5 
HYPERTROPHY AND DILATATION OF THE HEART. 
We have seen in an earlier chapter that the circulation of the blood 
may be impaired by deficient cardiac power, such as may result from 
innutrition of the muscle from general causes, or from obstruction of the 
coronary arteries, from degenerative changes in the muscle, faulty 
innervation, the action of poisons, etc. 
But with unimpaired vigor of the heart muscle the circulation may 
be interfered with by many abnormal conditions. If the orifices of the 
heart are narrowed the blood is forced through them with difficulty; 
if the valves are defective the blood regurgitates. If there be obstruction 
in the vascular system the flow of blood is retarded. 
Under these and many other conditions an unusual amount of work 
is thrown upon the heart muscle, which may adapt itself to its unusual 
tasks by a hypertrophy which more or less fully compensates for the 
difficulties of the circulation.6 This is compensatory hypertrophy of the 
heart. The portion of the heart muscle especially involved in hyper- 
1 See Erlanger, ref. above, for more detailed description of the His bundle and ref. to His and 
Retzer. 
The following summary descriptive of the bundle is given by Erlanger after Retzer: "The auriculo- 
ventricular bundle runs posteriorly in the septum of the ventricles about 10 mm. below the posterior 
leaflet of the aortic semilunar valves; with a gentle curve it passes posteriorly just over the upper edge 
of the muscular septum and sends its fibres into the musculature of the right auricle and of the auricular 
valves. . . In the heart of the adult the bundle is 18 mm. long,2.5 mm. wide, and 1.5 mm. thick." 
See also for description of the bundle, with illustrations, Keith and Flack, Lancet, 1906, vol. ii., 
p. 359. Also Tawara, Ziegler's Beit., 1906, xxxix., 563, ibid, Reizleitungssystem, Jena, 1906. 
2 See Ashton, Norris, and Lavenson, Am. Jour. Med. Sci., vol. cxxxiii., p. 28, 1907. 
3 See Stengel, Amer. Jour. Med. Sciences, vol. cxxx., p. 1083, 1905. 
4 See Schmoll, Deutsch. Arch. f. klin. Med., Bd. Ixxxvii., p. 554, 1906. 
6 For details see Mackenzie, Diseases of the Heart, London, 1908; Lewis, Mechanism of the 
Heart Beat, London, 1911; and Lewis, Clinical Disorders of the Heart Beat, London, 1912. 
•For a suggestive study of cardiac hypertrophy as an adaptive process see Welch, "Adaptation in 
Pathological Processes," Trans. Congr. of American Phys, and Surg., vol. iv., 1897. 
For a comprehensive risumi of the normal and pathological physiology of the heart and its mor- 
phological and functional lesions see Heinz, " Handbuch d. exp. Path, und Pharmakoi.," 1905, Bd. i. THE CIRCULATORY SYSTEM 
551 
trophy is determined by the location of the obstruction to the circulation. 
The hypertrophy is usually associated with dilatation of one or more of 
the heart cavities. 
Hypertrophy may involve the walls of one or more or all the cavities 
of the heart. While the wall of a ventricle is thickened, its cavity may 
retain its normal size-simple hypertrophy; or be dilated-excentric hyper- 
trophy; or it may be contracted-concentric hypertrophy. Simple hyper- 
trophy is not common, but may occur in connection with the atrophied 
kidneys of chronic diffuse nephritis. 
Care should always be exercised in judging of cardiac hypertrophy, for 
a firmly contracted heart seems to have a small cavity and thick walls 
Fig. 343.-Cross-sections of Hearts Showing Hypertrophy. 
The heart at the left is normal. The heart at the right shows hypertrophy (concentric) with contrac- 
tion of the left ventricle. 
(Fig. 343). It should also be borne in mind that an increase in the 
amount of fat in and about the heart may make the organ appear larger, 
when there may be actually a considerable decrease in the amount of 
muscle tissue. The existence of such a condition as concentric hyper- 
trophy is denied by some authors. Excentric hypertrophy is the most 
common form. The muscle tissue in hypertrophied hearts is firmer and 
denser than normal, and is apt to have a darker color. Fatty degenera- 
tion may, however, be associated with it, giving the walls a lighter appear- 
ance. It is probable that the increase of tissue in the hypertrophied 
heart wall is the result of increase both in size and number of the muscle 
fibres. 552 
THE CIRCULATORY SYSTEM 
Hypertrophy of both ventricles increases both the length and breadth 
of the heart. Hypertrophy of the left ventricle (alone) increases its 
length. The apex is then lower and farther to the left than usual. 
Hypertrophy of the right ventricle (alone) increases the breadth of the 
heart toward the right side; but sometimes the right edge, of the heart 
retains its normal situation and the apex is displaced to the left. With 
large hypertrophy of both ventricles, the base of the heart may sink, so 
that its long axis approaches a horizontal direction. 
Hypertrophied hearts may weigh from forty to fifty ounces, or even 
more. 
Hypertrophy of the heart may depend upon a variety of conditions 
which increase its work. 
LESIONS OF THE HEART VALVES IN RELATION TO HYPERTROPHY AND 
DILATATION. 
As the result of acute infective processes in the endocardium the heart 
valves may undergo numerous changes. These are most frequent in 
connection with acute articular rheumatism, various forms of sep- 
ticaemia, typhoid fever, scarlatina, gonorrhoea, etc. We have already 
seen in detail the alterations induced in infections of the endocardium. 
As the result of these and other processes the heart valves suffer ulcera- 
tion, thrombosis, adhesions, distortions; the chordae tendineae may be 
shortened or the papillary muscles deformed; while the orifices may be 
less exactly controlled than normally as the result of myocardial lesions. 
Thus it frequently occurs that the orifices of the heart are too narrow 
or the valves close imperfectly, or both conditions are present together. 
' The narrowing of the orifices is called stenosis; the failure of the valves 
to close properly is called insufficiency. 
AORTIC INSUFFICIENCY AND STENOSIS. 
In insufficiency of the aortic valves the blood which has been sent 
forward into the aorta by the contraction of the left ventricle in part 
returns to the ventricle in the following diastole through the incompletely 
closed aortic orifice. This, unless the ventricle wall adapts itself to the 
changed conditions, may lead to an interference with the entrance of 
blood from the left auricle and so to pulmonary congestion. Under these 
conditions, then, of aortic insufficiency more work is thrown upon the 
muscle of the left ventricle, which may undergo compensatory hyper- 
trophy. With this there is usually associated a dilatation of the ventricle 
cavity on account of the larger amount of blood which it is forced to 
accommodate. , > 
In stenosis of the aortic valves there is obstruction to the passage of the 
blood into the aorta, and the muscle of the left ventricle is forced to do 
so much extra work that the wall of the ventricle becomes hypertrophied. 
This hypertrophy'may be followed by dilatation of the ventricle through 
a subsequent weakening of the wall. THE CIRCULATORY SYSTEM 
553 
MITRAL INSUFFICIENCY AND STENOSIS. 
In mitral insufficiency a part of the blood during systole of the left 
ventricle is forced back into the auricle. As the result of this the auricle 
is forced to do more work; its wall undergoes more or less hypertrophy 
and dilatation. Under these conditions the blood cannot properly flow 
from the pulmonary veins, which become congested. This in turn brings 
more work upon the right ventricle, which undergoes hypertrophy. But 
when the diastole of the left ventricle occurs, blood flows into it from 
the auricle and the pulmonary system under increased pressure, while 
it is forced to do more work in systole to compensate for the backward 
current through the faulty mitral valve. Thus the wall of the left 
ventricle becomes hypertrophied and at the same time becomes dilated 
from the increased amount of blood which it is forced to accommodate. 
In mitral stenosis the flow of blood from the left auricle into the left 
ventricle is obstructed so that more work must be done by the muscle of 
the wall of the auricle. This undergoes a certain amount of hypertrophy 
and also of dilatation on account of the increased pressure in the pul- 
monary veins. For the pulmonary vessels become overfilled owing to 
the resistance which the blood encounters in the obstructed mitral 
orifice. The heightened pressure of the pulmonary vessels is felt in the 
right ventricle, which must do more work, and undergoes hypertrophy. 
As to the left ventricle, the wall may remain unaffected in uncom- 
plicated mitral stenosis or may suffer degenerative changes or atrophy 
if the right heart fails to compensate properly for the obstructive lesion. 
INSUFFICIENCY AND STENOSIS IN THE RIGHT HEART. 
We need not trace these lesions of the right side of the heart in detail, 
for the changes are quite similar in principle to those which we have just 
considered. But they are by no means as frequent or as pronounced, 
nor is the compensatory mechanism as perfect as in the left heart. 
Lesions of the valves of the right heart are less frequent than those of the 
left. Tricuspid lesions infrequently develop in adult life. Lesions of the 
pulmonary valves developing in the adult are rare. During foetal life, 
however, lesions of both of these valves are not infrequent. Congenital 
heart lesions, such as stenosis of the pulmonary artery, may lead to hyper- 
trophy of the right ventricle. 
While we have thus briefly touched upon some of the more common 
and obvious of the conditions associated with the lesions of one or the 
other of the heart valves, there are many intricacies and variations for 
the details of which we must refer to special works on the subject.1 
But we should remember that there are frequent combinations of valvu- 
lar lesions on both sides of the heart. Thus simple mitral insufficiency 
is common, while uncomplicated mitral stenosis or aortic insufficiency 
or stenosis is less frequent than are combinations of insufficiency with 
stenosis in either the mitral or aortic valves. 
1 See Krehl, "Clinical Pathology," Hewlett's Eng. Trans., 1905. 554 
THE CIRCULATORY SYSTEM 
SUMMARY OF CONDITIONS LEADING TO HYPERTROPHY OF THE 
VENTRICLES. 
Hypertrophy of the Right Ventricle. 
This occurs especially under conditions which lead to increased 
resistance to the flow of blood in the pulmonary vessels, for exam- 
ple, in interstitial pneumonia, pulmonary tuberculosis, emphysema 
with chronic bronchitis and pleuritis, rarely with sclerosis of the pul- 
monary artery or incompetence or stenosis of the pulmonary or tricuspid 
valves. But lesions of the mitral valve or lesions of the wall of the left 
ventricle interfering with the pulmonary circulation may indirectly lead 
to hypertrophy of the right ventricle. 
Hypertrophy of the Left Ventricle. 
Aside from the valvular lesions already considered, hypertrophy of 
the left ventricle may arise from stenosis of the aorta, from an increased 
resistance of the flow of blood through the peripheral arteries as in various 
forms of obliterating endarteritis or arterio-sclerosis, and from certain 
forms of diffuse nephritis.1 
Arteries whose walls are stiffened from new-formed tissue or from 
degeneration or calcareous infiltration, or whose lumina are obstructed 
through obliterating endarteritis, do not so readily dilate as in normal 
conditions, nor do they promptly and readily recover when the heart 
pressure is reduced in diastole. Thus it is that, since the elasticity of 
the arteries is an important factor in the maintenance of the circulation, 
more work in the conditions above indicated is thrown upon the heart, 
which may lead to its hypertrophy. 
The relationship of arterio-sclerosis to hypertrophy of the heart is 
most complex and the results of recorded observations conflicting. One 
of the chief reasons for this uncertainty is doubtless the crude methods 
of determination of both the degree and seat of the hypertrophy and the 
character and grade of the arterial lesion. The common method of 
determining hypertrophy of the heart by simple inspection or by measure- 
ment of the thickness of the heart wall is essentially faulty because no 
account is taken of the degree of contraction of the muscle wall of the 
heart which makes the greatest difference in its thickness. Only by the 
method of W. Muller, in which, after the removal of the fat about the 
heart, the muscle wall of each cavity is separated and weighed and the 
weight of each part compared with the weight of the whole heart, and 
its proportional weight to that of the whole body, or by some similar 
method, can exact data be obtained.2 
Furthermore, the full significance of arterio-sclerosis can be deter- 
mined only by the more exact methods suggested by Thoma.3 
1 For an experimental study of hypertrophy of the left ventricle with diminished kidney structure 
see Passler and Heineke, ref. foot-note, p. 768. 
2 See Midler, " Die Massenverhaltnisse des menschl. Herzens," 1883; also summary by Hasenfeld, 
Deutsch. Arch. f. klin. Med., Bd. lix., p. 205, 1897; and Hirsch, Deutsch. Arch. f. klin. Med., Bd. 
Ixviii., pp. 55 and 321, 1900. 
3 Thoma, Virchow's Arch., Bd. civ., and following volumes. THE CIRCULATORY SYSTEM 
555 
The arterial lesions which appear to be of most significance in relation 
to hypertrophy of the heart are those of the upper aorta and those of 
the splanchnic system.1 To what extent the association of kidney lesions 
and hypertrophy of the heart are dependent upon arterial lesions can be 
determined only by the accumulation of data by the more exact methods 
above indicated. 
Hypertrophy of Both Ventricles from General Conditions. 
Hypertrophy of the heart may accompany any condition which 
leads to a prolonged increase in the rapidity of its contractions. It 
may accompany exophthalmic goitre. It may be associated with severe 
or persistent muscular exertion, or excesses in beer-drinking or other 
indulgences. It may be associated with chronic pericarditis with 
adhesions. With the hypertrophy arising under these general conditions 
there may be also varying degrees of dilatation.2 
The Limitations of Compensatory Hypertrophy. 
While the hypertrophy of the heart may for a longer or shorter time 
measurably compensate for the various disturbances of the circulation 
which have been considered, it is by no means always a perfect or per- 
manent adaptive measure. 
Excessive functional demands upon the heart, interstitial myocar- 
ditis, which may have preceded the hypertrophy or followed it, degener- 
ation of the muscle, dilatation of the cavities, obliterating inflammation 
and degeneration of the coronary arteries, singly or in various combina- 
tions, may in hypertrophied as in other hearts lead to irreparable damage 
to the organ. 
DILATATION OF THE HEART. 
In certain valvular lesions of the heart, as we have seen above (p. 552), 
there occurs a dilatation of the heart cavities associated with hyper- 
trophy of the muscle. This provides for the larger amount of blood which 
the cavities are obliged to receive and propel, and is thus compensatory 
and conservative. This is called active dilatation. On the other hand 
there may be no increase of muscle tissue, but a thinning of the walls 
proportionate to the dilatation of the cavity-passive dilatation. 
Either one or all of the heart cavities may be dilated, the auricles 
most frequently; next the right ventricle; least often the left ventricle. 
Active dilatation has been already considered with hypertrophy. 
Passive dilatation may be associated with: 
1. Changes in the valves. Mitral or aortic stenosis or insufficiency 
may lead to dilatation of the auricles and right ventricle. Pulmonary 
stenosis or insufficiency may lead to dilatation of the right auricle and 
1 See Hasenfeld, ref. above. 
2 Howard's table of 105 cases of cardiac hypertrophy shows its association with arterio-sclerosis in 
59 per cent.; with nephritis in 13.4 per cent.; with valvular lesion in 12.4 percent. Johns Hopkins 
Hospital Reports, vol. iii., p. 265, 1894. For possible errors in such statistics see p. 554. 556 
THE CIRCULATORY SYSTEM 
right ventricle. Aortic insufficiency, with or without stenosis or mitral 
insufficiency, may lead to dilatation of the left ventricle. Dilatations 
under these conditions are often succeeded and compensated for by 
hypertrophy of the heart walls. 
2. Changes in the muscle tissue of the heart walls. Serous infiltra- 
tion from pericarditis, myocarditis, fatty degeneration and infiltration, 
atrophy of the muscle fibres, may all lead to dilatation. 
3. A heart which is already hypertrophied may, as we have seen, from 
degeneration of the muscle, become dilated. 
4. Acute exudative inflammation of the lungs and acute pleuritic 
exudations, by rendering a large number of vessels suddenly imperme- 
able to the blood current, may produce sudden stasis in the pulmonary 
artery and dilatation of the right heart. 
5. There are curious and often serious cases of acute and chronic 
dilatation of the ventricles for which no mechanical explanation is 
found. 
TUMORS 
Primary tumors in the heart are rare, but sarcomata, myxomata,1 
fibromata, and lipomata may occur. Rhabdomyomata, probably con- 
genital, may occur in the heart wall as circumscribed nodular masses.2 
A cavernous tumor of this kind has been described. Secondary tumors, 
as a result of metastasis or of continuous growth from the pleura or 
cesophagus or other adjacent parts, are not very infrequent. These are 
usually carcinomata or sarcomata. Secondary chondromata have been 
observed.3 A few tumors of the heart valves have been described.4 
PARASITES. 
Echinococcus sometimes occurs in the heart wall and may perforate 
into the cavities. Cysticercus cellulosae has been observed. 
The Blood-Vessels. 
HYPOPLASIA, ATROPHY, AND HYPERTROPHY. 
Hypoplasia.-The aorta and larger vessels are sometimes dispro- 
portionately small as a congenital condition-hypoplasia-in which 
the heart may also share.5 This condition may be associated with the 
so-called "status lymphaticus" (p. 439), and may accompany chlorosis. 
Atrophy of the blood-vessels may involve the entire trunk or some of 
its elements. It may occur as a part of general malnutrition of the body, 
1 See for study of myxoma of heart Leonhardt, Virch. Arch., Bd. clxxxi., p. 347, 1905, bibl.; also 
Bacmeister, Cbl. f. allg. Path., Bd. xvii., p. 257, 1906. 
2 Seiffert, Ziegler's Beitr., Bd. xxvii., p. 145, 1900, bibliography; also Knox and Schorer, Arch, of 
Pediat., Aug., 1906; also Wolbach, Jour. Med. Res., xvi., 495, 1907. 
3 For bibliography of heart tumors consult Berthenson, Arch, de m6d. exp., vol. v., p. 386, 1893. 
4 See Djewitzky, Virch. Arch., Bd. clxxxv., p. 195, 1906. 
6 For a study of hypoplasia of the arterial system see von Ritodk, Zeits. f. klin. Med., Bd. Ixi., p. 
32, 1907. THE CIRCULATORY SYSTEM 
557 
or in connection with atrophy of particular organs, or as an accompani- 
ment of various diseases of the vessels themselves. 
Hypertrophy, which is especially seen in the arteries, may occur in the 
establishment of a collateral circulation upon the closure of arterial 
trunks; or it may occur as the result of increased blood pressure, as in 
some forms of hypertrophy of the heart, or from overwork. While all 
the coats of the vessel may be involved in hypertrophy the media is apt 
to be especially affected. This is seen in chronic diffuse nephritis. The 
hypertrophied media is liable to degeneration and weakening leading 
to arterio-sclerosis (see p. 564). 
The Arteries. 
RUPTURE AND WOUNDS. 
The arteries are predisposed to rupture by fatty degeneration, arterio- 
sclerosis with atheroma, and in various forms of acute inflammation.1 
Stenosis of the aorta may be followed by rupture between the occlusion 
and the heart. The rupture may be complete or a dissecting aneurism 
may form (see p. 568). Rupture of the aorta may lead to sudden 
death (Fig. 344). There may be partial or complete rupture of an artery 
from contusions, wrenchings, falls, etc. The injury to an artery from a 
penetrating wound may be fatal if the vessel be large. The wound of a 
small artery may close or a false aneurism may develop at its seat. 
In the healing of a wounded artery the vessel retracts and contracts, 
and a thrombus is formed within it. The contraction alone may be 
sufficient to close the vessel; its coats thicken, and the inner surfaces 
finally are fused together; or the blood coagulates and forms a thrombus 
in the vessel near the wound. This thrombus later becomes organized 
and the vessel is converted into a fibrous cord. 
DEGENERATION. 
Fatty Degeneration.-This may occur in the walls of otherwise unal- 
tered vessels, or in those which have undergone a variety of inflamma- 
tory or degenerative changes. It may occur either in the intima or 
media, or both, and may be so extensive as to form a very prominent 
gross lesion, or so little developed as to require the microscope for its 
recognition. When marked, especially if occurring in the intima of 
large vessels, smaller and larger spots or stripes or patches may be seen, 
of a yellowish white color, usually sharply circumscribed, and sometimes 
smooth, sometimes roughened on the surface. It is most apt to occur in 
the aorta, but may be found in any of the vessels. In moderate degrees 
of the lesion we find on section that the cells of the intima contain fat 
droplets in greater or less number. When further advanced, not only 
are the cells crowded with fat droplets, but the intercellular tissue also 
may be more or less densely infiltrated with them. Sometimes the infil- 
tration is so dense that the tissue breaks down, and there may be an 
1 For a study of perforations of aorta in py®mia see Witte, Ziegler's Beitr., Bd. xxxvii., p. 151, 
1905. 558 
THE CIRCULATORY SYSTEM 
erosion of the surface, forming a so-called fatty ulcer. When the media 
is involved the muscle cells contain fat droplets. It may lead to the for- 
mation of aneurism or to rupture of the vessels. 
Amyloid degeneration, which may affect all the coats of the arteries, 
but especially the intima and media, has already been described in gen- 
eral (p. 48). It will be further considered under the lesions of the 
organs in which it most commonly occurs. 
Fig. 344.-Transverse Rupture of the Aorta. (Traumatic.) 
Hyaline degeneration may cause thickening of the intima of the blood- 
vessels by its conversion into or infiltration with a homogeneous matter 
somewhat similar to amyloid (see p. 48). Or it may involve the entire 
wall of smaller vessels, converting them into irregular lumpy cords. 
The lumen of vessels thus changed may be obliterated or occluded by 
thrombi. THE CIRCULATORY SYSTEM 
559 
Calcification usually occurs in vessels otherwise diseased, and may 
involve either the intima or media. It consists in the deposition of salts 
of lime either in the cells or intercellular substance. The lime may be 
in the form of larger or smaller granules or in dense translucent plates. 
INFLAMMATION. 
Acute Arteritis.-Acute inflammation of the walls of the arteries is, in 
the majority of cases, the result of injury, or of an inflammation in the 
vicinity of the vessel, or of the lodgment within it of some foreign body of 
an irritating or infectious nature. The inflammatory process may be 
largely confined to the inner coat of the vessels-endarteritis; or it may 
commence in the outer coats-periarteritis; or it may involve the entire 
wall. 
The blood-vessels in the outer coats may be congested, the tissue 
oedematous and infiltrated with pus cells, and the entire wall may 
become necrotic. The intima, if this layer be involved, loses its natural 
gloss and looks dull yellowish and is swollen and may then ulcerate. 
Under these conditions thrombi usually form, and in these may occur 
the various changes which have been already described on page 24. But 
the process may originate in an infective thrombus or embolus most 
commonly associated with Streptococcus or Staphylococcus pyogenes, 
-thromboarteritis-embolic arteritis. 
In cerebro-spinal meningitis, whether this be incited by the meningo- 
coccus, streptococcus, pneumococcus, or by the tubercle bacillus, there 
may be an acute endarteritis characterized by the accumulation of leuco- 
cytes and polyhedral cells beneath the endothelium, often raising this 
layer from the underlying tissue (Figs. 128 and 129). This lesion may 
occur with or without the involvement of the outer layers of the vessel.1 
Rupture of the artery with more or less extensive haemorrhage may 
follow acute suppurative and necrotic inflammation of these vessels. 
Thus false aneurisms (see p. 568) may be formed. Or true aneurisms 
may be developed at the weakened point. In healing, fibrous tissue may 
form, leading to various phases of arterio-sclerosis. Finally, as the result 
of organization of thrombi (see p. 27), which may be present, new tissue 
may form within the lumen of the involved vessel-thromboarteritis 
proliferans. 
Arterio-sclerosis (Chronic Arteritis).-Since the publication of the 
studies of Gull and Sutton on arterio-capillary fibrosis, attention has been 
every year more and more directed to chronic pathological changes in 
the arteries as of great frequency and importance. These changes 
are productive and degenerative in character and have an important 
bearing upon the circulation and upon the integrity of the vessel walls. 
They are in part primary, in part secondary, and may involve single 
vessels or vascular territories or may affect the entire vascular system. 
The lesions differ somewhat in the small and large vessels. In very 
1 For a study of this lesion of the subendothelial layers of the arteries in tuberculosis, see Hektoen, 
Jour. Exp. Med., vol. i., p. 112, 1896, bibl. See also Flexner, ref., p. 225. For a study of arterial 
lesions and infectious diseases see Frothingham, Arch. Int. Med., 1911, viii., 153. 560 
THE CIRCULATORY SYSTEM 
small arteries there is a more or less general though not uniform thicken- 
ing of the intima (Figs. 345 and 346). This is due in part to a prolifer- 
Fig. 345.-Chronic Arteritis- 
Arterio-sclerosis-Obliterating En- 
darteritis. 
Fig. 346.-Chronic Arteritis-Arterio- 
sclerosis-Obliterating Endarteritis. 
The new-formed tissue is most abundant at 
one side of the vessel, where the external coats 
are pouched. There is degeneration of the 
new-formed tissue. 
Showing a thickening of the intima in 
a small artery of the brain. 
ation of the endothelium, in part to increase in the connective tissue of the 
intermediary layer. In this way a considerable amount of moderately 
cellular fibrous tissue (Fig. 348) may form within the membrana elastica, 
Fig. 347.-Obliterating Endarteritis. 
Complete occlusion of the lumen followed by gangrene of the toe. There is also fibrous thickening of 
the muscular coat. 
and the lumen may be largely or wholly obliterated-obliterating endarter- 
itis. The middle coat as well as the inner may be thickened (Fig. 347). 
In larger arteries the new tissue may form beneath the endothelium THE CIRCULATORY SYSTEM 
561 
diffusely or in circumscribed masses, or may encircle the vessel. The 
endothelium over the involved areas may remain intact or it may pro- 
liferate or become fatty or necrotic. The new-formed fibrous tissue of 
the intima, which may contain also new elastic fibres,1 is usually dense, 
having few cells, and is prone to undergo 
fatty degeneration, to become necrotic, 
and to disintegrate, and thus larger and 
smaller cavities, filled with disintegrated 
tissue, fat, and cholesterin crystals, 
may develop in the new-formed tissue 
(Figs. 346 and 349). These are called 
atheromatous cysts.2 They may extend 
toward the lumen of the vessels, into 
which they may open, giving rise to emboli and forming rough-edged 
ulcers, often with undermined edges. Upon these thrombi may form. 
In the new-formed tissue of the intima, as well as in the necrotic foci 
and in the detritus of the cysts, calcification may occur. 
Fatty degeneration, atrophy, and calcification may occur in the mus- 
Fig. 348.-Connective Tissue Formed in 
the Intima in Arterio-sclerosis. 
Fig. 349.-Chronic Arteritis-Arterio-sclerosis-Cerebral Artery. 
Inner coat thickened; degeneration and softening (atheroma) of a part of the thickened area. 
cularis and adventitia of the involved vessels. There may be degener- 
ation and atrophy of the elastic laminae. 
Similar processes may occur in the aorta, the new tissue growth and 
the degeneration being less definitely limited to the inner layer of the 
wall. The elastic laminae may be degenerated, partially atrophied or 
1 See Jores, Ziegler's Beitr., Bd. xxiv., p. 458, 1898, bibl. 
2 The word atheroma is sometimes applied to the whole process of arterio-sclerosis, but it would be 
well to limit it to the degenerative phases which result in softening of the tissues. 562 
THE CIRCULATORY SYSTEM 
absent, in patches in the wall of the vessel (Fig. 350). The aorta may 
thus be beset with larger and smaller, irregular, white, hard, elevated 
Fig. 350.-Atrophy of Elastic Tissue in Wall of the Aorta in Atheroma. 
The elastic tissue is replaced by dense fibrous tissue. 
thickenings (Fig. 351), often yellowish from fatty degeneration. Beneath 
these there may be atheromatous softening, or these sclerotic areas may 
Fig. 351.-Atheroma of the Aorta. 
There are fatty degeneration, thickening of the intima, calcification, and erosion. Thrombi have 
formed over the roughened surface of the erosions. 
be calcified and project as hard, often brownish plates with smooth or 
rough edges. The surface of the aorta may be rough from erosion over THE CIRCULATORY SYSTEM 
563 
the degenerated areas, and upon these or elsewhere parietal thrombi may 
form (Fig. 352). Such sclerotic areas are often well marked at the 
junction of smaller vessels with the aorta. 
We have seen that in the smaller vessels arterio-sclerosis may lead to 
extreme narrowing or occlusion of the lumen. When this does not occur, 
Section showing involvement of all the layers. The thickening of the intima is irregular, and 
areas of degeneration are seen in its deeper portion. Patches of fibrous tissue are present in the muscu- 
laris. A small thrombus has formed upon the surface. 
Fig. 352.-Chronic Inflammation of the Aorta-Atheroma of the Aorta. 
and especially in the medium-sized arteries, since the new tissue is less 
elastic than normal and liable to yield to the pressure of the blood, the 
lumen may in places be dilated (Fig. 353) or the wall may rupture. In 
this w'ay aneurisms may form. This is especially apt to occur when 
atheromatous degeneration has taken place and the muscularis is either 
Fig. 353.-Chronic Arteritis-Arterio-sclerosis. 
Showing pouching of the wall of the artery at the side on which is the largest formation of new fibrous 
tissue. 
atrophied or degenerated. In the aorta also dilatation and rupture may 
occur. 
Arterio-sclerosis may be largely limited to the aorta or to other single 
vessels, or it may occur in special vascular tracts, such as those of the 
brain or heart. 564 
THE CIRCULATORY SYSTEM 
As the result of arterio-sclerosis a great variety of circulatory dis- 
turbances may arise, both local and general. The effect upon the heart 
of the narrowing of the lumen of the arteries, as well as the loss of their 
elasticity, we have seen above (p. 554).1 
The Conditions Leading to Arterio-sclerosis.-The lesions of 
arterio-sclerosis often occur with gout, syphilis, chronic lead and alcohol 
poisoning, overwork, and overfeeding. They are usual in senility,2 and 
predisposition to them may be inherited. They may be associated with 
cardiac hypertrophy from valvular lesions or with chronic diffuse nephri- 
tis or other conditions involving increased arterial tension. They 
may occur locally in connection with tumors. In various acute infec- 
tions-diphtheria, scarlatina, typhoid fever, influenza, pneumonia, and 
pyaemia-localized lesions of the medium-sized arteries may occur, leading 
to sclerosis. There is degeneration of the smooth muscle cells and the 
elastic tissue of the media occurring in patches and followed by necrosis. 
These local lesions may heal by connective-tissue formation, or they may 
involve the intima, leading to sclerosis and more or less obstruction of the 
lumen. The aorta, the arteries of the brain, and the coronaries are 
frequently involved.3 
While the mechanical conditions under which arterio-sclerosis devel- 
ops are not very fully understood, the studies of Thoma have pointed 
the way along which fruitful research may be confidently expected. 
In accordance with the results of Thoma's experiments one may 
regard the primary lesions of arterio-sclerosis as a compensatory hyper- 
plasia of the intima. If for any reason-congenital defects, for example 
-the wall of the artery in a given region, as is the case in the circum- 
scribed or nodular forms of arterio-sclerosis, be weakened and yields 
to the blood pressure, it is at this point that the new tissue forms in the 
intima and restores the lumen to its natural calibre (see Figs. 346 and 
353) with restitution of the rate of blood flow. That this compensation 
is often incomplete or temporary, or that it brings with it other and often 
serious complications, does not militate against this view of the signifi- 
cance of these blood-vessel lesions, and is only one of many examples of 
imperfect adaptation in pathological processes.4 
Many conditions other than congenital defects in the vessel walls 
may result in arterio-sclerosis. In fact any long continued disturbance 
of the normal balance between the blood pressure and the resistance of 
the vessel wall apparently may lead in a variety of ways to arterio- 
sclerosis. Thus syphilitic inflammation of the arterial wall with necrosis 
may result in the formation of scar tissue, replacing the muscular and 
elastic supports of the walls by less resistant structures. The effects of 
alien substances or of natural substances in undue amount in the blood, 
which induce a continuing contraction of the muscularis of the arteries, 
or of overwork may lead through a primary hypertrophy followed by 
1 For a comprehensive resume? of the normal and pathological physiology of the blood-vessels see 
Heinz, Handbuch d. exp. Path, und Pharmakoi., 1905, Bd. ii. 
2 For changes in elastic tissue in aorta in advancing age, Foster, Jour. Med. Res., xxi., 297, 1909. 
3 See Wiesel, Zeits. f. Heilkunde, Abt. d. path. Anat., Bd. xxvii., p. 262, 1906. 
4 See reference to Welch, p. 110. THE CIRCULATORY SYSTEM 
565 
degeneration of the muscle cells to a general weakness of the walls with 
coincident general or local thickening of the intima. Senile or other 
general degeneration of the media with widespread calcareous de- 
posits may determine sclerotic changes in the intima. In all these cases 
the intimal thickening is not, according to the widely entertained view, 
inflammatory, but has the nature of a replacement hyperplasia in walls 
damaged and weakened in various ways. 
But this view, largely inspired by the work of Thoma,1 that the 
intimal lesions in arterio-sclerosis are compensatory, has not found 
universal acceptance. Indeed there are many conditions under which 
it seems clear that the sclerotic lesions of the intima, while often asso- 
ciated with damaging or destructive changes in the other layers, especially 
the media, are not secondary to them but are due to common agents 
acting on both. Furthermore, there appear to be intimal inflammatory 
thickenings induced by infective or toxic agents acting primarily on the 
intima.2 
Finally, there may be lesions of the intima secondary to those of the 
media, without the former being in any sense compensatory. 
Classification of the Forms of Arterio-sclerosis.-Various 
classifications of the lesions of arterio-sclerosis have been made. These 
must all be considered somewhat arbitrary and superficial until our 
knowledge of the mechanics of the circulation and the evolution of the 
lesions are more clearly defined. Much of the uncertainty in the inter- 
pretation of arterial lesions is due to the fact that observations in the past 
have been made largely on vessels in the contracted condition in which 
the cessation of blood pressure at death left them. So that the exact 
condition of the lumen during life in various sclerotic lesions is not really 
known. Thoma places in one class the primary and more limited nodular 
forms of fibrous-tissue growth, especially in the larger vessels, which he 
regards as compensatory in the way just indicated; in another the diffuse 
or secondary form, which is attributable to an increased resistance to the 
flow of blood in peripheral vessels, such as those of the kidney, a weak- 
ening of the muscularis through degeneration, the consequent dilata- 
tion, and then the compensating fibrous-tissue growth in the vessels 
at large. 
Councilman3 has grouped the lesions into three forms: 1st, the nodu- 
lar, corresponding with the primary form of Thoma; 2d, a senile form, in 
which there are often great distortion of the vessels, calcification, and 
frequent thinning of the walls; atrophic changes in the viscera are apt to 
be associated with this form of senile arteritis; 3d, a diffuse form of 
marked obliterating endarteritis with fibrous involvement of the muscu- 
lar layer. This is apt to be associated with hypertrophy and often with 
1 Thoma, see Virch. Arch., Bd. xciii., p. 443; ibid., Bd. cxvi., p. 1; also Thoma's " Text-book, of 
General Pathology," vol. i., Eng. trans.; also reference to Thoma's works, Arch. f. Entwickl. Meeh., 
Bd. xii., p. 352. 
2 For summaries of more recent conceptions of arterio-sclerosis see Adami, Am. Jour. Med. Sci. 
cxxxviii., 485, 1909; Klotz, Jour. Exp. Med., xii., 707, 1910; and Frothingham, Bull. Johns Hopkins 
Hosp., 1913, xxiv., 323. 
3 For a resume of views based upon Thoma's studies see Councilman, Trans. Assn. Am. Phys., 
vol. vi., p. 179, 1891. For a general study of pathogenesis of arterio-sclerosis see Pic and Bonnamour, 
Jour, de phys. et. path, gen., t. viii., p. 495, 1906, bibl. 566 
THE CIRCULATORY SYSTEM 
dilatation of the heart, and with chronic diffuse nephritis often with 
atrophy. The arterial changes may be marked in the liver as well as in 
the kidneys. 
The experimental study of arterio-sclerosis has thrown much light 
on the subject within the last few years. But into this we cannot enter 
here.1 
Periarteritis Nodosa. 
A few cases have been described in which many of the small arteries in the muscles 
and in the viscera were beset with small white knobs projecting from the side or sur- 
rounding the vessels. These circumscribed thickenings of the vessel walls are apt to 
involve all the layers of the vessel, and may encroach upon the lumen. The thickened 
portions are infiltrated with small spheroidal cells. Multiple aneurisms may develop 
at the seat of the local thickening.2 
Fig. 354.-Tuberculous Arteritis in the Lung. 
Showing the encroachment of an area of tuberculous inflammation upon the wall of the artery, 
and the formation of a mass partly occluding the lumen of the vessel. This section shows how the 
generalization of the tuberculous inflammation through the body may occur by the sweeping away 
of the tubercle bacilli by the blood and the establishment of new foci in various parts of the body. 
Tuberculous Arteritis.-Tuberculosis of the arteries is usually second- 
ary, the process extending to their walls from an already established 
focus (Fig. 354).3 Tubercle tissue with necrosis may involve the external 
layers, while an obliterating inflammation often closes the lumen. Thus 
it is that in tuberculous cavities of the lungs large arterial trunks may 
1 For a more comprehensive consideration of arterio-sclerosis with references to experimental 
studies see Adami and Nicholls, "Principles of Pathology." vol. ii., 171, 1909. 
2 Consult v. Kahlden, Ziegler's Beitr. z. path. Anat., etc., Bd. xv., p. 581, 1894; also Graf, ibid., 
Bd. xix., p. 181, 1896. 
3 For a study of tuberculosis of arteries see Geissler, Virch. Arch., Bd. clxxxvi., p. 135, 1906, bibl. THE CIRCULATORY SYSTEM 
567 
be laid bare (see Plate X.) without a distribution of the bacilli through 
the body and without haemorrhage. Tuberculosis of the aorta is of occa- 
sional occurrence.1 
Syphilitic Arteritis.-In the more characteristic forms of this lesion 
there may be gummata formed in the walls. Or there may be a diffuse 
formation of new cells and new fibrous tissue, especially in the adven- 
titia of the vessels. This may extend to the middle and internal layer 
and lead to narrowing of the lumen. There may be degeneration and 
ulceration. Such lesions may be circumscribed or extensive and may 
result in aneurism or rupture or closure of the lumen.2 
Save for the occasional formation of gummata and the frequent 
development of considerable new polyhedral-celled tissue there appear 
to be no distinctive morphological characteristics of syphilitic arteritis. 
ANEURISM. 
An aneurism is a dilatation of an artery, either cylindrical, fusiform, 
or sacculated, the walls consisting of all or part of the coats of the artery 
variously altered. 
The conditions which commonly lead to aneurisms are arterio- 
sclerosis, either with or without associated degeneration; or such local 
weakening of the walls of the vessels, from various causes, as often leads 
to compensatory arterio-sclerosis, but in which protective compensation 
does not take place; or the blocking of a vessel by embolus or trauma. 
Aneurism may develop at the point of partial rupture of the walls of an 
artery. Aneurisms may follow the local necrotic and ulcerative process 
in the walls of the vessels or on the heart valves incited by infectious 
agents, which as emboli or otherwise have reached these parts. Such 
mycotic aneurisms are frequently multiple.3 
In cylindrical or fusiform aneurism there is apt to be at first a disten- 
tion of all the walls of the vessel; but this is often irregular, so that the 
sac may bulge more in one place than in another (Fig. 355). The walls 
may become thin or through new-formed tissue they may become 
thickened; they may undergo degeneration or calcification. Such aneu- 
risms are most frequent in the aorta, but may occur in other vessels. 
In the sacculated aneurism there is either a dilatation of the entire 
circumference of an artery over a short portion of its length, or there 
may be a dilatation of only a small portion of one side of the wall, so 
that the aneurism looks like a swelling attached to one side of the artery. 
The aneurism may commence as a dilatation of all the coats of the vessel; 
but the middle coat soon atrophies, so that the wall is composed of the 
inner and outer coats; or the inner coat is destroyed by endarteritis, so 
that the outer coat alone forms the wall of the aneurism; or thedilata- 
1 Hay thorn, Jour. Am. Med. Assn., 1913, lx, 1413, and Woolley, Bull. Johns Hopkins Hosp., 1911, 
xxii, 82. Consult Blumer, Am. Jour. Med. Sei., vol. cxvii., p. 19, 1899, bibl. 
2 For a review of syphilitic aortitis see Longcope, Arch. Int. Med., 1913, xi, 15; for a study of syphil- 
itic lesions of blood vessels see Brooks, Am. Jour. Med. Sci., 1913, cxlvi, 513. 
3 For a study of mycotic aneurisms, with bibl., see McCrae, Jour, of Path, and Bact., vol. x., p. 373, 
1905. 568 
THE CIRCULATORY SYSTEM 
tion may commence at the seat of rupture of one or more coats of the 
vessels. As the aneurism increases in size it may press upon and lead to 
partial destruction of neighboring tissues and viscera, so that portions of 
these tissues and viscera may take the place of the wall of the aneurism. 
The cavity of the aneurism is filled with fluid or clotted blood, or with 
layers of fibrin (Fig. 356) which adhere closely to its wall. The com- 
munication between the aneurism and the artery may be small or large. 
Fig. 355.-Fusiform Aneurism of the Arch of the Aorta. 
If arterial branches are given off from the aneurism they may remain 
open or become plugged with fibrin; or their walls are thickened and 
their cavities narrowed by endarteritis. Death may occur by the pres- 
sure and interference of the aneurism with the adjoining viscera, or by 
rupture. 
Dissecting aneurisms are those in which, owing to a solution of con- 
tinuity of the inner layers of the artery, the blood gets between the media 
and adventitia, and forces its way for a greater or less distance between 
them. Or it may separate the media into twro layers.1 
Spurious or false aneurisms are most frequently connected with ves- 
sels of the extremities. When an artery is wounded the blood escapes 
1 For a study of dissecting aneurism see Adami, Montreal Med. Jour., June and July, 1896. THE CIRCULATORY SYSTEM 
569 
into the surrounding soft parts, and a cavity is formed filled with blood 
and broken-down tissue. > 
The wound in the artery may h,eal and the effused blood be absorbed; 
or it may become the seat of secondary inflammatory processes. 
Finally a wall of fibrous tissue may be formed, while the wound of 
the artery remains open, so that there is an aneurismal sac through 
which the blood is constantly pouring. This is called a false aneurism. 
Aneurismal Varix: Varicose Aneurism.-If an artery be wounded, 
and at the same time the vein which accompanies it, we have as the result 
the conditions called aneurismal varix and varicose aneurism. In aneu- 
Fig. 356.-Aneurism of the Popliteal Artery. 
Showing lamellated clot. 
rismal varix the artery and vein become adherent at the seat of injury, so 
that the arterial blood passes directly into the vein. There is a smooth, 
rounded opening between the two vessels, the vein is dilated into a sac, 
and the veins emptying into it are dilated and tortuous. In varicose 
aneurism the artery and vein do not communicate directly, but a false 
aneurismal sac is formed between the vessels, into which the blood is 
poured before passing into the vein. Varicose aneurism may also be 
formed by the spontaneous rupture of an aneurism into a vein. The 
aneurism presses against the vein, becomes adherent, and finally ruptures 
into it. This condition has been observed between the aorta and 
pulmonary artery; the aorta and inferior and superior vena cava; the 
popliteal artery and vein; the femoral artery and vein; the splenic 
artery and vena azygos; the internal carotid and sinus cavernosus. 
Cirsoid aneurism is one formed by the dilatation and lengthening of 
large or small arteries or arterial tracts. The walls of the arteries are 570 
THE CIRCULATORY SYSTEM 
thinned, the vessels are tortuous and in places sacculated. These 
changes are most frequent in small arteries, especially the temporal and 
occipital. They involve the trunk of the vessel and its branches, or 
may extend to the capillaries and small veins. They form larger or 
smaller tumors beneath the skin. 
The aorta may be dilated over its entire length, or there may be diffuse 
or circumscribed dilatations at any portion of its course; or there may 
be several aneurisms, situated at different points. The ascending portion 
of the arch of the aorta may be uniformly dilated in a fusiform shape 
(Fig. 355), or there may be circumscribed dilatations on its anterior 
wall, or, more rarely, on its posterior wall. The sacculated aneurisms 
vary in size and may rupture within the pericardium; or they may 
form a cavity in the upper part of the ventricular septum and commu- 
nicate by openings into the pulmonary artery and left ventricle; or they 
may dilate downward between the visceral and parietal pericardium, in 
front of the heart, pushing that organ backward. They may perforate 
into the right or left auricle or right ventricle, the superior vena cava, 
or the pulmonary artery; or they may reach a large size, press on and 
erode the right side of the sternum and adjoining ribs, project under the 
skin, and even rupture externally.1 
The transverse portion of the arch may be dilated in a fusiform shape, 
or there may be sacculated aneurisms at any point in its wall. The sac- 
culated aneurisms usually reach a considerable size. They press on the 
sternum and ribs in front, or on the oesophagus, trachea, and bronchi 
behind. The large arteries given off from the arch may be occluded. 
They cause death by pressure on the air passages, the oesophagus, and 
the vena cava; or may rupture externally or into the oesophagus, trachea, 
bronchi, pulmonary artery, or pleural cavities. 
On the abdominal aorta aneurisms are usually sacculated. If they 
are situated high up they may project into the pleural cavities; if lower 
down, into the abdomen. They may compress and displace the vis- 
cera, vessels, and nerves, and erode the vertebrae. They may rupture 
behind the peritoneum, into the peritoneal cavity, the pleural cavities, 
the inferior vena cava, the bronchi, the lungs, the duodenum, the colon, 
the pelves of the kidney, or the posterior mediastinum. Rupture of the 
aorta with the development of a long dissecting aneurism parallel to the 
vessel may give rise to a condition simulating a double aorta.2 
The coronary arteries may be dilated throughout, or may be the seat 
of small sacculated aneurisms.3 These may rupture into the pericardium, 
or may lead to rupture of the heart wall. 
The pulmonary arteries are rarely the seat of aneurisms. Diffuse and 
circumscribed dilatations, however, sometimes occur on the main trunk 
ANEURISMS OF THE DIFFERENT ARTERIES. 
1 For extension of aortic aneurism into the heart, and dissecting aneurisms of the heart, see Hektoen 
Trans. Assn. Am. Phys., vol. xvi., p. 127, 1901. 
2 See case reported by G. P. Biggs, Proc. New York Path. Soc., 1897-98, p. 109. 
3 Consult Capps, Am. Jour. Med. Sci., vol. cxviii., p. 312, 1899, bibl.; also Griffith, Brit. Med. Jour. 
February 2d, 1901, p. 266, bibl THE CIRCULATORY SYSTEM 
571 
and on the two principal branches of the artery. They do not usually 
reach a large size, but may cause death by rupture. General dilatation 
of all the branches of the pulmonary artery is more common. It is 
found in connection with stenosis of the mitral valves and with compres- 
sion or induration of the lung tissue. Small multiple aneurisms-miliary 
aneurisms-may occur in the cerebral arteries; less frequently in the 
pulmonary and mesenteric. These are probably due to some congenital 
weakness of the walls at the point of formation of the aneurism. 
Of the other arteries of the body there is hardly any one which may 
not become the seat of an aneurism.1 
This lesion near the entrance of the ductus arteriosus has been 
observed in a considerable number of cases. The degree of stenosis varies. 
The aorta may be entirely closed and converted into a solid cord for a 
half-inch; or there may be a constriction through which there is a 
larger or smaller opening. The walls of the aorta at this point may be 
thickened and sclerosed. The ductus arteriosus may be closed or open. 
Above the constriction the aorta is usually dilated; below it, it is normal, 
dilated, or stenosed. 
Stenosis of the aorta is followed by hypertrophy of the left ventricle, 
and, later, of the right ventricle, with venous congestion throughout the 
body; or there may be a collateral circulation developed between the 
arteries given off above and below the constriction; or there may be 
rupture of the aorta, the right ventricle or auricle. 
This condition is found at all ages, but is induced during foetal life 
or in the first year of extra-uterine life. It is probable that it may be 
caused after birth by an abnormal closure of the ductus arteriosus. This 
vessel normally becomes closed without the formation of a thrombus. 
If a thrombus be formed it may extend into the aorta and obstruct it; or 
the ductus arteriosus is filled with a thrombus, but increases for a time 
in size; afterward, as the thrombus is absorbed, the vessel contracts and 
draws the walls of the aorta together. 
STENOSIS AND OBLITERATION OF THE AORTA. 
TUMORS OF THE ARTERIES. 
Secondary tumors, chiefly carcinomata and sarcomata, may occur in 
the walls of the arteries by continuous growth from without, involving 
first the external layers. To these layers they are usually confined, for 
the density of the inner layers affords such marked resistance to the 
infiltration of the tumor cells that arteries are apt to pass intact through 
the tumor, which grows around them. More frequently the arteries 
become secondarily involved in the growth of malignant tumors by the 
occurrence within them of emboli formed by larger and smaller masses of 
tumor cells. 
These emboli are usually of small size, and are apt to get into the 
1 For details concerning form, distribution, and frequency of aneurisms see the larger works on the 
practice of medicine or surgery. 572 
THE CIRCULATORY SYSTEM 
circulation by growing through the walls of the veins into their lumina. 
Large emboli from tumors are most apt to lodge in the branches of the 
pulmonary artery. The emboli, formed as they are for the most part 
by cells capable of growth and proliferation, are apt soon to form con- 
nection with the walls of the vessels, and, by the growth into them of 
blood-vessels from the vasa vasorum, to find the conditions necessary 
for their development, and they may thus soon involve the entire wall of 
the vessel and grow out into adjacent parts. 
The Veins. 
DILATATION. (Phlebectasia.) 
Dilatation of the veins, or phlebectasia, presents itself under a variety 
of forms: 
1. Simple Dilatation.-The vein is uniformly dilated in a cylindri- 
cal or fusiform shape; its length is not increased; its walls may be thicker 
than normal or thinned; the valves may be thickened, or are insufficient, 
or atrophic, or are torn. 
2. Cirsoid Dilatation.-The vein is cylindrically dilated, but is 
also increased in length, so that it assumes a very tortuous course. The 
walls may be thickened or thinned. 
3. Varicose Dilatation.-Portions of the wall of the vein undergo 
saccular dilatation. The wall of the sac is formed of the coats of the 
vein, but these may be thickened or thinned; the middle coat may dis- 
appear entirely. There may be only one such dilatation, or there may 
be a number on the same vein, or a number of veins may be affected at 
the same time. The vein may be otherwise normal, or, more frequently, 
is more or less uniformly dilated. 
4. Anastomosing Dilatation.-A number of contiguous and 
anastomosing veins are dilated, both in the cirsoid and varicose forms. 
The vein then looks like a series of cavities separated by thin partitions. 
The dilatations of the same vein become adherent to each other and to 
those of the adjoining veins; portions of the walls of the dilated parts 
may atrophy so that there may be a number of cavities containing venous 
blood and separated from each other by thin partitions. 
Distribution, Causes, and Effects of Phlebectasia.-There is 
hardly one of all the veins of the body which may not be dilated. The 
haemorrhoidal veins forming "haemorrhoids"; the veins of the leg and 
thigh; those of the pelvis and pelvic viscera; those of the spermatic cord, 
scrotum, and labia; those of the abdominal wall; those of the neck and 
arms-are most frequently involved. The immediate cause of dilatation 
is usually some obstruction to the passage of the blood through the veins 
toward the heart; but alterations in the walls of the vessels from degen- 
eration, inflammation, or injury are often important predisposing factors. 
Spontaneous restitution of dilatations of the veins is not common, 
and usually occurs only in the lesser degrees of the lesion. The tendency 
of the dilatation is to increase. Thrombi frequently form in the dilated THE CIRCULATORY SYSTEM 
573 
veins, and either partially or completely fill them. These thrombi 
may become organized, or they may.dry arid become calcified, forming 
phleboliths, and by the formation of new' connective tissue in the walls 
they may become enclosed in a fibrous capsule, with the obliteration 
of the vessel. The wall of the dilated sac may become so thin that it 
finally ruptures. Inflammation of the dilated vein may occur, followed 
by fibrous thickening. When occurring in mucous membrane, dilated 
veins are usually associated with persistent catarrh. 
WOUNDS-RUPTURE. 
Wounds of the veins usually heal by a simple contraction and an 
adhesive inflammation of their walls; sometimes by the formation of a 
thrombus. Rupture of the veins may be produced by severe contusions 
and crushings of the body and by violent falls. Perforation of a vein 
may be produced by suppuration of the soft parts and the invasion of 
the walls of the vessel; by the pressure of an aneurism or of a new growth; 
by the thinning of the wall of the vein in phlebectasia. 
THROMBOSIS. 
Thrombosis of the inferior vena cava has been many times recorded. 
It is usually due to pressure on the vessel or may occur as an extension 
of thrombi from the contributory veins.1 
Thrombosis of the superior vena cava usually follows pressure from 
without by tumors, aneurisms, or enlarged lymph-nodes. 
Thrombosis of other large venous trunks may occur under various local 
and general conditions (see below, Thrombosis and Phlebitis, and p. 24).2 
DEGENERATION. 
Fatty degeneration and calcification may occur in the walls of the veins 
under conditions similar to those in which these changes take place in 
the arteries. 
INFLAMMATION. (Phlebitis.) 
Inflammation of the veins, phlebitis, may involve chiefly the external 
layers-periphlebitis; or the internal-endophlebitis; or, as is very fre- 
quently the case, the entire wall may be affected. Phlebitis may be due 
to an infectious thrombus, to injuries, or to an infectious inflammation 
of the surrounding tissues. Thrombosis of the vein, either primary or 
secondary, is a very constant accompaniment of phlebitis. Thrombosis 
and phlebitis are not infrequent in association with or following infec- 
tious diseases, in cachectic conditions, and with rheumatism and gout. 
Acute infective phlebitis may follow a suppurative periphlebitis. The 
outer layers of the vein wall are congested, swollen, infiltrated with serum 
1 For a case of complete fibrous obstruction of superior and inferior vense cavae see Meyer, Mt. Sinai 
Hosp. Rep., vol. iii., 1903, p. 35. 
2 For a consideration of peripheral venous thrombosis id heart disease consult Welch, Trans. Assn. 
Am. Phys., vol. xv., p. 441, 1900, bibl. 574 
THE CIRCULATORY SYSTEM 
and pus. The inner coats may become infiltrated with pus; they may 
become necrotic and disintegrate. A thrombus is constantly formed 
under these conditions, which may for a time stop the circulation and 
keep the products of inflammation and degeneration and infectious 
material from mixing with the blood; but the thrombus itself is prone to 
disintegration, and thus the exudates and fragments of disintegrated 
thrombi or tissue or bacteria may enter the circulation. 
On the other hand, owing to the presence of irritating or infectious 
material within the vein, and the formation of a thrombus, the inflamma- 
tory process may be at the commencement an endophlebitis, but usually, 
if the inflammation be at all severe, the entire wall of the vessel is even- 
tually involved. 
Acute phlebitis may terminate in the absorption of the thrombus and 
the return of the vein to its normal condition, or in the obliteration of 
the vein. The pyogenic cocci, the typhoid bacillus, the pneumococcus, 
and several other micro-organisms have been found in phlebitis. In the 
Fig. 357.-Tuberculous Phlebitis. 
The section is from one of the pulmonary veins in a child dead of acute general miliary tuberculosis. 
phlebitis with thrombosis, which frequently complicates infectious dis- 
eases such as typhoid fever, pneumonia, etc., the bacteria present are 
frequently not those which are the excitants of the primary disease. 
The most important results of phlebitis are usually those which depend 
upon the introduction into the blood of infectious or other emboli (see 
p. 28). The relationship between non-infectious thrombi and phlebitis 
is in many cases not clear.1 
Chronic periphlebitis results in thickening, principally of the outer 
coats of the veins, but the inner coats may also be involved. The sur- 
rounding tissue may also be thickened and coalesce with the walls of the 
vein. There may or may not be thrombosis. 
Chronic endophlebitis is a not very common lesion, of the same general 
character as chronic endarteritis, with which it is often associated. 
More or less circumscribed patches of new connective tissue are formed 
in the inner coats, which may undergo fatty or calcareous degeneration. 
1 Consult in this connection Welch on "Thrombosis," Allbutt's "System of Medicine," vol. vi., p. 
170. THE CIRCULATORY SYSTEM 
575 
Tuberculous inflammation of the walls of the veins may occur as an 
extension of the process from without or from a lodgment of the tubercle 
bacilli in the blood current on the intima (Fig. 357). This is not infre- 
quent in the pulmonary veins, and Weigert has called attention to the 
fact that in acute miliary tuberculosis the growth of tubercle tissue into 
the lumina of these veins from tuberculous lymph-nodes is of frequent 
occurrence and readily explains the topography and mode of occurrence 
of the general disease. The tubercle bacilli which are present in the 
tuberculous tissue growing into the lumen of the veins find thus an easy 
distribution.1 
Syphilitic inflammation may involve the walls of the veins either as 
gummy tumors or as more diffuse thickenings. 
TUMORS. 
Primary tumors of the veins are rare. Small leiomyomata have been 
described in the saphenous and ulnar veins. A myo-sarcoma as large as 
a man's fist has been described, situated in the dilated vena cava inferior. 
The veins are not infrequently secondarily involved by sarcomata and 
carcinomata, and sometimes by chondromata. The thin walls of the 
veins offer comparatively little resistance to the encroachment of malig- 
nant tumors, which thus gain access to the circulation and may form 
metastases in various parts of the body. 
PARASITES. 
Echinococcus is sometimes found in the veins, having either devel- 
oped there or perforated from without. 
Two species of distoma (liver fluke) occur in man. D. hepaticum 
occurs rarely and, while usually found in the bile-ducts, may occur in 
the vena cava. D. haematobium is very common in man in Egypt and in 
other parts of Africa, and usually occurs in the portal vein or its branches, 
and frequently in other veins. 
The Capillaries. 
The walls of the capillaries are so thin and so intimately connected 
with the surrounding tissues that their lesions are studied most appro- 
priately among the diseases of the several organs. Dilatation of the 
new-formed capillaries in tumors, granulation tissue, etc., fatty amyloid 
and hyaline degeneration of their walls, and capillary aneurisms, may 
be mentioned here as readily observed lesions occurring under a variety 
of conditions. Angiomas and telangiectases, usually congenital, are 
occasionally seen. 
The changes which we assume to occur in the walls of the smaller 
veins and capillaries in exudative inflammation, by reason of which 
fluids and blood cells pass through them, are not yet sufficiently under- 
stood to be described with definiteness. 
1 See references under "Miliary Tuberculosis," p. 252. 576 
THE CIRCULATORY SYSTEM 
The Lymph-Vessels. 
General Characters of the Lymph-Vessels. 
The smaller lymph-vessels can hardly be treated as independent structures, since 
their walls are so closely joined with the tissues through which they pass. It is per- 
haps wiser to follow the suggestion of Adler and Meltzer1 and call the spaces of the con- 
nective and other tissues into which transudations from the smaller blood-vessels 
takes place, not lymph radicles or "lymph capillaries" as is commonly done, but to 
consider them tissue spaces from which the transudates of varying composition are 
gathered into the lymph-vessels. But the larger lymph-vessels we find the seat of 
various more or less independent lesions. 
LYMPHANGIECTASIS. 
Dilatation of the lymph-vessels occurs under a variety of conditions. 
It may be congenital, or it may be due to some hindrance to the flow of 
lymph onward-as by pressure from any cause, or from the occlusion of 
the vessels by inflammation. If the dilated vessels form a circumscribed 
mass, this is often called a lymphangioma (Fig. 240). In certain forms 
of elephantiasis and in macroglossia the dilatation of the lymph-vessels is 
an important factor. Its occurrence is not infrequent in the labia, pre- 
puce, and scrotum. Dilatation of the chyle vessels may occur in the 
mucous membrane of the intestine and in the mesentery. Filarial lym- 
phatic varix is of occasional occurrence.2 
Obstruction of the thoracic duct may be due to tumors,3 or enlarged 
lymph-nodes, or inflammatory processes in the mediastinum; to aneu- 
rism, to thrombosis of the left innominate vein, to insufficiency of the 
tricuspid valve; or to inflammatory processes in the wall of the duct. It 
may occur under various other conditions. It may be compensated by 
collateral lymphatic anastomoses, or it may lead to various lymph- 
angiectasiae and to transudation of lymph. Thus chylous ascites may 
occur. 
Congenital doubling or division and other abnormalities of the tho- 
racic duct are recorded.4 
LYMPHORRHAGIA. 
If through injury, necrosis, or other pathological process, the walls 
of the lymph channels suffer solution of continuity the lymph may escape 
into surrounding tissues or spaces. Thus upon the surface of the skin 
or into loose connective-tissue spaces or into the great body cavities, 
lymph may be poured out. A chylous hydrothorax or chylous ascites 
may occur from a rupture of the thoracic duct or its radicles. 
THROMBOSIS. 
Thrombi may form in the lymph-vessels by the coagulation of the 
lymph or by the deposition of fibrin on the walls of the vessels at the seat 
1 Adler andMeltzer, Jour. Exp. Med., vol. i., p. 482, 1896. 
2 See Opie, "Filarial Lymphatic Varix," Trans. Assn. Am. Phys., vol. xvi., p. 331, 1901. 
3 For bibliography of carcinoma involving the thoracic duct see A. H. Smith, Med. Record, vol. Ivi., 
p. 813, 1899. 
4 Butler, Jour. Med. Res., vol. x., p. 153, 1903, bibl. THE CIRCULATORY SYSTEM 
577 
of degeneration or inflammation. These lymph thrombi are formed 
largely of fibrin and leucocytes. Such thrombi may cause disturbances 
of the lymph circulation or portions of them may become detached, form- 
ing emboli.1 
Acute Infective Lymphangitis.-Inflammation of the larger lymph- 
vessels is usually secondary and often connected with an infected wound 
or injury. Owing to the entrance into the lymph trunk of bacteria or 
other infectious agents, poison of venomous reptiles, insects, etc., the 
vessels, sometimes for a considerable distance away from the wound, 
become red, tender, and painful. Under these conditions the appear- 
ances which the vessels present vary. In some cases the redness dis- 
appears after death and we find no appreciable alteration. In other 
cases, the walls of the lymph-vessels are more or less densely infiltrated 
with pus cells, there is proliferation of the endothelium, and the lumen 
may contain variable quantities of pus and fibrin and desquamated 
degenerated endothelium. The vessel may be occluded by a thrombus. 
The tissue about the vessels may also be infiltrated with serum and pus. 
These lesions may undergo resolution and the vessel be restored to its 
normal condition; or the vessel wall and surrounding tissue may die or 
become involved in abscess; or new connective tissue may form in and 
about the vessel, sometimes with obliteration of its lumen. The asso- 
ciated lymph-nodes may participate in the inflammatory process. 
Tuberculous Lymphangitis.-Tuberculous inflammation occurs both 
in large and small lymph-vessels. Miliary tubercles and diffuse tubercle 
tissue may form in the walls and project into the lumen of the larger 
trunks; or in the smaller vessels the new growth may entirely fill the 
lumen, and grow within it, with more or less involvement of the walls. 
This may occur independently, but it is most frequently seen in connec- 
tion with tuberculous inflammation of adjacent tissues. Thus from 
tuberculous lymph-nodes in the vicinity of the thoracic duct there may 
be a direct extension of the tuberculous inflammation, an involvement 
of the walls of the duct, and a growth of tubercle tissue into its lumen. 
Such growths in the thoracic duct have been shown by Weigert to occur 
in acute general miliary tuberculosis (see p. 252). In the vicinity of 
tuberculous ulcers in the intestines, furthermore, we often see the sub- 
serous lymph-vessels, which pass from the vicinity of the ulcers, distended 
with the products of tuberculous inflammation and looking like dense 
white knobbed cords (Fig. 435). 
Syphilitic lymphangitis not infrequently occurs in the vicinity of 
syphilitic ulcers in the primary stage. In later stages there may be 
thickening of the walls of the vessels and the development of gummy 
tumors in and about them. 
INFLAMMATION. (Lymphangitis.) 
TUMORS. 
The relation of the endothelium of the lymph-vessels and spaces to 
endotheliomata has been already mentioned in the section on Tumors. 
1 Opie, Jour. Med. Research, 1913, N. S. xxiv, 131. 578 
THE CIRCULATORY SYSTEM 
The dissemination of malignant tumors through the lymph channels 
is of frequent occurrence, and is particularly marked in the case of 
carcinoma. In the vicinity of carcinomata the lymph-vessels are not 
infrequently crowded with the tumor cells, forming white, irregular 
cords; or small masses of the tumor cells may be found in the lymph- 
vessels, either near to or remote from the tumor. White, irregular 
networks are often formed in this way beneath the pleura in carcinoma of 
the lung, or beneath the capsule of the liver. Transverse sections of 
lymph-vessels thus distended show sometimes swelling and detachment 
of the endothelium and a crowding of the lumen with tumor cells. CHAPTER VI. 
THE RESPIRATORY SYSTEM.1 
The Nose and its Associated Cavities. 
The mucous membrane lining the nose under normal conditions cleanses from dust 
the air which impinges upon and sweeps across it in respiration. It is in this way- 
exposed to various deleterious agencies. It is subject also to such sudden changes of 
temperature as may involve great and abrupt alterations in the condition of its 
blood-vessels. 
MALFORMATIONS. 
Absence or deformity of the nose or some of its parts, deviations of 
the septum, clefts, usually associated with cleft palate and harelip (Figs. 
175 and 176), are among the more frequent of the congenital anomalies 
of the nose. 
HAEMORRHAGE. (Epistaxis.) 
This may result from injury; it may be an expression of local or 
general hyperemia from cardiac or vascular lesions, obstruction of 
vessels, etc. It not infrequently occurs 
in an early stage of acute infections, 
such as typhoid fever. It may accom- 
pany general conditions such as haemo- 
philia, pernicious anaemia, etc. Epis- 
taxis may result from lesions of the 
nasal mucous membranes, ulcers, telan- 
giectasis, etc. 
Acute catarrhal inflammation is com- 
mon and often associated with a similar 
process in the pharynx and larynx. 
There is at first a hyperaemic swelling 
followed by an increased production of 
mucus and transudation of serum from 
the blood-vessels; emigration of leuco- 
cytes and desquamation of epithelium 
may follow. This and other inflamma- 
tory processes may extend to the fron- 
tal sinuses and the antrum, where the 
INFLAMMATION. (Rhinitis.) 
Fig. 358.-Catabbhal Inflamma- 
tion OF THE Mucous MeMBBANE OF 
the Antbum. 
Showing migration of leucocytes 
through the epithelium. 
1 For general considerations relating to the lungs see p. 593. 
579 580 
THE RESPIRATORY SYSTEM 
exudates may collect (Fig. 358). As the process resolves, the exudation 
ceases, the epithelium regenerates, and the mucosa is restored to its 
normal condition.1 
Pseudo-membranous inflammation, either simple or diphtheritic, 
may involve the nasal cavities. Phlegmonous inflammation involving 
adjacent parts is of occasional occurrence. Bacteria apparently play 
an important part as excitants of acute catarrhal and pseudo-membranous 
inflammation.2 
Fig. 359.-Mucous Polyp of the Nose. 
Chronic catarrhal inflammation may follow the acute form, and is 
marked by hyperplasia of the fibrous tissue in the submucosa, often 
followed by atrophy of the mucosa. Ulceration of the mucosa may 
occur; the exudate may assume a fetid character. A hyperplasia of the 
mucosa may lead to the formation of the so-called mucous polyps3 (Figs. 
359 and 360). These often contain hyperplastic mucous glands and 
they are often cedematous. 
Tuberculous and syphilitic inflammation with the usual morpholog- 
ical characters of these processes are common in the nasal cavities. 
1 For a study of the pollen of plants as excitants of hay fever see Liefmann, Zeits. f. Hyg., etc., 
Bd. xlvii., p. 153, 1904, and for resume with Dunbar serum.treatment see Glegg, Jour, of Hyg., vol. 
iv., p. 369, 1904. 
2 For a study of the bacteriology of nasal inflammation see Howard and Ingersoll, Am. Jour.Med.Sci., 
vol. cxv., p. 520, 1898. See also for bacteria of the nose, Neumann, Zeits. f. Hyg., etc., Bd. xl., p. 33, 
also Hasslauer, Cbl. f. Bak., I. Abt. Ref., Bd. xxxvii., p. 1, bibl., 1906. For a study of the lymph- 
vessels of the nose and pharynx see Most, Arch. f. Anat. u. Phys., 1901, p. 75. 
3 For a summary of facts concerning the nature' of the ordinary nasal polyps see Wright, Med. 
Record, vol. lix., p. 132, 1901, bibl. THE RESPIRATORY SYSTEM 
581 
TUMORS. 
Aside from the nasal polyps which may be adenomatous in character, 
the most common tumors are epithelioma and sarcoma. 
Dermoid cysts have been described. 
Adenoids.-In children, especially when ill-nourished, there is often 
a hyperplasia of the lymphoid tissue of the posterior pharyngeal region. 
This is often associated with nasal or pharyngeal catarrh. These new 
Showing branching cells with loose delicate stroma containing much fluid. 
Fig. 360.-Mucous Polyp of the Nose. 
growths form irregular projections or lobular masses (Figs. 359 and 360), 
often blocking the naso-pharyngeal passage. These hyperplasise are 
covered with squamous or columnar epithelium. They are called 
"adenoids." Some of these growths are tuberculous; others, without 
obvious morphological tubercles, contain tubercle bacilli.1 
The Pharynx. 
The lesions of the pharynx similar to those just described as involving 
the nasal cavities are reviewed on p. 647. 
The Larynx and Trachea. 
Malformations. 
The larynx and trachea may be absent. The larynx may be abnormally large or 
small; the epiglottis also may be too large or too small, or may be cleft. There may 
be communications between the trachea and the oesophagus, and then the pharynx 
generally ends in a cul-de-sac, and the oesophagus opens into the trachea. There may 
1 Lartigau and Nicoll, Amer. Jour. Med. Sci., vol. cxxiii., p. 1031, 1902. 582 
THE RESPIRATORY SYSTEM 
be imperfect closure of the original branchial arches, so that there are fissures in the 
skin leading into fistula; which open into the pharynx or trachea. The fissure in the 
skin is small and is situated about an inch above the sterno-clavicular articulation, 
usually on one or both sides, more rarely in the middle line. Individual cartilages, as 
the epiglottis, or one or more rings of the trachea, may be absent, or there may be 
supernumerary rings. The trachea may divide into three main bronchi instead of 
two, and in that case two bronchi are given off to the right lung and one to the left. 
The trachea may be on the left side of the oesophagus or behind it. 
HAEMORRHAGE. 
In trauma and acute inflammatory processes, in syphilis and tubercu- 
losis, and when tumors are present, especially carcinoma and some forms 
of vascular papilloma, there may be haemorrhage from the larynx. 
It may occur also under the general favoring conditions, such as haemo- 
philia, scurvy and various abnormal conditions of the circulation leading 
to local or general hyperaemia.1 
(EDEMA OF THE GLOTTIS. 
This is a condition in which there is an accumulation of serous fluid 
in the submucosa of the upper part of the larynx. This may be due to 
simple circulatory disturbances, local or general, or it may be inflamma- 
tory in character. The greatest accumulation of fluid is in places in 
which the submucous tissue is abundant and loose in texture, as in the 
posterior wall of the epiglottis, in the ary-epiglottidean folds, and in the 
false vocal cords. The swelling of these parts may be so great as to 
occlude the air passage. After death the oedematous swelling may 
largely disappear, but the mucous membrane may be left unusually 
wrinkled and flabby. 
(Edema of the glottis is comparatively infrequent in association with 
such heart, kidney, and lung lesions as lead to general oedema. It is, on 
the contrary, frequent in connection with various forms of laryngeal 
inflammation. It may occur in drunkards or others who are poisoned 
and fall asleep in a sitting posture so that the head drops sharply forward 
with constriction of the neck. Under these conditions the individual 
may die from asphyxia with no obvious lesion accounting for it other 
than the oedema of the glottis. 
INFLAMMATION. (Laryngitis.) 
Acute Catarrhal Laryngitis.-This occurs as an independent process 
in common "colds." It may be a complication of the infectious dis- 
eases, or may be induced by the inhalation of irritating vapors and of 
hot steam and smoke. The inflammation varies in its intensity in dif- 
ferent cases. The mucous membrane is at first congested, swollen, and 
dry; then the mucous glands become more active and an increased quan- 
tity of mucus is formed. There is desquamation of the superficial 
1 For a study of haemorrhage of the larynx see Rhodes, Jour. Amer. Med. Assn., vol. xliii., p. 1284, 
1904. THE RESPIRATORY SYSTEM 
583 
epithelial cells, while through emigration leucocytes may infiltrate the 
submucosa, and together with mucus and desquamated epithelium form 
the exudate. There may be oedema of the glottis. All of these lesions 
may disappear with complete restoration of the mucous membrane. 
After death the congestion of the mucous membrane marking an 
acute form of the disease frequently disappears altogether. 
Chronic Catarrhal Laryngitis.-;This may follow repeated attacks of 
acute inflammation or be the result of the persistent inhalation of harm- 
ful substances. It may accompany chronic hyperaemia from cardiac 
or vascular lesions. It may be associated with syphilis and tuberculosis. 
The surface of the mucous membrane is dry or coated with muco-pus. 
The epithelium is thickened in some places, thinned in others, or in 
places entirely destroyed. The submucosa may be infiltrated with cells, 
Fig. 361.-Localized Hyperplasia of the Epithelium and Submucous Connective Tissue of 
the False Vocal Cords. 
The section shows a portion of a small rough wart-like or papillary growth. 
diffusely thickened, or form little papillary outgrowths; it may be 
thinned, or necrotic and ulcerated. 
The mucous glands may be swollen and prominent. The inflamma- 
tion may extend to the perichondrium of the cartilages, which may 
become necrotic. In chronic laryngitis there may be a more or less 
diffuse thickening of the epithelium, often associated with a hyperplasia 
of the submucous tissue. This is called pachydermia diffusa. A sim- 
ilar process, if localized, may lead to larger and smaller wart-like excres- 
cences-pachydermia verrucosa (Fig. 361). 
Pseudo-membranous Laryngitis (Croupous Laryngitis).-This occurs 
most frequently as the characteristic local lesion in diphtheria, of which 
the Bacillus diphtherias is the excitant (see p. 282). It may, however, 
be incited by the Streptococcus pyogenes and other bacteria, and not 
infrequently accompanies other infectious diseases, scarlatina, typhoid 
fever, and the exanthemata (see p. 303). The false membrane may 
be continuous with a similar structure in the pharynx, and it may extend 
down into the bronchi (Fig. 362). 584 
THE RESPIRATORY SYSTEM 
Phlegmonous Laryngitis.-Suppurative inflammation involving the 
mucosa and submucosa is usually secondary to catarrhal, croupous, 
tuberculous, or syphilitic laryngitis; or it may be associated with pyaemia, 
erysipelas, smallpox, or typhoid fever. It may follow mechanical 
injury from a foreign body. It is 
not uncommon on the posterior sur- 
face of the epiglottis or in the ary- 
epiglottidean folds, and may be as- 
sociated with oedema of the glottis. 
Abscesses may form which rupture 
into the larynx, or they may ex- 
tend into the neck or the pharynx 
or oesophagus. 
Tuberculous Laryngitis.-This 
lesion is most frequently associated 
with pulmonary tuberculosis. Early 
in the process there is a formation 
in the submucosa of miliary tuber- 
cles together with more or less new 
small-celled tissue; with this is a 
catarrhal inflammation with an exu- 
date* of mucus, pus cells, and des- 
quamated epithelium. 
As coagulation necrosis of the 
subepithelial tubercles occurs, ulcers 
are formed, often with an increase 
of the catarrhal exudate. The proc- 
ess may extend so as to involve the 
walls of the larynx, and necrosis of 
the cartilages may follow. Adjacent 
ulcers may become confluent so 
that considerable areas of the mu- 
cous membrane may be destroyed 
(Fig. 363). 
Syphilitic Laryngitis.-This form 
of inflammation may have the ordi- 
nary characters of an acute or chronic 
catarrhal inflammation, or it is pro- 
ductive in character with the forma- 
tion of new tissue in the stroma of 
the mucous membrane. This new 
tissue is principally composed of 
small cells, which often degenerate 
and become necrotic. In this way the mucous membrane of the larynx 
and the tissues beneath are thickened in some places and destroyed in 
others, giving rise to erosions and ulcers. These changes are especially 
marked in the upper portion of the larynx. If the perichondrium be 
involved there may be necrosis of the laryngeal cartilages. Owing to 
Fig. 362.-Diphtheria of the Larynx and 
Trachea. 
The membrane extends from the epiglottis 
down to the bifurcation of the trachea. THE RESPIRATORY SYSTEM 
585 
the cicatricial contractions of healed syphilitic ulcers there may be 
great deformity of the larynx. 
Lesions of the trachea are often associated with those of the larynx 
and are in general similar in character. 
TUMORS OF THE LARYNX AND TRACHEA. 
Retention cysts of the mucous glands of the larynx may form sacs 
projecting into its cavity. 
Papilloma, single or multiple, is the most common form of benign 
tumor of the larynx (Fig. 364). It is most frequent upon the vocal cords 
and is usually associated with chronic inflammation. Adenoma, fibroma, 
lipoma, myxoma, and angioma occasionally occur. Chondromata 
The posterior surface of the epiglottis and the adjacent tissue are involved in tuberculous ulcers. 
Fig. 363.-Tuberculous Laryngitis. 
grow from the normal cartilages and are usually multiple and sessile. 
They may project into the cavity of the larynx. 
Fusiform or spheroidal-celled sarcomata of the larynx have been seen 
in a considerable number of cases, both in children and in adults. 
Carcinomata, usually the epitheliomatous type, may originate in the 
larynx, most commonly upon the false vocal cords. But from adjacent 
structures, usually from the oesophagus, cancer may invade the larynx. 
In the trachea tumors are of rare occurrence, but occasional examples 
of growths similar to those in the larynx have been found. Tuberculous 586 
THE RESPIRATORY SYSTEM 
and otherwise altered bronchial lymph-nodes may by ulcerative processes 
enter and obstruct the trachea. 
Single or multiple amyloid masses, often associated with cartilage, 
have been described in the larynx and trachea.1 
The Bronchi and Lungs. 
The Bronchi. 
HEMORRHAGE. 
In haemorrhage from the bronchi the source of the blood is often to 
be sought in the parenchyma of the lung (see p. 595) or in a ruptured 
aneurism. But haemorrhage from the bronchial walls may occur in 
tuberculous or other forms of 
ulceration, chronic bronchitis, ma- 
lignant tumors, etc. 
INFLAMMATION. (Bronchitis.) 
Acute Catarrhal Bronchitis.- 
This is frequently associated with 
a similar process in the trachea. 
It is characterized by hyperemia 
and swelling of the mucous mem- 
brane, with the formation of 
exudate, which usually consists 
largely of mucus formed by the 
hypersecretion of the mucous 
glands or degeneration of the 
epithelial cells. Mingled with this 
are exfoliated and more or less 
degenerated epithelium from the 
mucous membrane, leucocytes 
from the dilated vessels of the 
submucosa, varying numbers of 
red blood cells, and bacteria. 
The microscopic appearances 
differ in different parts of the 
bronchial tubes in accordance 
with the differences in struc- 
ture. Mucous glands, when these 
are present, may reveal great 
functional activity, and their 
ducts may be distended with mucus which, often mingled with exfoliated 
and degenerated cells, streams out upon the surface. Swelling and 
proliferation of the connective-tissue cells and endothelium of the vessels 
of the submucosa, oedema, and emigration from the dilated vessels are 
The left vocal cord is involved in the tabulated 
growth, A tracheotomy opening is seen below the 
tumor. 
Fig. 364.-Papilloma of the Larynx. 
1 See Manasse, Virch. Arch. Bd. clix., p. 117, 1900. THE RESPIRATORY SYSTEM 
587 
often marked. The leucocytes may be seen making their way through 
the epithelium into the other exudates upon the surface. The epithelium 
may be loosened, single or clustered cells falling off here and there, or 
shreds of cells may exfoliate together (see Fig. 365).1 The deeper sphe- 
roidal epithelia, the so-called mother cells from which the new ciliated 
cells on the surface are formed in both physiological and pathological 
regeneration, usually remain in place upon the basal membrane. In the 
small bronchi whose walls are thin, little else may be seen than an irreg- 
ular exfoliation of the epithelium. On the other hand, the smaller 
bronchi may be much involved and their lumina filled with exudate; 
when this, which has been called "capillary bronchitis," occurs, the 
inflammatory process usually involves the adjacent and associated terri- 
tories of lung tissue, constituting one of the important forms of broncho- 
This section of a small portion of the bronchial wall shows considerable exfoliation of the epithe- 
lium, but many of the deeper so-called "mother cells" remain in place. There are swelling of the 
connective-tissue cells and congestion of blood-vessels in the submucosa, with oedema and emigration 
of leucocytes. Some of the leucocytes are passing through the epithelium to mingle with the mucous 
exudate and exfoliated cells in the lumen of the bronchus. Some of the ciliated cells show the "beaker" 
shape with a homogeneous interior indicating the production of mucus within them. 
Fig. 365.-Acute Catarrhal Bronchitis. 
pneumonia. In some forms of bronchitis the exudate may consist 
largely of pus-"purulent bronchitis." 
Atelectasis of corresponding tracts of the lung may follow the occlu- 
sion of the bronchi with exudate. As recovery advances, the submucosa 
assumes its normal thickness and character and the epithelium is regener- 
ated from the cells of the deeper layers. 
Various forms of bacteria may be associated with acute bronchitis, and 
are presumably the excitants under favorable conditions of the lesions; 
the etiological relationship has, however, not yet been experimentally 
established. The most common forms of bacteria are Streptococcus 
1 For a study of physiology and pathology of ciliated epithelium of the respiratory organs see 
Lommel, Deutsch. Arch. Klin. Med., xciv., 365, 1908. 588 
THE RESPIRATORY SYSTEM 
pyogenes, the pneumococcus, Staphylococcus aureus, and the influenza 
bacillus.1 
Chronic Catarrhal Bronchitis.-This form of bronchitis may be the 
sequel of one or more attacks, of acute bronchitis. More frequently it is 
associated with emphysema, heart disease, interstitial pneumonia, 
phthisis, pleuritic adhesions, or the inhalation of irritating substances. 
There is in most cases a constant production of mucus, pus, and serum 
in considerable quantities, and these inflammatory products may have a 
very foul odor. Less frequently these products are very scanty-dry 
catarrh. The epithelium is deformed and desquamating, with a pro- 
duction of new cells in the deeper layers. There may be epithelial 
Fig. 366.-Chronic Bronchitis with Moderate Bronchiectasia. 
This transverse section of a portion of the wall of a dilated bronchus shows atrophy of the epithe- 
lium; fibrous hyperplasia of the submucosa with the formation of longitudinal ridges on the interior 
of the tube (cut across in this section); thickening of the wall of the bronchus and atrophy of the mucous 
glands. 
hyperplasia or atrophy; the mucous glands are large or atrophied; there 
may be hyperplasia or atrophy of the submucosa; the muscularis may 
show hypertrophy or atrophy. These changes in the fibrous and mus- 
cular elements of the walls lead to the so-called " trabeculation " of their 
inner surfaces (Fig. 366). Obliterating arteritis of the associated vessels 
may occur. These changes in the walls of the bronchi may lead to 
bronchiectasia. 
Acute Pseudo-membranous Bronchitis-Croupous Bronchitis-may 
occur with croupous laryngitis, as a lesion of diphtheria, with lobular 
pneumonia, and sometimes without these associations. The bronchi 
are lined or filled with a mass of fibrin, pus, and desquamated epithelium. 
Fibrin and pus may also be found beneath the epithelium and infiltrated 
in the stroma. 
1 For a study of the bacteria found in bronchitis see Ritchie, Jour. Path, and Bact., vol. vii., p. 
1, 1901; also Karcher, Deut. Arch, f klin. Med., Bd. Ixxxiii., p. 244, 1905; also reference to bacteria in 
lungs p. 614. THE RESPIRATORY SYSTEM 
589 
Chronic Fibrinous Bronchitis is attended with the formation in one or 
more bronchi of masses of fibrin which are expectorated by the patient 
in the form of branching casts of the bronchi (Fig. 367). After death 
the bronchi are said to be but little altered from the normal.1 
Curschmann has described under the name 11 bronchiolitis exudativa" 
a form of bronchitis in which small threads and bands of gray or yellow, 
partly transparent, coagulated material are formed in the small bronchi 
-"Curschmann's spirals." These sometimes occur in pneumonia. In 
different forms of bronchitis, especially in those associated with asthma. 
Fig. 367.-Chronic Fibrinous Bronchitis. 
Fibrinous casts of the bronchi, similar to those shown in the photograph, were coughed up at irregular 
intervals for several years. 
the exudation may contain numerous octahedral bodies-Charcot-Ley- 
den crystals-and also a very large number of eosinophile cells. 
Tuberculous Inflammation of the bronchi frequently occurs in con- 
nection with pulmonary tuberculosis. The lesion may be miliary or 
larger involvement of the walls may lead to ulceration. 
Syphilitic Inflammation may lead to ulcers and to distortions and 
stenosis through cicatrization. 
BRONCHIECTASIA. 
Dilatations of the bronchi may be cylindrical, fusiform, or sacculated. 
The sacculated dilatations are usually the largest. These communicate 
with one side of the bronchus. The peripheral portion of the bronchus 
may be obliterated; the bronchus leading to the cavity may be of normal 
size, or dilated, or stenosed, or even completely obliterated. Such sac- 
culated dilatations may reach a very large size and may communicate 
with each other. Dilatations are apt to occur under conditions which 
interfere with the integrity of the bronchial wall. 
1 For a resume and bibliography see Bettmann, Am. Jour. Med. Sei., vol. cxxiii., 1902, p. 304. 590 
THE RESPIRATORY SYSTEM 
In acute general bronchitis and broncho-pneumonia in children, 
cylindrical dilatation of a number of the medium-sized bronchi often 
occurs. 
In the persistent broncho-pneumonia of children such dilatations may 
reach a still greater development.1 Chronic bronchitis may lead to cylin- 
drical or sacculated dilatations, sometimes of great size. 
Occlusion of some of the bronchi, consolidation of portions of the 
lung, and extensive pleuritic adhesions may also lead to bronchiectasia 
(Fig. 368). 
The walls of bronchiectatic cavities may be lined with mucous mem- 
brane, which, however, is apt to undergo various changes as the process 
Portion of anterior free border of lungs. From an adult after unresolved lobar pneumonia. 
Fig. 368.-Multiple Bronchiectasije with Interstitial Pneumonia. 
advances. Thus the subepithelial layer may be vascular and cellular and 
thrown into folds, or it may be thin and dense. The epithelium is often 
irregular, sometimes irregularly thickened, sometimes thin, or it may be 
largely absent. The glands, muscle, and cartilages of the walls of the 
bronchi may disappear through atrophy. The presence of certain forms 
of bacteria in the exudate in bronchiectasia may lead to offensive putre- 
factive process and even to gangrene. Moulds may be present. 
In acute and chronic phthisis the tuberculous inflammation of the 
1 For a study of bronchiectasia in children see Lapin, Arch. f. Kinderheilkunde, Bd. xxxvii., 1903, 
p. 406. THE RESPIRATORY SYSTEM 
591 
walls of the bronchi often gives rise to sacculated dilatations, which 
expand with time and become still larger by the destruction of the adja- 
cent lung tissue-tuberculous bronchiectasiae. 
TUMORS. 
Primary tumors of the bronchi are rare. Lipoma, chondroma, and 
fibroma have been observed. Sarcoma is rare, but may occur, especially 
Fig. 369.-Primary Adenoma of the Bronchi. 
in spheroidal-cell forms, or as an extension of similar growths in the 
mediastinum. Adenoma (Fig. 369) and primary carcinoma are rare.1 
Fig. 370.-Lung Stones. {From a case of Tuberculous Bronchitis.) 
These calcified masses were found in the dilated bronchi. 
Secondary carcinoma is not uncommon and may also involve the 
trachea or the lungs. 
Occlusion of bronchi, partial or complete, may occur from tumors, 
1 See Weller, Arch. Int. Med., 1913, xi, 314, bibl. 592 
THE RESPIRATORY SYSTEM 
polypi, metazoan parasites, foreign bodies, exudates, etc., or through 
obstructive lesions in the walls. 
Calcified masses called "lung stones" (Fig. 370) may be found in the 
bronchi. 
LESIONS OF THE TRACHEAL AND BRONCHIAL LYMPH-NODES. 
The tracheal and bronchial lymph-nodes may be the seat of a variety 
of lesions which, owing to their situation, as well as for other reasons, 
are of considerable practical impor- 
tance. They may be enlarged from 
hyperplasia in acute infectious dis- 
eases; by the development in them 
of tumors; in leukaemia and with es- 
pecial frequency in tuberculosis (Plate 
HI.). They may become pigmented 
from inhaled coal or other dust and 
may atrophy or become fibrous or 
calcified.1 In cheesy degeneration 
following tuberculosis (Fig. 371), or in 
suppurative inflammation, perfora- 
tion may take place into the air pas- 
sages, the oesophagus, the pulmonary 
blood-vessels, or aorta, or into the 
pericardial or pleural cavities;2 in 
this way haemorrhage or secondary 
inflammatory processes or gangrene 
may occur. Death may occur from 
pressure upon the trachea by tumors 
of the adjacent lymph-nodes. Sud- 
den death from asphyxia may result 
from perforation into the trachea. 
Pressure upon the pulmonary veins 
may lead to pulmonary oedema. The 
bronchial lymph-nodes are very im- 
portant as distributing centres of 
infectious micro-organisms, and par- 
ticularly as points of lodgment of tubercle bacilli, which have been 
gathered from the pulmonary air spaces, from the pharynx or elsewhere.3 
Fig. 371.-Tuberculous and Caseous 
Bronchial Lymph-nodes. 
The nodes are much enlarged and press 
upon the larger bronchi. 
1 For the association of pigmentation and tuberculosis of the bronchial lymph-nodes and the 
pleura see p. 640. For a study of alleged intestinal origin of lung pigment, see Montgomery, Jour. Med. 
Res. xxiii, 111, 1910. 
2 See Sternberg, Wiener klin. Wochenschrift, 1905, p. 1214. 
3 Consult for summary of lesions of bronchial lymph-nodes Hall, Phila. Med. Jour., Dec. 1st, 
1900, bibl. See also concerning tuberculosis reference Northrup and Bovaird, p. 487, and Harbitz, 
Jour. Inf. Dis., vol. ii., p. 143, 1905. See also statistics of Hand, Phila. Path. Soc., vol. vi., p. 132, 1903. 
For an excellent resume concerning normal and pathological tracheal and bronchial lymph-nodes see 
Marfan in Bouchard and Brissaud's "Traite de Medecine," t. vii., p. 525; also Zuber in Grancher, 
Comby, and Marfan's "Traite des Maladies de 1'Enfance," t. iv., p. 235. For a study of the relation of 
the bronchial lymph-nodes to the lymph-vessels of the thorax see Weleminsky, Berl. klin. Woch., 1905, 
p. 743. For a study of the relationship of the cervical and bronchial lymph-nodes see Beitzke, Virch. 
Arch., Bd. clxxxiv., p. 1, 1906. THE RESPIRATORY SYSTEM 
593 
The Lungs. 
Malformations. 
One or both lungs may be wanting or only partially developed. One lung is some- 
times converted into a number of sacs formed of dilated bronchi, while the lung 
parenchyma is undeveloped. Supernumerary bronchi are recorded. 
The lobes may be subdivided by deep fissures, accessory lobes may be present, or 
an accessory lung may be present. An accessory lung in the abdominal cavity has 
been described.1 There may be, with absence of part of the wall of the thorax, hernia 
of the lung. There may be transposition of the lungs, with similar changes in the 
position of the heart and the abdominal viscera. 
INJURIES-PERFORATIONS. 
Severe contusions of the thorax may produce rupture of the lungs, 
with extravasations of blood into the pleural cavities. 
The lungs may be wounded by a fractured rib and by penetrating- 
weapons and projectiles. Such injuries often lead to bleeding into the 
lung tissue, followed by inflammatory changes. The lungs, however, 
exhibit a considerable degree of tolerance for such injuries. 
Collections of pus in the pleural cavities, the mediastinum, the liver, 
the spleen, the kidneys, and the peritoneal cavity may perforate the lungs. 
See also Hydro-pneumothorax. 
DISTURBANCES OF CIRCULATION. 
It is very useful to anticipate a study of the diseases of the lungs by an examina- 
tion of the circulation in the lung of a curarized frog on the Thoma frog-plate (see 
p. 111). In no other way can one gain so vivid a conception of the complexity and 
abundance of the circulatory mechanism. 
Anaemia.-The lungs may be anaemic in connection with a general 
anaemia of the body; or from compression of a part or a whole organ, as 
by pleural exudates, tumors, or new'-formed fibrous tissue; from occlu- 
sions of blood-vessels or in atrophy of these in emphysema. 
Hyperemia and (Edema. 
Hyperaemia may occur as the result of the inspiration of irritating 
gases; from the presence of toxic substances in the blood; in early phases 
of inflammation, or as the result of such an occlusion of vessels in one 
part as causes the accumulation of blood in another. 
On the other hand, hyperaemia of the lung is often due either to some 
hindrance to the exit of blood through the pulmonary vein, such as 
mitral stenosis or insufficiency, or to enfeeblement of the ventricular 
contractions, as in fatty degeneration of the heart muscle or interstitial 
myocarditis. In the last hours of life the feeble action of the heart dis- 
poses to pulmonary congestion. The position of the body upon the back 
in bed favors an accumulation of blood in the posterior portions of the 
1 Consult Vogel, Virch, Arch., Bd. civ., p. 235, 1899, bibl.; also Hammar, Ziegler's Beitr., Bd. 
xxxvi., p. 518, 1904. 594 
THE RESPIRATORY SYSTEM 
lungs-hypostatic congestion. Hyperaemic lungs are in varying degrees 
darker and heavier than normal; an unusual amount of blood flows from 
the cut surface. (Edematous fluid is often also present. Red blood 
cells often pass through the capillary walls in hyperamiia, and these with 
more or less exfoliated epithelium may be found in the air vesicles. 
Chronic Congestion.-In prolonged hypera*mia of the lungs, notably in 
connection with lesions of the mitral and aortic valve, or degeneration 
or dilatation of the left ventricle, the veins and capillaries, especially 
the capillaries, become permanently distended, pouched, and elongated, 
so that they often stretch in loops into the air spaces (Fig. 372). Red 
blood cells find their way from the contorted vessels by diapedesis or small 
haemorrhages into the air vesicles or interstitial tissue of the lung. Here 
Fig. 372.-Chronic Congestion of the Lung. (Brown Induration.) 
Showing dilated capillaries of the walls of the air vesicles and hjematogenous pigment in the 
exfoliated epithelial cells of the air vesicles. 
decomposition of the haemoglobin leaves brownish pigment particles 
which may remain free or be taken into cells. In the air vesicles the 
epithelial cells usually desquamate in considerable numbers, and take up 
the pigment in varying amount. This pigment gives to the lungs a pecu- 
liar brownish pink or salmon color. The appearance of these lungs may 
be modified by haemorrhagic infarctions, by pre-existing emphysema or 
oedema, or by exudative inflammation. Associated with these changes 
there is usually a new formation of fibrous tissue, so that the lung becomes 
indurated, leathery, and dry, and collapses less readily than normal. 
This condition is often called brown induration of the lung. This for- 
mation of fibrous tissue is analogous with that which occurs in other 
organs, such as the kidney and liver in chronic congestion. Emigration 
of leucocytes is not infrequently associated with diapedesis from the Pathology-Delafield and Prudden. 
Plate III. 
Tuberculous Bronchial Lymph-Nodes. 
The nodes are enlarged and caseous, with areas of commencing softening. An isolated 
tubercle in the lung tissue above the enlarged nodes indicates a local dispersion of the 
tubercle bacilli. The lung was hardened in alcohol. THE RESPIRATORY SYSTEM 
595 
dilated capillaries, and these, with the desquamated epithelium, may 
accumulate in the air vesicles. 
CEDEMA OF THE LUNGS. 
This condition is rarely independent, but is usually associated with 
other lesions of the circulatory or respiratory systems. It may be 
circumscribed or involve one or both lungs. The lungs in pronounced 
cedema do not collapse, as is usual on opening the thorax. They may 
appear translucent. Fluid runs or is readily squeezed from the cut 
surfaces. 
In cedema of the lungs the vesicles contain a clear, sometimes foamy 
albuminous fluid, occasionally tinged with blood, usually mixed with 
exfoliated vesical epithelium. Leucocytes and red blood cells may also 
be present. The oedematous fluid may be present in the bronchi and 
in the interstitial tissue of the lungs. (Edema is often associated with 
hyperaemia, and like this may vary in different parts of the lung. On 
the other hand, there may be extensive oedema without overfilled blood- 
vessels; these in excessive cedema may indeed be nearly empty and 
compressed. (Edema of the lungs may occur in general infections and 
intoxications, or in association with local inflammatory processes. 
It may be associated with cardiac and renal lesions. It may be a 
part of general dropsy or exist independently of this. It frequently 
occurs in the last hours of life-agonal oedema. (Edema of the lung may 
occur suddenly without the obvious inciting accompaniments above 
noted, and may be fatal. Fatal oedema of the lungs may be associated 
with fat embolism.1 
The studies of Welch2 show that with diminished force exerted by 
the left side of the heart, the vigor of the right remaining unimpaired, 
cedema of the lungs may follow.3 
HEMORRHAGE AND INFARCTIONS. 
Haemorrhage. 
Haemorrhages into the lung tissue and air spaces of the lungs may 
occur from trauma, from rupture of aneurism, in acute infectious dis- 
eases and intoxications, in scurvy and haematophilia, in asphyxia from 
brain lesions or other conditions, from tuberculous ulcerations involving 
the blood-vessels. Multiple ecchymoses may occur in fat embolism. 
Haemorrhage is of frequent occurrence in excessive hyperaemia of the 
lungs, notably in connection with mitral stenosis and insufficiency. 
Under these conditions the extravasation of blood may take place by 
diapedesis or by rhexis. The accumulations of blood may be single or 
1 See ref. fat embolism, foot-note, p. 34. 
2 Welch, Virchow's Archiv, Bd. Ixxii., p. 375; resume by Meltzer, Amer. Med., vol. viii., p. 391, 1904. 
3 For a study of cedema of the lungs based on numerous cases, see Coplin, Proc. Path. Soc. of 
Phila., vol. ix., p. 77, 1906; also Riesman, Am. Jour. Med. Sci., vol. cxxxiii., p. 88, 1906. For a study of 
the disturbances of circulation in the lungs under various abnormal conditions see Esser, Centralbl. f. 
ges. Med., Jan. 26th, 1901, bibl. 596 
THE RESPIRATORY SYSTEM 
multiple, localized or diffuse, dense and firm, or, when oedema is present, 
soft and fluid in character. During the last hours of life, owing to 
enfeeblement of the heart, extravasation of blood may occur which sinks 
to the posterior dependent portions of the lungs. 
Thrombosis, Embolism, Infarcts. 
As a result of thrombosis or embolism of the pulmonary artery, 
hemorrhagic infarcts may be formed. They are not very common in the 
lungs because the supply of blood is through both the pulmonary and 
bronchial arteries, so that even with stoppage of the pulmonary artery 
by a thrombus or embolus, haemorrhagic infarcts are not necessarily 
formed. When, however, the pulmonary circulation is faulty as in var- 
ious cardiac lesions, haemorrhagic infarcts are more apt to form as the 
result of embolism or thrombosis of the pulmonary artery. 
These infarcts are often multiple, usually circumscribed, and rounded 
or wedge-shaped, from the size of a walnut to that of an orange. They 
are of dark red color, hard and unaerated, with the air spaces distended, 
with blood, and are often surrounded by a zone of inflammatory exudate. 
They may be situated in any part of the lungs, but are most common 
in the lower lobes. At the apices of the infarcts, the occluding throm- 
bus or embolus may be discovered. When, as is usually the case, they 
are near the surface of the lungs, a circumscribed inflammation of the 
pleura often occurs. The air spaces within the infarcts are filled with 
blood and the capillaries distended. 
Such infarcts may be followed by death; they may become gan- 
grenous, or if the emboli or thrombi be not infectious, the blood may 
become absorbed, and, especially in the smaller forms which are more 
often due to embolism, they may be gradually changed into a smaller 
mass of pigmented fibrous tissue.1 
A large part of the lungs may be involved in haemorrhage due to 
thrombosis of large trunks of the pulmonary artery. Haemorrhagic 
infarctions from thrombosis or embolism are most frequent in lungs 
which are the seat of chronic congestion. The most common source of 
the emboli of the pulmonary artery is the right heart or peripheral 
thrombi.2 
ATELECTASIS. 
In atelectasis the walls of the air spaces lie together, either because 
they are collapsed or compressed, or because, as in congenital atelectasis, 
the lungs, or portions of them, have not been expanded in respiration. 
In foetal or congenital atelectasis defects in the respiratory mechanism, 
or blocking of the air passages, may be responsible for the unaerated 
condition which may affect only parts of a lung or a whole organ. The 
1 For a study of experimental infarction of lung see Karsner and Ash, Jour. Med. Research, 1912, N.S. 
xxii, 205. 
2 For a fuller consideration of embolism and thrombosis of the pulmonary artery consult Welch, 
in Allbutt's "System of Medicine," vol. vi., p. 261. THE RESPIRATORY SYSTEM 
597 
atelectatic portions of the lungs are dark red in color and of fleshy con- 
sistence.1 
Atelectasis may, on the other hand, be acquired, either in childhood 
or in adult life. In young children collapse of portions of the lung is 
of frequent occurrence, through occlusion of bronchi by inflammatory 
exudate. The region thus cut oft is gradually deprived of air, so that, 
as the blood continues to circulate, it is dark red and firm in texture. 
Compression atelectasis may be due to exudates, tumors, etc., in the pleu- 
ral cavities. Under these conditions the portion of lung involved may 
be paler than normal from the pressing out of the blood. In adults, 
Showing enlargement of the air spaces and thinning of their walls 
Fig. 373.-Vesiculak Emphysema. 
large or small portions of lung tissue may collapse from occlusion of 
a bronchus by exudate or stenosis, by paralysis of the vagus, or in long- 
continued feebleness of respiration. CEdema may be associated with 
collapse. 
Atelectasis may resolve by an early admission of air to the collapsed 
region. On the other hand, if prolonged, fibrous tissue may form and 
the involved portion may be finally converted into a cicatricial mass, 
sometimes containing bronchiectatic cavities. 
Vesicular Emphysema.-In forcible inspiration or expiration through 
obstruction of the air passages, in coughing, or in the use of wind instru- 
ments, or with consolidation or compression of portions of the lungs, the 
walls of the air spaces of the lungs may be more or less distended, either 
in circumscribed regions or over large areas of the lungs. This may 
EMPHYSEMA. 
1 Collapsed lungs, from their red color and fleshy consistence, are often spoken of as "camified." 598 
THE RESPIRATORY SYSTEM 
develop in a short time, and then the condition is designated acute 
emphysema. 
If the conditions which induce emphysema be persistent, as in chronic 
bronchitis with difficult respiration and coughing, atrophy of the walls 
of the air vesicles and alveolar passages may take place-chronic emphy- 
sema. The walls become thinner 
and are often perforated; adja- 
cent air spaces coalesce, so that 
larger and smaller irregular, thin- 
walled cavities are formed (Fig. 
373). Destruction of the capil- 
lary network of the atrophied 
walls occurs, and the lung may 
thus become pale and anaemic. 
As a rule, the distention of the 
air spaces is most marked along 
the anterior margins of the lungs, 
but it may be more general. 
Through the atrophy of the elas- 
tic tissue of the lungs, when the 
lesion is general and advanced, 
these organs do not collapse when 
the chest is opened. They ap- 
pear pale, are dry and soft, and 
pit on pressure by the finger. 
The microscopic picture is 
that of varying degrees of atro- 
phy; desquamation and fatty 
degeneration of the vesical epi- 
thelium are common. 
As already indicated, emphy- 
sema of the lungs is often asso- 
ciated with chronic bronchitis. 
With this may be more or less 
hyperplasia of the interstitial 
tissue. Dilatation or hypertro- 
phy of the wall of the right 
ventricle is common. Chronic 
endarteritis of the pulmonary 
vessels may be associated with 
emphysema. There may be chronic venous congestion of the ab- 
dominal viscera and dropsy. Delafield holds that the more essential 
lesion in some forms of emphysema is the development of new connective 
tissue with which dilatation of the air vesicles and atrophy of their 
walls are in varying degrees associated. 
In old age, atrophic processes in the lungs may be associated with 
Fig. 374.-Interlobular Emphysema of Lung. 
Child two months old. After whooping-cough.1 
1 For a fuller description of this unusual case see Northrup, Am. Jour. Med. Sci., vol. Ixxxvi., 1883, 
p. 147. THE RESPIRATORY SYSTEM 
599 
dilatation and mergence of the air spaces. This is called senile emphy- 
sema. Excessive emphysema, apparently congenital, may be present 
in young children (see Fig. 374). 
Interstitial Emphysema.-Rupture of the walls of the air spaces 
may permit the escape of air into the interstitial tissue of the lungs 
Fig. 375.-Interstitial Emphysema of the Lung of a Child. 
The irregular darker areas in the lower lobe indicate the air largely in the interlobular septa. 
(Fig. 375). Rupture of the pulmonary pleura may admit air into the 
mediastinum and thence into the tissues of the neck. Gas may form 
after death in the interstitial tissue of the lungs, from the presence of the 
Bacillus aerogenes capsulatus or other putrefactive bacteria. 
GANGRENE. 
Circumscribed gangrene occurs in the form of one or more rounded 
or irregular masses of variable size. The gangrenous portion of lung is 
at first brown and dry. The surrounding lung tissue is congested or 
cedematous, or infiltrated with blood, or inflamed. If the gangrenous 
focus is near the pleura, the latter will be coated with fibrin. Gradually 
the gangrenous portion of lung assumes a dirty green color and a putrid 
odor. It becomes soft, disintegrated, and separated from the surround- 600 
THE RESPIRATORY SYSTEM 
ing lung. The blood-vessels may be obliterated by thrombi, or eroded, 
so that there are profuse haemorrhages. 
Such a gangrenous process may extend to the adjacent lung tissue, or 
a zone of gray or red hepatization or of connective tissue may be formed. 
The fluid from the gangrenous lung may pass into the bronchi and be 
expectorated; or it may run from one bronchus into another and incite 
new gangrenous foci or diffuse gangrene. The pulmonary pleura may be 
perforated and a gangrenous pleurisy produced. Gangrene may follow 
lobar or broncho-pneumonia, especially such phases of the latter as result 
from the inspiration of foreign material containing micro-organisms from 
the mouth; it may arise from infectious emboli in the lungs, or by an 
extension of a gangrenous process from an adjacent part. It may be 
associated with oesophageal diverticula.1 
Diffuse gangrene may follow the circumscribed form; it may compli- 
cate lobar pneumonia or occur as an independent condition. A large 
part of a lobe or of an entire lung becomes greenish, putrid, and soft, 
and the pulmonary pleura is inflamed. There may be haemorrhages from 
eroded vessels. There may be general septicaemia. 
Various forms of bacteria may be present in gangrenous areas of 
the lungs. Among the more common are Streptococcus pyogenes, 
Staphylococcus pyogenes, pneumococcus, and various saprophytic 
micro-organisms.2 
INFLAMMATION. (Pneumonia, Pneumonitis.) 
General Considerations. 
Before commencing the study of inflammation of the lungs it is well to recall some 
of those features of structure and function which influence the local manifestations of 
disease in these organs and largely determine the special character of its lesions. In 
the first place, the lungs, like the gastro-intestinal canal, while in a topographic sense 
within the body, are still in open communication with the exterior, and are thus more 
directly exposed to various deleterious agencies than are those structures and organs 
wholly enclosed by living tissues. Notwithstanding this vulnerability of location, the 
recesses of the lungs are guarded by protective mechanisms of great efficiency. 
Since many of the lesions of the lungs, as we shall presently see, are induced by 
the entrance of foreign material into them in the form of dust, it will be useful here to 
glance at some of the ways in which the body is protected against the entrance of dust 
and the means by which it is disposed of when it does pass, as is frequently the case, 
even the most effective barriers. 
In normal breathing through the nose, the air impinging upon the moist surface of 
the tortuous passages loses a considerable part of its dust and bacteria. In the 
throat, larynx, and trachea, a similar clearing occurs, so that at the end of 
inspiration the air has been so far freed from its floating particles that it emerges in 
the expiration practically dust- and germ-free. 
If the nasal passages are not normal, or breathing through the mouth is practised, 
the air contaminations may pass more deeply into the recesses of the lungs, or may 
still remain to a certain extent suspended in the expired air. 
Many of the dust particles which may lodge upon the walls of the deeper air pas- 
sages are swept upward by the ceaseless ciliary movement and cast out, as are the 
secretions and dust accumulations from the nose and throat. The growth of many 
1 See reference to Starck, p. 652. 
2 See for "acid-proof" bacilli in gangrene, Ophuls, Jour. Med. Res., vol. viii., p. 242, 1902. THE RESPIRATORY SYSTEM 
601 
micro-organisms is inhibited by the mucus of the air-passages. Many inert dust 
particles which are taken into the tissues at the tonsils or in the deeper recesses of the 
air tubes are carried in the lymphatics to places of temporary or permanent deposit. 
Many micro-organisms within the tissues are destroyed by phagocytes or by the body 
fluids. 
Thus it is that although large numbers of dust particles may enter the respiratory 
passages at every breath, the larger proportion are usually safely disposed of, most of 
them through the secretions of the throat and nose. 
It has long been known that a certain number of inert dust particles from the in- 
spired air, in spite of the tortuous and narrow passages which they must pass in the 
deeper recesses of the lungs, do reach the air vesicles, from which they may be largely 
removed to the adjacent tissues or to the bronchial lymph-nodes by way of the pleural 
and other lymph-vessels. 
Whether living bacteria can reach the air vesicles under the ordinary conditions of 
respiration is a much discussed question, which has given rise to many painstaking 
researches. One group of workers has concluded that the lungs, except for the larger 
air passages, are usually germ-free. On the other hand, many have concluded from 
equally careful studies that the lungs of both men and animals often, if not always, 
contain a moderate number of living micro-organisms. The technical difficulties in 
this research are so great, and the conditions under which they have been undertaken 
are so various, that this difference of opinion is not surprising. 
Without attempting to marshal the evidence adduced on both sides of the question 
it appears that in most of the earlier studies on the artificial introduction of living 
micro-organisms into the lungs, the time which was allowed to elapse between the 
introduction of the germs and the examination of the lungs was too long, so that the 
possibility that the lungs might rapidly dispose of germs lodged in their deeper 
recesses by lysis or phagocytosis, was overlooked. 
In fact, it has been found that in experiments in which animals are exposed to an 
atmosphere laden with bacteria-containing dust or spray, if the animals be killed at 
once after the exposure, living micro-organisms may be found even in the deepest 
portions, while if even a short time be allowed to elapse they will have entirely 
disappeared. 
While, however, in the air passages and lungs we have a most efficient protective 
mechanism against the entrance and permanent lodgment under ordinary conditions 
of both inert dust particles and living micro-organisms in such situations as would 
involve serious damage to these delicate organs, it should be remembered that the 
efficiency of these safeguards may be greatly diminished if they are overworked and 
abused. 
The lungs of practically all persons who live indoors contain a considerable amount 
of soot, which blackens them (see p. 616). The irritation incited by this foreign stuff 
leads in most adults to some part of the lungs becoming dense and useless. The over- 
working of the delicate mechanism for filtering the foreign matter out of the lymph 
flowing from the lungs to the interior blood channels leads to serious damage of this 
mechanism and to an increased vulnerability to infection which the healthy body 
should and could resist. 
The responses of the lung tissue to the excitants of inflammation are not funda- 
mentally as distinct nor as variable as the common classifications of pneumonia would 
seem to indicate. Exudation from the smaller blood-vessels is one of the most com- 
mon features of the acute phases of pulmonary inflammation. 
The formation of exudates is favored by the extensive capillary network which is 
almost directly exposed to such deleterious agents as may gain access to the air spaces; 
while a great accumulation of exudates is possible owing to the spongy structure of the 
organs. The transitional character of the epithelium lining the air vesicles predis- 
poses to cell proliferation and exfoliation, and thus to the formation of exudate. On 
the other hand, the abundant blood and lymph channels 1 favor the speedy removal 
from the air spaces in the lungs of large quantities of exudate. 
There are two sets of lymph-vessels in the lung; first, those which accompany the 
1 See Miller, Arch. f. Anat, und Physiologic, Anat. Abth., 1900, p. 197, bibl. 602 
THE RESPIRATORY SYSTEM 
pulmonary artery and pour their lymph into the bronchial nodes at the hilum of the 
lung; second, those which ramify in the interacinous and interlobular tissue of the lung 
(Fig. 376) and join the branches of the pleural plexus between the lobules. It is 
evident from this arrangement of the pulmonary lymphatics that a close relationship 
is maintained between even the deeper recesses of the lung and the pleura.1 
Fig. 376.-Lung Showing Tubercles with Pigmentation in the Pleura. 
At the lower left-hand portion the lobules of the lung are outlined by the thickening of the 
walls of the lymph channels and of the interlobular septa. 
1 Note by Councilman, "The Lobule of the Lung and Its Relation to the Lymphatics," Boston 
Jour. Med. Sci., vol. iv., p. 165, 1900. For a study of the comparative histology of the lungs of 
domestic animals see Muller, Arch. f. Mik. Anat., Bd. Ixix., p. 1, 1906. THE RESPIRATORY SYSTEM 
603 
Along the subpleural lymph-vessels are numerous islets of lymphoid tissue and 
often a few small lymph-nodes.1 
While the abundant lymphatics of the lungs aid in the rapid disposal of exudates, 
they, on the other hand, favor the absorption of toxic substances into the body at 
large when bacteria, for example, are the excitants of the local inflammation. So that 
although exudative pneumonia is commonly considered a local disease, it is often 
rather a local expression of a general infection or is doubly significant on account of the 
associated toxaemia. In addition to the development and accumulation of exudates, 
necroses and the formation of fibrous tissue are the most noteworthy general pathologi- 
cal processes in the lungs. 
While the conspicuous differences in the various forms of pneumonia are largely 
due to differences in the nature, virulence, and distribution of their excitants, predis- 
posing factors dependent upon age, constitutional condition, and the protective 
mechanism of the lungs are of great significance. 
The common classifications are based partly upon etiology, partly upon morphol- 
ogy, and the names used suggest now the topography of the lesions or the character of 
the tissue which is especially affected, and again the species of the bacterial excitant. 
Thus the term lobar pneumonia is topographical; tuberculous pneumonia emphasizes 
the excitant; while interstitial pneumonia suggests the form of tissue involved.3 
Acute Lobar Pneumonia. (Fibrinous Pneumonia- 
Croupous Pneumonia.) 
This is an infectious disease incited by the Diplococcus pneumoniae 
(pneumococcus of Fraenkel).3 It is especially characterized by an exu- 
dative inflammation in which red and white blood cells, serum, and fibrin 
accumulate in the air spaces of the lungs, usually involving, especially in 
adults, the whole of one lobe or lung or portions of both lungs.4 Toxae- 
mia from the absorption of poisons formed locally in the lungs is an 
important and often most significant factor in the disease. The pneumo- 
coccus is usually widely disseminated in the blood. 
During the first hours of the inflammation the capillaries of the air 
spaces are congested, the lung is cedematous, firmer than normal, but 
not markedly consolidated. The air spaces contain varying numbers of 
leucocytes, red blood cells, serum, and fibrin (Fig. 377). The epithelial 
cells lining the air vesicles may be swollen, they sometimes proliferate, 
and are usually detached in considerable numbers. Catarrhal bronchitis 
and pleuritis may at this time develop. This is called the stage of " con- 
gestion" or " engorgement " and may last for a few hours or for several 
days. 
As the process continues, red blood cells, but especially polymor- 
phonuclear leucocytes, and fibrin accumulate in the air spaces and smaller 
1 See for a study of pleural lymph-nodes and lymphoid tissue Heller, Deut. Arch. f. klin. Med. 
Bd. lv„ p. 141, 1895. 
2 For a comprehensive resume of the normal and pathological physiology of the lungs see Heinz, 
" Handbuch d. exp. Path, und Pharmak.," 1905, Bd. 2. 
3 We shall use here as synonymous the names Diplococcus pneumoniae and pneumococcus; when 
pneumococcus is used the pneumococcus of Fraenkel is referred to. For a description of this organism 
see p. 218. 
4 The clinical course and the morphological characters of the inflammation of the lungs associated 
with the Diplococcus pneumoniae are so typical that we seem justified in limiting the term lobar or 
fibrinous pneumonia to this condition, even though inflammations of the lungs due to other excitants 
are occasionally lobar in extent and may have a fibrinous exudate, and though exceptionally the pneu- 
mococcus inflammation itself fails to reach lobar proportions. 604 
THE RESPIRATORY SYSTEM 
bronchi, so that the portion of lung involved becomes solid and friable, 
somewhat resembling the liver in color and consistence; hence the term 
This'single air vesicle shows congestion of the capillaries in the walls, and a small amount of exu- 
dates, fibrin, leucocytes, red blood cells, and exfoliated epithelium. 
Fig. 377.-Acute Lobar Pneumonia-Early Stage. 
11 red hepatization" which has been used to indicate this condition. The 
cut surface of the consolidated portion is dry and coarsely granular, 
the granules being plugs or casts of exudate in the air spaces. A light 
Fig. 378.-Acute Lobar Pneumonia-Stage of "Red and Gray Hepatization." 
The air vesicles are filled with exudate consisting largely of leucocytes, fibrin, and serum with a 
few epithelial cells. 
scraping of the cut surface of the lung with the knife readily removes 
these granules or plugs of exudate, which consist largely of fibrin and 
leucocytes with red blood cells and exfoliated epithelium (Fig. 378). The THE RESPIRATORY SYSTEM 
605 
relative amount of leucocytes, red blood cells, and fibrin in the air spaces 
varies greatly, sometimes one, sometimes the other, preponderating 
(Fig. 379). The fibrin fibrils often coalesce or swell, forming homogene- 
ous, irregular masses. On staining, large numbers of pneumococci may 
be found mingled with the other elements or within the cells of the 
exudate. While the general appearance of the lung in this stage is red, 
it is often mottled with gray and frequently is not uniformly solid. 
Although the capillary blood-vessels are compressed, they for the most 
part remain pervious; but thrombosis is not infrequent. Fibrinous 
pleuritis is commonly present, and the interstitial tissue of the lung, 
Fig. 379.-Acute Lobar Pneumonia. 
Showing fibrinous exudate stained by Weigert's method. 
while usually free from exudate, may be cedematous and contain a few 
leucocytes and some fibrin. 
The quantity of exudate in the lung is often very large. Hodenpyl 
has found it sometimes to be from three to four or even six pounds in 
weight. 
In the usual course of events the red blood cells now lose their haemo- 
globin, the exudate begins to soften, and the lung assumes a grayish 
color-gray hepatization or commencing resolution. The leucocytes and 
exfoliated epithelium undergo granular and fatty degeneration1 or necro- 
1 See on fatty degeneration of pneumonic exudates Christian, Jour. Med. Res., vol. x., p. 109, 
1903, bibl. 606 
THE RESPIRATORY SYSTEM 
sis, and these with the fibrin soften and disintegrate (Fig. 380). The cut 
surface of the lung is now moister, less granular, and is often covered 
with a grumous fluid. In view of the new studies on cytolysis it seems 
probable that here, as in the removal of alien and dead organic material 
elsewhere in the body, the exudate 
is softened and rendered capable 
of solution by an exaggeration of 
the normal autolytic processes (see 
p. 106).1 The softened exudate is 
gradually absorbed or may be in 
part expectorated. The involved 
portion of lung again contains air; 
the epithelium of the air spaces is 
regenerated. 
While it is customary and con- 
venient to describe definite stages 
of lobar inflammation of the lung- 
red and gray hepatization and reso- 
lution-these in fact not only merge 
gradually into each other, but often 
coexist in different parts of the lung. 
The process of reparation also 
usually occurs irregularly, so that a lung in resolution may show side by 
side in neighboring air spaces well-formed cellular and fibrinous exudate, 
degenerated exudate, and various phases of epithelial cell repair.2 
The nature of the characteristic crisis in pneumonia marked by a 
sudden fall in the temperature and improvement of the general symp- 
toms is not clear. It is not accompanied by obvious changes in the 
pulmonary exudate. Many studies have been made on this subject, 
upon which we cannot enter here.3 
For the evidence of communicability of the infectious agent in lobar 
pneumonia see page 219.4 
Associated Lesions in Other Organs.5-Fibrinous or sero-fibrinous pleu- 
ritis, usually with slight but often with voluminous exudate, commonly 
accompanies lobar pneumonia. Catarrhal and fibrinous bronchitis is also 
usually associated with the pneumonic process. Pericarditis and endo- 
carditis are not infrequent complications; meningitis occasionally occurs. 
The excitant of these complications is usually the pneumococcus.6 
Chromatolysis of the ganglion cells, albuminous degeneration in the 
Fig. 380.-Exudate from the Lung in 
Resolving Lobar Pneumonia. 
The cells show various phases of granular 
and fatty degeneration with fragmentation of 
the nuclei and disintegration of the cell bodies. 
1 For a study of the chemistry of resolution of the exudate see Simon, Deut. Arch. f. kl. Med., Bd. 
Ixx., 1901, p. 604. See also references to studies on autolysis, p. 107. 
2 For a study of the histology of acute lobar pneumonia with bibl. see Pratt, Contr. to Welch Anniv. 
Vol. 1900, p. 265, and Johns Hopkins Hosp. Rep., vol. ix. 
3 See for a study of the crisis Tchistovitch, Ann. Inst. Pasteur, t. xviii., p. 304, 1904, bibl.; also 
discussion of opinion p. 219. 
4 See for a general study of communicability Edsall and Ghriskey, Trans. Col. of Phys., Phila., vol. 
xxvi., p. 6, 1904. 
6 See for resumi of statistics of complications Kerr, Trans. Chicago Path. Soc., vol. v., 1903, p. 274. 
Also, for an analysis of four hundred and eighty-six cases, McCrae, Fyshe, and Ainley, Am. Med., vol. 
vii„ p. 135, 1904. 
6 For a study of pneumococci in the blood in pneumonia see Rosenow, Jour, of Infec. Dis., vol. i., 
1904, p. 280, bibl; also Dochez, Jour. Exper. Med., 1912, xvi, 680. THE RESPIRATORY SYSTEM 
607 
kidney, liver, and heart, hyperplasia of the bronchial lymph-nodes, 
together with leucocytosis, fever, and frequent serious enfeeblement of 
the heart action, are marks of toxaemia. The bronchial lymph-nodes may 
contain, especially in the perifollicular sinuses, and often within phago- 
cytes, red blood cells, cell detritus, and pneumococci brought from the 
lungs; fibrin is frequently also present. 
In lobar pneumonia in young children, in those enfeebled by acute 
and chronic disease, and in the aged, the lungs are often less uniformly 
consolidated and less dense and hard than in vigorous adults. When 
lobar pneumonia occurs in lungs already the seat of chronic lesions, such 
as chronic congestion, emphysema, interstitial pneumonia, or tuberculo- 
sis, the gross appearances of the organs may differ in various ways from 
those of uncomplicated pneumonia. 
While Diplococcus pneumoniae is the regular excitant of lobar pneu- 
monia, other bacteria-see below-are not infrequently associated with 
it, sometimes, though by no means always, leading to clinical complica- 
tions and to modifications of the appearance of the lesion. Predisposition 
of the individual is an uncommonly conspicuous and important factor 
in the etiology of this as other forms of pneumonia, so that, as is well 
known, exposure, fatigue, etc., may induce the favoring bodily condi- 
tions under which the pneumococcus becomes harmful. The experiments 
upon animals are most conclusive in demonstrating that intrapulmonary 
injections of pneumococcus cultures, which may be entirely without 
obvious effects in a healthy animal, may induce exudative inflammation 
or become quickly fatal after such exposure to cold or fatigue or injury, 
or to the action of drugs, as interferes with the integrity of the blood or 
locally damages the pulmonary tissues.1 
Delayed Resolution after Lobar Pneumonia ("Organizing Pneumonia"). 
-Instead of undergoing resolution, the fibrinous and cellular exudate 
in the air spaces in lobar pneumonia may persist, and by a process similar 
to that which is called organization of a thrombus (p. 27) may be 
gradually replaced by new vascular fibrous tissue. New connective- 
tissue cells grow out from the walls of the air spaces into the exudate; 
these cells become elongated. Intercellular fibrils develop, and long 
masses or bands of this new tissue, often containing blood-vessels, may 
extend for considerable distances through the air channels of the lung 
(Fig. 381). These may gradually coalesce with the wyalls, and together 
with an interstitial connective-tissue growth may lead to a fibrous con- 
solidation of the lung. 
Delafield describes such an intra-alveolar formation of connective 
tissue leading to fibrous induration of lobes of the lung and occurring as 
an independent lesion apart from the exudative form of lobar pneumonia. 
CONCURRENT INFECTION AND SUPPURATIVE INFLAMMATION OF THE 
Lung Following Lobar Pneumonia. 
Although, as stated above, Diplococcus pneumoniae usually occurs 
alone in typical lobar pneumonia, it may be accompanied by the Strepto- 
1 For reference to experimental excitation of pneumonia see p. 614. 608 
THE RESPIRATORY SYSTEM 
coccus and Staphylococcus pyogenes and occasionally by other micro- 
organisms. The exact significance of these mixed or concurrent infections 
in lobar pneumonia is not always clear. But instead of the usual 
resolution there may be gangrene; or suppuration of the interstitial lung 
tissue with the formation of abscess may occur. In such cases Strepto- 
coccus pyogenes and Staphylococcus pyogenes aureus or putrefactive 
bacteria may be present with the pneumococcus in the exudate. 
Fig. 381.-"Organizing" Pneumonia-Delayed Resolution After Lobar Pneumonia. 
Anastomosing fascicles of fusiform connective-tissue cells lie within the air vesicle and are con- 
tinuous with similar new formations in adjacent air spaces. 
Suppurative inflammation of the interstitial tissue of the lungs may 
involve not only the larger fibrous-tissue bands, but the walls of the air 
vesicles and other air spaces. It is often called "purulent infiltration." 
From the cut surface of the lungs in resolving lobar pneumonia a gru- 
mous fluid resembling pus often exudes, and this is sometimes mistaken 
for a mark of interstitial suppuration of the lung. 
Suppurative inflammation of the interstitial tissue of the lung may 
occur without association with lobar pneumonia. 
Lobular Pneumonia and Broncho-Pneumonia. 
In distinction from that common form of pulmonary inflammation 
induced by the Diplococcus pneumoniae, which as we have seen is usu- 
ally lobar in character, there are exudative inflammations of the lungs, 
due to many different excitants, which are "patchy" or "lobular" in 
extent, the consolidated areas varying in size from such as are scarcely 
visible to those several centimetres in diameter.1 These patches of lobu- 
lar consolidation often join and merge, so that solidification of whole 
lobes or lungs is not uncommon. But the mottled, uneven surface and 
color of the lungs on section, and the usual absence of the peculiar granu- 
1 The term lobular does not refer exclusively to the anatomical "lobule" of the lung, since the 
masses or patches of consolidation often embrace several lobules or parts of these. THE RESPIRATORY SYSTEM 
609 
lation ordinarily suffice for the distinction, even to the naked eye, of the 
lobar from the coalescent lobular forms of exudative pneumonia. 
It is convenient to recognize several types of lobular exudative pneu- 
monia, although the character of the exudate is not distinctive. 
Broncho-pneumonia.-Lobular Pneumonia with Inflammation of the Smaller Bronchi. 
This most important type of lobular pneumonia frequently develops 
in connection with, and as an extension of that form of inflammation of 
the smaller bronchi commonly called "capillary bronchitis." At first 
dark red in color, the lobular areas of consolidation in broncho-pneumonia 
become more gray at the centre through degeneration of the exudate, 
while the advance of the process in the periphery is marked by a less 
solid, redder zone. On section of the fresh lung these areas (Fig. 382) 
Showing several areas of consolidation with the central bronchus filled with exudate-stained 
dark in the section from which the photograph was made. 
Fig. 382.-Broncho-Pneumonia in an Adult. 
usually project somewhat above the general surface, and at their cen- 
tres the involved bronchi may appear as lighter spots, from which pus 
may exude or be easily pressed out. Such areas may coalesce, forming 
larger consolidations. The exudate, which more or less completely fills 
the air spaces (Fig. 383), consists of serum, old and new-formed epithe- 
lial cells from the walls of the air spaces, red blood cells, and often fibrin 
and polymorphonuclear leucocytes (Fig. 384) with various forms of 
micro-organisms. As a rule, however, fibrin and leucocytes are not as 
abundant as in the exudate of lobar pneumonia. Mucus and bronchial 
epithelium may be aspirated into the air spaces and mingled with the 
exudates. 610 
THE RESPIRATORY SYSTEM 
Broncho-pneumonia involves a direct extension of the inflammatory 
process from the bronchi to the contiguous lung tissue, so that there is 
both an interstitial and exudative pneumonia about the bronchial tubes, 
the whole forming the lobular areas of consolidation (Fig. 385). This 
The section shows a single lobular area of consolidation with its bronchus whose thickened wall 
merges with the surrounding zone of exudative pneumonia. 
Fig. 383.-Broncho-Pneumonia in a Child. 
involvement of the bronchial wall in inflammation with a direct exten- 
sion of the process to the surrounding lung tissue has been urged especially 
by Delafield as the process to which the term broncho-pneumonia should 
be par excellence applied. 
Between the consolidated areas there may be atelectasis of lung tissue 
from the occlusion of the smaller bronchi 
with exudate. When the consolidated 
areas are situated at the surface of the 
lungs, fibrinous pleuritis may be present 
over the affected regions. 
This form of broncho-pneumonia is 
frequent in children, sometimes as an 
independent process, but often associated 
with or following diphtheria, scarlatina, 
measles, etc. It occurs also in adults, 
either as a complication of infectious 
diseases such as typhoid fever, smallpox, 
influenza, etc., or as a primary process. 
It may occur in the aged or in those 
enfeebled by chronic wasting diseases. 
Resolution may take place in the 
areas of broncho-pneumonia by processes of cell degeneration and 
absorption identical with those through which restoration is secured in 
lobar pneumonia. If, however, resolution in broncho-pneumonia do not 
presently take place, and the lesion persist, dense connective tissue is 
Fig. 384.-Broncho-Pneumonia-Ex- 
udate in A Single Air Vesicle. THE RESPIRATORY SYSTEM 
611 
apt to form about the bronchi and in the interstitial tissue of the lungs, 
which may lead to induration and distortion of the organs, atelectasis, 
chronic bronchitis with dilatation of the bronchi, etc. A photograph 
of a section of such a chronic or "persistent" broncho-pneumonia is 
reproduced in Fig. 386. 
Other Forms of Lobular and Broncho-Pneumonia.-There are forms 
or types of lobular pneumonia in which serum and epithelial cells with 
more or less fibrin and leucocytes collect in the air spaces of a limited 
Fig. 385.-Broncho-Pneumonia-Child. 
Showing slight change in the epithelium of the bronchus; a purulent exudate in the lumen; thickening 
of the wall of the small bronchus, and exudate in the adjacent air vesicles. 
region without primary bronchitis and without involvement of the walls 
of the bronchi and air spaces. 
In one type of lobular pneumonia and broncho-pneumonia the exu- 
date may consist largely of pus cells which infiltrate the walls of the air 
spaces and bronchi as well as fill the air spaces themselves. This type 
of inflammation may be induced by the aspiration in feeble persons of 
irritating substances or bacteria-containing material of various kinds, 
particles of food, saliva, etc. This is called aspiration pneumonia and 
may result in necrotic or gangrenous processes in the involved regions 
of the bronchi and lungs. Again there may be circumscribed areas of 
exudative pneumonia, often suppurative in type and involving the walls 
of the air spaces, which originate through the transportation by the 
blood-vessels of various forms of bacteria, especially the Streptococcus 
and Staphylococcus pyogenes, as in pyaemia; this is called lobular pneu- 
monia of hcematogenous origin, or pycemic or septic pneumonia. Thus, 
abscesses of the lungs may be formed. 
In the lobular pneumonia of bubonic plague the exudate is said to 612 
THE RESPIRATORY SYSTEM 
contain few leucocytes and epithelial cells, and to consist largely of blood 
and plague bacilli.1 
In the aged or those long in bed in an enfeebled condition, hyperaemia 
and oedema with more or less exudate, usually epithelial in character, 
may develop in the dependent posterior portions of the lungs-hypo- 
static congestion and hypostatic pneumonia. 
There is a peculiar and rare form of broncho-pneumonia associated 
with necrosis in which forms of streptothrix have been isolated which 
are undoubtedly the excitants of the disease.2 Actinomyces is also an 
occasional excitant of broncho-pneumonia. 
Fig. 386.-Persistent-Chronic-Broncho-Pneumonia. 
In all these forms of lobular pneumonia oedema and atelectasis of 
uninvolved portions of the lung may occur.3 
It is evident that in lobular pneumonia the infectious agent may reach 
the lungs either through the air passages or through the blood- or lymph- 
vessels, and that differences in the portals of entry as well as in the 
nature and virulence of the excitant and the susceptibility of the indi- 
vidual have an important bearing both upon the course of the disease 
and the morphology of the lesion. 
1 Consult Flexner, Trans. Assn. Am. Phys., vol. xvi., p. 481, 1901. 
2 Consult Norris and Larkin, Jour, of Exp. Med., vol. v., p. 155, 1900, bibl.; also reference on 
p. 232. 
3 For a type of lobular pneumonia in which the alveolar contents simulate giant cells see Karsner 
and Meyers, Arch. Int. Med., 1913, xi, 534. THE RESPIRATORY SYSTEM 
613 
The Excitants of Lobular and Broncho-Pneumonia.-The exci- 
tants of broncho-pneumonia and other types of lobular pneumonia are 
most frequently Streptococcus pyogenes (Fig. 387), the pneumococcus, 
Staphylococcus pyogenes, the typhoid, diphtheria, influenza, and 
plague bacilli, and the pneumobacillus of Friedlander; the streptothrix, 
above mentioned, and other bacteria have been occasionally found.1 
Pathogenic moulds may be excitants of acute forms of lobular pulmonary 
inflammation. 
Fig. 387.-Air Vesicle in Broncho-Pneumonia with Streptococci. 
This specimen is from a case of broncho-pneumonia complicating a pseudo-membranous inflam- 
mation of the larynx in scarlatina. Exfoliated epithelium, leucocytes, and e little fibrin with the strep- 
tococci form the scanty exudate. 
It will thus be seen that while it is convenient to group the exudative 
forms of pulmonary inflammation on the basis of distinctions which are 
in part morphological, in part etiological, the types in fact frequently 
merge or concur. This should not lead to confusion if we remember 
that these are infectious diseases whose most conspicuous lesion is located 
in the lungs, and that they are not species in the natural-history sense, 
for which fixed and definite characters must be established, but that the 
groups only indicate various forms and phases of response of a living 
organ in various conditions of susceptibility to the damage inflicted by 
one or another, and not infrequently by two or more combined forms of 
micro-organisms. These pneumonias are not considered among the 
infectious diseases where they logically belong, partly because there are 
practical advantages in grouping pulmonary lesions together and partly 
because our knowledge of the relative frequency and significance of the 
bacterial excitants of the various types is still in many cases too incom- 
1 For a study of the bacteriology of lobular pneumonia, especially in adults, see Blumer, Albany 
Med. Annals, vol. xxii., Aug. 1901. 614 
THE RESPIRATORY SYSTEM 
plete to permit the establishment of a distinctive and clearly defined 
form of infection.1 
This name is given to a chronic productive inflammation, which 
involves the connective-tissue framework of the lung and the walls of the 
Interstitial Pneumonia. 
With emphysema. The walls of the enlarged air vesicles and spaces are converted into dense 
fibrous tissue. 
Fig. 388.-Interstitial Pneumonia. 
air spaces, and results in the formation of new connective tissue and the 
obliteration of the air spaces (Fig. 388). 
Such an interstitial pneumonia may follow acute lobar pneumonia 
with the production of new intra-alveolar connective tissue, broncho- 
pneumonia, chronic pleurisy, chronic bronchitis, and atelectasis, or may 
1 For a study of experimental cooling of the body which may induce changes in the blood, predispos- 
ing to infection with the pneumococcus, see Reineboth and Kohlhardt, Deut. Arch. f. klin. Med., Bd. 
Ixv., p. 192, 1900. For a study of the effects of cooling in general as a predisponent to infection, see 
Lode, Arch. f. Hygiene, Bd. xxviii., p. 344, 1897; also Kisskalt, ibid., Bd. xxxix., p. 142, 1901, bibl. 
For a study of the portals of entry in lung infection, with special reference to the pleura, see Grober, 
Deutsch. Arch. f. klin. Med., Bd. Ixviii., p. 296, 1900, bibl. 
For a comprehensive resume of studies of experimental pneumonia, see Wadsworth, Jour. Exper. 
Med., 1912, xvi, 54 and 78, bibl. For experimental pneumonia in dogs by bronchial insufflation see 
Lamar and Meltzer, Jour. Exper. Med., 1912, xv, 133; and for study of lesions produced by bronchial 
insufflation of streptococci see Wollstein and Meltzer, Jour. Exper. Med., 1913, xviii, 548. 
Concerning circulatory changes in the lungs under various pathological conditions see reference 
to Esser, p. 595. THE RESPIRATORY SYSTEM 
615 
be induced by the inhalation of the dust of coal, stone, or other inor- 
ganic substances. Diffuse interstitial pneumonia may occur in syphilis. 
The topography of the lesion varies considerably in the different con- 
ditions under which the new tissue growth occurs. If it follow acute 
lobar pneumonia, one lobe or the whole of one lung may be involved and 
covered with pleuritic adhesions. The lobe or the lung is small, smooth 
on section, and firm in texture. The air spaces and small bronchi may 
be largely obliterated by the new connective tissue. If it follow broncho- 
pneumonia, one or more lobes are studded with fibrous nodules, which 
correspond to the affected bronchi and the associated lung territory; or 
a large part of a lobe is converted into dense fibrous tissue; the pleura 
may be thickened; there may be chronic bronchitis and bronchiectasia. 
Fig. 389.-Chronic Interstitial Pneumonia. Reversion of Epithelium in 
Isolated Air Vesicles. 
If interstitial pneumonia be associated with thickening of the pleura, 
bands of connective tissue extend from the pleura into the lung, the 
bronchi are inflamed and often dilated. When associated with chronic 
bronchitis there are fibrous nodules around the bronchi, with more or 
less diffuse connective tissue. 
The changes in interstitial pneumonia may occur by a slow hyperpla- 
sia of the fibrous tissue or by the formation of granulation tissue, which 
gradually becomes denser with contraction. Although this process is 
primary in the interstitial tissue, exudates are often present in the air 
spaces; atelectasis may occur, while emphysema and bronchiectasia are 
common. 
Sometimes a noteworthy change occurs in the epithelium lining air 
vesicles which have been cut off from their neighbors by the new fibrous 
tissue. The epithelial cells increase in number, become thicker, and 
finally the small or distorted cavities may be lined with a complete 
investment of cuboidal cells (Fig. 389). This reversion of the epithelium 
of the air vesicles to a less differentiated type occurs in many chronic 
processes in the lungs. 
Pigmentation of the Lung.-The inhalation of dust and smoke is so 
continuous among those who live much indoors that the lungs of nearly 616 
THE RESPIRATORY SYSTEM 
all persons from the earliest years are more or less pigmented. The for- 
eign particles which get into the deeper recesses of the lungs are in part 
taken up by the epithelium of the air spaces, in part are carried by 
phagocytes or otherwise to the interstitial tissue of the lungs (Fig. 390). 
Here, either within cells or without, they are deposited along and within 
the lymph channels or in the lymph-nodules of the pleura and interstitial 
Fig. 390.-Anthracotic Pigmentation of the Lung. 
Showing pigment beneath the thickened pleura and in the thickened septa of the emphysematous 
lung. 
tissue (Fig. 391), or they may be carried to the lymph-nodes at the root 
of the lungs. Rarely, this inhaled dust passes the tracheal and bron- 
chial lymph-nodes and may be deposited in the viscera, especially in the 
liver and spleen. 
Under ordinary conditions a moderate deposit of inhaled pigment 
particles in the lungs does not seem to be of great significance, but it does 
lead, if present in amounts as large as are frequently found in the air 
of many private houses, stores, factories, theatres, and other places of 
public assembly, to obliteration of lymph-channels and conversion of 
lymph-nodes into masses of pigmented fibrous tissue and in this way 
there is little doubt that it may predispose to more serious lesions.1 
On the other hand, miners and others -working or confined in smoky 
air, stone or metal workers, and the like, are liable to excessive pig- 
mentation and to develop interstitial pneumonia, especially marked at 
first along the interlobular septa and frequently associated with chronic 
bronchitis, emphysema, atelectasis, or bronchiectasia. This condition of 
the lung when due to the inhalation of coal dust is called anthracosis; 
when due to dust of various minerals, chalicosis; when due to iron dust, 
siderosis.2 The general process has been called pneumokoniosis. The 
color varies in these lungs with the character and amount of the deposited 
material, which is frequently quite unevenly distributed. The amount 
of foreign material in such lungs is sometimes large.3 
1 For a study of the significance of pulmonary anthracosis see Haythorn, Jour. Med. Research, 1913, 
N. S. xxiv, 259. 
2 For a study of the condition of iron pigment in cells and tissues see Arnold, Virch. Arch., Bd. 
clxi., p. 284, 1900. 
3 For a study of the lungs in extreme anthracosis see Hodenpyl, Proc. New York Path. Soc., 1899- 
1900. For a summary of the protective mechanism of the respiratory passages see p. 600. For sum- 
mary of dusty trades and consumption, see Hoffman, Bureau of Labor, Dept, of Commerce and Labor, 
U. S. A., Bull. 79, 1908, and Bull. 82, 1909, bibl. THE RESPIRATORY SYSTEM 
617 
A few tubercles are seen at the centres of the pigmented areas. There are slight pleuritic adhe- 
sions between the lobes. This is from a photograph of the lung of an actor who had been for many 
years upon the stage in the nearly always dusty air of theatres. 
Fig. 391.-Anthracosis of the Lung. 618 
THE RESPIRATORY SYSTEM 
Tuberculous Pneumonia. 
General Considerations.-Tuberculous inflammation of the lungs is 
similar in nature to tuberculous inflammation in other parts of the body. 
But since the morphological features of the response of a tissue to injury 
are largely dependent upon the form and capacities of its cells, it is not 
surprising that in such complex organs as the lungs, the lesions of tuber- 
culosis should present many variations from the usual type elsewhere. 
The bronchial passages and the connecting air spaces, the numerous 
blood- and lymph-channels, especially favor the distribution of the 
tubercle bacillus within these organs; the open texture of the lungs per- 
mits, as in other forms of pneumonia, of great accumulation of exudate, 
while the delicacy and thinness of the air chambers favor extensive 
disintegration of the old or new-formed tissues or exudates when these 
have become necrotic under the influence of the poisons of the tubercle 
bacilli. 
Thus the variety of cells and tissues involved and their peculiar rela- 
tionships to one another and to the invading organisms render the lesions 
of pulmonary tuberculosis more complex in morphology than are tuber- 
culous lesions in any other part of the body. 
The classification of these lesions is largely based upon topographic 
considerations and is not to be regarded as indicating fundamental differ- 
ences in the reaction of the tissues. 
Portals of Entry.-Tubercle bacilli may enter the lungs either through 
the blood- and lymph-vessels, being brought from a focus of tuberculous 
inflammation in another part of the body, or, as is frequently the case, 
they are introduced through the air passages by the inhalation of floating 
dust particles, among which are living tubercle bacilli. There is evidence 
that tubercle bacilli may enter the body through the nasal and buccal 
mucosa or the tonsils or through gastro-intestinal mucous membrane 
without the development of tuberculous lesions at the point of entry.1 
Reaction of Tissue.-The introduction of tubercle bacilli into the 
lungs may induce an exudative inflammation with the accumulation of 
fibrin, leucocytes, and exfoliated epithelium in the air spaces; a produc- 
tive inflammation with the growth of epithelial cells, or of round-celled 
tissue, or of a tissue composed of basement substance, large and small 
cells, and giant cells called tubercle tissue (see p. 252); or there may be 
added necrosis of the new tissue and of portions of the lung. All of these 
phases of tuberculous lesions may and usually do occur together. 
The character of the inflammation in each case seems to be governed 
by the type of cells especially involved, by the number, virulence, and 
proliferative capacity of bacilli which are introduced into the lungs, and 
the way in which these enter, as well as by the susceptibility of the indi- 
vidual. If a large number of virulent tubercle bacilli be inhaled or 
aspirated through the bronchi, or if the bacilli grow with great rapidity, 
1 For a discussion of the sources and portals of entry of the tubercle bacillus see p. 264. 
For a study of tubercle bacillus in the blood in pulmonary tuberculosis see Liidke, Wiener klin 
Woch., p. 949, 1906. See also ref. Anderson, p. 264. THE RESPIRATORY SYSTEM 
619 
both productive and exudative inflammations may be set up in a consid- 
erable portion of the lungs. If, on the other hand, but few bacilli enter 
and their proliferation or virulence be not extreme, or if these find their 
way in small numbers into the lungs through the blood-vessels or lym- 
phatics, then there may be small foci of productive inflammation with 
but little exudation. The tuberculous alterations in the lungs are usually 
accompanied or followed by a series of secondary processes which often 
complicate the condition of the patient as well as the morphological 
appearances of the organs. The obliteration or destruction of the 
smaller blood-vessels of the lungs in the tuberculous areas contributes to 
the gray or whitish appearance of the lesions, due largely to new-formed 
tissue or accumulated exudate. The formation of fibrous tissue in the 
attempts at repair of the damage wrought by the tubercle bacillus often 
dominates the structural picture. 
Classifications.-The traditional distinctions between acute and 
chronic forms of pulmonary tuberculosis are often morphologically not 
at all well defined and are of value chiefly for clinical purposes. 
It has been customary to set apart those forms of acute tuberculosis 
of the lungs in which the lesions are in the form of small discrete so- 
called "miliary" foci, calling the condition Acute Miliary Tuberculosis. 
The other tuberculous lesions involving in varying degree the lungs and 
the bronchi with associated and often extensive exudative necrotic and 
reparative processes have been commonly jumbled together as Acute and 
Chronic Phthisis, many phases of which have been elaborately described 
as if they were the expression of independent processes. 
With our present knowledge of the nature and etiology of tuberculosis 
it seems better to let the word phthisis fall into disuse as speedily as 
possible, and to consider under more exact and significant designations 
such phases of pulmonary tuberculosis as the morphological characters 
of the lesions justify. We shall review the lesions of pulmonary tuber- 
culosis then under the following primary headings: 
1. Focal or miliary tuberculosis. 
2. Tuberculous broncho-pneumonia. 
3. Complex forms of nodular and diffuse tuberculous lesions. 
4. The formation of cavities. 
5. Secondary lesions in pulmonary tuberculosis. 
6. Concurrent infection. 
Focal Tuberculosis. {Miliary Tuberculosis'). 
Acute Miliary Tuberculosis.-The rapid and widespread development 
of miliary tubercles in the lungs is often a part of general tuberculosis, 
although the lesion may be most extensive in the lungs. Both lungs are 
apt to be involved, but the distribution, number, size, and character of 
the miliary tubercles differ in different cases. The tubercles are found 
in the parenchyma of the lung, in the connective tissue forming the 
septa, along and in the walls of the bronchi and blood-vessels, and in the 
pulmonary pleura. They may be scattered singly through the lungs 620 
THE RESPIRATORY SYSTEM 
(Plate IV.), or aggregated in groups (Plate VI. and VII.). They may 
be separated by considerable interspaces, or so close together that the 
lung is rendered nearly solid. Some are so small and transparent that 
they can hardly be seen with the naked eye; others are larger and more 
opaque and may have a lighter centre marking the area of necrosis. 
In many cases it is evident that the lungs are infected through the 
blood-vessels or the lymphatics, for the general tuberculous infection 
is secondary to a localized tuberculosis either in the lungs or in some 
other part of the body. In a considerable proportion of cases of miliary 
This tubercle has replaced several air vesicles whose walls are obliterated. In the centre is an 
area of coagulation necrosis; outside of this is a zone of organized tubercle tissue; the surrounding air 
vesicles contain a cellular exudate. 
Fig. 392.-Miliary Tubercle of Lung. 
tuberculosis of the lungs, tuberculous lesions of the bronchial lymph- 
nodes or of the lung tissue at the apex of much longer standing indicate 
the probable immediate source of origin of the widely distributed tubercle 
bacilli. Very often in miliary tuberculosis of the lungs the tubercles in 
one part of the lungs are larger and appear to be older than those in 
other parts. Thus it is not infrequent to find the tubercles in the upper 
portion of the lungs more abundant, larger, and more fibrous than in the 
lower lobes (see Plate VII.). It is in fact probable that in many cases 
of acute miliary tuberculosis of the lung, either associated or not with 
older local tuberculous lesions from which the distribution of bacilli may 
have taken place, the generalization has not occurred at once, but by 
successive fresh infections.1 
1 For references to the origin of miliary tuberculosis see Benda, Lubarsch and Ostertag's "Ergeb- 
nisse," Jahrg. v., p. 447, 1898; see also ref. to Ribbert, foot-note p. 252. Pathology-Delafield and Prudden. 
Plate TV. 
The miliary tubercles, small and irregular in shape, are distributed 
throughout the lung-more abundantly in the upper and middle thirds. 
The blood-vessels are injected with blue gelatin, so that in this 
photographic reproduction of the specimen the uninvolved portions of 
the lung are dark, while the tubercles-in which the blood-vessels are 
compressed or obliterated-are light. 
Miliary Tuberculosis (Acute) of the Lung. THE RESPIRATORY SYSTEM 
621 
Miliary tubercles in the lungs are in structure essentially similar to 
those formed elsewhere in the body, except that the filling of the air 
spaces with exudate makes the lesion somewhat more complex. 
The tubercles may be composed of small spheroidal cells or of larger 
polyhedral cells with more or less fibrous stroma, or of small and large 
cells and stroma. Giant cells may be present, coagulation necrosis is 
Fig. 393.-A Miliary Tubercle of the Lung. 
Involving only two air vesicles, of which the walls are infiltrated and the cavities filled with tuber- 
cle tissue. The blood-vessels of the air vesicles are injected, except where these are obliterated by the 
tuberculous involvement of their walls. 
usual (Fig. 148, p. 254). Such forms of miliary tubercles may be and 
commonly are associated with the presence of an exudate in the adjacent 
or involved air vesicles (Fig. 392). This exudate may be largely made 
up of exfoliated epithelial cells which have proliferated; or with these 
there may be serum, leucocytes, and fibrin. The blood-vessels within 
the tubercles which replace the lung tissue are partially or wholly oblit- 
erated (Fig. 393). 
But the miliary foci of tuberculous inflammation in the lungs may 
consist wholly of inflammatory exudate which early becomes necrotic, 622 
THE RESPIRATORY SYSTEM 
often with necrosis of the walls of the involved air spaces. Such tuber- 
cles of the exudative type are apt to occur in children and usually con- 
tain large numbers of tubercle bacilli. They may occur in connection 
with various other phases of acute and chronic pulmonary tuberculosis. 
When miliary tubercles are situated in the parenchyma of the lung 
the walls of the air spaces may be visible in the new growth or they 
may be largely or wholly obliterated (Fig. 394). 
In the obliteration of the walls of the air vesicles, their former situa- 
tion may be indicated by structureless bands or streaks of necrotic 
material, or they may disappear altogether. 
This tubercle is largely caseous, the walls of the involved air vesicles being merely indicated in 
the dead mass by slightly stained streaks or bands. There is cellular exudate in the surrounding air 
vesicles. 
Fig. 394.-A Miliary Tubercle of the Lung. 
Chronic and "Healed" Miliary Tubercles.-The small foci of tubercu- 
lous inflammation which are called miliary tubercles may, as we shall 
see later, extend and coalesce so that with more or less exudative pneu- 
monia large areas of the lung may become consolidated, thus developing 
one of the forms of pulmonary tuberculosis called phthisis. 
On the other hand, small tuberculous foci in the lungs may with or 
without extensive necrosis become surrounded by or converted into 
masses of dense fibrous tissue. These fibrous-tissue masses, which are 
often called "healed tubercles" (Figs. 395 and 396), may contain necrotic 
material, are often mottled black from anthracotic pigment, or they may 
be calcified at the centre. Tubercle bacilli may be absent from them, or 
the bacilli may remain alive within them for a long time quiescent but, 
as Lartigau and others have shown, still virulent. When such circum- 
scribed masses of more or less fibrous tubercle tissue are scattered 
through the lungs, although the individual masses may be of considerable 
size, the process is sometimes called "chronic miliary tuberculosis." THE RESPIRATORY SYSTEM 
623 
Fig. 395.-An Old Fibrous Tubercle of the Lung-"Healed Tubercle." 
The central portion is necrotic and irregularly pigmented. The periphery is composed of dense 
pigmented fibrous tissue. There are emphysema and distortion from cicatricial contraction of'the fi- 
brous tissue. 
Fig. 396.-A Fibrous Tubercle-"Healed Tubercle" of the Lung. 
The centre is caseous, the fibrous tissue surrounding this is dense, the walls of the surrounding 
air spaces are thickened. A giant cell at the right is calcified. 624 
THE RESPIRATORY SYSTEM 
It should be remembered that the new fibrous tissue which forms in 
and about miliary tubercles, as well as other tuberculous lesions, is the 
result of a distinctly reparative process in which the already formed 
tubercle tissue or its products apparently act somewhat as foreign bodies 
may in inducing fibrous-tissue growth. 
Tuberculous Broncho-Pneumonia. 
In another most important phase of tuberculous inflammation of the 
lung there is an involvement of the walls of the smaller bronchi and the 
associated groups of air spaces. This may occur through inhalation of 
bacilli or by their aspiration from an established tuberculous focus; for 
Fig. 397.-Tuberculous Inflammation of the Lung with Cheesy Degeneration about the 
Bronchi in a Single Lobule of the Lung-Tuberculous Broncho-Pneumonia. 
example, from a lesion at the apex, or, as is often the case in children, 
from tuberculous bronchial lymph-nodes; or infection may take place 
through the blood- or lymph-vessels. In the early stages of tuberculous 
broncho-pneumonia the cut surface of the fresh lung may present small 
gray or yellowish white areas of consolidation with necrosis clustered 
about the small or terminal bronchi (Plate V.). The process is at. first 
largely exudative, involving a catarrhal and necrotic inflammation of the 
mucous membrane of the bronchus with more or less exudate-which also 
may soon become necrotic-in the associated groups of air spaces (Fig. 
397). Sometimes organized tubercle tissue may form in the walls of Pathology-Delafield and Prudden. 
Plate V. 
The walls of the smaller bronchi are involved, being thickened and 
caseous, while the ulceration of many of them has led to the formation 
of numerous small cavities. 
The blood-vessels are injected with blue gelatin, so that the less 
affected and the intact parts of the lungs are the darker. 
Tuberculous Broncho-Pneumonia. THE RESPIRATORY SYSTEM 
625 
The walls of the bronchi are thickened and caseous and are surrounded by zones of exudative and 
caseous pneumonia. This cut shows a small region, more highly magnified, of a lesion similar to that 
shown in Plate V. 
Fig. 398.-Tuberculous Broncho-Pneumonia. 
Fig. 399.-Tuberculous Broncho-Pneumonia. 
The wall of this medium-sized bronchus is caseous, tubercle tissue is formed about it and is extending 
into the surrounding lung tissue. A cellular exudate is seen in the contiguous air vesicles. 626 
THE RESPIRATORY SYSTEM 
the bronchi, with thickening of the walls and obliteration of the blood- 
vessels of the adjacent air spaces. 
By the extension of the process from one and another affected bron- 
chus, and the coalescence of these, large areas of the lungs may become 
involved. In this more advanced stage of broncho-pneumonia the larger 
and smaller consolidated areas may be dark red with firmer gray or yel- 
lowish gray central portions, in which the blood-vessels are obliterated, 
or the whole area may be solid and in the fresh lung grayish white. This 
new-formed tissue may undergo necrosis and ulceration so that with an 
advancing consolidation of the lung tissue about the bronchi numerous 
Showing the formation of cavities in the lung in acute phthisis. To the right are small, in the 
centre large, tuberculous bronchiectatic cavities. At the left are areas of tuberculous consolidation 
with caseation in their central portions. 
Fig. 400.-Tuberculous Broncho-Pneumonia. 
larger and smaller, rough, irregular cavities may be formed (Fig. 398). 
The walls of the larger bronchi also may become the seat of a tubercu- 
lous inflammation with more or less necrosis (Fig. 399). Ulceration 
of these necrotic bronchial walls may lead to the formation of ragged 
cavities (Plate IX. and Fig. 400). 
The secondary development of dense fibrous tissue in connection with 
tuberculous broncho-pneumonia is a marked feature of the persistent or 
chronic forms. Tuberculous broncho-pneumonia is one of the most 
important of that complex of pulmonary lesions called phthisis, and is 
commonly associated with other forms of tuberculous involvement of the 
organ-miliary tubercles, larger areas of consolidation, etc. Pathology-Delafield and Prudden. 
Plate VI. 
Miliary Tubercles and Tuberculous Broncho-Pneumonia with 
Diffuse (Chronic) Tuberculous Lesions in the Apex. 
There is in the apex tuberculous consolidation with coagulation 
necrosis (caseation), new fibrous tissue, and a small cavity. The middle 
third of the lung contains many small single and clustered miliary tuber- 
cles and foci of tuberculous broncho-pneumonia. The lower third con- 
tains a few similar small tuberculous foci, also scattered and in clusters. 
The appearance of the lung leads to the conjecture that tubercle 
bacilli may have been gradually disseminated from the earlier lesion in 
the apex. The blood-vessels are injected with blue. THE RESPIRATORY SYSTEM 
627 
Complex Forms of Nodular and Diffuse Tuberculous Lesions. 
(Phthisis.) 
With or without the various well-defined forms of tuberculous bron- 
cho-pneumonia and miliary tubercles above described, there may be 
more or less circumscribed small or large areas of productive and exuda- 
tive tuberculous inflammation of the lung with necrosis, both of the lung 
tissue, the new-formed tissue, and the exudate (Plate XII.). These may 
develop as the result of fresh infections of the lung through the lym- 
phatics or otherwise. These areas or nodules may coalesce so that whole 
lobes or parts of lobes of the lungs may become consolidated (Plates VII. 
and VIII.). Microscopically, these consolidated areas may be composed 
of tubercle tissue more or less necrotic, with partial or total obliteration 
of the walls of the air spaces. On the other hand, when the process has 
been exudative as well as productive in character, one may see in the solid 
areas the outlines of the air vesicles and larger spaces; but these, to- 
gether with the enclosed exudate, may be necrotic and granular with 
few stained nuclei and fragments of chromatin. Much of the exudate 
which fills the air vesicles either within or about these more densely con- 
solidated areas may not be caseous or necrotic, but may consist of well- 
preserved or fatty epithelial cells, or of these with varying quantities 
of leucocytes and fibrin. 
Aside from these complex forms of nodular and diffuse tuberculous 
lesions one may recognize a Diffuse Exudative Tuberculous Inflammation 
of the Lungs of Acute and of Chronic Type.-Cheesy Pneumonia; Pneu- 
monic Phthisis. 
1. Acute Type.-Sometimes large areas or whole lobes or the whole 
lung may be the seat of an exudative process by which the affected region 
becomes solidified, the exudate consisting of epithelium with more or less 
fibrin and pus. This exudate, together with the lung tissue, soon under- 
goes necrosis, so that the solidified lung becomes dense, mottled, and 
gray in color. Extensive disintegration (Fig. 401) of the consolidated 
and necrotic portions of the lung may take place, with the formation of 
large ragged cavities (see Plate X.). In many cases enormous numbers 
of tubercle bacilli are present in the exudate of the involved region in 
this type of exudative and necrotic pulmonary tuberculosis. 
2. Chronic Type.-There may be a more gradual development of 
the exudate, involving larger or smaller areas, often with tuberculous 
thickening and necrosis of the walls of the air spaces. With this as with 
other forms of pulmonary tuberculosis there may be associated a growth 
of simple fibrous tissue with the formation of cavities. 
Not infrequently the exudate in such forms of diffuse tuberculous 
inflammation of the lung is less cellular and more serous or sero-fibrinous 
in character, when the appearance of the consolidated region is trans- 
lucent and gelatinous. 
Obliteration of the larger blood-vessels by thrombosis or inflamma- 
tion of the wall often plays an important part in most forms of tubercu- 
lous lesions of the lungs. When large trunks are involved, large lung 628 
THE RESPIRATORY SYSTEM 
areas, supplied by the occluded vessels, particularly those in which exu- 
date is present, may become necrotic en masse, then often appearing on 
section smooth, shining, grayish-white in color, and bloodless. 
Fig. 401.-Acute Pulmonary Tuberculosis-Exudative Type (Acute Phthisis-Cheesy Pneu- 
monia); with Extensive Disintegration and Formation of Cavities. 
The pleura is much thickened. 
The Formation of Cavities in Pulmonary Tuberculosis. 
We have seen that in tuberculous broncho-pneumonia ragged cavities 
may form by a progressive necrosis and disintegration of the thickened 
walls of the affected bronchi and the adjacent lung tissue (Plate IX. Pathology-Delafield and Prudden. 
Plate VII. 
Diffuse and Focal (Chronic) Pulmonary Tuberculosis- 
"Chronic Phthisis." 
In the upper third of the lung there is tuberculous broncho-pneu- 
monia with commencing ulceration of small bronchi: nearly complete 
consolidation from the extension and coalescence of small tuberculous 
foci and diffuse formation of fibrous tissue. 
In the lower third of the lung are irregular, dense, sharply outlined 
tuberculous foci (chronic miliary tubercles). 
In the middle third there is tuberculous pneumonia of the exudative 
type, the incompletely consolidated areas having become, in part, caseous. 
The less involved portions of the lung in this, as in the other in- 
jected specimens, are the darker. THE RESPIRATORY SYSTEM 
629 
and Fig. 400). Similar destructive alterations may occur in the areas 
of tuberculous and necrotic tissue which involve larger and smaller 
portions of whole lobes (Plate 
XL). This is most often rapid 
and extensive in solidified and 
necrotic areas of the exudative 
type (Plate X. and Fig. 401). 
These ragged cavities may com- 
municate with one another as 
well as with the bronchi. 
While at first without dis- 
tinct limiting walls, if the ne- 
crotic process be not too active 
and extensive, new fibrous tis- 
sue may gradually form about 
tuberculous cavities (Plate XII. 
and Fig. 402); and these may 
become lined with granulation 
tissue or a layer of new-formed 
tubercle tissue. Here an enor- 
mous proliferation of tubercle 
bacilli may occur for long pe- 
riods. These may be cast out 
in the sputum or aspirated into 
other parts of the lungs. The 
old blood-vessels of the in- 
volved portion of the lung may 
lie upon the walls or stretch 
across these cavities, sometimes 
with obliterated lumina, some- 
times still permeable; and from 
these haemorrhages may occur. 
There may be continuous and 
prolonged suppuration of the 
walls of the cavities and putre- 
factive processes may be incited 
by the advent through the air 
passages of various forms of bacteria. The walls of cavities may become 
fibrous with an arrest of the tuberculous process, and they may become 
shut off from bronchial communication. 
Fig. 402.-Chronic Pulmonary Tuberculosis 
(Chronic Phthisis), with Cavities. 
There is much dense fibrous tissue in the upper lobe 
surrounding and between the cavities, as well as in the 
upper portion of the lower lobe. 
Secondary Lesions in Pulmonary Tuberculosis. 
A variety of secondary processes may be associated with the various 
phases of pulmonary tuberculosis which we have briefly reviewed. The 
blood-vessels in affected regions may be intact, or, as we have seen, their 
walls may be involved in the productive and necrotic processes, with 
thrombosis or obliteration of the lumen; or more or less extensive hfemor- 630 
THE RESPIRATORY SYSTEM 
rhages may occur. If the consolidation be not complete, lung tissue, 
often in a condition of atelectasis or emphysema and with more or less 
cellular or granular exudate, may remain between the tuberculous 
areas. Miliary tubercles may be scattered among the larger consolidated 
masses or in parts of the lung otherwise free. 
In chronic forms of pulmonary tuberculosis the anthracotic pigment 
is often conspicuous, particularly in the cheesy and fibrous areas, stand- 
ing out in masses and streaks in contrast to the new or dead tissue. 
Furthermore, there may be associated with the lung lesions acute 
exudative or chronic fibrous pleuritis with adhesions; or tuberculous 
pleuritis of varying extent; empyema and pneumothorax. There is 
nearly always more or less chronic catarrhal bronchitis or broncho-pneu- 
monia and frequently bronchiectasia. 
Tuberculous inflammation in the bronchial lymph-nodes frequently 
accompanies and often precedes the development of pulmonary tuber- 
culosis. In children the tuberculous lymph-nodes often extend far into 
the lung and may on softening give rise to cavities at a considerable 
distance from the hilus of the lung. 
Tuberculosis in other parts of the body is common in connection with 
pulmonary tuberculosis. 
In all these various processes new'-formed fibrous tissue, not tuber- 
culous in character, may develop, variously distorting the lungs and 
sometimes enclosing the tuberculous areas. There is much reason for 
the belief that the characteristic so-called tubercle-tissue formation in all 
phases of tuberculosis is a response of the living cells to injury, which as 
in other phases of inflammation is fundamentally conservative (see p. 
107). But whether this be so or not, it is certain that it is through the 
development of fibrous tissue, which is so important a feature in persist- 
ent phases of pulmonary tuberculosis, that the delimitation or replace- 
ment of tuberculous foci, the encapsulation of tuberculous cavities, etc., 
occur. While, therefore, fibrous-tissue formation in the lung is fre- 
quently associated with the necrotic and other destructive tuberculous 
lesions, and is often a very conspicuous factor, it should be remembered 
that the healing which takes place in the majority of cases in man after 
moderate infection is achieved through its agency. 
It is especially upon the presence or absence of fibrous tissue in the 
lesions that the distinction between acute and chronic phthisis is based. 
It will be seen from this brief outline of various prominent phases 
of pulmonary tuberculosis that the gross appearances of the lungs are 
most diverse, although the processes by which these changes are induced 
are few and comparatively simple. While no two lungs are quite simi- 
lar in the complex phases of the lesion, systematic gross and micro- 
scopical examinations soon enable the student to recognize the type of 
lesion under great complexity of detail. 
The Distribution of the Lesions in Pulmonary Tuberculosis. 
Aside from general miliary tuberculosis in which the tubercles are 
widely distributed throughout one or both lungs, the most common seat Pathology-Delafield and Prudden. 
Plate VIII. 
Diffuse (Chronic) Pulmonary Tuberculosis-"Chronic Phthisis." 
In the upper half of the lung there are scattered miliary tubercles 
and irregular areas of consolidation, with a diffuse formation of fibrous 
tissue; the pleura is thickened. A large portion of the lower lobe is 
densely consolidated from tubercle tissue and exudate with coagulation 
necrosis of the involved regions. These regions are light in color, 
dense, hard, and bloodless. Such dead caseous areas may persist for 
some time, or may soften and disintegrate, giving rise to cavities. Pathology-Delafield and Prudden. 
Plate IX. 
Tuberculous Bronchiectatic Cavities in Pulmonary Tuberculosis, 
The advancing tuberculous involvement of the walls of the larger 
bronchi in the upper lobe is associated with ulceration, so that the bron- 
chiectatic cavities gradually become larger. In the upper portion of the 
upper lobe there is diffuse consolidation with caseation: the lower por- 
tion of the lobe shows miliary tubercles and partial consolidation of the 
lung about them by exudate. 
The lower lobe is free save for a few scattered tubercles. The 
blood-vessels are injected with blue so that the uninvolved portions of 
the lung are dark. THE RESPIRATORY SYSTEM 
631 
and starting-point of tuberculous lesions in adults is the apical region or 
the depth of the lung, particularly the right, somewhat below the apex.1 
In children, the tuberculous process more frequently commences in the 
bronchial lymph-nodes (Plates III. and XI.). 
From the apex the tuberculous process may extend downward, and 
with various forms of lesions involve more or less of the lungs. It is 
common to find at autopsies older fibrous lesions about the apices while 
marks of more active processes are to be seen below (Plate XII.). In a 
considerable percentage of bodies examined at autopsies, small and often 
healed tuberculous foci are found at the apex or in the bronchial lymph- 
nodes without evidence of extension of the process. 
Concurrent Infection in Pulmonary Tuberculosis. 
While it has been definitely established that tubercle bacilli are the 
excitants of both the productive and exudative forms of tuberculous 
inflammation, these bacilli are not infrequently associated in pulmonary 
tuberculosis with other organisms, especially with the Streptococcus and 
Staphylococcus pyogenes, with Diplococcus pneumoniae, and the 
influenza bacillus. 
There is reason to believe that in many cases at least the concurrent 
infection of tuberculous lungs with the Streptococcus pyogenes may be an 
important factor in the formation of cavities in areas of consolidation 
already established.2 The pyogenic cocci apparently play an important 
part in the bronchitis which so often accompanies acute and chronic 
phthisis. 
Bactericomia has been shown to exist in a certain proportion of cases 
of active progressive pulmonary tuberculosis, but in many such cases 
the blood is sterile.3 
Artificial Pulmonary Tuberculosis in Animals. 
Much light may be gained upon the successive steps in the development of the 
lesions of pulmonary tuberculosis as well as upon the rapidity with which in a suscepti- 
ble animal the lesion may develop, by the study of the tuberculosis artificially induced 
in rabbits with pure cultures. 
By the injection of tubercle bacilli alone and associated with streptococci into the 
lungs of rabbits through the trachea, it has been possible to reproduce very closely the 
lesions of pulmonary tuberculosis in man.4 
If a small quantity of a pure culture of the tubercle bacillus in very minute flocculi 
be mixed with a considerable quantity of salt solution and introduced into the lungs 
of rabbits through the trachea, a number of small areas of consolidation are produced 
which have the gross appearance of miliary tubercles (Fig. 403). These small areas of 
consolidation are composed of epithelial cells and leucocytes. After the development 
of these cell masses, which may occur within a few hours, they may remain with little 
apparent change, or become more or less infiltrated with leucocytes, or become cheesy, 
1 For a suggestive consideration of apical vulnerability see Hutchinson, "Studies in Human and 
Comparative Pathology," 1901, p. 81. 
2 For bibliography of concurrent infection in tuberculosis see Avery and Lyall, Jour. Med. Re- 
search, 1913, xxiii, 111; Pettit, Jour. Infec. Dis., 1911, ix, 237; also Prudden, ref. below. 
3 For a study of bacteriemia in pulmonary tuberculosis see Jochmann, Deut. Arch. f. klin. Med., 
Bd. Ixxxiii., p. 558, 1905. 
4 Prudden, New York Med. Jour., July 7th, 1894. 632 
THE RESPIRATORY SYSTEM 
or be surrounded by a dense zone of small spheroidal cells; or small foci of new tissue 
with more or less exudate, and necrosis, may form. 
When larger quantities of the tubercle bacillus are introduced into the lungs 
through the trachea, large areas of consolidation are formed (Fig. 404), which may 
involve whole lobes or whole lungs. 
Microscopically, these consolidated areas are practically identical with those which 
are found in man in various forms of tuberculous broncho-pneumonia. A later fibrous- 
tissue development may occur, and blood-vessels may be obliterated. 
Fig. 403. 
Fig. 404. 
The rabbit's lung shows miliary foci of tuberculous inflammation twenty-two days after the 
injection through the trachea of a small quantity of broth culture of the tubercle bacillus. 
Fig. 403.-Experimental Tuberculous Inflammation (Miliary) in the Lung of a Rabbit. 
Fig. 404.-Experimental Tuberculous Inflammation in the Lung of a Rabbit. 
Large areas of solidification in the lung twenty-eight days after the injection through the trachea 
of a considerable quantity of a pure culture of the tubercle bacillus. The lesions resemble those of 
acute phthisis in man. 
In the presence of the tubercle bacillus alone the consolidated and caseous areas 
rarely soften and break down so as to form cavities. If, however, after the tubercu- 
lous lesion of the lung has been induced and allowed to continue for a number of days, 
a culture of Streptococcus pyogenes be introduced into the trachea of the rabbit, 
within twenty-four hours the caseous areas often begin to soften. The softening may 
begin at the centre, or may surround a central portion of the necrotic mass. The 
softening is soon followed by absorption, and so cavities are formed of varying sizes 
and shapes (Fig. 405). 
It will thus be seen that in the rabbit a concurrent infection with the tubercle Pathology-Delafield and Prudden. 
Plate X. 
Pulmonary Tuberculosis-Exudative Type-with Large Cavities. 
The entire lung is solid from new-formed tubercle tissue and exudate which are both 
largely in a condition of coagulation necrosis. 
The thickened trunks of the larger pulmonary vessels are exposed in the depths of 
the ragged communicating cavities. 
This lung was hardened in alcohol without injection of the blood-vessels. THE RESPIRATORY SYSTEM 
633 
bacillus and the streptococcus has an important bearing upon the breaking down of 
lung tissue which leads to the formation of cavities. While it would not be wise to 
assume from these experiments on the rabbit that a similar condition is always 
present w'hen cavities form in man, we have seen that in fact a similar concurrent 
infection in man in acute phthisis actually does often exist. 
Fig. 405.-Experimental Tuberculous Inflammation in the Lung of a Rabbit, with the 
Formation of Cavities. 
The lung was injected with a considerable quantity of tubercle-bacillus culture through the trachea, 
followed after twenty-eight days by the injection of the broth culture of the Streptococcus pyogenes. 
Animal killed seven days after the streptococcus injection. The specimen shows large areas of consoli- 
dation with cavities. The lesions resemble those of acute phthisis with cavities in man. 
Syphilitic Pneumonia. 
Persons suffering from inherited or acquired syphilis sometimes 
develop inflammations of the lungs which seem to be due to the syphilitic 
infection. The lungs may then be affected in several different ways. 
There may be well-defined large or small gummata with or without 
interstitial and more or less exudative pneumonia. There may be a 
formation of new fibrous tissue in the walls and lung tissue about the 
bronchi, often with ulceration of the mucous membrane and distortion of 
these structures. There may be, particularly in the new-born, lobular or 
lobar hepatization, the affected region appearing reddish or gray or white. 
This is due to a growth of new cellular tissue in the walls of the air 634 
THE RESPIRATORY SYSTEM 
spaces and to an exudate largely of epithelial cells in the air spaces. 
Infarctions of the lung from obliterating endarteritis may be present. It 
is often difficult to determine in many cases of interstitial inflammation 
of the lungs whether the lesion be syphilitic or not.1 
TUMORS. 
Fibroma and osteoma are rare. Enchondroma may occur as a pri- 
mary tumor originating in the cartilages of the bronchi. Sarcoma is not 
Fig. 406.-Secondary Carcinoma of the Lung. 
The primary tumor involved the gall-ducts, liver, and pancreas. The metastatic tumors in the 
lung were in part white, in part dark red from interstitial haemorrhage. 
common and is usually secondary.2 "Lymphoma" may develop in the 
lungs in leukaemia and pseudo-leukaemia. Endothelioma is of occasional 
occurrence in the lung, and, following the subpleural lymph-vessels, may 
1 For a bibliography of pulmonary syphilis consult Flockemann, Centralbl. f. Path., Bd. x., 
p. 449, 1899. 
2 For a study of primary sarcoma of the lung see Eckersdorff, Centralbl. f. Path., Bd. xvii., p. 355, 
1906; also Pater and Rivet, Arch, de med. exp., t. xviii., p. 85, 1906. THE RESPIRATORY SYSTEM 
635 
form a reticular raised white network on the surface of the lung (Figs. 
407 and 408). Adenoma as a primary tumor is rare. Primary carci- 
noma of the lung, originating in the bronchi, is of occasional occurrence.1 
The inner surface of a segment of the costal pleura, containing three of the ribs, is shown in the cut. 
Fig. 407.-Endothelioma of the Pleuha. 
It may be associated with exudative pneumonia and involve large por- 
tions of the lungs as well as the pleura. Secondary carcinoma of the 
lung is not infrequent. The malignant growths in the lung may occur 
Fig. 408.-Endothelioma of the Pleura. 
Showing the growth of the tumor along the superficial lymph-vessels. 
as circumscribed nodular masses, displacing the lung tissue (Fig. 406), 
or they may infiltrate the lung, often following the bronchi and larger 
blood-vessels. The cells of such tumors often grow into and fill up the air 
1 See Henrici, Jour. Med. Research, 1912, N. S. xxi, 595; also Adler, Primary malignant Growths 
of the Lungs and Bronchi, New York, 1912 636 
THE RESPIRATORY SYSTEM 
spaces of the lung, over large areas, without immediate involvement of 
their walls.1 
Dermoid cysts have been found in the lung. 
THE MEDIASTINUM. 
Inflammation.-Suppurative inflammation may occur either in the anterior or 
posterior mediastinum. It may be caused by fractures, caries or necrosis of the ster- 
num and vertebrae, by perforation of the oesophagus, by suppuration of the lymph- 
nodes, or by pleurisy, or may occur without discoverable cause. 
The pus may infiltrate the connective tissue, or may form abscesses which may 
attain a large size. The inflammation may extend to the pleura or the pericardium, 
the abscesses may displace the heart, the lungs, or the sternum; or they may perforate 
through the skin, into a pleural cavity, the oesophagus, the trachea, or a bronchus.2 
A few cases of chronic inflammation of the tissues of the mediastinum have been 
reported-chronic mediastinitis.3 Lesions of the tracheal and bronchial lymph-nodes 
are considered on page 592. 
Tumors.-The most common form of new growth in the mediastinum is that 
known by the names of lymphoma, lymphosarcoma, and lymph-adenoma. 
These tumors are confined to the mediastinum, or they are associated with similar 
growths in other parts of the body in the disease called "pseudo-leukaemia." Persons 
between the ages of twenty and thirty years seem to be the most liable to the growth, 
but it is also not uncommon in children. It begins in the lymph-nodes in the medias- 
tinum, and at the root of the lung. It increases at first slowly, then more rapidly, and 
gradually infiltrates the adjoining tissues. In this way the walls of the trachea, 
bronchi, aorta, the pericardium, the pleura, and the lung, become infiltrated with 
compression of the surrounding organs. 
The growth is composed of a fibrous stroma associated with small round cells, the 
relative quantity of cells and stroma varying in the different cases. 
Besides this form of tumor there may also occur in the mediastinum tumors similar 
to those which grow in the pleura and behind the peritoneum-tumors which resemble 
both the sarcomata and carcinomata, and which it is difficult to classify. Aberrant 
thyroid-gland tissue may be found in the mediastinum. 
Complex tumors belonging among the foetal inclusions or teratomata are of occa- 
sional occurrence in the anterior mediastinum.4 They may contain bone, cartilage, 
connective tissue, muscle, hairs, skin, etc. Cysts sometimes lined with ciliated epithe- 
lium may form in such tumors.5 
The Pleura. 
Non-inflammatory accumulations of clear serum in the pleural cavi- 
ties are of frequent occurrence. They occur under conditions similar 
to those which lead to dropsy in other parts of the body-lesions of the 
heart, liver, and kidneys, and changes in the circulation and in the com- 
position of the blood. 
If the amount of serum be large it may compress the lower lobes of 
the lungs. 
HYDROTHORAX. 
1 For a consideration of the diagnosis of malignant tumors of the lung consult Adler, New York 
Med. Jour., Feb. 8th and 15th, 1896, bibl. 
2 For tuberculous lesions of the tracheo-bronchial lymph-nodes see reference, p. 592. 
3 Whipham, Lancet, 1899, vol. i., pp. 882, 947, bibl. 
4 See Mandlebaum, Am. Jour. Med. Sciences, vol. cxx., p. 64, 1900. 
6 Consult Hare, ''Tumors of the Mediastinum," Phila., 1889; also Zahn, Virchow's Archiv, Bd. 
cxliii., pp. 170 and 416, 1896; also Lohrisch, Lubarsch and Ostertag's "Ergebnisse," Jahrg. vii., 1900- 
1901, p. 912, bibl.; also, for a study of dermoid cysts of the mediastinum, see Morris, Med. News, vol. 
Ixxxvii., pp. 404, 438, 494, 538, 1905. Pathology-Delafield and Prudden. 
Plate XI. 
Pulmonary Tuberculosis (Chronic), with Large Cavities. 
The ragged communicating cavities involve a large part of the lung and are bronchiec- 
tatic in origin. The bronchial lymph-nodes are enlarged, tuberculous, and caseous. The 
pleura and interlobar septum are thickened by the formation of dense fibrous tissue. Pathology-Delafield and Prudden. 
Plate XII. 
Chronic Pulmonary Tuberculosis with a Fibrous-Walled Cavity at the Apex. 
The fibrous wall of the cavity is dense and is continuous with the 
greatly thickened pleura and with the diffuse new-formed connective 
tissue throughout the upper lobe. The upper lobe is greatly reduced in 
size by the cicatricial contraction of the fibrous tissue. The lower lobe 
shows two areas of tuberculous consolidation; both are caseous in the 
central portions; the upper shows commencing tuberculous bronchiec- 
tasia. The upper part of the fibrous wall of the cavity, firmly adherent 
to the thoracic wall, has been cut away. THE RESPIRATORY SYSTEM 
637 
HYDRO-PNEUMOTHORAX-PYO-PNEUMOTHORAX. 
The presence of air in the pleural cavities is usually associated with 
a serous or purulent exudate. It may occur as the result of perforation 
of the lung, from rupture, from ulceration of tuberculous lesions at the 
pleural surfaces, from injuries to the chest wall, perforation of the dia- 
phragm by suppurative or cancerous lesions of the oesophagus, stomach, 
or intestine, as well as in a variety of other conditions. Gas may form 
in the pleural cavities in infection by the Bacillus aerogenes capsulatus.1 
HEMORRHAGE. 
Subpleural ecchymoses may occur in asphyxia or during infectious 
diseases or intoxications. More extensive extravasations of blood- 
hsemothorax-may be the result of injuries to the wall of the thorax or 
the rupture of aneurism. 
Haemorrhagic Exudates are usually associated with tuberculous 
inflammation of the pleura or with infarctions of the lungs, carcinoma, 
or injuries, infectious diseases, or cirrhosis of the liver. 
INFLAMMATION. (Pleuritis, Pleurisy.) 
Inflammation of the pleura may occur as an independent lesion, but 
it is commonly associated with pathological processes in the lungs, peri- 
cardium, abdomen, or chest wall. It may be exudative in character, 
usually associated with more or less proliferation of the mesothelial 
("endothelial") and connective-tissue cells, or it may be productive 
with the formation of new connective tissue. These phases of inflamma- 
tion may be associated. Through the production of new connective 
tissue, repair of the acute inflammatory lesion is commonly effected. 
In the exudative forms of pleurisy the exudate may consist of fibrin, or 
of serum and fibrin, or of serum with fibrin and pus. 
Simple Fibrinous Pleurisy (Dry Pleurisy; Pleuritis Sicca).-This may 
involve circumscribed areas of the costal, mediastinal, diaphragmatic, 
or pulmonary pleura, less frequently the entire pleura of one side of the 
chest. The affected portions of pleura are dull and lustreless and coated 
with fibrin, opposing surfaces often being joined by bands of fibrin. 
There are swelling, degeneration, proliferation, and exfoliation of the 
mesothelium, with swelling and proliferation of the connective-tissue 
cells beneath. Exceptionally, there is involvement of the entire pleura 
of one side, with the production of such a large amount of fibrin as 
seriously to compress the lung.2 
Sero-fibrinous Pleurisy (Pleurisy with Effusion).-This is the most 
common form of pleurisy. As a rule, it involves the greater part of the 
1For a study of pneumothorax see Emerson, Johns Hopkins Hosp. Rep., vol. xi., p. 1, 1903. 
2 For a study of the origin of fibrin and adhesions of the serous membranes consult Heinz, Virch 
Arch., Bd. clx., p. 365, 1900; also Gaylord, Jour. Exp. Med., vol. iii., p. 1, 1898, bibl. 638 
THE RESPIRATORY SYSTEM 
pleura of one side of the chest. Sometimes, however, the pleura of both 
sides of the chest is involved, and then the pericardium also is often 
inflamed. 
While the inflammation is in progress the surface of the affected 
pleura is coated with fibrin, and bands of fibrin stretch between the 
parietal and pulmonary pleurae. In the pleural cavity is serum in vari- 
able quantity. This serum is clear, or turbid from the presence of 
exfoliated mesothelium, leucocytes, and flocculi of fibrin or red blood 
cells. The lung is compressed in different degrees and positions, accord- 
ing to the quantity of the serum and the character of the adhesions. The 
heart may also be displaced by the accumulated exudate. 
The natural termination of such a pleurisy is the recovery of the 
patient, with thickenings of the pleura and adhesions. The irregular 
terminations are: The death of the patient, the protracted existence of 
the fibrin and serum, and the change of the character of the inflammation 
so that pus is produced. 
If the patient recover, the serum is absorbed, the fibrin disappears, 
and repair is effected, as in simple fibrinous pleurisy, by the formation 
of granulation tissue, which gradually becomes dense and cicatricial in 
character and may remain as local or general thickenings or firm adhe- 
sions of the opposed pleural surfaces. The lung may be distorted by 
contraction of the new-formed connective tissue. The exudates in the 
sero-fibrinous form of pleurisy do not usually infiltrate the pleura, but 
gather upon its surface and in the cavity. 
The Excitants of Sero-fibrinous Pleurisy.-Cultivations from 
the exudate give in the larger proportion of cases negative results; but 
the pneumococcus, Streptococcus pyogenes, Staphylococcus aureus and 
albus, and the typhoid bacillus have been isolated. When the inflam- 
mation of the pleura is consecutive to acute lobar pneumonia, the 
pneumococcus may still not be found in the exudate. The presence 
of the streptococcus is frequently followed by the formation of pus. 
The organisms named above may be present alone or in various associa- 
tions. Many cases with simple sero-fibrinous exudate prove on inocula- 
tion to be tuberculous.1 
Suppurative Pleurisy (Empyema).-Suppurative pleurisy may occur 
either with or without the formation of a considerable sero-fibrinous 
exudate. The exudate may be purulent from the beginning, or a sero- 
fibrinous exudate may assume this character. 
The pleural cavity in empyema is partly or completely filled with 
purulent fluid, and the lung is either compressed against the vertebral 
column or partly adherent to the chest wall. Sometimes, however, the 
purulent fluid is shut in by adhesions, either between parts of the lung 
and the thoracic wall, or between the lung and the diaphragm, or between 
the lung and the pericardium, or between the lobes of the lung. 
The fluid in the pleural cavity is usually a thin, purulent serum, 
1 For a study of the bacteria in exudative pleuritis, with the earlier bibliography, consult Prudden, 
New York Med. Jour., June 24th, 1893. For fuller data see Netter, Bouchard and Brissaud's "Trait6 
de Medecine," t. vii., p. 399, 1901. THE RESPIRATORY SYSTEM 
639 
composed of serum, pus cells, mesothelial cells, and flocculi of fibrin; 
but sometimes this fluid is thick and viscid. 
While in children the more or less active suppurative process in the 
pleura may continue for a long time without deep involvement of the 
pleura, in adults granulation tissue may form upon the pleura, which 
thus becomes gradually thickened and may so remain for months with 
its inner vascular surface covered with pus and fibrin. In such cases, as 
well as in less chronic forms, the fibrin fibrils are often swollen and 
coalesce to form irregular homogeneous or finely granular masses. 
Resolution may occur in one region of the pleura while the exudate in 
another may become encapsulated by new-formed connective tissue. 
In old cases the thickening of the pleura may be great and it may 
become calcified.1 The perichondrium of the cartilages and the peri- 
osteum of the ribs may become inflamed, with necrosis of the cartilages 
and ribs or a production of new bone. Necrosis and gangrene of the 
involved pleura may occur and putrefactive process be set up in the exu- 
date. The suppurative process may extend from the pleura involving 
adjacent parts, such as the fasciae, the muscles, the skin, the diaphragm, 
or the lungs. Thus the pus may find an exit, through the wall of the 
thorax, into the peritoneal cavity or into the lungs. 
In inflammation of the pleura the process may extend to the lym- 
phatics in the interlobular septa, around the bronchi, and around the 
blood-vessels. This interlobular lymphangitis occurs more frequently in 
children than in adults. The lymphatics in the interlobular septa and 
those around the bronchi and blood-vessels are distended with pus cells, 
the septa are much thickened, and the lobules separated from each other. 
Sero-fibrinous pleurisy and empyema may occur as complications of 
infectious diseases, such as scarlatina, typhoid fever, and various forms 
of septicaemia, or by an extension of an inflammatory process from such 
adjacent parts as the pericardium, lungs, mediastinum, etc.2 The vari- 
ous forms of pneumonia are frequently associated with local or general 
inflammation of the pleura. 
The Excitants of Empyema.-Streptococcus pyogenes is the most 
frequent excitant of suppurative inflammation of the pleura. According 
to the statistics of Netter this organism has been found in a little over 
forty per cent, of the cases examined of all ages. The pneumococcus 
has been found in over twenty-five per cent, of cases examined. The 
streptococcus and the pneumococcus are associated in a small proportion 
of cases. Of less frequent occurrence are Staphylococcus pyogenes, 
Bacillus typhosus,3 Bacillus coli communis, the gonococcus, the pneumo- 
bacillus of Friedlander, and the influenza bacillus. In empyema with 
fetid exudate, various forms of bacteria may be present. While in the 
adult the streptococcus is most often found in the empyemic exudate, 
1 For a risumi of our knowledge of various calcifications in the lungs, and allied conditions often 
called "lung stones," consult Polaillon, "Les Pierres du Poumon," etc., Paris, 1891; or Legry, Arch, 
gen. de med., vol. i., pp. 337 and 466, 1892. 
2 For a study of relation of oesophageal diverticula to empyema see Starck, Arch. f. Verdauungskr., 
Bd. vii., 1901, p. 1. 
3 Consult for cases and bibl. Gordinier and Lartigau, Am. Jour. Med. Sci., vol. cxxi., p. 43, 1901. 640 
THE RESPIRATORY SYSTEM 
in young children the pneumococcus is, according to Netter,1 most 
common. 
Chronic Pleurisy with Adhesions.-This form of pleurisy may follow 
one of the varieties of pleurisy just described, it may be associated with 
emphysema and chronic phthisis, or it may occur by itself. 
After death the pulmonary and costal pleura are found thickened and 
joined together by numerous adhesions. These changes may involve 
only a part or the whole of the pleura on one or both sides of the chest. 
The thickened pleura is covered with mesothelium; the new connec- 
tive tissue may be very dense and may contain few or many cells. 
Blood-vessels may be numerous and irregular in distribution or few in 
number. New lymph-vessels are formed with the growth of the new 
tissue.2 These, as well as the old lymph-vessels, may be dilated, forming 
small cysts. 
Tuberculous Pleuritis.-Acute general tuberculosis of the pleura is 
usually secondary to tuberculous inflammation elsewhere in the body, 
either in the lungs, which is most common, or the bronchial lymph-nodes, 
peritoneum, bones, etc., or it may be a part of a general miliary tuber- 
culosis. There may be localized or widely disseminated miliary tuber- 
cles upon or beneath the pleural surfaces, either in direct association 
with lesions beneath the pulmonary pleura or apart from these or upon 
the costal pleura. The tuberculous foci may be larger and more diffuse. 
The minute characters of the inflammation are not essentially different 
from those found in tuberculosis in connective tissue elsewhere, but the 
mesothelial cells covering the pleura may share largely in the early 
phases of the new growth. 
If the process be prolonged, much dense fibrous tissue may be formed 
in which are miliary tubercles in various stages of coagulation necrosis, 
or larger patches of necrotic tissue surrounded by miliary tubercles or 
diffuse tuberculous tissue. 
With acute types of tuberculous inflammation of the pleura more or 
less exudate may form. This may be sero-fibrinous, often with very 
little fibrin, or, as is frequently the case, it may be tinged or deeply colored 
with blood. The exudate may be purulent. The tubercle bacillus may 
be associated with other bacteria, most often with the Staphylococcus 
pyogenes in the purulent exudate. 
Many cases of pleuritis with a sero-fibrinous exudate giving no growth 
of bacteria on the ordinary culture media are found to be tuberculous, by 
the inoculation of guinea-pigs with the fluid. 
Chronic Miliary Tubercles.-Miliary tubercles of the pleura, chronic 
in form, mostly composed of fibrous tissue, with cheesy degeneration 
or calcification, are very common, and are frequently associated with 
tuberculous bronchial lymph-nodes without tuberculosis in other parts 
of the body. These tubercles are usually widely scattered over the pleura 
(and are almost always associated with anthracotic pigmentation. 
1 Netter, Bouchard and Brissaud's "Traite de Medecine," t. vii., p. 445, 1901. For a study of the 
ways of infection of the pleura see Grober, Deut. Arch. f. klin. Med., Bd. Ixviii., p. 296, 1900, bibl. 
2 For a study of the formation of new lymph-vessels in pleurisy see Guyot, Ziegler's Beitrage, Bd. 
xxxviii., p. 207, 1905. THE RESPIRATORY SYSTEM 
641 
The dense fibrous tubercle or the cheesy or calcified portion may be 
seen as a lighter spot in the pigmented area (Fig. 376). Such tuber- 
cles are sometimes accompanied by minute cystic dilatations of the 
lymph-vessels on which they are formed. 
These pleural tubercles develop along the subpleural lymphatic 
vessels, or in the areas of lymphoid tissue or in the minute subpleural 
lymph-nodes.1 
The presence of these healed tubercles, which rarely harbor stainable 
tubercle bacilli, together with the simultaneous involvement and pig- 
mentation of the bronchial lymph-nodes, affords strong evidence of the 
frequency of the direct infection of the lungs through the respiratory 
passages. They are formed along the lines of lymph drainage of the lungs 
which ultimately enter the bronchial nodes. Since in this drainage 
inhaled pigment particles and tubercle bacilli are deposited together, the 
frequent association of pigmentation and tuberculosis is comprehensible. 
Hodenpyl2 has shown the great frequency of those chronic pleural 
pigmented tubercles, and Ribbert3 believes that the tuberculous process 
precedes the local pigmentation and furnishes suitable conditions for it. 
TUMORS. 
Fibroma, sarcoma, and endothelioma may occur as primary tumors of 
the pleura. Small, white, slightly projecting, often pigmented eleva- 
tions of the pleura, either single or multiple, are common. These were 
formerly regarded as mostly miliary fibromata. But Hodenpyl and 
Fig. 409.-Endothelioma of the Lung. 
The growth is in the subpleural lymph-vessels, which seen from the pleural surface in the fresh 
lung formed a white raised network over a considerable portion of one lung. The lymph-vessels in 
the cut are seen in transverse section. 
others have shown that while some may be fibromata or lymphangio- 
mata or air cysts, they are mostly fibrous masses which replace or enclose 
miliary tubercles.4 Fibroma and lipoma formed in the subpleural tissues 
may encroach upon the pleural cavity. Endothelioma usually occurs in 
the form of larger and smaller, flat or projecting, irregular nodular masses 
1 See p. 603. 
2 Hodenpyl, Med. Record, vol. lv., p. 903, 1899. 
8 Ribbert, Deut. med. Woch., p. 1615, 1906. 
4 See ref. Hodenpyl, above. 642 
THE RESPIRATORY SYSTEM 
(Fig. 407), frequently most marked and extensive upon the costal pleura 
(Figs. 408 and 409).1 This as well as other tumors of the pleura may 
be associated with an exudative pleuritis. 
Carcinoma, primary in the thyroid, mamma, oesophagus, and stomach, 
may invade the pleura. Echinococcus and other cysts of the pleura have 
been recorded.2 
1 For bibliography of endothelioma of the pleura consult Glockner, Zeits. f. Heilkunde, Bd. xxviii., 
p. 209, 1897. 
2 For a description of ciliated cysts of the pleura see Zahn, Virchow's Arch., Bd. cxliii., p. 170,1896. CHAPTER VH. 
THE DIGESTIVE SYSTEM. 
The Mouth. 
Malformations of the lips and cheeks are usually associated with defective forma- 
tion of the bones of the mouth. The entire process is generally due to an arrest of 
development or a failure of the branchial arches to fuse normally (see Figs. 175 and 
177). 
1. The lower jaw is absent; the upper jaw and hard palate are small and imper- 
fectly formed; the temporal bones nearly touch in the median line. The lower part of 
the face is, therefore, wanting; the mouth is absent, or small and closed posteriorly; 
the tongue is absent. Such a malformation is rare; the foetus is not viable. 
2. The face remains in its early foetal condition of a large cleft; the mouth and nose 
form one cavity; the orbits may be united in the same cavity. The foetus is not viable. 
3. There is a cleft in the upper lip, upper jaw, and hard palate. The cleft corre- 
sponds to the point of junction of the processes of the superior maxilla with the inter- 
maxillary bone. There may be one cleft or two, one on either side of the intermaxil- 
lary bone. The cleft involves the lip alone,-harelip (Fig. 176)-or the lip and supe- 
rior maxilla, or the lip, maxilla, and palate. There may be a single, or a double cleft in 
the palate, and the cleft may involve either the hard or soft palate, or both. If there 
are two clefts of the lip and maxilla the portion of lip and bone between them may be 
small, or entirely absent so as to leave a large open space. The soft palate may be 
entirely absent. This is a common malformation and does not endanger life. 
4. Rarely there is a cleft involving the middle of the lower lip, and sometimes 
extending into the inferior maxilla. 
5. Either the inferior, or the superior, or both maxillary bones may be abnormally 
small. 
6. The edges of the lips may be partly or completely joined together. The open- 
ing of the mouth may be only a round hole. 
7. The lips may be absent or imperfectly developed. 
8. The corners of the mouth may be prolonged by clefts in the cheeks nearly to the 
ears. 
Malformations. 
INFLAMMATION.-(Stomatitis.) 
Catarrhal stomatitis is most frequent in children and occurs with a 
great variety of local and general disturbances. 
During life the congestion and swelling of the mucous membrane may 
be well marked and there are often white patches, produced by the death 
of the superficial epithelial cells. There may be an increased production 
of mucus, or, instead of this, the entire mucous membrane is unnaturally 
dry. In addition to hypersemia and local oedema there may be prolifer- 
ation, exfoliation, and degeneration of the epithelium. 
Extravasated leucocytes may infiltrate to a moderate degree the 
stroma of the mucous membrane and appear upon its surface. Small, 
clear vesicles may form beneath the epithelium from the collection of 
serous exudate. 
643 644 
THE DIGESTIVE SYSTEM 
Croupous stomatitis is incited by local irritants, by local infection, or 
by the extension of the same form of inflammation from the pharynx; it 
frequently occurs with diphtheria and other infectious diseases. 
Portions of the mucous membrane are swollen and congested, and 
covered with a false membrane. This false membrane is composed of a 
thickened layer of epithelium in the condition of coagulation necrosis, 
and of fibrin and pus in variable relative quantity. The stroma of the 
mucous membrane may be infiltrated with pus and fibrin, and portions 
of it may become necrotic. 
Aphthous Stomatitis.-In this condition small whitish projecting 
patches surrounded by a zone of hyperaemia may form upon the mucous 
membrane. These consist of a more or less fibrinous exudate beneath 
the epithelium which may exfoliate, leaving small ulcers. 
Ulcerative Stomatitis.-This form of stomatitis is apt to occur in 
ill nourished children or in young adults, in scurvy, or in mercurial poison- 
ing. It usually begins at the margin of the gums of the lower jaw and 
extends to the cheeks and tongue. The affected parts are swollen and 
coated with a grayish, soft pellicle composed of bacteria and necrotic 
tissue. The gums may be destroyed around the teeth, and these may 
fall out. The surrounding soft parts are swollen, and there may be 
necrosis of the jaws. 
In noma or gangrenous stomatitis similar changes may be associated 
with extensive gangrenous destruction of the cheeks. This most often 
occurs in young children in connection with measles, scarlatina, or 
typhoid fever. It has been claimed that a special micro-organism is the 
excitant of this disease, but this has not yet been proved. 
Thrush. (Soor; Parasitic Stomatitis.)-In ill-nourished children or in 
adults suffering from chronic disease a fungus related to the yeasts- 
o'idium albicans-may grow among the epithelial cells of the mouth, form- 
ing white membranous patches. These may involve large areas of the 
mouth and pharynx and extend to the oesophagus or upper respiratory 
passages. 
Phlegmonous Stomatitis.-Exudative inflammation of the mouth may 
result from infected wounds, in connection with erysipelas or suppurative 
or other infectious process near the mouth. Various pyogenic bacteria 
may be its excitants. 
Chronic Stomatitis.-This may follow acute catarrhal or other inflam- 
matory processes, or most frequently syphilis, and may be due to per- 
sistent irritation-for example, from the use of tobacco. Owing to hyper- 
plasia of the epithelium and submucous tissue, white patches of varying 
extent may form on the tongue or elsewhere-leucoplakia buccalis. 
These through excessive increase in the epithelium may project in wart- 
like form from the surface-ichthyosis. 
Tuberculous stomatitis commences with the formation of miliary 
tubercles or of larger tuberculous masses in the stroma of the mucous 
membrane. These masses soon degenerate, soften, and form ragged 
ulcers. 
Syphilitic Stomatitis.-As a result of syphilis there may be produced THE DIGESTIVE SYSTEM 
645 
either the so-called mucous patches or gummy tumors. In the mucous 
patches the epithelial layer is at first thickened and the papillae of the 
stroma are swollen and infiltrated with cells (see Fig. 157, p. 271 and 
Fig. 158, p. 272). This may be followed by desquamation of the epi- 
thelium and ulceration. 
TUMORS. 
Fibroma, lipoma, and enchondroma have been seen in a few cases in 
the lips. When in the mouth they usually grow from the bones. Epulis 
is a tumor of the jaw, fibrous, sarcomatous, or epitheliomatous. 
Papillomata occur most frequently at the edges of the lips, but are 
also found on the gums, the floor of the mouth, and the cheeks. They 
are formed of hypertrophied papillae, covered with thickened epidermis. 
They often ulcerate. Angioma, either congenital or developed after 
birth, occurs in the lips. Adenoma may be formed in the mucous mem- 
brane covering the mouth, lips, and soft palate. The tumors are rounded, 
usually small, sometimes as large as a hen's egg. They may be situated 
in the thickness of the mucous membrane, or project in a polypoid form. 
Carcinoma is of frequent occurrence and is usually of the epithelioma- 
tous form. Such tumors may form at any part of the mucous membrane 
of the mouth, but often begin in the edge of the lower lip as a result of 
persistent irritation, as in pipe smokers. 
They may originate in an ulcerating papilloma, or as a flat, super- 
ficial growth from the deeper layers of the epithelium, or as deep nod- 
ules starting in the mucous glands. They are composed of large masses 
of epithelial cells, closely packed together, often forming nests, and 
arranged in anastomosing tubular masses. The stroma surrounding 
these masses is infiltrated with cells. In a few cases the infiltration of 
the stroma with small round cells may be very marked, so marked that 
the epithelial growth may be obscured. The new growth may increase 
in size, ulcerate, infiltrate the adjacent tissues, and may give rise to 
metastatic tumors. 
Cysts.-Dermoid cysts and cysts of the embryonal branchial clefts 
may involve the mouth. Simple cysts may form in the jaws from aber- 
rancies in the development of the teeth. For a description of the so-called 
adamantinoma, see p. 415. Complex congenital tumors of the gums are 
of rare occurrence, apparently arising in some congenital anomaly.1 
The Tongue. 
Malformations. 
Absence of the tongue may be associated with the extreme defects of development 
of the face already mentioned. 
The anterior portion of the tongue may be absent while its base remains. The 
lower jaw is then small. The tongue may be cleft or lobulated. 
It may be partly or completely adherent to the floor of the mouth. The frenulum 
1 For a study of such complex tumors of the mouth see Schorr, Ziegler's Beitr., Bd. xxxix., p. 82, 
1906. 646 
THE DIGESTIVE SYSTEM 
may be abnormally short, or may extend to the tip of the tongue. In rare cases the 
sides of the tongue are adherent, or its upper surface may be adherent to the roof of the 
mouth. 
HYPERTROPHY AND INFLAMMATION. 
Macroglossia, or hypertrophy of the tongue, is almost always a con- 
genital lesion, and is especially common in cretins. The tongue may be 
so large that it protrudes through the lips. The lips may also be simi- 
larly enlarged. There is hyperplasia of the fibrous and other tissues of 
the tongue, and in addition to this there may be a dilatation of the lym- 
phatic vessels. 
Inflammations of the tongue-glossitis-may be associated with sim- 
ilar changes in the mouth, or may occur by themselves. In catarrhal 
inflammation the accumulation of epithelium may give rise to the 
" furred tongue. " Most of the inflammatory processes above indicated 
as occurring in the mouth may affect the tongue also. 
TUMORS. 
Cysts.-The most common forms of cysts are the sacs beneath or 
partly in the substance of the tongue-ranula. They are formed by 
dilatation of the ducts of the mucous glands, or of the submaxillary and 
sublingual glands. Amyloid tumors of the tongue have been reported.1 
Lipoma and fibroma are rare. They form nodules in the substance 
of the tongue or project in a polypoid form. Composite tumors, com- 
posed largely of fat, are found on the tongue as a congenital condition. 
Angioma.-Cavernous vascular tumors are found in the substance of 
the tongue and projecting from its surface. 
Sarcoma is not common in this situation, but may occur both in chil- 
dren and in adults. Carcinoma, usually of the epitheliomatous type, may 
originate in the tongue or may extend to it from the adjacent tissues. 
MICRO-ORGANISMS OF THE MOUTH. 
Micro-organisms of various forms-bacteria, moulds, and yeasts-are 
always present in the mouth, often in enormous numbers. They are for 
the most part not of significance save for the putrefactive processes 
which they initiate and maintain in mouths not properly cleansed. On 
the other hand, Staphylococcus and Streptococcus pyogenes and the 
pneumococcus are of frequent occurrence in the mouths especially of 
those who live in towns and crowded dwellings, and, while usually harm- 
less, they may under favorable conditions become excitants of serious 
disease. 
The tubercle bacillus may be present in the mouth as well as in the 
nose of those who care for uncleanly consumptives. 
The fungus of thrush (soor), and leptothrix, which under usual 
conditions are not harmful, may incite serious local disease. 
1 See Schmidt, Vireh. Arch., Bd. cxliii., p. 369. 1896, bibliography of amyloid tumors in general. THE DIGESTIVE SYSTEM 
647 
The so-called Mycosis pharyngis is apparently due to the growth in 
susceptible persons of a form of leptothrix not yet thoroughly studied, 
on account of the technical difficulties in the way of its artificial cultiva- 
tion.1 
The Pharynx. 
Malformations. 
Branchial Fistula and Cysts.-When, as not infrequently occurs, the embry- 
onal gill clefts do not properly close, fistulce may remain.2 These may in rare cases be 
complete, so that an opening exists from the pharynx, larynx, or trachea to the side of 
the neck (see Fig. 175, p. 322). More frequently, however, these fistula: are incom- 
plete and shallow, and open either inward into one of the above-named organs or 
Formed from the imperfect closure of an embryonal gill cleft. The cyst is lined with ciliated epithe- 
lium, and the wall is largely formed of diffuse lymphoid tissue. 
Fig. 410.-Section of the Wall of a Branchial Cyst of the Neck. 
outward on to the neck. Small portions of the gill clefts may persist without external 
openings, and from these subcutaneous cysts of the neck are often developed. Or a 
portion of the cleft may be cut off, forming a cyst, while the fistula persists with its 
external opening. 
The walls of these fistulse and cysts may be covered with mucous membrane having 
cylindrical or flattened or ciliated surface cells. Or, when formed from the outer 
clefts, they may be lined with skin. 
Not infrequently the walls of these cysts and fistulse are embedded in lymphatic 
tissue, which may be diffuse or gathered in nodular form (see Figs. 410 and 411).3 
Diverticula of the pharynx have been observed. 
1 For methods of cultivating spirochetes (Treponema) found in the mouth see Noguchi, Jour. Exper. 
Med., 1912, xv, 81; and 1912, xvi, 194. 
2 For details of the formation of fissures in the cervical region from incomplete closure of the 
branchial clefts see Thoma, "Text-book of General Pathology," Eng. transl., 1896, p. 201. 
3 For bibliography of branchial cysts and fistula; see Coplin, Proc. Path. Soc. of Phila., N.S., vol. 
iv., p. 109, 1901. 648 
THE DIGESTIVE SYSTEM 
INFLAMMATION. (Pharyngitis, Angina.) 
Catarrhal pharyngitis is usually associated with the same forms of 
inflammation in the mouth and has similar characters. 
In catarrhal inflammation involving the tonsils and those portions of 
the pharynx richly supplied with the so-called submucous adenoid- 
lymphoid-tissue, leucocytes may in considerable numbers pass through 
the thin epithelial layer and mingle with the exudate upon the exposed 
surface. 
In chronic inflammation of the pharynx there may be a large and 
permanent hyperplasia of the lymphoid tissue, with more or less dense 
Fig. 411.-Section of the Wall of a Branchial Cyst of the Neck. 
This cyst, like that shown in Fig. 410, has much lymphoid tissue in the wall, but nodular in 
character; while the epithelial lining is squamous in type. 
fibrous tissue, leading to diffuse or circumscribed nodular or peduncu- 
lated masses of vascular new tissue in the vault or elsewhere in the 
pharynx, called "adenoids."1 
Phlegmonous pharyngitis may occur with inflammations of the 
mucous membrane, with caries of the cervical vertebrae, with inflammation 
of the cervical and parotid glands, with periostitis of the cranial bones, or 
it may occur independently. It may result in swelling and oedema, in 
induration, or in suppuration. It is most important when it affects the 
posterior wall of the pharynx and forms retro-pharyngeal abscesses. 
Such abscesses may cause death by suffocation. 
Diphtheritic pharyngitis is that form of pseudo-membranous or 
croupous inflammation of which the Bacillus diphtherise is the ex- 
citant. The general characters of the diphtheritic infection have been 
considered in an earlier part of this book. The local process, often 
1 See p. 650. For a study of the uvula in various abnormal conditions see Hoen, Jour. Exp. Med., 
vol. iii., p. 549, 1898. THE DIGESTIVE SYSTEM 
649 
affecting the fauces, pharynx, and tonsils, may involve the mouth as 
well as the larynx and trachea. (For details of the local lesion 
see p. 282.) 
Tonsillitis.-The tonsils may share in the inflammatory processes of 
the pharynx or be independently affected. The structural characters 
of the tonsils render them liable to infection and involve certain pecu- 
liarities in the lesions.1 
In Follicular Tonsillitis the swollen organ shows upon section an 
increase in the number of the lymphoid cells of the nodules and a hyper- 
plasia of the endothelium of the reticulum. These new-formed and 
often exfoliated endothelial cells are similar to those found in the lymph- 
nodes in general in the presence of bacterial or other toxic substances. 
There may be an increase in the cells of the stroma of the tonsil. The 
epithelial cells of the surface and the crypts may increase in number 
and exfoliate. Epithelial cells and leucocytes and other forms of exudate 
may gather in the crypts or over the surface of the tonsil, forming white 
plugs or a whitish pellicle.2 
In Exudative Tonsillitis (suppurative or phlegmonous tonsillitis, 
quinsy) there are, in addition to hyperplasia and catarrhal inflammation, 
oedematous swelling and suppuration often leading to abscess. 
Acute inflammation of the pharynx and tonsils is usually infectious 
in character, and may be due to various forms of pyogenic and other 
organisms. Thus in tonsillitis and other forms of acute angina, the most 
common micro-organisms concerned are Streptococcus and Staphylo- 
coccus pyogenes, the pneumococcus, and the Micrococcus tetragenus. 
Many other forms have been isolated.3 
In Chronic Tonsillitis (the so-called hypertrophy of the tonsils) 
there is hyperplasia of the lymph-nodules with increase in the fibrous 
stroma. The mouths of the crypts may be occluded and distended with 
exfoliated cells and cell detritus; these deposits may become calcified.4 
Tuberculous Pharyngitis.-Tuberculous inflammation of the pharynx 
may be primary or secondary to tuberculous lesions elsewhere; ulcers 
may form and the tonsils may be involved. 
The hyperplasiae of the pharyngeal mucosa in children, commonly 
called "adenoids," have been found in a considerable number of cases to 
be tuberculous. Whether in these instances the lesion is tuberculous in 
origin or whether the hyperplastic tissue affords a portal of entry and 
local vulnerability to infection by the tubercle bacillus is not yet clear.5 
'Consult Dobrowolski, "Lymph Nodules of the Larynx, (Esophagus, etc.," Ziegler's Beitrage 
z. path. Anat., Bd. xvi., p. 43, 1894. 
2 See Hodenpyl, "Anatomy and Physiology of the Faucial Tonsils," Am. Jour. Med. Sciences, 
vol. ci., p. 257, 1891; also Packard, Phila. Med. Jour., vol. v., 1900, pp. 914, 957. For a study of the 
lymph drainage of the faucial tonsils see Wood, Am. Jour. Med. Sci., vol. cxxx., p. 216, 1905. For a 
study of absorption in the tonsils see Wright, N. Y. Med. Jour., vol. Ixxxiii., p. 17, 1906. 
3 For a study of actinomyces-like structures in the tonsillar crypts see Gappisch, Verh. Deutsch. 
Path. Ges., Bd. ix,. 1905, p. 130; also Wright, Am. Jour. Med. Sci., vol. cxxviii., p. 74,1904. For study 
of bacteriology and pathology of tonsils with reference to articular rheumatism and cardiac disease see 
Davis, Jour. Infect. Dis., 1912, x, 148. 
4 For resume of tonsillar calculi with bibliography see Robertson, British Med. Jour., 1899, vol. i., 
p. 14. For a study of bone in tonsils see Lubarsch, Virch. Arch., Bd. clxxvii, p. 371, 1904; also Ruckert, 
ibid., p. 387. 
6 For a study of hyperplasia of the pharyngeal lymphoid tissue (adenoids) with reference to 650 
THE DIGESTIVE SYSTEM 
The possibility should be borne in mind that from tuberculous "ade- 
noids" tubercle bacilli may pass through the lymph-channels to the 
bronchial lymph-nodes, and that the pharynx may thus be a more impor- 
tant portal of entry in tuberculosis than has been hitherto recognized. 
TUMORS. 
Fibromata grow from the periosteum of the bones at the base of the 
skull, and project into the cavity of the pharynx and posterior nares in 
the form of large polypoid tumors. Soft polypoid tumors, consisting 
Fig. 412.-"Adenoid" Polyp of Pharynx. 
largely of loose succulent connective tissue and lymphatic tissue, and 
often called "adenoid polyps" (see Fig. 412), are of frequent occurrence. 
They are usually to be regarded rather as hyperplasiae than true tumors. 
Hairy polyps of the pharynx have been described by Arnold1 and others. 
primary tuberculosis of the pharyngeal tonsil see Lartigau and Nicoll, Am. Jour. Med. Sc., vol. cxxiii,, 
1902, p. 1031, bibliography. 
Also for a study of the tonsils as portals of entry of tubercle bacilli see v. Scheibner, Ziegler's Beitr., 
Bd. xxvi., p. 511, 1899; also Friedmann, ibid., Bd. xxviii., p. 66, 1900. Also bibliography in Wood, 
Bull. Univ. Penna., vol. xvi., 1903, p. 368. See also reference to Grober, p. 640. For relation of 
cervical and bronchial lymph-nodes in tuberculous infection see Beitzke, Virch. Arch., Bd. clxxxiv., 
p. 1, 1906. 
For general bibliography on the tonsils see Ullman, Medical News, January 26th, 1901, p. 137. 
1 Arnold, Virchow's Arch., Bd. cxi., p. 176, 1888, bibl. THE DIGESTIVE SYSTEM 
651 
Sarcoma, carcinoma,1 and various tumors of mixed type are of fre- 
quent occurrence in the pharynx.2 
The (Esophagus. 
Malformations. 
Malformations of the oesophagus are rare. The oesophagus may be entirely absent 
or its lower portion may be present and joined to the pharynx by a solid cord; or 
the pharynx, or the lower part of the oesophagus, may be continuous with the trachea; 
or the entire oesophagus may be represented by a solid cord. Dilatations of the oesoph- 
agus and division of the middle portion of the oesophagus into two branches have been 
observed.3 The mucosa may be folded across the lumen partially occluding it. 
PERFORATION AND RUPTURE. 
Foreign bodies in the oesophagus may, as already mentioned, perfo- 
rate its wall. Perforation of the oesophagus from without may be pro- 
duced by inflamed bronchial glands, by the extension of cavities and 
gangrene of the lungs, by abscesses in the mediastinum, by abscesses 
accompanying caries of the vertebrae, and by aneurisms of the aorta. 
Rupture of the wall of the oesophagus by violent coughing and vomiting 
has been described, but it seems improbable that this should occur with- 
out some previous local lesion.4 A few cases of perforating ulcer of the 
oesophagus have been recorded. 
HAEMORRHAGE. 
Aside from injuries, ulceration, etc., haemorrhage may take place 
from the lower veins of the oesophagus, which, in obstructed circulation, 
especially in atrophic cirrhosis, may be much dilated-oesophageal varices.5 
DILATATION. 
Simple Cylindrical Dilatations of the oesophagus are usually the result 
of long-continued stenosis of the oesophagus or of the cardiac end of the 
stomach, although not nearly all the stenoses are followed by dilatation. 
These dilatations are formed at first immediately above rhe stenosis and 
then extend upward. Dilatation may occur below the stricture. Only 
in rare cases does the dilatation involve the whole length of the tube. 
The entire wall of the dilated portion of the oesophagus is thickened, and 
there may be polypoid growths from the mucous membrane. 
In rare cases there is cylindrical dilatation of part or of the whole of 
1 For a study of carcinoma originating in the branchial cleft see Powers, Annals of Surgery, Febru- 
ary, 1898. 
2 For literature of malignant disease of the tonsils consult Newman, Am. Jour. Med. Sciences, 
vol. ciii., p. 487, 1892; also Honsell, Beitr. zur klin. Chirurgie, Bd. xiv., 1895. 
3 For a study of aberrant islets of gastric mucosa in the upper end of the oesophagus see Schaffer. 
Virch. Arch., Bd. clxxvii., p. 181, 1904. 
4 For a study of rupture of oesophagus see McWeeney, Lancet, 1900, vol. ii., p. 158, bibl. 
5 See Preble, Am. Jour. Med. Sci., vol. cxix., p. 263, 1900. 652 
THE DIGESTIVE SYSTEM 
the oesophagus without a stenosis or any discoverable cause. In these 
cases the dilatation is usually greatest near the middle of the oesophagus 
and diminishes upward and downward, so that the oesophagus has a fusi- 
form shape. The dilatation may reach a very considerable degree, the 
walls of the oesophagus are thickened, its mucous membrane may be 
covered with papillary outgrowths of ulcerated. 
The Sacculated Dilatations of the oesophagus are of two kinds: those 
due to pressure, and those due to traction. 
The dilatations due to pressure are situated in the posterior wall of 
the pharynx, just at its junction with the oesophagus. The smaller sacs 
are from the size of a pea to that of a hazelnut; the larger sacs may 
reach a large size and hang down between the oesophagus and the verte- 
bral column, the opening into the oesophagus remaining comparatively 
small. It is supposed that a limited area of the wall of the oesophagus 
loses its power of resistance against the pressure exercised upon it in 
each act of swallowing; it then is forced outward by the pressure, and 
so there is formed first a protrusion and then a sac. When a sac is 
formed the food enters it, accumulates there, and the sac becomes larger 
and larger. 
The dilatations due to traction are situated on the anterior wall of 
the oesophagus, at a point nearly corresponding to the bifurcation of 
the trachea. They are of funnel shape, with the small end outward. 
Their length varies from two to twelve millimetres; the width of the 
opening into the oesophagus is from six to eight millimetres. 
These dilatations are due to inflammation of the parts adjoining the 
oesophagus, especially of the bronchial nodes, followed by adhesions to 
some part of the anterior wall of the oesophagus. These adhesions then 
contract and draw the wall of the oesophagus outward, and in this way 
the dilatations are formed. 
At a later time these sacs may perforate into the bronchi, the lungs, 
the pleural cavity, the pericardium, the aorta, or pulmonary artery.1 
STENOSIS. 
Congenital Stenosis.-Besides the defects of development of the 
oesophagus which are incompatible with life, there may be a congenital 
stenosis of some part of it which causes difficulty in swallowing, but yet 
does not destroy life. 
Compression Stenosis is not uncommon. Tumors of the neck and 
mediastinum, and aneurisms of the aorta are the usual causes. Stenosis 
from vertebral ecchondroses has been reported.2 
Obstruction Stenosis.-Foreign bodies may be lodged in the oesopha- 
gus. Tumors may hang down from the pharynx into the oesophagus, or 
may be situated in the wall of the oesophagus. Inflammation of the 
1 For bibliography of oesophageal diverticula see Brosch, Deutsch. Arch. f. klin. Med., Bd. Ixvii., 
p. 44, 1900; also Starck, Arch. f. Verdkr., Bd. vii., 1901, p. 1. For later cases see Pfaff, Trans. Assn. 
Am. Phys., vol. xvi., 1901, p. 656. 
2 See Zahn, Munch, med. Wochenschr., May 8th, 1906. THE DIGESTIVE SYSTEM 
653 
oesophagus, due to the ingestion of irritating poisons, may induce cica- 
tricial stenosis. A few cases of stenosis due to syphilitic inflammation 
have been reported. 
INFLAMMATION. ((Esophagitis.) 
Catarrhal (Esophagitis may be either acute or chronic. The chronic 
form may lead to ulceration, or relaxation and dilatation of the walls, 
or to hypertrophy of the muscular coat. Leukoplakia is not uncommon. 
Pseudo-membranous (Esophagitis may occur with a similar process in 
the pharynx, with the exanthemata and other severe diseases, or under 
other conditions. It may be diphtheritic in character or due to other 
excitants than the diphtheria bacillus. 
Other Forms of Inflammation of the (Esophagus.-Foreign bodies 
which are swallowed and become fixed in the oesophagus may incite 
inflammation of the mucous membrane and of the adjoining soft parts. 
Abscesses may form around the oesophagus, or destroy the wall of the 
canal, and the foreign body may find its way into the trachea, aorta, or 
pericardium. 
Inflammation of the submucous tissue of the oesophagus, apart from 
the cases just mentioned, is not common. It may result in abscess or 
the formation of fibrous tissue, causing stenosis. 
Irritating and caustic acids and alkalies may destroy larger or smaller 
portions of the mucous membrane. The necrosed portions are of a black 
or whitish color, surrounded by a zone of intense congestion. If the 
patient recover, the patches of membrane which have been destroyed 
slough and fall off, leaving a surface covered by granulation tissue. As 
this assumes cicatricial characters and contracts, serious stenosis of the 
oesophagus may be produced. 
Tuberculous (Esophagitis may occur in generalized miliary tuberculo- 
sis or by local infection from tuberculous sputa, either with or without 
obvious predisposing local lesion, or through an extension of a tubercu- 
lous process from adjacent structures. Ulceration is apt to occur.1 
Syphilitic (Esophagitis.-There may be gummata which encroach upon 
the lumen, or ulceration followed by cicatrices may lead to stenosis. 
TUMORS. 
Small Papillomata may occur singly or in considerable numbers 
throughout the entire length of the oesophagus. Large papillary tumors 
are more rare. Small submucous fibromata and lipomata, angiomata, 
and leiomyomata of considerable size may occur in the oesophagus. Sar- 
comata are rare.2 Adenomata and myxomata have been observed. 
Carcinoma may originate at any part of the wall of the pharynx and 
oesophagus. The tumor may encircle the tube; it may remain as a fiat 
1 For bibliography of tuberculous oesophagitis see Flexner, Johns Hopkins Hosp. Bull., vol. iv., p. 4, 
1893; and also Cone, ibid., vol. viii., p. 229, 1897. 
2 Livingood, Johns Hopkins Hosp. Bull., vol. ix., p. 159, 1898, bibl. 654 
THE DIGESTIVE SYSTEM 
infiltration (Fig. 413), or project inward in large, fungous masses. In 
either case it is prone to ulceration. The growth may extend up and 
down the oesophagus, and even involve the pharynx or stomach. The 
ulcerative process may extend outward so as to lead to perforation into 
the air passages, the lungs, pleura?, pericardium, and large blood-vessels. 
The new growth may extend outward and infiltrate the surrounding soft 
parts, so that the oesophagus is surrounded by large, solid, cancerous 
masses. Metastatic tumors are also sometimes formed.1 
Fig 413.-Infiltrating Carcinoma of the Oesophagus 
Cysts.-Small retention cysts of the follicles of the mucous membrane 
are sometimes found. Larger cysts of the oesophagus lined with ciliated 
epithelium have been described.2 
The Stomach. 
Malformations. 
Malformations of the stomach are not common. The organ may be entirely want- 
ing in acephalous foetuses. It may be of various degrees of smallness, sometimes no 
larger than the duodenum. It may be divided into two halves by a deep constriction 
in the middle. It may be vertically placed. Diverticula are noted. The stomach 
may be outside of the abdominal cavity from a hernial protrusion through the dia- 
phragm or at some point in the abdominal wall. It is found on the right side, instead 
of the left, when the other viscera are transposed, and the position of the cardiac and 
pyloric orifices is correspondingly inverted. 
Congenital stenosis of the pylorus in infants is of occasional occurrence. It is com- 
1 For a risum^ of tumors of the oesophagus see Coplin, Am. Med., vol. vii., 1904, p. 773. 
2 For recent bibliography of lesions of oesophagus see Thorel, Lubarsch and Ostertag's " Ergebnisse, 
Jahrg. v. for 1898, p. 128. THE DIGESTIVE SYSTEM 
655 
monly due to fibrous hyperplasia of the submucosa, sometimes involving the internal 
muscular layers.1 
Cadaveric Changes. 
The mucous membrane of the stomach is liable to undergo considerable alterations 
soon after death, owing to changes in the distribution and composition of the blood and 
to the action of the digestive fluids. The blood is apt to collect in the small veins, 
especially at the fundus, while, by diffusion of the coloring matter, red or brown or 
black streaks and patches form in the mucous membrane. 
Those portions of the mucosa on which the food and digestive fluids collect, usually 
at the fundus and on the posterior aspect of the stomach, frequently appear gray and 
turbid, and are soft and easily rubbed off. The epithelium in these regions is unusu- 
ally granular or disintegrated, and is often detached. Sometimes this post-mortem 
softening involves the entire thickness of the stomach wall, which is converted into a 
gray or yellow or brown gelatinous pulp. Thus large or small post-mortem perfora- 
tions may occur. 
INJURIES. 
Perforating wounds of the stomach usually give rise to a fatal perito- 
nitis. It is possible, howrever, for the wound to heal, or a gastric fistula 
may be formed. 
Rupture of the stomach may be produced by severe blows or falls. 
HEMORRHAGE. (Haematemesis.) 
Small extravasations of blood in the wall of the stomach are fre- 
quently found in persons who have died from one of the infectious 
diseases. 
Haemorrhage into the cavity of the stomach may occur in a variety 
of ways. It may take place from injuries or poisons; from ulcers or 
carcinoma; from rupture of small aneurisms of the stomach, or from the 
rupture into the stomach of aneurisms elsewhere. It may occur in 
infectious diseases, especially in yellow fever, or in diseases of the blood. 
It may be associated with passive congestion of the stomach in hepatic 
cirrhosis of the liver, obstruction of the portal vein, chronic disease of 
the heart and lung; with an enlarged spleen, and in chronic gastritis. In 
the new-born and young infants haemorrhage into the stomach not infre- 
quently occurs without apparent lesions which would account for it; or 
there may be ulcers of the mucous membranes, or cardiac disturbances, 
or infection. While the source of haemorrhage into the stomach is often 
evident, in many cases none can be discovered. Considerable bleeding 
can evidently take place by diapedesis in congested vessels. 
Some cases of chronic gastritis are characterized by general bleeding 
from the mucous membranes of the stomach.2 
i See Meltzer, N. Y. Med. Record, vol. liv., p. 253, 1898, bibl.; also Rolleston and Crofton Atkins, 
Brit. Med. Jour., 1900, vol. ii., p. 1768; also W achenheim, Am. Jour. Med. Sci., vol. cxxix., p. 636,1905. 
2 For a study of occult haemorrhage in the gastro-intestina canal see Jaworski and Korolewicz 
Wiener klin. Wochenschr., p. 1129, 1906. 656 
THE DIGESTIVE SYSTEM 
ATROPHY AND DEGENERATION. 
Atrophy of the stomach occurs in a variety of cachectic conditions, 
in chronic inflammation, and in stenosis of the cardiac orifice. 
Albuminous degeneration of the epithelium may occur in infectious 
diseases and in inflammation of the stomach. 
Fig. 414.-Fatty Degeneration of the Epithelium of the Gastric Tubules in Phosphorus 
Poisoning. 
Fatty degeneration is often associated with arsenic and phosphorus 
poisoning (Fig. 414). 
Amyloid degeneration of the small vessels is associated with a similar 
process in other parts of the body. 
INFLAMMATION. (Gastritis.) 
Acute Catarrhal Gastritis is usually due to the ingestion of irritating 
decomposing or infectious substances and may accompany general 
infectious diseases. 
After death the mucous membrane may be congested and swollen, 
or the congestion may have disappeared. The mucous membrane is 
coated with an increased amount of mucus, especially at the pyloric end 
of the stomach. 
The structural changes in the mucous membrane consist chiefly in 
swelling and albuminous degeneration, and sometimes exfoliation of the 
epithelium with an increase in the production of mucus by the cylindrical 
cells (Fig. 415), while the intertubular tissue and the submucosa may be 
oedematous and contain a few emigrated leucocytes. The solitary lymph- 
nodules may be enlarged from hyperplasia, and haemorrhagic erosions 
may be present. 
Chronic Gastritis.-This, with the continuance of the exciting condi- 
tions, may follow the acute form. It is often associated with the persist- 
ent use of alcohol, with ulcers and carcinoma, with venous congestion 
from heart lesions, cirrhosis of the liver, obstruction of the portal vein 
or ascending vena cava, or chronic diffuse nephritis. These are doubtless 
predisposing conditions rather than actual excitants of the disease. 
The stomach may be normal in size or small or dilated. Its inner THE DIGESTIVE SYSTEM 
657 
surface is usually covered with tenacious mucus. The mucous mem- 
brane may be congested with minute haemorrhages or erosions, or it may 
Showing' the open ends of two gastric tubules. There is a considerable formation of mucus by the 
epithelial cells, many of which have the so-called "beaker" form. There is exfoliation of epithelium 
which, with mucus and a few leucocytes and red blood cells, covers the surface of the mucous mem- 
brane. 
Fig. 415.-Acute Catarrhal Gastritis. 
be pale and gray or pigmented from former haemorrhages. It may be 
thickened or thinner than normal. Often, owing to irregular thickening, 
it projects in places in the form of minute granules, or it is irregularly 
Fig. 416.-Chronic Gastritis. 
Showing a small portion of the new-formed tissue between the gastric tubules. There are many large 
polyhedral cells in the new tissue. 
roughened-etat mamelonne-or there may be distinct polypoid out- 
growths. These alterations are usually most marked in the pyloric 658 
THE DIGESTIVE SYSTEM 
region. Microscopical examination shows alterations varying in differ- 
ent parts of the organ and in different stages of the disease. The surface 
epithelium may be degenerated and exfoliated. The detached epithe- 
lium with leucocytes may be mingled with the mucus covering the surface. 
The gastric glands may be variously altered. They may be dilated, or 
elongated and tortuous, or hyperplastic1 or atrophied; their epithelium 
may be flattened; degenerated, or detached. The interstitial tissue and 
the submucosa may be infiltrated with small spheroidal cells or new- 
formed larger polyhedral cells (Fig. 416), and new fibrous tissue may 
form (Fig. 417), thus often greatly thickening the mucous membrane 
and causing atrophy of the glands. The lymph-nodules at the base of 
the glands may be enlarged from hyperplasia. On the other hand, the 
Fig. 417.-Chronic Gastritis. 
Shewing atrophy of the mucous membrane 
with much new-formed fibrous tissue. 
Fig. 418.-Chromic Gastritis. 
Showing the new-formed fibrous tissue 
between the gastric tubules. 
mucous membrane, as contraction takes place in the new-formed intersti- 
tial tissue, may undergo great atrophy (Fig. 418), so that it is pale, thin, 
often gray in.color, with, more or less pigmentation. 
The formation of new fibrous tissue may later involve the muscularis 
also, leading to various distortions of the stomach. 
Croupous Gastritis (Membranous or Diphtheritic Gastritis).-This 
form of gastric inflammation, most common in children, may be asso- 
ciated with diphtheria or with other infectious diseases, but may occur 
independently. In adults it is usually secondary to typhus fever, 
pneumonia, pyaemia, typhoid fever, the exanthemata, and other infec- 
tions, and may follow the ingestion of irritant poisons. The excitants 
are thus of the most varied kinds, as is the case in pseudo-membranous 
inflammation elsewhere in the body. The false membrane may be in 
small patches or line a considerable portion of the stomach. 
Exudative Gastritis (Suppurative or Phlegmonous Gastritis).-This 
1 See Cone, "Welch Anniversary Contributions to the Science of Medicine, p. 877, 1900, biM. THE DIGESTIVE SYSTEM 
659 
process is characterized by the formation of. purulent and other exudate 
in the connective tissue of the mucosa and submucosa. The exudate may 
be diffuse or localized in the form of abscess. As an independent affec- 
tion it is rare. It is more frequent in connection with puerperal fever 
and other infectious diseases; it has been ascribed to injury. 
The accumulation of exudate may be slight, the interglandular and 
submucous tissue being oedematous with few pus cells. The mucous 
membrane may under these conditions remain intact or show slight 
catarrhal lesions. When this relatively slight accumulation of exudate 
occurs in the pyloric region it may apparently occasion temporary 
stenosis. On the other hand, a considerable or large amount of exudate 
may form, and the process may involve diffusely a large part of the wall 
of the stomach; or the process may be circumscribed and abscesses may 
form. The suppurative process may extend to the mucous membrane, 
or to the serosa, and thus perforations may occur and the incitement 
of peritonitis. Little is known of the direct excitants of phlegmonous 
gastritis.1 Streptococcus pyogenes has been found in the exudate.2 
Toxic Gastritis.-The mineral acids, the caustic alkalies, arsenic, 
corrosive sublimate, and the metallic salts, phosphorus, camphor, and 
other irritating materials, induce different lesions of the stomach, accord- 
ing to their quantity, their strength, and the length of time which has 
elapsed before death. 
In large quantities they destroy arid convert into a soft, blackened 
mass both the mucous membrane and the other coats, so that perforation 
may take place. In smaller quantities they produce black or white 
sloughs of the mucous membrane, surrounded by a zone of intense con- 
gestion. If death does not soon ensue, the ulcerative and cicatricial 
processes which follow such sloughs may contract and deform the stom- 
ach in various ways. 
If the poisons are of less strength they may induce a diffuse conges- 
tion of the mucous membrane, with catarrhal or croupous exudation on 
its surface and serous infiltration of the submucous coat (see chapter on 
Poisons). 
Tuberculous Gastritis of the stomach is rare and is usually secondary 
to tuberculous lesions elsewhere. There may be miliary tubercles or 
small or large, single or multiple ulcers involving especially the mucosa 
and submucosa.3 
Syphilitic Inflammation of the stomach with ulceration has been 
occasionally observed.4 
1 Reference to the bibliography of micro-organisms of the normal stomach may be found in an 
article by Weiss on " Bacteria in the Stomach of the Cat," Jour, of Applied Microscopy, vol. iii., p. 827, 
1900; also Coyon, "Flore microbienne de 1'estomac," Thfese de Paris, 1900, bibliography. For bibl. of 
phlegmonous gastritis see Leith, Edinburgh Hospital Reports, vol. iv., p. 51, 1896. For a later study see 
Schnarrwyler, Arch. f. Verdkr., Bd. xii., p. 116,1906, bibl. 
2 See Kinnicutt, Trans. Assn. Am. Phys., vol. xv., p. 127, 1900, bibl. For a study of lesions of the 
stomach as portals of entry of bacteria see James, Trans. Assn. Am. Phys., vol. xvi., p. 72, 1901. 
3 For tuberculosis of the stomach see Dewey, Jour., Infect. Dis., 1913, xii, 236. 
4 Consult for bibliography Flexner, American Journal of Medical Sciences, vol. cxvi., p. 424, 1898. 660 
THE DIGESTIVE SYSTEM 
ULCERS OF THE STOMACH. 
Chronic Perforating Ulcers-This form of ulcer is often seen; accord- 
ing to Brinton, in five per cent, of persons dying from all causes. It 
occurs in females nearly twice as frequently as in males. As regards the 
age, Brinton concludes that the liability of an individual to become the 
subject of gastric ulcer gradually rises, from what is nearly a zero at the 
age of ten, to a high rate, which it maintains through the period of mid- 
dle life; at the end of which period it again ascends, to reach its maximum 
at the extreme age of ninety. 
The analysis of 793 hospital cases by Welch1 shows that the ulcers 
were on the lesser curvature in 288, in the posterior wall in 235, at the 
pylorus in 95, on the anterior wall in 69, at the cardia in 50, at the fundus 
in 29, on the greater curvature in 27. 
Fig. 419.-Chronic Ulcer of the Stomach. 
Showing a section through the stomach wall at the central part of the round ulcer. 
As regards the number of ulcers, two or more are present in about 
twenty-one per cent.; there may be two, three, four, or even five ulcers. 
In cases of multiple ulcers these are often developed successively. 
In size the ulcers vary from one-quarter of an inch to five or six 
inches. They are usually of circular shape, sometimes oval; sometimes 
two or more are fused together. 
i । The ulceration is largest in the mucous membrane (Fig. 419). It 
may remain confined to this, or extend outward and involve the connec- 
tive tissue, muscular and peritoneal coats, its diameter becoming smaller 
as it advances. The ulcer looks like a clean hole punched out of the 
wall of the stomach (Fig. 420). Its floor may show no active inflamma- 
tory changes. Its edges may be in the same condition, or they may be 
thickened by the growth of connective tissue and cell. The rest of the 
mucous membrane of the stomach is apt to be in a condition of chronic 
catarrhal inflammation. 
The ulcer may perforate directly through the wall of the stomach, and 
the contents of the latter are discharged into the peritoneal cavity; or 
1 Welch, Pepper's "System of Practical Medicine," vol. ii., p. 504, 1885. Many important data are 
to be found in this excellent article. THE DIGESTIVE SYSTEM 
661 
adhesions are formed between the wall of the stomach and the neighbor- 
ing viscera, so that the bottom of the ulcer is closed; or if the liver, the 
intestines, or the abdominal wall become adherent, these may be invaded 
by the ulcerative process, and cavities or fistulae are formed communi- 
cating with the stomach; or, if the adhesions are incomplete, a local 
peritonitis and collections of pus may be developed. Perforation may 
take place into the colon or duodenum, or into the pericardium or pleura. 
During the progress of the ulcer there may be repeated small haemor- 
rhages from the erosion of small blood-vessels, or large haemorrhages 
from the erosion of larger arteries. 
Fig. 420.-Chronic Perforating Ulcer of the Stomach. 
In many cases these ulcers cicatrize, and such a cicatrization may 
produce various deformities of the stomach. 
The origin of such ulcers is often obscure. It seems probable that 
the nutrition of a circumscribed part of the wall of the stomach is inter- 
fered with, and that this portion is then destroyed by the action of the 
gastric juice. But we are in most cases still ignorant of the way in which 
the obliteration of the arteries is effected. It has, indeed, been demon- 
strated in animals that an artificial embolism of the branches of the 
gastric arteries may lead to ulcers of the stomach; and in the human 
stomach we occasionally find cases of embolism of the branches of the 
gastric artery and ulcers. But the clinical history of most cases of ulcer 
of the stomach does not correspond with such a mode of origin. A 
chronic obliterating endocarditis would seem to be a more probable 
cause. The possibility of a bacterial origin in some cases should not be 
overlooked. 
Follicular Ulcers, similar to those in the small intestine, are of occa- 
sional occurrence in the stomach. They are formed by the degenerative 
changes and necrosis in the solitary lymph-nodules of the stomach. 
For Tuberculous Ulcers, see above. 662 
THE DIGESTIVE SYSTEM 
Haemorrhagic Erosions occur as rounded spots or narrow streaks; 
formed by a loss of substance of the mucous membrane. The mucous 
membrane at these points may be -congested, soft,: and covered by-small 
blood-clots. The destruction of the mucous -membrane is usually super- 
ficial, but may involve its entire thickness. The internal surface of the 
stomach may be studded with these erosions. They give rise to repeated 
haemorrhages, and are accompanied by catarrhal inflammation of the rest 
of the mucous membrane. J ' ■ ; i. . 
They occur at all periods of life, even in infants. Their usual seat is 
the pyloric portion of the stomach. They may occur independently of 
other obvious lesions, .but are most frequent in connection with chronic 
congestion of the mucosa, chronic gastritis, in infectious diseases, and 
intoxications. 
DILATATION AND DISPLACEMENT. 
Very considerable degrees of dilatation of the stomach are found at 
autopsies, without stenosis of the pylorus or other mechanical cause to 
account for them. It is usually difficult to determine how long these 
dilatations have existed and their influence in the illness or death. 
Acute dilatation of the stomach, with vomiting of very large quanti- 
ties of thin fluid, has been observed in a few cases, the dilatation being 
developed suddenly and without discoverable cause. 
Of the mechanical factors which lead to dilatation of the stomach a 
stenosis of the pylorus is the most common. Such a stenosis may be 
effected by a tumor, by chronic inflammation and thickening, and by the 
cicatrization of ulcers. Less frequently obstructions of the small and 
large intestines act in the same way. Some forms of chronic gastritis are 
attended with dilatation of the stomach without stenosis. In rare cases 
circumscribed, sacculated dilatations are produced by the presence of 
foreign bodies-portions of wood, metal, etc. 
The stomach may be variously displaced by pressure from without. 
TUMORS. 
Papillomata.-It has already been mentioned that in some cases of 
chronic gastritis there are small, polypoid hypertrophies of the mucous 
membrane. Besides these we find polypoid tumors which may reach a 
considerable size. They are composed of a connective-tissue stroma 
arranged in tufts covered with cylindrical epithelium. In some cases 
there are also tubules lined with cylindrical epithelium, so that the tumor 
has partly the structure of an adenoma (Fig. 421). Fibromata of small 
size are sometimes found in the connective-tissue coat. Lipomata are 
formed in the submucous connective tissue in the shape of rounded or 
polypoid tumors. They usually project inward, but sometimes outward 
beneath the peritoneum. They may also appear in the form of numer- 
ous yellow -nodules beneath the mucous membrane. 
Myomata occur in the form of rounded tumors which originate in the THE DIGESTIVE SYSTEM 
663 
muscular coat, but may gradually separate themselves from it and pro- 
ject inward or outward. The submucous myomata are at first small 
tumors lying loosely attached in the submucous tissue. As they grow 
larger they push the mucous membrane inward and take the shape of 
polypoid tumors. Small multiple angiomata may be found in the stom- 
ach in connection with similar tumors in the submucosa throughout 
the gastro-intestinal canal.1 Lymphomata in the wall of the stomach 
are seen in some cases of leukeemia. 
Sarcomata of the stomach are rare. In some of the tumors of the wall 
of the stomach, which are ordinarily called cancerous, the structure is 
not well defined, and it. is possible that some of them are sarcomata. 
Sarcomata of the stomach may be round-celled or spindle-celled, and 
mixed forms occur-myxo-sarcoma, angio-sarcoma, etc.2 
Fig. 421.-Small Papillary Adenoma of the Stomach. 
This is confined to the mucous membrane, forming a small polypoid growth into the cavity. En- 
larged about five diameters. 
Adenoma.-It has been already mentioned that in some of the papil- 
lary tumors of the mucous membrane there is a considerable growth of 
tubules lined with cylindrical epithelium (Fig. 421). Besides these we 
find in the submucous coat circumscribed, tumors composed of tubules 
irregular in form and lined with one or more layers of cylindrical epithe- 
lium, like those of the gastric mucous membrane. (See Adeno-carcinoma 
below.) : . s • h 
Carcinoma of the stomach is usually primary, but is occasionally sec- 
ondary to cancer elsewhere. It is of relatively common occurrence, the 
1 See references to Bennecke.&xid MacCallum, foot-note, p, 688. , ... , 
2 See Dock, Trans. Assn. Amer. Phys., vol. xv., p. 165, 1900, bibl.; also Fenwick, Lancet, vol. 
i., p. 463, 1901, bibl.; also Corner and Fairbanks, Practitioner, Ixxii., 810, 1904. 664 
THE DIGESTIVE SYSTEM 
stomach in Welch's analysis of over 30,000 cases being, next to the uterus, 
the organ most frequently affected. 
The situation in Welch's summary of 1,300 cases1 was: in the pyloric 
region, 791; lesser curvature, 148; cardia, 104; posterior wall, 68; involv- 
ing a greater part of the stomach, 61; greater curvature, 34; anterior 
wall, 30; fundus, 19; multiple tumors in 45 cases. Carcinoma of the 
stomach is rare in childhood.2 
Carcinomata of the stomach occur in various forms. There may be 
larger or smaller, flat or rounded or lobulated growths projecting from 
Fig. 422.-Carcinoma of the Stomach. (Pyloric Region.) 
A large globular tumor mass projects into the cavity. 
the inner surface of the stomach (Fig. 422). The mucous membrane 
over them may be intact or with a portion of the tumor may ulcerate. 
The destructive process may advance so that some of the ragged or 
smooth-edged ulcers may reach a large size. The wall of the stomach 
may be involved; peritoneal adhesions may form, or perforation may 
occur. On the other hand, the carcinoma may grow in the form of a 
1 Welch, Pepper's "System of Practical Medicine," vol. ii., p. 561, 1885. 
2 See Osler and McCrae on "Carcinoma of the Stomach in the Young," N. Y. Med. Jour., vol. Ixxi., 
p. 581, 1900. THE DIGESTIVE SYSTEM 
665 
diffuse infiltration of the wall of the stomach (Fig. 423). Such tumors 
are less liable to ulcerate. They may be overlooked or mistaken for a 
chronic inflammatory lesion. 
Fig. 423.-Gelatinous Carcinoma of the Stomach. 
Showing the infiltrating form of tumor occupying the pyloric end of the stomach and advancing along 
the wall. 
Metastatic tumors in the liver, the lymph-nodes, and the peritoneum 
are common, but such metastases may occur in any part of the body. 666 
THE DIGESTIVE SYSTEM 
The most common type of carcinoma of the stomach is the medullary, 
or so-called adeno-car cinoma, in which often to a considerable extent the 
glandular type is maintained in many parts of the growth (Fig. 246, 
p. 400). The cylindrical or polyhedral epithelial cells line variously 
shaped alveoli, which frequently maintain well-marked lumina. Cystic 
distention of these may occur. 
Fibrous carcinoma, scirrhus, is the next most frequent type, and such 
are often the infiltrating forms (Fig. 266, p. 414). 
The third type, gelatinous carcinoma (Fig. 267, p. 415), often forms 
extensive growths and is apt to invade adjacent structures and to estab- 
lish metastases.1 
Fig. 424.-Hair Balls from Human Stomach. 
This specimen consists largely of hairs, cotton and woolen threads, straws, etc 
Stenosis of the pylorus and chronic gastritis, adhesions, fistulae, 
distortion of the stomach, perforations, etc., haemorrhage, suppurative 
inflammation, are among the frequent secondary complications of gastric 
cancer. 
Among the relatively infrequent secondary cancers of the stomach, 
those originating in the breast are proportionately large.2 
Cysts of the stomach wall have been recorded.3 
For general bibliography of lesions of the stomach see Thorel, Lubarsch and 
Ostertag's "Ergebnisse," Jahrg. V. for 1898, p. 142.4 
1 For a case of squamous epithelioma of the stomach see Borst, "Geschwulste," 1902, p. 665; also 
Filtterer, Jour. Am. Med. Assn., voL xliii., p. 1129, 190'4. 
2 For .statistics see Welch, reference above. < ju 
3 Schultze has seen a large cyst of undetermined origin, Proc. N. Y. Path. Soc., 1899-1900. 
4 For a study of retrograde metastases of carcinoma through the lymph-channels from the stomach 
to the liver see Jacob, Arbeiten Path. Anat. Tubingen, Bd. v., p. 121, 1904. See also monograph on the 
growth and mode of extension of carcinoma by Borrmann, Mittheil a. d. Grepzgebiet. d. Med. u. Chir., 
First Suppl. Heft, 1901. THE DIGESTIVE SYSTEM 
667 
FOREIGN BODIES. 
'Among the various foreign bodies which by accident or design may 
be present in the stomach may be mentioned hairs, thread, string, etc., 
which have been swallowed from time to time, usually by hysterical 
women. These may be closely packed together into a large mass nearly 
filling the cavity of the stomach, to which in shape it may correspond 
(Fig. 424).1 
The Intestines. 
Malformations. 
Atresia Ani.-Absence of the anal opening is frequent. This may be associated 
with partial or complete atresia of the rectum or of the colon which may be represented 
by solid cords. Blind terminations of the small intestine may occur, or there may be 
complete closure of the gut. There may be absence 
of continuity between the large and small intestine. 
The appendix may be absent, but this is a very 
rare anomaly. 
Transposition.-The position of the intestines 
may be the opposite to that which is usually found. 
The transposition may affect all the abdominal vis- 
cera, or only a single viscus is transposed. 
Anomalous Positions.-The intestines with the 
other abdominal viscera may be partly without the 
abdominal cavity in failure of the abdominal walls 
to close in development (see Fig. 178, p. 324). Dis 
placements of the colon are not infrequent.2 
Diverticula.-Congenital Diverticula.-These are 
most frequent in the lower part of the ileum. They 
usually spring from the convex surface of the intes-* 
tine, more rarely from its attached border. In the 
latter case they are joined to the mesentery by'a fold 
of peritoneum. The diverticulum forms a pouch 
from one to six inches long, of about the same diam- 
eter as the intestine, smallest at its free extremity. 
Such diverticula do not interfere with the func- 
tions of the intestines.' They occasionally form part 
of a hernia. Sometimes the remains of these intes- 
tinal diverticula-called Meckel's diverticula-form 
soft, projecting tumors at the umbilicus3 in children. 
Microscopical examination of slich tumors often 
shows the structure of the intestinal mucosa and muscularis' or even pancreas at the 
tip. If they reinain attached by a fibrous cord to the navel, this cord may be the 
cause of incarceration of a portion of the intestines? 
Acquired Diverticula.-Not infrequently one finds at autopsies either in the small 
or large intestine diverticula or herniae, which project from the exterior of the gut, 
usually near its mesenteric attachment. These consist of the mucous membrane 
Fig. 425.-Diverticulum of the 
SMall Intestine.' 
1 Such a specimen, mentioned by Osler, is in the museum of McGill University; another, reported 
by Findler (see Fig. 394), is in the museum of the College of Physician^ and Surgeons, N. Y. See 
Jacobson, Med. News, Feb. 16th,' 1901; Fenwick, Brit. Med. Jour., vol. ii'., p. 1696, 1902, bibl., and 
Heazlit, Jour. Amer. Med. Assn., 1914, Ixii, 107, bibl. 
2 For bibliography of reported cases see Shober, Am. Jour. Med. Sci., vol. cxvi., p. 405, 1898. 
3 For bibliography of umbilical tumors see Giannettasio, Ajch. gen. de Med., t, iii,, p 65, 1900. For 
diverticula of duod,enum see Davis,. Trans. Chicago Path. Soc., 1913, ix, 1. 
4 For bibliography see fliesman, Proc. Path. Soc. of Philadelphia, N. 8., voj. i., p. 193, 1898. For 
case of volvulus of Meckel's diverticulum see Taylor, Johns Hopkins Hosp. Bull., vol. xij,, p. 326,1901. 668 
THE DIGESTIVE SYSTEM 
which has been crowded through the muscularis and is covered by serosa. They may 
form in connection with the appendix. These so-called "false diverticula" may be 
large, but are generally not larger than a pea; they may be single or numerous (Fig. 
396.). They as a rule cause no functional disturbance, but may, through the accumu- 
lation of faecal material within them, be the seat of perforation, inducing abscesses or 
peritonitis. Or they may lead to local adhesion to adjacent parts.1 
Fig. 426.-Multiple False Diverticula of the Intestine. 
Cloacae.- The rectum may open into the bladder, urethra, or vagina. Thus 
cloacae are formed which are often associated with other malformations of the abdomi- 
nal wall, intestines, and generative organs. 
Incarceration, Volvulus. 
1. The most common form is that in which a portion of intestine is strangulated by 
a fibrous band. Such fibrous bands are the result of peritonitis or may be of foetal 
origin. The intestine becomes in some way caught under one of these bands and is 
compressed by it. The structure thus produced may lead to a gradual accumulation 
of faeces in the intestine above it, and may last for a long time before death ensues. In 
other cases the structure interferes at once with the circulation of the blood; the intes- 
tine is intensely congested, becomes gangrenous, and death takes place with the symp- 
toms of general peritonitis. 
2. A portion of intestine becomes caught in some abnormal opening in the mesen- 
tery or omentum, or in the foramen of Winslow, or between the two layers of the mes- 
entery. We have seen a case in which twelve feet of intestine had passed through 
a small opening in the mesentery. 
3. A coil of intestine makes a half turn at its base, so that the two sides of the 
loops cross at its base. In this way the lumen of the intestine is completely closed 
and the vessels are compressed, so that congestion, peritonitis, and gangrene result. 
In the small intestine it may occur when the gut is fixed by old adhesions. This twist- 
ing of the gut is called volvulus. 
4. A portion of the intestine, with its mesentery, makes one or more complete 
turns on itself, closing the canal and compressing the vessels. 
5. A portion of the intestine makes a half or entire turn about its longer axis. 
6. The mesentery of a part of the intestine is long and loose, in consequence of a 
dragging down of the intestine by a hernia or by habitual constipation. The portion 
1 Consult Fischer, "False Diverticula of the Intestine," Jour. Exp. Med., vol. v., p. 333, 1901, 
bibl.; also Beer, Am. Jour. Med. Sci. vol. cxxviii., p. 135, 1904. For diverticula of appendix see Corn- 
ing, Albany Med. Annals, Dec. 1905. For studies of acute diverticulitis see Rosenheim, Ztschr. f. klin. 
Med., 1904, liv, 475; v. Hansemann, Virchows Arch., 1896, cxliv, 400; and the numerous publications 
from the Mayo Clinic. THE DIGESTIVE SYSTEM 
669 
of intestine thus permitted to hang down is habitually filled with faeces, and by its 
pressure on some other part of the intestine produces an incomplete stricture. 
This change of position consists in the invagination of one portion of intestine in 
another portion (Fig. 427). Usually this takes place in the direction of the peristaltic 
movements, from above downward; more rarely in the opposite direction. 
Intussusception. 
Fig. 427.-Intussusception. 
A portion of the gut is completely invaginated in the segment below and strangulated. 
The parts are found in the following condition: There are three portions of intes- 
tine, one within the other. The inner portion is continuous with the intestine above 
the intussusception; its peritoneal coat faces outward. The outer portion is continu- 
ous with the intestine below; its peritoneal coat also faces outward. The inner portion 
Fig. 428.-Intussusception-Agonal or Post-mortem in Intestine of Infant. 
is turned inside out, its mucous membrane is in contact with the mucous membrane of 
the outer portion. In rare cases the intussusception is complicated by the invagination 
of a second portion of intestine in the inner tube, and even by a third intussusception 670 
THE DIGESTIVE SYSTEM 
into the second one. These changes occur both in the large and small intestine; most 
frequently the lower part of the ileum is invaginated in the colon. The invaginated 
portion may be from a few inches to several feet in length. The lesion is most fre- 
quently found in early childhood. 
The intussusception, by the dragging and folding of the mesentery which it 
involves, may lead to intense congestion of the parts, and even to large haemorrhages 
between the coats of the intestine. The congestion may induce fatal peritonitis, or 
Fig. 429.--Inguinal Hernia-Intestinal. 
Fig. 430.-Inguinal Hernia-Omental. 
gangrene of the intestine, or chronic inflammation and adhesions, and the patient may 
live for a considerable time with symptoms of stricture. In other cases the invagin- 
ated portion of the intestine sloughs, the outer and inner portions become adherent, 
and the patient recovers, with or without stricture. 
Besides this grave form of intussusception we often find, especially in children, one 
or more small invaginations not attended with congestion or inflammation. These are 
agonal or are formed immediately after death (Fig. 428). 
Hernia. 
The dislocation and protrusion of the whole or a part of an internal organ from its 
normal position is called hernia. This may occur in various parts of the body, but 
most frequently involves the abdominal viscera, especially the intestine or omentum. THE DIGESTIVE SYSTEM 
671 
In the most common form of the so-called inguinal hernia, which is of frequent occur- 
rence in men, there is a descent into the inguinal canal of either a loop of intestine 
(Fig. 429) or a portion of the omentum (Fig. 430). For a description of the various 
forms of hernia we refer to works on surgery. 
Dilatation of the Colon. 
This may be congenital or acquired and is sometimes excessive.1 
WOUNDS-RUPTURES. 
Penetrating wounds of the intestine usually prove rapidly fatal, either 
from shock or from peritonitis. Sometimes, however, the wound 
becomes closed by the formation of adhesions with the neighboring parts. 
Sometimes the wound in the intestines becomes adherent at the position 
of the wound in the abdominal wall, and an intestinal fistula is formed. 
Rupture of the small intestine is not infrequently produced by severe 
blows on the anterior abdominal wall. It is noticeable that such blows 
may not produce marks or ecchymoses of the skin. Such ruptures 
usually prove fatal very soon, but sometimes the patient lives several 
days and the edges of the rupture undergo inflammatory changes. 
Strictures of the intestine are sometimes followed by rupture of the 
dilated intestine at some point above the stricture.2 
DISTURBANCES OF THE CIRCULATION-HAEMORRHAGE. 
Hyperaemia of the intestine may be inflammatory in character or it 
may be associated with disturbance of the portal circulation. Under 
both of these conditions ecchymoses may occur. Pigmentation may fol- 
low large or small interstitial hemorrhages. 
As a result of' embolism or thrombosis of the mesenteric vessels 
haemorrhagic infarctions may occur, sometimes involving a considerable 
portion of the gut.3 Hemorrhage into the lumen may follow, or gangrene, 
or inflammation. The latter processes are readily induced in the injured 
regions by the bacteria constantly present in the intestinal contents. 
Septic emboli may induce suppurative inflammation in the mesentery 
and in the wall of the intestine. 
Intestinal haemorrhage may occur in venous congestion, as in certain 
forms of cirrhosis of the liver. It may follow' ulceration, in typhoid fever, 
in chronic colitis, in malignant tumors, etc.; it may accompany infarction.4 
DEGENERATION. 
Amyloid degeneration may be associated with a similar process else- 
where in the body. The iodine test may reveal the existence of this 
alteration in the villi of the small intestine. 
1 See Fitz, Am. Jour. Med. Sei., vol. cxviii., p. 125, 1899, bibl.; also Griffith, Trans. Assn. Am. 
Phys., vol. xiv., p. 1, 1899. 
2 See summary of cases by Gallaverdin, Gaz. des Hdpitaux, Aug. 24th and 31st, 1901, bibl. 
3 For a further consideration of thrombosis of the mesenteric veins consult Welch, Allbutt's "Sys- 
tem of Medicine," vol. vi., p. 218. See also study by Jackson, Porter, and Quinby, Jour. Am. Med. 
Assn., vol. xlii., p. 1469, 1604. 
4 For reference to occult haemorrhage in gastro-intestinal canal see Jaworski and Korolewicz, foot- 
note, p. 655. 672 
THE DIGESTIVE SYSTEM 
INFLAMMATION. 
Inflammation of the Small Intestine.0 (Enteritis.) 
Acute Catarrhal Enteritis.-This may occur under conditions similar 
to those inciting catarrhal inflammation in the stomach. It may be local 
or general and may be associated with similar processes in the stomach 
and colon. In "ptomain poisoning" the lesions are often severe. Com- 
paratively mild forms of the lesion may predispose the intestine to the 
incursions of intestinal bacteria and the development of more severe 
forms of destructive lesions. The mucosa may be reddened or ecchy- 
mosed, and covered with mucus 
mingled with degenerated epithelium 
and leucocytes. The epithelium may 
be degenerated and peeled off (Fig. 
431), and the cylindrical cells may be 
distended with mucus formed within 
them-11 beaker cells." 
The solitary and agminated 
lymph-nodules may be swollen from 
hyperplasia. When this hyperplasia 
is marked (Fig. 432), the lesion is 
often called follicular or nodular en- 
teritis, and erosions and ulceration 
may occur (Figs. 440 and 441).1 
This lesion is especially common in 
children suffering from various types 
of acute infection. For hyperplasia 
of the lymphoid tissue of the intestine 
in typhoid fever see p. 235. 
Chronic Catarrhal Enteritis.-This 
may follow the acute form or occur 
independently. It often accompanies 
many forms of chronic disease of the 
heart, kidneys, lungs, etc. The 
mucous membrane may be covered 
with mucus; ecchymoses, erosions, 
and pigmentation are frequent. There is hyperplasia of the inter- 
glandular tissue of the mucosa and the submucosa. In this way there 
may be atrophy of the glands, and the mucous membrane may be thin 
and fibrous. The muscularis may also be involved and atrophied. The 
submucosa and the muscular layer may, on the other hand, be thickened 
from the new-formed fibrous tissue. 
Pseudo-membranous Enteritis may occur in connection with a similar 
condition in the colon, in infectious diseases, in chronic diseases of the 
liver and kidney; in cachectic conditions, or as the result of the ingestion 
of irritant poisons. The mucous membrane may be the seat of superficial 
Fig. 431.-Acute Catarrhal Enteritis. 
Showing the open end of one of the tubular 
glands with exfoliating and disintegrating 
epithelium. 
1 It is better to abandon the name nodular enteritis for this lesion and call it nodular hyperplasia. THE DIGESTIVE SYSTEM 
673 
necroses, sometimes in patches, and the pellicle may consist largely of 
mucus with necrotic epithelium. Fibrin may be present, and fibrin and 
extravasated leucocytes and serous fluid may infiltrate the submucosa. 
Exudative or Suppurative Enteritis is rare. Purulent foci, usually 
Fig. 432.-Nodular Enteritis. 
From the intestine of a child. 
metastatic in origin, may form in the wall of the intestine. A more dif- 
fuse suppuration may follow infection after obstruction or strangulation.1 
Tuberculous Enteritis.-The lymph-nodules and Peyer's patches are 
often involved in intestinal tuberculosis and often ulcerate (Fig. 433). 
Miliary tubercles may be present with cheesy degeneration (Fig. 434) and 
In the larger ulcers the mucous membrane is almost entirely gone, leaving the muscularis exposed at 
the bottom. 
Fig. 433.-Tuberculous Ulcers of the Small Intestine. 
the subperitoneal lymphatic vessels are often involved and may appear 
as white, nodular, branching, slightly elevated cords, running around the 
gut (Fig. 435). Tuberculous ulcers are apt to extend most rapidly in a 
direction transverse to the axis of the gut (Fig. 436), differing in this 
1 See for a study of phlegmonous enteritis MacCallum, Johns Hopkins Hosp. Bull., vol. xvii., p. 
254, 1906, bibl. 674 
THE DIGESTIVE SYSTEM 
respect from typhoid ulcers (see p. 237). But to this there are fre- 
quent exceptions. Tuberculous ulcers rarely perforate. (See for other 
forms of tuberculosis of the intestine page 682.)1 
The mesenteric lymph-nodes are frequently involved in either active 
Fig. 434.-Section of a Tuberculous Ulcer of the Small Intestine. 
Showing tubercle tissue with miliary tubercles and caseation at the bottom of the ulcer. There are 
miliary tubercles beneath the serosa. (See Fig. 435.) 
or inactive tuberculosis in any part of the body. They may not show 
gross lesions, but the microscope may show characteristic lesions or 
tubercle bacilli. Frequently, when neither lesions nor bacilli are demon- 
strable, inoculation of guinea-pigs shows that the nodes are infected. 
Fig. 435.-Subsekous Tubercles Following the Lymph-vessels at the Bottom of a Tuber- 
culous Ulcer of the Small Intestine. 
The mesenteric nodes are frequently infected without other tuberculous 
lesions in the body.2 
Syphilitic Ulcers, originating in the lymphatic structures, are some- 
times found in infantile syphilis.3 
1 For statistics of intestinal tuberculosis see Zahn, Munch, med. Woch., p. 49, 1902; also Nebelthau, 
ibid., pp. 1246 and 1300, 1903; also Wagener, ibid., pp. 2036 and 2095, 1903; also Ipsen, Berl. klin. 
Wochenschr, p. 791, 1906. For presence of tubercle bacilli in mesenteric lymph-nodes see MacFadyen 
and MacConkey, Brit. Med. Jour., vol. ii., p. 129, 1903. 
2 See Rosenberger, Am. Jour. Med. Sci., vol. cxxx., p. 95,1905. For reference to intestines as portals 
of entry of tubercle bacilli, see p. 694. 
3 For study of acquired syphilitic ulcers of intestine see Arken, Trans. Chicago Path. Soc., 1912, viii, THE DIGESTIVE SYSTEM 
675 
Duodenal Ulcers may be tuberculous or may follow extensive burns. 
In the latter case their mode of origin is obscure. They may occur under 
a variety of other conditions.1 
Other Forms of Ulcers.-The solitary and agminated lymph-nodules 
frequently undergo hyperplasia, in infectious diseases, after extensive 
Showing the extension of the ulcers in a direction transverse to the axis of the gut. 
Fig. 436.-Tuberculous Ulcers of the Small Intestine. 
burns, in various forms of inflammation of the intestine. Hyperplasia 
of the lymphatic tissue-see p. 672-with ulceration is especially frequent 
in children. 
Inflammation of the Large Intestine. (Colitis.) 
The mucous membrane of the large intestine is frequently the seat of 
acute and chronic inflammatory and necrotic processes known clinically 
as dysentery.'2 The rectum is most often involved, but sometimes the 
upper part of the colon and sometimes the whole colon is affected. 
Acute Catarrhal Colitis.-This process is frequently limited to the 
lower end of the colon and presents several types. There may be an 
increased production of mucus, which coats the surface of the mucous 
membrane and is mixed with exfoliated and fatty or disintegrated epithe- 
lium and red blood cells. The surface epithelium may be degenerated 
and exfoliate, many "beaker cells" being present, indicating the source 
of over-production of mucus (Fig. 437). The mucous membrane may 
be congested and infiltrated with serum and leucocytes. Again, with 
conditions similar to those just described, there may be a purulent 
exudate in the mucous membrane. There is a form of catarrhal colitis 
in which there is a more or less extensive formation of new connective 
tissue between the glands and in the submucosa. Finally, there may 
be small or extensive ulceration in the involved areas of the mucosa. 
Acute Infectious Colitis (Tropical Dysentery) is of especially frequent 
occurrence in warm countries and is often epidemic. In one group of 
1 For a study of duodenal ulcers see Weir, Medical Record, vol. Ivii., p. 749, 1900, bibl. 
2 The classification of these lesions is with our present knowledge unsatisfactory, and is largely 
based upon morphology. In some phases of so-called dysentery-infectious colitis-however, the 
nature of the excitant is taken into the account. Consult for a special study of forms of colitis seen in 
New York, Delafield, Am. Jour. Med. Sci., vol. cxiv., p. 401, 1897. 676 
THE DIGESTIVE SYSTEM 
cases (a) the disease is probably incited by protozoa-Entamoeba histo- 
lytica; while in the other (6), bacteria, some apparently related to the 
typhoid-colon bacillus group, and possibly others, are believed to be the 
excitants. 
(a) Amoebic Colitis.-This form of colitis is apparently incited by 
the presence of the wall in the intestine of the Entamoeba histolytica. 
The amoebae are found in the gelatinous masses which are common in 
the stools. They are of rounded shape, and, when alive, change their 
Fig. 437.-Acute Catarrhal Colitis. 
The epithelium of the tubular glands, especially near their mouths, is forming an excessive amount 
of mucus with destruction and exfoliation of the cells. The tubules are dilated with mucus which 
covers the surface. The mucosa at the right is necrotic and forms the edge of an ulcerated area. 
position and shoot out and retract little projections (pseudopodia). 
Their outer portion is composed of a pale hyaline or homogeneous sub- 
stance; the inner contains vacuoles and is more refractive (see Fig. 73). 
In the colon the amoebae are found in the connective-tissue coat (Fig. 
438) and in the floors of the ulcers. 
Amoeba excites at first a moderate exudative and productive in- 
flammation followed by necrosis. Thus ulcers are formed. The ulcers 
may be superficial or deep, sometimes extending to the peritoneum; they 
enlarge by infiltration and necrosis at their edges, so that extensive 
destruction of the mucous membrane may occur. The amoebae may be 
present in the connective tissue at the base or sides of the ulcers. Not 
infrequently, owing to bacterial infection from the intestinal contents, 
varying degrees of suppurative inflammation may complicate the lesion. 
Necrotic and suppurative processes may be set up in the liver (see 
p. 722) and in the right lung, and in these lesions the amoeba may be 
found. THE DIGESTIVE SYSTEM 
677 
(&) Acute Infectious Colitis with Bacterial Excitants.- 
The lesions in those forms of infectious colitis which are not associated 
with amoeba are varied, and it is not yet possible to give a very precise 
morphological characterization of them. In general it may be said that 
the lesion when pronounced is pseudo-membranous, exudative, and 
necrotic, with or more less ulceration of the mucosa and submucosa. 
The earlier bacterial studies of the various types of infectious colitis 
-dysentery-tropical, epidemic, sporadic, or pseudo-membranous, gave 
little definite data. Many bacteria were found, most of them of species 
not infrequently present in the normal intestine. In 1897, however, 
Shiga made a careful study of a series of cases in a serious dysentery 
epidemic occurring at that time in Japan. Shiga found constantly in 
these cases a bacillus-Bacillus dysenteries-not normally present and 
pathogenic for animals, which gave agglutinative reactions with the serum 
of the dysentery patients. This bacillus was formerly regarded as simi- 
lar to the typhoid bacillus, but can now be readily differentiated from it.1 
Fig. 438.-Amcebic Colitis. 
Showing amoebae in the submucous fibrous tissue. 
Two years later Kruse found a similar bacillus in cases of dysentery 
occurring in Germany, and Flexner and Strong have found one which they 
believe to be identical in the Philippines. It has since been found in 
numerous instances in the United States.2 
Considerable doubt has arisen regarding the significance of many of 
the later determinations owing to the fact that until recently some of the 
distinctive biological characters were not generally known, and that the 
agglutination reactions, if not carried out with extreme care, may lead 
the observer astray. 
We cannot enter here upon the details of the various studies of this 
subject. But it has been shown that there are several groups of the 
Shiga bacillus which are the excitants of some forms at least of tropical 
and epidemic or sporadic dysentery. Whether the occurrence which has 
1 See Hiss and Russell, Med. News, vol. Ixxxii., p. 289, 1903. 
2 See Park and Williams, Pathogenic Bacteria, p. 276, 1910. 678 
THE DIGESTIVE SYSTEM 
been described of this bacillus or variants of it, in other forms of intestinal 
disorder, such as some types of infantile diarrhoea, is of significance or 
not, it is yet too early to say.1 
While the value of protective serum prepared by animal inoculations 
Showing commencing necrosis of the mucosa over the hyperplastic lymph-nodule. 
Fig. 439.-Nodular Colitis-Follicular Colitis. 
of Shiga's bacillus has been claimed, the evidence is yet too meagre to 
permit of final judgment.2 
Bacillus pyocyaneus has been repeatedly found in the discharges in 
cases of dysentery as well as in other intestinal disorders under conditions 
Fig. 440.-Nodular Colitis with Ulceration. 
Showing necrosis and ulceration of the lymph-nodule with opening into the lumen of the gut. 
which justify the conjecture that it is sometimes at least an excitant of 
intestinal inflammation and necrosis. Streptococcus pyogenes has been 
repeatedly found in association with enteritis and colitis. Intestinal 
infection with streptococcus is more frequent and significant in children 
than in adults.3 
1 For a study of experimental colitis see Flexner and Sweet, Jour. Exp. Med., vol. viii., p. 514, 1906. 
2 For a general statement of forms and lesions of dysentery and its relationship to micro-organisms 
der Flexner, Phila. Med. Jour., vol. vi., p. 414,1900; see also Lentz, Kolle and Wassermann's "Handbuch 
see Mikroorganismen," 2d ed., 1913, iii., 899. 
3 See v. Lingelsheim, Kolle and Wassermann's ''Path. Mikroorganismen," 2d ed., 1912, iv, 451. THE DIGESTIVE SYSTEM 
679 
Nodular Hyperplasia.-In many cases of catarrhal and croupous 
inflammation of the colon and of acute infections, especially in children, 
the solitary follicles (lymph-nodules) become more or less swollen and 
necrotic. Besides these cases, however, there are others in which the 
From the intestine of a child, showing numerous ulcers involving solitary nodules. (Compare Fig. 432.) 
Fig. 441.-Nodular Colitis. 
changes in the nodules form the principal part of the lesion, while the 
catarrhal or croupous inflammation is but slightly developed. The 
lesion is similar to that in nodular hyperplasia in the small intestine. 
The nodules are first swollen-hyperplastic-(Fig. 439), then necrotic, 
Eig. 442.-Pseudo-membranous (Croupous) Colitis. 
then slough away and leave little circular ulcers with overhanging 
edges (Fig. 440). These ulcers are usually numerous (Fig. 441) and 
may be scattered over a large part of the colon. The ulcers are apt to 
show but little disposition to heal, and the acute colitis often becomes 
chronic. 680 
THE DIGESTIVE SYSTEM 
Nodular Colitis.-In rare cases of typhoid fever and occasionally 
under other conditions there are foci of inflammation with necrosis and 
ulceration irregularly scattered and involving primarily not the mucous 
membrane but the underlying tissue. These lesions are not to be iden- 
tified with hyperplasise of the solitary lymph-nodules with ulcerations 
which occur with especial frequency in children suffering from acute 
infections.1 
Fig. 443.-Necrotic Colitis. 
Circumscribed congestion and necrosis of the glandular and connective-tissue coats. 
Pseudo-membranous (Croupous) Colitis.-This form of inflammation 
may involve the rectum alone, or the entire length of the colon, or only 
its upper portion. The mucous membrane is congested and swollen, and 
coated with a layer of false membrane; the connective tissue between and 
beneath the gland tubules is infiltrated with fibrin and pus, and in severe 
cases the inflammation involves the muscular and peritoneal coats also. 
The inflammation is usually more intense at some places than at others, 
so that the surface of the mucous membrane shows the false membrane 
in isolated patches. (Fig. 442.) Less frequently there is a uniform 
coating with the false membrane. In mild cases, as the inflammation 
subsides, the products of inflammation are absorbed and the wall of the 
intestine returns to its normal condition. In more severe cases the 
1 See Whipple, Johns Hop. Hosp. Bull., vol. xvii., p. 281, 1906. THE DIGESTIVE SYSTEM 
681 
quantity of the inflammatory products is so great that portions of the 
wall of the intestine become necrotic. This necrosis may involve only 
the glandular coat, or it may extend deeper into the wall of the intestine. 
The necrosed tissue after a time sloughs away, leaving behind ulcers of 
different sizes and depths. After this 
the ulcers may cicatrize, or their floors 
and walls may remain in the condi- 
tion of granulation tissue for an in- 
definite length of time. When the 
latter is the case there is added a 
chronic inflammation of the wall of 
the intestine between the ulcers, with 
changes in the mucous membrane and 
thickening of the connective-tissue 
and muscular coats. 
Necrotic Colitis.-There is a form 
of inflammation of the colon in which 
considerable areas of the connective- 
tissue coat become necrotic, leaving 
the glandular coat undermined and 
separated from the muscular coat. 
In this way large ulcers with over- 
hanging edges are developed. This 
form of colitis is very fatal. 
There is another very fatal and 
obscure form of necrotic colitis which 
appears to be septic in character. 
After death the inner surface of the 
colon is found studded with little 
blackish areas in which the blood- 
vessels are gorged with blood. The 
glandular and connective-tissue coats 
are infiltrated with pus cells and there 
is a superficial necrosis (Fig. 443). 
Various forms of micro-organisms 
have been found in connection w'ith 
suppurative and necrotic lesions of the 
ileum and colon-Streptococcus pyogenes, Staphylococcus pyogenes, 
Bacillus coli communis, Bacillus proteus, Bacillus pyogenes, and others. 
The significance of these organisms is not yet clear.1 
Fig. 444.-Chronic Ulcerative 
Colitis-Dysentery. 
There are small erosions of the swollen 
mucous membrane. 
1 See Kruse and Pasquale, Zeits. f. Hygiene und Infkr., Bd. xvi., p. 1, 1894; also Cerenville, Tavel, 
and others, Ann. Suisses des Sc. Med., ser. ii., p. 531, 1895. 
See, for consideration of Streptococcus enteritidis in infants, Hirsch, Centralbl. f. Bak., Abth. I., 
Bd. xxii., p. 369, 1897, bibl. 
For a study of intestinal bacteria see van Ermengem, Kolle und Wassermann's Handbuch, 
Jed., 1903, Bd. ii., p. 637; also Ford, "Studies Royal Victoria Hospital," Montreal, vol. i., 1903, 
resume and bibl.; also Weiss, Cbl. f. Bak., Abth. I., Bd. xxxvi., p. 13, 1904. For a study of the permea- 
bility of the intestinal wall for bacteria see Klimenko, Zeits. f. Hygiene, etc., Bd. xlviii., p. 67, 1904, 
and Uffenheimer, Deutsch, med. Woch., p. 1851, 1906, bibl. See, for a study of absorption in the large 
intestine, Bremer, Jour. Med. Res., vol. xv., p. 89, 1906. For a study of the cause of death of bacteria 
in the small intestine see Rolly and Liebermeister, Deut. Arch. klin. Med., Bd. Ixxxiii., p. 413, 1905. 682 
THE DIGESTIVE SYSTEM 
Mucous Colitis (Membranous Colitis).-Under a variety of obscure 
conditions, probably sometimes inflammatory in character, shreds or 
sheets or even cylindrical casts of the interior of the gut are passed from 
the bowels. These consist of dense mucus often mingled with degener- 
ated epithelium.1 
Chronic Colitis.-In prolonged inflammation of the colon, marked 
structural alterations may take place. The glandular coat may be 
uniformly thickened or thrown into the form of polypoid tumors, or atro- 
phied, or destroyed by ulcers of various sizes and shapes (Figs. 444 and 
In places only a few ragged islets of mucous membrane are left, the muscularis forming the bottom of 
the ulcers. 
Fig. 445.-Chronic Colitis with Extensive Ulceration of the Mucous Membrane. 
445). Small cysts may form from the retention of mucus in the follicles. 
The connective-tissue and muscular coats may be thickened or thinned. 
Apparently chronic colitis may follow any of the forms of acute colitis.2 
Repair may follow even considerable losses of substance in the intes- 
tinal mucous membrane. The new-formed connective tissue may un- 
dergo slight or marked cicatricial contraction. The denuded surfaces may 
become covered anew with epithelium derived from the intact cells.3 
The Caecum. 
Catarrhal Inflammation of the csecum is not uncommon. It is usually 
produced by an habitual accumulation of faeces in this part of the intes- 
tine. The course of the inflammation is usually chronic, but marked by 
acute exacerbations. At first the mucous membrane undergoes the ordi- 
nary changes of chronic catarrhal inflammation. To this may succeed a 
slow suppurative inflammation which extends through the wall of the 
intestine and gives rise to ulcers and perforations. 
Through these perforations the faeces may pass into the peritoneal 
cavity, or the perforations are partly closed by adhesions, and abscesses 
are formed, or sinuses into the surrounding soft parts. 
1 For observations and bibliography of membranous enteritis or colitis consult Butler, N. Y. Med. 
Jour. Dec. 28th, 1895, or Akerland, Arch. f. Verdauungskrankheiten, Bd. i., p. 396, 1896. 
2 For reference to syphilitic ulcers see Arken, footnote, p. 674. 
3 For a study of regeneration of intestinal epithelium see Quinu and Branca, Arch. d. med. exp., 
vol. xiv., 1902, p. 405. For a study of the association of the crypts of Lieberkuhn with lymph- 
nodules in the colon see Schultze, Centrbl. f. Path., Bd. xvi., p. 99, 1905. THE DIGESTIVE SYSTEM 
683 
Chronic Hyperplastic Tuberculosis of the Ileo-caecal Region and Other 
Parts of the Intestine.-Attention has recently been called to a peculiar 
form of tuberculous inflammation of the intestine which is characterized 
by the extensive formation of small spheroidal-celled and fibrous tissue, 
especially in the submucosa and often involving the muscular wall and 
the subserous layer. Miliary tubercles, cheesy degeneration, and ulcera- 
tion are not usually conspicuous features of the lesion. The ileo-caecal 
region is most often involved, the rectum less frequently, while the lesion 
is rarely limited to the ileum. Both the large and small intestines may 
be involved together. The new tissue may form a circumscribed annular 
thickening of the wall of the gut, or it may occur as a distinct tumor or 
as polypoid projections of the mucous membrane. The intestine in the 
vicinity of the involved portion may be enclosed in a mass of fibrous fat 
tissue. Owing to the thickening of the wall of the intestine the lumen 
may be much narrowed or nearly completely stenosed. On section of the 
thickened areas, caseous foci may be revealed; ulcerations, in rare cases, 
may be present; more often they are moderate or extensive. 
The microscopical examination shows that while miliary tubercles and 
cheesy degeneration are commonly to be detected, the new tissue consists 
in the main of collections of small spheroidal cells with more or less 
fibrous stroma and occasionally giant cells, and of moderately cellular or 
dense fibrous tissue. The polyhedral cells common in tuberculous 
inflammation are not as a rule conspicuous. The new tissue is usually 
most abundant in the submucosa. The mucosa may be similarly thick- 
ened, usually in polypoid form, or unchanged; it may show simple 
catarrhal alterations or may contain miliary tubercles or be ulcerated. 
The muscular coat may be also infiltrated and much thickened by the 
new-formed cellular and fibrous tissue and there may be muscular hyper- 
trophy. The associated lymph-nodes may be involved. Tubercle bacilli 
are present in the lesions, sometimes in enormous numbers. The process 
appears to be sometimes primary in the intestine; sometimes it occurs 
with or follows tuberculous lesions of the lungs. Hyperplastic tubercu- 
lous lesions limited to the caecum have frequently been operated upon 
under the impression that the process was cancerous.1 
The Rectum. 
Besides inflammatory changes similar to those already described as 
occurring in the colon, we sometimes find a suppurative inflammation of 
the connective tissue which surrounds the rectum, either associated with 
lesions of the mucous membrane or occurring by itself. 
In adults the lower end of the rectum is the part of the intestine 
which is the most frequent seat of syphilitic ulceration. Most of these 
ulcers seem to be the result of unnatural coitus, or of infection from 
specific sores of the vulva; but some of them seem to be due to the 
softening of gummy tumors. The gonococcus is an occasional excitant 
of inflammation of the rectum. 
'For a study and bibl. see Lartigau, Jour. Exp. Med., vol. vi., 1901, p. 23. See also Richter, 
Ziegler's Beitr., Bd. xxxix., p. 199, 1906, bibl. 684 
THE DIGESTIVE SYSTEM 
Strictures of the rectum may be due to tumors, to cicatrices following 
trauma or inflammation.1 
II amorrhoids (Piles).-Ectasiae of the haemorrhoidal veins are of fre- 
quent occurrence. They are most frequent in adults and are usually due 
to venous obstruction in cirrhosis, chronic constipation, pelvic tumors, 
chronic inflammation of the rectum, etc. The enlarged veins may be 
within or without the sphincter-internal or external haemorrhoids. The 
Section of an external haemorrhoid consisting of fibrous tissue and dilated vessels. Covered with 
epithelium except at the upper right portion where it was attached. 
Fig. 446.-Hemorrhoids. 
dilated veins may have thickened walls and may be surrounded by new- 
formed connective tissue. The projecting mass in external haemorrhoids 
may consist in part of dilated vessels, in part of fibrous tissue, and is 
covered by thickened epithelium (Fig. 446). Considerable haemorrhage 
may take place from haemorrhoids, and they may afford a portal of entry 
of bacteria leading to local or general infection. 
The Appendix Vermiformis. 
Inflammation-Appendicitis.-Inflammation of the appendix may 
present various phases. 
1. The mucous membrane may be the seat of acute catarrhal inflamma- 
tion. This is of mild type and short duration, with congestion, swelling, 
and an increased production of mucus; or it is of severer type, of longer 
duration, and the cavity of the appendix is distended by mucus and pus. 
2. The entire thickness of the wall of the appendix may be the seat 
of an acute exudative inflammation. The appendix is very much increased 
in size, sometimes to the size of a man's finger. (Fig. 417.) This increase 
in size is due, not to a dilatation of the cavity of the appendix, but to a 
thickening of its walls. The walls are congested, swollen, infiltrated with 
fibrin and pus, the peritoneal coat is covered with fibrin. There is 
neither necrosis nor perforation. If the appendix is behind the caecum, 
1 For bibliography of non-malignant rectal strictures see Peterson, Jour. Am. Med. Assn., vol. 
xxxiv., p. 259, 1900. THE DIGESTIVE SYSTEM 
685 
or if adhesions are formed early, there is only a localized peritonitis. If 
the appendix projects freely into the peritoneal cavity and no adhesions 
are formed, a general peritonitis may be soon established. 
3. At one or more points in the wall of the appendix there is an exu- 
dative inflammation with necrosis. In this way small or large portions of 
the wall of the appendix are destroyed, large or small perforations are 
formed, and the contents of the appendix escape into the abdominal cav- 
ity. In these cases the appendix usually contains a faecal concretion. 
Such perforations are usually followed by the collection of pus around 
Fig. 447.-Acute Appendicitis. 
A posterior view of the caput coli. The appendix is swollen and a pellicle of exudate covera 
it and the adjacent intestine. 
the appendix (Fig. 448). The pus may extend from this abscess-like 
collection in any direction and for long distances, so that collections may 
be found deep in the pelvic cavity, or under the diaphragm, or abscesses 
may form at other remote points. 
4. The entire appendix becomes gangrenous within one or two days, 
with the formation of an abscess, or general peritonitis. This is the most 
fatal form of appendicitis. 
5. Inflammation of the appendix may be secondary to catarrhal or 
croupous colitis. 
6. In typhoid fever there may be changes in the wall of the appendix 686 
THE DIGESTIVE SYSTEM 
of a character similar to those in the wall of the small intestine; that 
is, hyperplasia of the lymphoid tissue with necrosis (p. 235). 
7. There may be a tuberculous inflammation of the appendix, with the 
formation of ulcers. 
As the result of chronic inflammation in the appendix, atrophy of the 
glands and lymphoid tissue with increase of the fibrous tissue (Fig. 449) 
and strictures or obliteration of its lumen may occur (Fig. 450). 
Cystic dilatation of the appendix may be formed by obstruction of 
Appendix removed by operation twelve hours after first symptoms. Streptococcus was found in 
the exudate. 1, Mucous membrane of the appendix; 2, lymphatic nodules in the mucous membrane; 
3, submucosa; 4, muscularis; 5, mesentery of the appendix; 6, pus and fibrin covering the appendix; 
7, dense infiltration of the wall of the appendix with pus; 8, pus exudate in lumen. 
Fio. 448.-Acute Suppurative Appendicitis. 
the lumen. The cysts thus formed may be of considerable size-from 
one to fifteen centimetres in diameter or larger-and contain mucous, 
gelatinous, or watery fluid often turbid or colored.1 
The lumen of the appendix frequently contains concretions of faecal 
material which have often been mistaken for foreign bodies. Foreign 
bodies, such as grape and apple seeds, and various small objects which 
have been swallowed, sometimes, though rarely, find their way into the 
appendix.2 Both the faecal concretions and the foreign bodies may act 
as important predisposing agents of inflammation and perforation of the 
1 See for a study of cysts and diverticula of the appendix Corning, Albany Med. Annals, Dec., 
1905. Also Winkler, Erkrankungen des Blinddarmanhanges, Jena, 1910. 
2 For a study of foreign bodies in appendix see Mitchell, Johns Hopkins Hosp. Bull., vol. x., p. 35, 
1899. 687 
THE DIGESTIVE SYSTEM 
appendix, through pressure, erosion, etc., of the mucous membrane, 
affording portals of entry to various forms of pathogenic micro-organisms. 
Fig. 449.--Chronic Appendicitis. 
Showing obliteration of the glands and lymphoid tissue with new fibrous tissue in the mucosa 
and submucosa. 
Fig. 450.-Appendix with Obliteration of the Lumen by Fibrous Tissue. 
The bacteria most commonly found associated with the lesions of acute 
appendicitis and its accompanying peritonitis are Streptococcus pyog- 688 
THE DIGESTIVE SYSTEM 
enes, Staphylococcus pyogenes, the B. coli communis, B. proteus, and 
B. pyocyaneus. Anaerobic forms are also important.1 
Oxyuris and trichocephalus are frequently found in the appendix in 
children, and may by their destruction of the mucosa permit the entry of 
bacteria.2 
TUMORS OF THE INTESTINE.3 
Fibroma and lipoma may be developed from the submucous coat and 
grow inward, or from the subserous coat and project outward into the 
peritoneal cavity. Small multiple cavernous haemangiomata are of occa- 
sional occurrence in the submucosa of the small 
intestine. These tumors may be limited to the 
small intestine or may be found throughout the 
gastro-intestinal canal.4 
Myoma may originate in the muscular coat 
and project inward, obstructing the intestine. 
In the duodenum such tumors may obstruct 
the common bile duct. Less frequently these 
tumors project outward into the peritoneal 
cavity. 
Polypoid growths, projecting into the cavity 
of the intestine and composed of connective 
tissue and covered with epithelium are frequently 
found (Fig. 451). They are associated with 
catarrhal inflammation or occur by themselves. 
They are found throughout the intestinal tract 
and may be single or multiple. They grow 
from the submucous coat and project inward. 
Some of them are solid connective-tissue tumors, 
covered by the mucous membrane which they 
have pushed inward. Others are of the same 
character, but of large size. In others the con- 
nective tissue is arranged in branching tufts, 
covered with cylindrical epithelium; and in these last tumors there may 
also be tubules lined with cylindrical epithelium, giving to the growth the 
characters of an adenoma. 
Lymphoma.-Growths of tissue somewhat resembling that of the 
lymphatic tissue of the lymph-nodes may originate in the solitary and 
agminated nodules, and in the intestinal wall in cases of leukaemia and 
pseudo-leukaemia (Fig. 452). 
Fig. 451.-Small Polyp of 
the Mucous Membrane of 
the Small Intestine. 
1 Hodenpyl, "Etiology of Appendicitis," N. Y. Med. Jour., Dec. 30th, 1893. Consult also Kelynack. 
"Pathology of the Vermiform Appendix," London, 1893; Berry, Jour, of Path, and Bact., vol. iii., 
p. 160, 1895 (bibl.); Ribbert, Virch. Arch., Bd. cxxxii, p. 66, 1893. For bacterial reports see Low, Rep, 
Boston City Hosp., Ser. 11, 1900, p. 173; also Lanz and Tavel, Rev. de Chir., t. ii., 1904; also Perrone. 
Ann. Inst. Pasteur, t. xix., p. 367, 1905. For comprehensive treatise see Kelly and Hurdon on the 
vermiform appendix. Also Aschoff, Die Wurmfortsatzentziindung, Jena, 1908. 
2 Cecil and Bvlkley, Jour. Exp. Med, 1912, xv, 225. 
3 For a study of congenital tumors of the intestines consult Hueter, Ziegler's Beitrage zur path. 
Anat., Bd. xix., p. 391, 1896. 
4 See Bennecke, Virch. Arch., Bd. clxxxiv., p. 171, 1906; also MacCallum, Johns Hopk. Hosp. 
Bull., vol. xvii., p. 258, 1906. THE DIGESTIVE SYSTEM 
689 
Similar growths are found as independent lesions both in the large 
and small intestines, These are irregular, diffuse growths infiltrating 
Fig. 452.-"Lymphomata" of the Intestine in Pseudo-leukaemia. 
The growths are polypoid, many are pigmented, and they were in this case widely 
distributed over the intestinal mucosa. 
the wall of the intestine, the mesentery, and the neighboring lymph- 
nodules, and may reach a considerable size. They often ulcerate inter- 
nally and may lead to dilatation or stenosis of the intestine. The classi- 
Fig. 453.-Adeno-Carcinoma of the Rectum. 
Shows a portion of normal mucous membrane invaded by adenomatous growth. This type of 
tumor is frequently called malignant adenoma. 
fication of such tumors is difficult and it is often doubtful whether they 
should be grouped with the sarcoma or the so-called lymphoma. 690 
THE DIGESTIVE SYSTEM 
Sarcomata are of occasional occurrence in the intestine. They appear 
to be more frequent in the small intestine and in the rectum than in the 
large intestine. While various structural types are recorded, the so- 
called lympho-sarcomata are most common.1 
Adenomata are found in the duodenum, colon, and rectum. They 
form superficial infiltrations of the 
wall of the intestine or project 
inward as polypoid tumors. They 
are composed of tubular fol- 
licles, like those of the intestinal 
mucous membrane, and of a con- 
nective-tissue stroma. In some of 
these tumors the tubules have a 
regular shape and arrangement; 
there is no infiltration of surround- 
ing tissue; the tumor is of benign 
nature. In other tumors the 
tubules are irregular in shape and 
arrangement, and the growth infil- 
trates the surrounding parts (Fig. 
454). There is no sharp dividing 
line between these tumors and 
the carcinomata. 
Carcinoma develops most often 
in the colon and the duodenum.2 
The forms which have been described in the stomach occur also here, i.e.: 
1. The medullary /or ms with relatively little stroma, and epithelial cells 
either in solid masses within the alveoli, or maintaining in a measure the 
gland type-adeno-carcinoma. 2. Fibrous form-scirrhus. 3. Gelatinous 
forms, which are more common here than in the stomach. Epithelioma 
often involves the anus and rectum. 
Cysts of the intestine are uncommon.3 
Tumors of the appendix are not frequent. Fibroma, lipoma, 
myoma, sarcoma, endothelioma are rare,4 while several hundred cases of 
primary carcinoma of the appendix have been recorded.5 
Fig. 454.-Adenoma of the Rectum. 
The growth has extended through the mus- 
cularis mucosae into the submucosa. 
INTESTINAL CONCRETIONS. (Enteroliths.) 
The intestines may contain round, oval, or irregular masses of firm 
consistence, usually small, but sometimes as large as a man's fist. They 
consist of faecal matter, mucus, bile, the carbonate and phosphate of 
1 For resume and bibliography of sarcoma of small intestine see Libman, Am. Jour. Med. Sciences, 
vol, cxx., p. 309, 1900. For bibliography of sarcoma of large intestine seeJopson and White, ibid., 
vol. cxxii., p. 807. For a resume with bibliography of melano-sarcoma of the rectum see Wiener, 
Ziegler's Beitrage, Bd. xxv., p. 322, 1899. 
2 See Rolleston, Lancet, vol. i., p. 1121, 1901. 
3 See Ayer, Am. Jour. Med. Sci., vol. cxxxi., p. 89, 1906. 
4 For bibliography of tumors of the appendix see Kelly, Proc. Path. Soc. of Phiia., N. S., vol. iii. 
p. 109, 1900. Also Miloslavich and Namba, Zeit. f. Krebsf. 1913, xii, 14. 
6 Whipham, Lancet, 1901, vol. i., p. 319. Jessup, Med. Rec., vol. Ixii., p. 289, 1902. Mosch 
cowitz, Ann. of Surgery, June, 1903, bibl. Norris, Bull. Univ. Penna., xvi., 1903, p. 334. Baldauf, 
Albany Med. Annals, Dec., 1905. McWilliams, Med. and Surg. Rep., Presbyt. Hosp. N. Y., viii., 1908. THE DIGESTIVE SYSTEM 
691 
lime, and triple phosphate. They may induce inflammations, ulceration, 
and perforation. Small brown concretions-intestinal sand-may be 
found. 
PARASITES. 
Anthrax Infection of the Intestine (Mycosis Intestinalis).-The anthrax 
bacillus may lodge in the intestinal mucosa either through food contain- 
ing the germ or by metastasis through the blood from some infective 
focus, especially the skin. 
The intestinal lesions are most apt to occur in the small intestines and 
in the upper part of the colon. The mucous membrane is studded with 
larger and smaller brown or black, frequently elevated patches, or areas 
of local congestion, or hsemorrhage, or necrosis. The mucous membrane 
near the inflammatory and necrotic foci may be cedematous. Hyper- 
plasia of the spleen and lymph-nodes is apt to accompany the intestinal 
anthrax. The anthrax bacillus may be found about the seat of local 
lesion in the intestine, in the associated lymph-nodes; and when secondary 
to local infection elsewhere it may be found in the primary lesion and in 
the blood. 
It is believed that other forms of bacteria may cause intestinal lesions 
somewhat similar to those of anthrax, but the researches in this direction 
are not yet sufficiently numerous to permit of very definite statements.1 
ACTINOMYCOSIS OF THE INTESTINE. 
Actinomycosis involving the intestine is rare, but is most often found 
in the caecal region. Several cases of primary actinomycosis of the 
appendix are recorded.2 
The animal parasites of the gastro-intestinal canal have been already 
considered in another part of this book. 
The Peritoneum. 
Malformations. 
Arrest in development of the peritoneum may be manifested in fissures in the 
mesial line or external to it; in absence of the diaphragm; in fusion with the pleura; 
and in incomplete formation of the mesentery, the omentum, and the other folds of the 
peritoneum. 
Excess of development occurs in the shape of unusual length of the mesentery, the 
omentum, and the other folds of the peritoneum; or of supernumerary folds and 
pouches. These are chiefly found in the hypogastric, iliac, and inguinal regions and 
near the fundus of the bladder. There may be access to these sacs by a well-defined 
fissure or ring, which is frequently surrounded by a tendinous band lying in the dupli- 
cature. These may give rise to internal incarceration of the intestines. 
The left half of the diaphragm may have an abnormally high position with up- 
ward displacement of the abdominal viscera, particularly the stomach, on the left 
1 For reference to intestinal bacteria see pp. 214 and 681. 
2 For bibl. see Burnham, Johns Hop. Hosp. Bull., vol. xv., p. 136, 1904. 692 
THE DIGESTIVE SYSTEM 
side, and displacement of the heart to the right. This has been called eventration of 
the diaphragm. It may be mistaken in diagnosis for diaphragmatic hernia.1 
Large haemorrhage into the peritoneal cavity may result from injuries 
to the abdominal viscera, ruptured aneurism, etc. Punctate haemorrhages 
may accompany various acute infections and toxaemias. Haemorrhage 
may occur in acute localized or general peritonitis, in obstruction of the 
portal circulation, in thrombosis and in embolism of the mesenteric 
vessels. 
HEMORRHAGE. 
ASCITES. 
The collection of transudate in the peritoneal cavity may accompany 
chronic venous congestion, especially with obstruction of the portal cir- 
culation in cirrhosis from thrombi, emboli, etc., or with chronic heart 
and kidney diseases. It often accompanies similar conditions in the 
pleura and pericardium. It may accompany chronic peritonitis. 
Chylous ascites may result from a rupture of the thoracic duct or 
from a transudation from the chyle vessels.2 
Chyliform Ascites.-Most frequently in abdominal carcinoma and 
tuberculosis, but also in other forms of chronic peritonitis with serous 
exudate, the peritoneal cavity may contain fluid, milky from cell detritus 
and fat derived from the disintegration of degenerated mesothelial and 
other cells. This condition is called chyliform ascites. 
INFLAMMATION. (Peritonitis.) 
Acute Peritonitis.-Acute inflammation of the peritoneum may occur 
as a primary process, but is much more often secondary. In the latter 
case it may be associated with wounds and contusions of the wall of the 
abdomen; wounds, ulcers, new growths, incarcerations, intussusceptions, 
ruptures, perforations, and inflammations of the stomach and intestines; 
inflammation of the vermiform appendix; injuries, ruptures, and inflam- 
mations of the uterus, ovaries, and Fallopian tubes; rupture and inflam- 
mation of the bladder; inflammation of and about the kidneys; abscesses 
and hydatid cysts of the liver; inflammation of the gall-bladder and 
large bile ducts; thrombosis of the portal vein; inflammations of the 
spleen, pancreas, lymphatic glands, retroperitoneal connective tissue, 
vertebra?, ribs, and pelvic bones; pyaemia and other infectious diseases. 
The inflammation is at first either local or general. A local peritonitis 
may remain circumscribed, or it may spread and become general. 
We may distinguish two anatomical forms of acute peritonitis. 
1. Cellular Peritonitis.-This form of peritonitis may be induced 
by any irritant which does not act too energetically. It can be excited 
1 See Sailer and Rhein, Amer. Jour. Med. Sei., cxxix., p. 688, 1905. 
2 For a study of milky fluids in serous cavities consult Shaw, Jour. Path, and Bact., vol. vi., p. 
339, 1900, bibl. THE DIGESTIVE SYSTEM 
693 
in dogs by intraperitoneal injections of very small quantities of a solution 
of chloride of zinc. In the human subject we find it with perityphlitis, 
with circumscribed abscesses in the peritoneal cavity, in puerperal fever, 
and in other infectious diseases with early death. 
At the autopsy the entire peritoneum may be congested; but there 
are no exudates and no other lesions visible to the naked eye. Minute 
examination, however, shows a very marked change in the mesothelial 
(endothelial) cells. These are increased in size and number and the 
new cells coat the surface of the peritoneum and project outward in little 
masses (Fig. 455). This form of inflammation, in many cases, at least if 
Fig. 455.-Acute Cellular Peritonitis-Human Omentum. 
There are swelling and proliferation of the mesothelial cells as well as of the cells of the 
fibrillar tissue forming the omental trabecula;. 
life be prolonged, passes into the exudative phase, next to be considered. 
2. Exudative Peritonitis.-This, which is the common form of 
acute peritonitis, presents lesions similar to those which have been already 
described in pleuritis and pericarditis. Thus there is a form in which 
fibrin is the chief exudate with but little serum; or the exudate is sero- 
fibrinous, or purulent, or haemorrhagic.1 When fibrin is present, the 
intestinal coils may be more or less firmly adherent to the abdominal 
1 For a study of the forms of cells in exudative peritonitis see Lessen, Deut. Arch. klin. Med., Bd. 
xxxvi., p. 217, 1906. 694 
THE DIGESTIVE SYSTEM 
walls or to each other. If putrefactive bacteria be present, as in perit- 
onitis from perforation of the intestine, the exudate may be foul. 
In local inflammation of the peritoneum the position may be indicated 
by the name, thus perihepatitis, perisplenitis, perityphlitis, pelvic, sub- 
phrenic, etc. 
Acute exudative peritonitis may terminate in recovery with absorp- 
tion of the exudate, permanent connective-tissue adhesions and thicken- 
ings of the peritoneum often remaining. Chronic peritonitis may follow 
the acute phase. 
Bacteria are the usual excitants of acute exudative peritonitis. In 
primary forms of peritonitis the Streptococcus and Staphylococcus pyo- 
genes are the bacteria most frequently present. 
In secondary exudative peritonitis the pyogenic cocci and the colon 
bacillus have been most frequently found. Of the other bacteria which 
have been found in the exudate we may name the pneumococcus, the 
gonococcus,1 B. pyocyaneus, B. proteus, B. aerogenes capsulatus, B. 
typhosus. 
There is abundant evidence that bacteria can pass from the intes- 
tinal cavity through its wall into the peritoneum without perforation, 
especially in regions where the integrity of the tissues is impaired by 
disturbances in circulation and nutrition, or in necrosis, as in strangula- 
tion of the gut.2 
Absorption from the Peritoneum.-In connection with inflammation, recent 
studies which have been made of the absorption of alien substances injected into the 
peritoneal cavities of animals, especially rabbits and guinea-pigs, are of extreme in- 
terest and importance. Living bacteria as well as various kinds of inert particles may 
be rapidly disposed of through the action of the body fluids or phagocytic cells. The 
studies of Buxton and Torrey3 indicate that after an intraperitoneal injection of sus- 
pensions of inert particles there may be an immediate rush of these to the lymphatics 
of the diaphragm, whence they are carried almost immediately by the anterior medias- 
tinal lymph-trunks through the lymph-nodes to the thoracic duct and general circula- 
tion. In the earlier stages the transported particles may be free, but later may be 
taken up by phagocytes in the mediastinal lymph-nodes. But the omentum appears 
to be of significance in the disposal of inert particles injected into the peritoneal cavity. 
Buxton and Torrey show that almost immediately after the injection of such particles 
in the guinea-pig, fibrin is formed on the surface of the omentum in which the parti- 
cles and phagocytic cells become entangled. The phagocytes taking up the particles 
may then enter the tissues. These observers have furthermore shown that after intra- 
peritoneal injections of typhoid bacilli in the rabbit, the bacilli may become fixed upon 
the surface of the omentum where they may be destroyed.4 
Chronic Peritonitis may follow the acute exudative form or may occur 
independently. The lesions vary. In one group of cases the peritoneum 
1 See Cushing on gonococcus peritonitis, Johns Hopkins Hosp. Bull., vol. x., p. 75, 1899. 
2 Consult for studies and bibliography of various phases of peritonitis Tavel and Lanz, "Peritonitis," 
Mitth. a kl. u. med. Inst. d. Schweiz, 1 Reihe, Heft 1, p. 1, 1893; Silberschmidt, ibid., Heft 5, p. 432; 
Flexner, Phila. Med. Jour., November 12th, 1898; Cullen, Johns Hopkins Hosp. Rep., vol. iv., p. 411, 
1895; Abramow, Ziegler's Beitr., Bd. xxiii., p. 1, 1898; BUttner, ibid., Bd. xxv., p. 453, 1899. 
For special studies on the entrance of micro-organisms into the body from the gastro-intestinal 
canal see Opitz, Zeits. f. Hygiene, Bd. xxix., p. 505, 1898; Birch-Hirschfeld, Ziegler's Beitr., Bd. xxiv., 
p. 304, 1898; Buchbinder, Deut. Zeits. f. Chir., Bd. Iv., H. 6 and 7, 1900; Marcus, Zeits. f. Heilk., Bd. 
xx., p. 427, 1899; also Wiener klin. Woch., p. 11, 1901; Ravenel, Jour. Med. Res., vol. x., 1903, p. 460. 
3 Buxton and Torrey, Jour. Med. Res., vol. xv., p. 5, 1906. 
4 For a study of the local accumulation of eosinophile leucocytes after intraperitoneal injections 
of bacteria see Opie, Trans. Assn. Amer. Phys., vol. xix., p. 136, 1904. THE DIGESTIVE SYSTEM 
695 
is beset with minute translucent nodules, sometimes visible, sometimes 
invisible to the naked eye. These are apparently formed by a local 
proliferation of the mesothelial and connective-tissue cells. Associated 
with this there may be a general irregular proliferation of the peritoneal 
mesothelium. This has been called chronic cellular peritonitis. 
In other cases there are local or general fibrous adhesions, sometimes 
firm, sometimes loose, between the intestinal coils or between the intes- 
tine and the abdominal wall or the viscera (Fig. 456). In this way 
sacculated collections of sero-fibrinous or purulent exudate may form in 
Fig. 456.-Old Peritoneal Adhesions between the Under Surface of the 
Liver and the Intestine. 
L is the liver turned over to expose the inferior surface. Many delicate fibre cords and 
bands pass from the liver to the intestine, I. The gall-bladder, G. B., is distended. 
the abdominal cavity. Finally chronic peritonitis may result in a dense 
fibrous thickening of the peritoneum, either local or widespread. 
In some cases the parietal peritoneum is principally involved; in 
others the peritoneum of the stomach, intestines, liver, and spleen. The 
thickening of the capsule of the liver may be attended with a diminution 
in the size of that viscus. There may or may not be adhesions; serous 
or other exudate may be present. Great distortion of the omentum, 
mesentery, and other abdominal viscera may occur. 
Tuberculous Peritonitis may occur in acute general miliary tuberculo- 
sis or it may be secondary to tuberculous inflammation elsewhere, as in 
the lungs or genito-urinary organs or intestines; or it may be an inde- 
pendent process. The process may be local or general in the peritoneum. 696 
THE DIGESTIVE SYSTEM 
The lesions may be miliary in character (Fig. 457) or there may be large 
foci of the new-formed tubercle tissues with considerable necrosis. There 
may be more or less serous or sero-fibrinous or purulent or haemorrhagic 
exudate. Fibrous adhesions may form between the intestinal coils and 
the peritoneal walls with the encapsulation of exudate. Ulceration of the 
tubercle tissue may occur, or it may become dense and fibrous and is then 
Fig. 457.-Miliary Tubercles of the Omentum. 
often pigmented. The tuberculous inflammation may be limited to the 
vicinity of tuberculous ulcers of the intestine. It may involve the omen- 
tum, which is converted into a hard, thick, dense mass at the upper part 
of the abdominal cavity.1 
TUMORS. 
Fibromata are developed from the subperitoneal connective tissue and 
project inward into the peritoneal cavity. They are found beneath the 
parietal peritoneum and that covering the intestines. Such tumors may 
reach a very considerable size. Papillary fibromata of the peritoneum 
(Fig. 458) may be secondary to papillary fibroma of the ovary. 
Lipomata.-Circumscribed tumors composed of fat tissue are formed 
beneath the intestinal and parietal peritoneum and in the mesentery. 
These tumors may become changed into fibrous tissue or calcified. Their 
pedicles may become atrophied so that they are left free in the peritoneal 
cavity. 
When they grow beneath the parietal peritoneum they may form fat 
1 For bibliography with reference to operative treatment see Bottomley, Reports Boston City 
Hosp., ser. 11, p. 118, 1900. For a full critical summary of the literature of peritonitis from 1885 to 
1900 see Brunn, Centralbl. f. Path., Bd. xii., pp. 1, 65, 1901. THE DIGESTIVE SYSTEM 
697 
herniae. At the umbilicus, in the inguinal canal, along the vas deferens, 
in the crural ring, and in the obturator foramen, fatty tumors may grow, 
project outward under the skin like hernia?, and, by drawing the perit- 
oneum after them into a pouch, may open the way for a future intestinal 
hernia. Very large retroperitoneal and perirenal lipomata are of occa- 
sional occurrence.1 Myxoma, chondroma, osteoma, and angioma are 
recorded. 
Retroperitoneal sarcomata are found both in children and adults. 
They usually originate behind the peritoneum, covering the posterior 
This growth was secondary to a similar tumor originating in the ovary and connected with that 
organ (see Fig. 565), Detached portions of the original tumor were transplanted to various regions 
of the peritoneum. 
Fig. 458.-Papillary Fibroma-Papilloma-of Peritoneum. 
part of the abdominal wall, and may grow between the folds of the 
mesentery.2 
They may be of the small spheroidal-celled type (lympho-sarcoma) or 
of the fusiform-celled type. They are often very vascular. At first 
they grow slowly inward, pushing forward the peritoneum and abdominal 
viscera. After a time they assume a more noxious character, infiltrating 
the soft parts with which they come in contact, and forming metastatic 
1 For bibliography of such tumors see Adami, Montreal Med. Jour., vol. xxv., pp. 529, 620, 1897. 
2 For a study of the retroperitoneal lymph-nodes and retrograde metastases from the thorax 
into the abdomen of bacteria, dust, and tumor cells see Tendeloo, Munch, med. Wdch., p. 1537, 1904. 698 
THE DIGESTIVE SYSTEM 
tumors in the omentum, mesentery, intestinal wall, liver, lungs, and in 
other viscera.1 
Endotheliomata similar in structure to those originating in the pleura 
are of occasional occurrence in the peritoneum. They may form single 
Fig. 459.-Cystic Papilloma of the Omentum. 
Secondary to papilloma of the ovaries. 
well-defined tumors or flattened masses in the thickened peritoneum. 
Cuboidal or polyhedral cell masses often grouped along the side of anas- 
1 See for bibliography Steele, Am. Jour. Med. Sci., vol. cxix., p. 311, 1900. 
For a study of sarcoma and mixed tumors of the greater omentum see Conforti, Centralbl. f. Path., 
Bd. xvii., p. 817, 1906. THE DIGESTIVE SYSTEM 
699 
tomosing channels in the new-formed or old connective-tissue stroma 
sometimes lend a glandular appearance to the type of growth. 
These tumors apparently originate in the true endothelium of the 
subperitoneal lymph-channels and not in the flat cells often called endo- 
thelial-mesothelium-lining the peritoneum. 
Carcinoma of the peritoneum is usually secondary to this disease in 
adjacent regions, stomach, liver, uterus, etc. Its structural characters 
correspond with those of the primary growth. It is apt to appear in 
the form of numerous larger and smaller whitish nodules, sometimes 
local, sometimes widely disseminated over the peritoneal surfaces. Such 
tumors, when small and numerous, may readily be mistaken for tubercles. 
Gelatinous carcinoma is not infrequent and sometimes seems to be 
primary in the peritoneum. But in such cases the possibility of an origin 
in the mucous membrane of the colon, in which such growths are com- 
mon, and the extension outward without evidence of growth in the gut, 
is always to be considered. Gelatinous cancer often forms large masses, 
which widely involve the peritoneum and distend the cavity. 
Various forms of tumors of the umbilicus have been described.1 
CYSTS. 
Cysts of the mesentery are of occasional occurrence.2 They may be 
filled with chyle, with blood, or with serous fluid, or may be due to the 
echinococcus. 
Multiple cysts of the omentum may form by transplantation of papillary 
cyst-adenomata from the ovary (see Fig. 459).3 
Dermoid cysts may be found in the peritoneal cavity. Retroperitoneal 
cysts have been a few times recorded. 
PARASITES. 
Echinococci can be formed in their regular way at any part of the 
visceral and parietal peritoneum, or be free in the peritoneal cavity. 
These cysts may be small, or so large as nearly to fill the abdominal 
cavity. 
Cysticercus cellulosae may also be developed in the subperitoneal 
connective tissue. 
The Salivary Glands-The Parotid, Submaxillary, and Sublingual. 
INFLAMMATION. 
Acute Parotitis, occurring as an epidemic disease known as mumps, 
is usually confined to the parotid gland of one side; the submaxillary and 
sublingual may be at the same time involved. The gland is swollen and 
1 See Giannettasio, Arch. gen. de Med., t. iii., p. 52, 1900. 
2 For bibl. of cysts of the mesentery see Dowd, Annals of Surgery, vol. xxxii., p. 461, 1900; Ayer, 
Am. Jour. Med. Sci., vol, cxxxi., p. 89, 1906 and Frazier, Jour. Amer. Med. Assn., 1913, Ixi., 97. 
3 For bibl. of cysts of the omentum see Jacobi, Trans. Assn. Am. Phys., vol. xvi., p. 232, 1901; 
also Dowd, Ann. Surg., 1911, liv., No. 5. 700 
THE DIGESTIVE SYSTEM 
there is often oedema of the mucous membrane of the mouth and pharynx. 
Very little is known of the minute changes which the gland undergoes in 
this disease. 
Suppurative Parotitis may occur as a secondary lesion in many 
diseases, typhoid and scarlet fever, pyaemia, pneumonia, etc., and by 
bacterial invasion or extension of inflammation from the mouth. Under 
these conditions the process is usually suppurative and frequently results 
in abscess or sloughing. The interstitial tissue of the gland is more or 
less densely infiltrated with pus cells, and the parenchyma cells may 
undergo fatty degeneration and disintegration. The inflammation may 
be confined to the gland or it may spread to adjacent parts, sometimes 
causing much destruction of tissue, and may give rise to inflammation of 
the brain or of the inner ear, or even to metastatic pyaemic abscesses in 
different parts of the body. Healing may occur, with formation of 
salivary fistulse. 
The submaxillary gland may be involved with the parotid in the 
suppurative inflammation. Acute suppurative inflammation of the 
connective tissue about the submaxillary gland is sometimes of serious 
import. Sloughing and gangrene may occur and are apt to spread to 
adjacent parts. Septicaemia, oedema of the glottis, or pneumonia may 
complicate the process and cause death. 
The sublingual gland is not often the seat of inflammation. 
Chronic inflammation, leading to the formation of dense interstitial 
tissue, sometimes occurs in the salivary glands. This may occur by 
itself or follow an acute inflammation. Tuberculous inflammation of the 
parotid is not infrequent.1 
The excretory ducts of the salivary glands may become inflamed from 
the presence of foreign bodies or of concretions formed in them. They 
may become occluded from the presence of calculi or as the result of 
inflammation, and may thus become widely dilated both in the main 
branches and in the finer ramifications. The dilatation of Wharton's 
duct to form larger and smaller cysts containing salivary fluid sometimes 
gives rise to very large and troublesome tumors which constitute one of 
the forms of ranula.2 
Fibromata are of occasional occurrence in the parotid. Chondromata, 
endotheliomata, sarcomata and fibro -sarcomata, and myxomata, or more 
frequently mixed tumors formed of various combinations of these, are of 
frequent occurrence in the parotid and of occasional occurrence in the 
submaxillary gland. These complex or mixed tumors are of more 
frequent occurrence in these glands than in any other part of the body. 
They are sometimes rendered still more complicated in structure by the 
formation of cysts, and what has been regarded usually as an atypical 
TUMORS OF THE SALIVARY GLANDS. 
1 Consult Meslay and Parent, Gaz. des Hopitaux, Feb. 11th, 1899, bibl.; also Wood, Bull. Univ. 
Penna., vol. xvi., 1903, p. 368. 
2 For bibliography of lesions of the salivary glands see Thorel, Lubarsch and Ostertag's 
"Ergebnisse," Jahrg. v. for 1898, p. 221. THE DIGESTIVE SYSTEM 
701 
glandular growth, lending them an adenomatous character (Fig. 460)- 
Earlier studies upon the mixed tumors of the salivary glands led to the 
belief that a large part of these complex growths are endotheliomata,1 
but more recent studies indicate that many cell forms formerly interpreted 
as endothelial are epithelial.2 The present view is that these complex 
tumors of the parotid and other salivary glands are probably largely of 
epithelial origin, starting in congenital displacements of the glandular 
structures.3 
Fig. 460.-Endothelioma of the Parotid. 
Fibro-sarcoma and melano-sarcoma have been described. 
A case of rhabdomyoma of the parotid gland, with evidences of atypi- 
cal development of portions of the gland, has been described.4 Primary 
carcinoma of these glands is rare. 
The Pancreas. 
Malformations and Displacements. 
The pancreas may be entirely absent in acephalous and double monsters. The 
pancreatic duct may be double; it may open into the duodenum at some distance from 
the biliary duct, or into the stomach. The head of the pancreas may be unduly 
developed and sometimes even completely separated from the rest of the organ, 
opening into the duodenum with a duct of its own. The gland may be variously lobed 
and distorted. Occasionally there is a small accessory pancreas situated beneath the 
serosa of the duodenum or stomach.5 
The pancreas is so firmly bound dowm that its position is not often changed. 
Sometimes, however, it is found pressed downward by tight lacing, displaced by 
aneurisms, or contained in umbilical and diaphragmatic herniae. 
1 Volkmann, Deutsche Zeits. f. Chir., Bd. xli., p. 61. 
2 For a critical study of the mixed tumors of the salivary gland see Wood, Ann. of Surgery, vol. 
xxxix., 1904, p. 57, bibl.; Krompecher, " Basalzellenkrebs," 1903, and Wilson and Willis, Amer. Jour. 
Med. Sc., 1912, cxliii., 654. 
3 For an admirable series of studies along this line see Schulte, Huntington, and Carmalt, Publica- 
tions of the George Crocker Special Research Fund, vol. iv., New York, 1913. 
4 Prudden, ''Rhabdomyoma of the Parotid Gland," Am. Jour, of the Med. Sci., Apr., 1883. 
6 For obliteration of pancreas and ducts with congenital obliteration of gall-ducts see Hess, Arch. 
Int. Med., 1912, x., 37. 702 
THE DIGESTIVE SYSTEM 
ATROPHY, DEGENERATION, AND NECROSIS. 
Atrophy of the pancreas may occur in old age and as a result of pres- 
sure from tumors or other adjacent structures, and maybe associated with 
fatty infiltration. It occurs in a certain proportion of cases of diabetes 
mellitus. 
Fig. 461.-Fatty Infiltration with Atrophy of the Pancreas. 
Auto-digestion of portions of the pancreas, intra vitam, has been 
described, and may, it is believed, lead to localized formation of fibrous 
tissue in the organ.1 
1 Chiari, Prager med. Woehenschrift, vol. xxv., No. 14, 1900. THE DIGESTIVE SYSTEM 
703 
Albuminous Degeneration may occur in acute infectious diseases. 
The organ may be red, swollen, and cedematous. The most marked 
minute lesions are swelling and albuminous degeneration of the gland 
epithelium with hyperaemia and interstitial oedema. 
Fatty Degeneration may follow albuminous degeneration and is most 
common in poisoning, especially by phosphorus. 
Fatty Infiltration, which should be distinguished from fatty degenera- 
tion, consists in the accumulation of fat in the interstitial tissue of the 
Fig. 462.--Fat Necrosis in the Mesentery. 
From a case of acute haemorrhagic pancreatitis. 
gland (Fig. 461). This when excessive may be associated with almost 
complete atrophy of the gland structures. Under these conditions the 
outline of the organ may be preserved, the fat being enclosed by the 
capsule. It occurs in obesity and in atrophy and fibrosis of the gland. 
Amyloid Degeneration.-This usually occurs in connection with 
similar degeneration in other organs, and is confined to the walls of the 
blood-vessels and the interstitial tissue. 
Hyaline Degeneration, involving and limited to the islands of Langer- 704 
THE DIGESTIVE SYSTEM 
hans, has been described by Opie and others in diabetes without other 
marked lesions of the pancreas.1 
Fat Necrosis.-This is a peculiar lesion of the fat tissue, most fre- 
quently seen about the pancreas or between its lobules, but sometimes in 
fat tissue in other parts of the body. White or yellowish nodules (Fig. 
462), varying from the size of a pin's head to that of a pea or larger, are 
seen embedded in the fat, the central portion being often soft and grumous. 
They are sometimes calcified and sometimes surrounded by a connective- 
tissue capsule. Microscopical examination shows necrosis, degeneration, 
and disintegration of the fat tissue (Fig. 463). 
Fat necrosis is usually associated with lesions of the pancreas- 
haemorrhagic infiltration, necrosis, gangrene, and acute and chronic 
Fig. 463.-Fat Necrosis in the Pancreas. 
inflammatory processes. The lesion has been shown to be due to some 
ferment in the pancreatic secretion which splits the fat molecule into 
fatty acids, which may crystallize, and soluble substances; calcification 
is of later occurrence. Experimental studies have shown that fat necrosis 
can be induced by such operative procedures as direct the pancreatic 
secretion into fat tissue either immediately about the pancreas or else- 
where. 2 
1 Opie, Jour. Exp. Med., vol. v., p. 527, 1901; also Opie, "Disease of the Pancreas," on structure, 
function, and lesions of the pancreas with bibl. For development of the islands of Langerhans in 
human embryo see Pearce, Am. Jour. Anat., vol. ii., 1903, p. 445. For morphology and physiology 
of these structures see Dewitt, Jour. Exp. Med., vol. viii, p. 193, 1906. For hypertrophy of the 
islands of Langerhans see MacCallum, Amer. Jour. Med. Sei., vol. cxxxiii., p. 432, 1907, and Cecil, 
Jour. Exper. Med., 1911, xiv., 500. For adenoma of islands of Langerhans see Cecil, Jour. Exper. 
Med., 1911, xiii., 595; and LeComte, Jour. Med. Res., 1913. N. S. xxiv., 251. 
2 For studies in fat necrosis, with bibl. see Opie, "Disease of the Pancreas;" also Wells, Jour. Med. 
Research, vol. ix., p. 70, 1903. THE DIGESTIVE SYSTEM 
705 
HAEMORRHAGE. 
Haemorrhage into the substance of the pancreas may occur as the 
result of injury; in the haemorrhagic diathesis; in connection with valvu- 
lar diseases of the heart or interference with the portal circulation; or 
in connection with extensive fatty degeneration, or with local necrosis, 
or with fat necrosis of the organ. Such haemorrhages may be minute or 
extensive. Several cases of sudden death are recorded in which the only 
discoverable lesion was an extensive haemorrhage into the substance of 
the gland and the tissue about it. The haemorrhage may be moderate 
and limited to the pancreas, or it may extend into the subperitoneal 
tissue for a considerable distance. 
Haemorrhage of the pancreas may be associated with acute inflamma- 
tory changes and with more or less extensive gangrene of the organ.1 
Haemorrhagic Pancreatitis.-In this form of disease haemorrhage 
similar to that above described is associated with suppurative inflamma- 
tion or gangrene or both. The gangrenous pancreas may be more or less 
encapsulated; it may be surrounded by pus. Haemorrhagic pancreatitis 
is often associated with fat necrosis. 
The conditions leading to pancreatic haemorrhage and haemorrhagic 
pancreatitis are not yet fully clear, but experimental studies of Flexner 
and Opie indicate that in some cases at least the presence of gastric juice 
or of bile or other substances in the pancreatic duct may be of impor- 
tance. The frequent association of gall-stones with haemorrhagic 
pancreatitis is significant.2 
Suppurative Pancreatitis is not very common, and may be primary or 
due to the extension of a suppurative inflammation from adjacent or 
distant parts of the body. There may be a diffuse infiltration of the 
organ with pus cells or larger and smaller abscesses. The abscesses may 
open into the gastro-intestinal canal or into the peritoneal cavity. The 
causes of primary suppurative pancreatitis are often obscure. It may 
accompany fat necrosis and haemorrhage and gangrene of the pancreas. 
It is probably usually due to bacterial invasion through the duct. 
Various forms of bacteria have been found in the necrotic, haemor- 
rhagic, and inflammatory lesions of the pancreas, but in most cases the 
significance of their presence is not clear, since necrotic and haemorrhagic 
foci may afford regions favorable to the lodgment and proliferation of 
micro-organisms which are secondary invaders and whose lesions, if such 
be induced, are complicating and not primary.3 
INFLAMMATION. (Pancreatitis.) 
1For a study of Haemorrhagic Necrosis of the Pancreas, see Opie and Meakins, Jour Exp. 
Med., bibl. xi., 561, 1909. 
2 For a study of the relationships between cholelithiasis and diseases of the pancreas see Opie, 
"Disease of the Pancreas." 
For a study of experimental pancreatitis see Flexner, University Medical Magazine, vol. xiii., 
p. 780, 1901; and Jour. Exp. Med., vol. viii., p. 167, 1906; also Flexner and Pearce, Trans. Assn. Am. 
Phys., vol. xvi., p. 348, 1901; also Opie, loc. cit. 
3 For a detailed consideration of acute inflammation, haemorrhage, gangrene, and fat necrosis of 706 
THE DIGESTIVE SYSTEM 
Chronic Interstitial Pancreatitis.-This lesion consists in an increase of 
interstitial connective tissue, which may be general or confined to some 
particular portion of the gland. The new-formed tissue may be inter- 
lobular or interacinar in distribution. 
The organ is sometimes enlarged, sometimes smaller than normal. It 
is usually dense and hard; secondary atrophy of the parenchyma regu- 
larly occurs. It may be associated with chronic inflammatory processes 
in the vicinity of the organ, and obstruction of the pancreatic duct. It 
may accompany cirrhosis of the liver.1 
Tuberculous Inflammation.-Larger and smaller tubercles and tuber- 
culous cheesy nodules are occasionally found in the pancreas in con- 
nection with acute general miliary tuberculosis or with tuberculous 
inflammation in some other organ, particularly with that of adjacent 
lymph-nodes, the lungs, and the intestine. 
Syphilitic Inflammation.-Chronic interstitial pancreatitis is frequently 
found in congenital syphilis of the new-born. The fibrous tissue is 
increased with atrophy of gland parenchyma, but the islands of Langer- 
hans persist.2 It is not definitely established whether or not a similar 
lesion may be caused by acquired syphilis. Gummata are very rare in 
the pancreas, but have been described in congenital syphilis in very 
young children. 
TUMORS. 
Carcinoma is the most common and important of the tumors of the 
pancreas. It may be primary or secondary. Primary carcinoma is 
most frequent in the head of the organ, but may occur in other parts.3 
The scirrhous form is most common, but soft and gelatinous forms are 
found. They often involve adjacent parts by continuous growth, and 
may form metastases in the liver, adjacent lymph-nodes, etc. Secondary 
carcinoma in the pancreas may occur in carcinoma of the stomach and 
duodenum, and of the gall-ducts and gall-bladder. As a result of car- 
cinoma of the pancreas, aside from the extension of the growth, there 
may be pressure on the ductus choledochus, with jaundice; or on the 
pancreatic duct, with cystic dilatation; or pressure on the duodenum, 
with stenosis of the gut; or pressure on the vena cava, or portal vein, or 
superior mesenteric vein, etc., with disturbances of the circulation. 
Adenoma and sarcoma are recorded. 
Cysts.-These are mostly due to dilatation of the pancreatic ducts. 
1. The entire duct may undergo a uniform cylindrical dilatation. 
With this cylindrical dilatation we sometimes find associated small 
sacculi. 
2. There may be sacculated dilatations at some points in the ducts. 
the pancreas, with bibliography, consult Fitz, Middleton Goldsmith lecture on "Acute Pancreatitis,'' 
Trans. New York Path. Soc., 1889. For later bibliography see Warthin, Phila. Med. Jour., Nov. 19th, 
1898, and Opie, "Disease of the Pancreas." 
1 See reference to Lando, foot-note, p. 728. 
2 For a study of the pancreas in congenital syphilis see Pearce, Am. Med., vol. vi., p. 1020, 1903. 
3 For recent bibliography of primary carcinoma of the pancreas see Baldwin, Phila. Med. Jour., 
Dec. 22d, 1900, bibl. THE DIGESTIVE SYSTEM 
707 
These dilatations form cysts of large size, as large even as a child's head. 
Their walls frequently undergo degeneration and calcification. These 
cysts often become filled with blood, and may then be mistaken for 
aneurisms. 
3. The small branches of the pancreatic duct may be dilated so as to 
form a number of small cysts. These cysts are filled with serum, mucus, 
pus, or a thick, cheesy material. 
Cysts of the pancreas may result from trauma, inflammatory closure 
or obstruction of the ducts, from old areas of necrosis or haemorrhage, 
and in other ways.1 
Concretions of carbonate and phosphate of lime are frequently found 
in the pancreatic ducts. They are usually multiple, small, whitish, 
smooth, or of rough and irregular shape. Sometimes, however, they 
reach a diameter of more than an inch. They consist chiefly of calcium 
phosphate and carbonate. Besides these free concretions the walls of 
the ducts are sometimes encrusted with salts of lime. Such concretions 
may produce dilatation of the pancreatic ducts and large cysts, or more 
rarely abscesses. 
Foreign Bodies.-Gall-stones sometimes find their way into the 
pancreatic duct. Ascarides have been found in the ducts in a consider- 
able number of cases. 
1 Consult Tilger, "Cysts of Pancreas," Virch. Arch., Bd. cxxxvii., p. 348, 1894, bibl.; also Fitz, 
Trans. Assn. Am. Phys., vol. xv., p. 254, 1900. CHAPTER VIII. 
THE LIVER. 
Congenital malformations of the liver are not common and are of little practical 
importance. The organ may be entirely wanting; the lobes may be diminished or 
increased in number; its form may be altered, so that it is rounded, flattened, triangu- 
lar or quadrangular. The gall-bladder or gall-ducts may be wanting; the ductus 
choledochus may be double, both ducts emptying into the duodenum, or one emptying 
into the duodenum, the other into the stomach. The single ductus choledochus may 
also empty into the stomach. Owing to abnormal openings in the diaphragm or the 
abdominal parietes, the liver may suffer'displacement upward or forward. In con- 
genital transposition of the viscera the liver is found on the left side, the stomach and 
spleen on the right side. 
Small, isolated bodies, having the same structure as the liver, have been a few 
times found in the suspensory ligament and in the lesser omentum. 
Malformations. 
Acquired Changes in Size and Position. 
As a result of tight lacing very marked changes are sometimes produced in the 
shape of the liver. By the narrowing of the base of the thorax the organ is compressed 
from side to side, and its convex surface is pressed against the ribs. In consequence 
of this there are found ridges and furrows on its convex surface. In consequence also 
of the circular constriction, a part of the right, and usually of the left lobe also, be- 
comes separated by a depression (Fig. 15). Over this depressed and thinned portion 
of the liver the capsule is thick and opaque. In extreme cases the depression and 
thinning reach such an extent that there is only a loose, ligamentous connection 
between the separated portion and the liver. 
A series of depressions are sometimes found on the upper surface of the right lobe 
of the liver, running from front to back, apparently caused by folds of the organ. 
Structural alterations in the liver may induce changes in its size and shape. It 
may be increased in size by tumors, hydatid cysts, abscesses, fatty and amyloid degen- 
eration, by congestion, and sometimes by cirrhosis, etc. 
It may be diminished in size by atrophy, by cirrhosis, by acute parenchymatous 
degeneration, etc. 
Changes in the position of the liver are produced by alterations in its size, by pres- 
sure downward from the thoracic cavity and upward from the abdomen, by the con- 
striction of tight lacing, by tumors or circumscribed serous exudation between the 
liver and diaphragm, by curvature of the spine. 
The liver is readily turned, by pressure from above or below, on its transverse axis. 
The transverse colon may be fixed above the liver so as to push it backward, down- 
ward, and to the right. There are a few cases recorded of dislocated and movable 
livers. These occurred in women who had borne children and whose abdominal walls 
were lax. With ascites it is not uncommon to find the liver quite movable.1 
WOUNDS, RUPTURE, AND HEMORRHAGE. 
Wounds of the liver may induce haemorrhage, which, if life continue, 
is followed by inflammation. Serious wounds of the liver are usually 
1 See Graham, "Displacements of the Liver," Trans. Assn. Am. Phys., vol. x., p. 258, 1895, bibl. 
708 THE LIVER 
709 
fatal, but recovery may occur even after the destruction of a considerable 
portion of the organ. 
Rupture of the liver may be produced by severe direct contusions or 
by falls. It may be produced in children by artificial delivery. The 
rupture usually involves both the capsule and a more or less consider- 
able portion of the liver tissue. It is commonly accompanied by large 
haemorrhage, and is usually fatal. 
Haemorrhage.-Extravasations of blood in the substance of the liver, 
or more frequently beneath the capsule, may be found in new-born chil- 
dren after tedious or forcible labors. In adults, haemorrhage, except as 
the result of injury, is uncommon. Extravasations of blood are some- 
times seen in malignant malarial fevers, especially in tropical climates; 
in scurvy, purpura, and phosphorus poisoning; and bleeding may occur 
in and about soft tumors, abscesses, and echinococcus cysts. It may 
also occur as a result of thrombosis of the hepatic vein. 
ANEMIA AND HYPEREMIA. 
Anaemia of the liver may be general or partial. It may be due to 
general anaemia or to local disturbances of the circulation, such as swell- 
ing of the cells in parenchymatous or other degeneration, pressure of 
Fig. 464.-Chronic Congestion of the Liver-"Nutmeg Liver." 
The liver cells are completely atrophied except in the peripheries of the lobules. The central 
portions of the lobules, which in the fresh organ are darker than the periphery, are lighter in the pre- 
served specimen from which this section was cut, because the haemoglobin has been dissolved out of 
the red blood cells. 
tumors, etc. The organ appears pale, often of slightly yellowish or 
brownish color. It may be harder than usual, and smaller. 
Hyperaemia of the liver is either an active or a passive process. In 
health the amount of blood in the liver varies at different times, being 710 
THE LIVER 
regularly increased during the process of digestion. When the digestive 
process is unduly influenced by the ingestion of spirits, spices, etc., 
the hyperaemia assumes abnormal proportions, and when this is often 
repeated it may lead to structural changes in the organ. Severe contu- 
sions over the region of the liver sometimes cause a hyperaemia, which 
may result in suppurative or in productive inflammation. In hot 
climates and in malarious districts active and chronic hyperaemia of the 
liver are frequent and often incite structural lesions. In scurvy, also, 
the liver is sometimes congested. Cessation and suppression of the 
menses and of haemorrhoidal bleeding may be followed by hyperaemia of 
Showing a single lobule. The capillaries about the central vein are widely distended with blood- 
decolorized; the liver cells on the borders nearest the dilated capillaries show various phases of pressure 
atrophy. 
Fig. 465.-Chronic Congestion of the Liver. 
the liver. In all these varieties of active congestion the liver is enlarged, 
of a deep red color, and blood flows freely from its cut surface. 
Passive congestion of the liver is produced by an obstruction to the 
current of blood in the hepatic veins. Valvular diseases of the heart, 
emphysema and fibrous induration of the lungs, large pleuritic effusions, 
intrathoracic tumors, angular curvature of the spine, aortic aneurisms 
pressing on the vena cava, and constrictions of the vena cava and of the 
hepatic veins, may all lead to a chronic hypersemia of the liver. In such 
cases, since the congestion affects principally the hepatic veins, we find 
the centre of each acinus congested and red, while its periphery is lighter 
in color. This gives to the liver a mottled or nutmeg appearance (nut- 
meg liver) (Fig. 464). The liver cells in the centre of each acinus are 
frequently colored by little granules of red or black pigment, and the 
cells at the periphery become fatty, so that the nutmeg appearance is still 
more pronounced. A liver in this condition is usually of medium size, 
but may be smaller or larger than normal. 
When the congestion is long continued the veins at the centre of each 
acinus may become permanently dilated, and the hepatic cells in their THE LIVER 
711 
meshes become atrophied (Figs. 465 and 466), so that the centre of each 
acinus consists only of dilated capillaries or of these and new connective 
tissue; or the dilatation and atrophy of the liver cells may, in circum- 
scribed portions of the organ, involve the entire acinus. In long- 
Fig. 466.-Chronic Congestion of the Liver. 
Showing atrophy of the liver cells. 
continued congestion the liver is usually small and hard-cyanotic 
induration-and may be rough or uneven on the surface; but it is some- 
times enlarged. The peculiar nutmeg appearance may be very well 
marked, or it may not be evident, the organ being of a dark-red color.1 
LESIONS OF THE HEPATIC VESSELS. 
The Hepatic Artery. 
The hepatic artery is in rare cases the seat of aneurisms which may 
attain a large size. Such aneurisms may displace the liver tissue, com- 
press the bile ducts so as to cause jaundice, and may rupture into the 
stomach or abdomen. 
Owing to its abundant anastomoses, emboli of the branches of the 
hepatic artery usually induce no marked lesions, but they sometimes 
result in single or multiple anaemic infarcts.2 
The Portal Vein. 
Thrombosis, Embolism, and Inflammation.-Thrombosis of the 
branches of the portal vein may be produced by weakening of the circu- 
lation from general debility-marasmatic thrombi; by pressure on the 
vessel from without, as in cirrhosis, chronic peritonitis, tumors, gall- 
xFor another view of chronic passive congestion of the liver see Mallory, Jour. Med. Res., 1911, 
N. S. xix., 455. 
2 For a critical summary of recorded cases of anaemic infarcts of the liver see Baldwin, Jour. Med. 
Res., vol. viii., 1902, p. 431. For a study of experimental closure of the hepatic artery and the gall- 
ducts see Tischner, Virch. Arch., Bd. clxxv., p. 90, 1904. 712 
THE LIVER 
stones, dilatation of the bile ducts, etc.; by injury; by the presence of 
foreign materials within the vessel; and as a result of inflammation, 
especially syphilitic, of its wall-phlebitis-or of embolus. The throm- 
bus may form in the vessels in the liver or be propagated into them from 
without. It may partially or entirely occlude them. The clot may 
become organized as a result of endophlebitis, and a permanent occlusion 
of the vessel ensue. If the clot be a simple, non-irritating one, leading to 
occlusion, the consequences are usually more marked in the abdominal 
viscera than in the liver itself. The branches of the hepatic artery form 
sufficient anastomoses usually to nourish the liver tissue and prevent its 
necrosis, even in complete occlusion of the portal vein; and if occlusion 
occur slowly, the organ may continue to perform its functions. But this 
obliterative form of thrombosis is usually attended by ascites, enlarge- 
ment of the spleen, dilatation of the abdominal veins, and sometimes by 
haemorrhage from the stomach and intestines. 
In another class of cases, in addition to the local and mechanical 
effects of a thrombus, the latter may be infectious, then there are necrotic 
changes and suppurative inflammation in the walls of the vessels or 
in the liver tissue about them. The thrombi are apt to soften and 
break down, and the fragments may be disseminated through the smaller 
trunks of the portal vein. In this way, by the distribution through the 
smaller vessels of a disintegrated thrombus from a large trunk, or by the 
introduction into the branches of the portal vein of purulent or septic 
material from some of the abdominal viscera or from wounds, multiple 
foci of purulent inflammation in the portal vein, and multiple abscesses 
involving the liver tissue, may be produced. In many cases the pres- 
ence of bacteria may be detected in the inflammatory foci. 
These soft thrombi of the portal vein and the accompanying pyle- 
phlebitis and abscess are induced in a variety of ways. Ulceration of 
the intestines and stomach, abscesses of the spleen, suppurative inflam- 
mation of the mesentery and mesenteric glands, inflammation and ulcer- 
ation of the bile ducts from gall-stones, inflammation of the umbilical 
vein in infants, may all induce thrombi in their respective veins, which 
may be propagated to the portal vein or may give rise to purulent or 
septic emboli. Two cases are recorded in which a fish-bone in the portal 
vein induced suppurative inflammation in that vessel.1 
In infants inflammation of the umbilical vein may induce not only 
inflammation of the portal vein and abscesses in the liver, but multiple 
abscesses in various parts of the body, and acute peritonitis may follow. 
Infarcts.-Infarcts of the liver seldom form, owing to the abundant 
anastomosis of its blood-vessels. But under exceptional conditions, 
as we have seen, ancemic infarcts may form as the result of the closure 
of the hepatic artery or also of small branches of the portal vein. There 
may then be a larger or smaller mass of dead liver tissue surrounded by 
a zone of congestive or inflammatory reaction (Fig. 467). Occasionally 
also, owing usually to the occlusion of branches of the portal vein, lim- 
1 For a study of primary portal thrombosis see Lewis and Rosenow, Arch. Int. Med., iii., 232 
1909, bibl. THE LIVER 
713 
ited areas of liver tissue may suffer disturbance of the circulation leading 
to atrophy of the liver cells and the formation of fibrous tissue. This 
condition has been called haemorrhagic atrophic infarction. It is appar- 
ently rather localized atrophy of the liver than true infarction. 
It is probable that the rare occurrence of hepatic infarcts is closely 
The infarcts, multiple and large, are due to extensive thrombosis of branches of the portal vein. 
Fig. 467.-Infarction of the Liver. 
dependent in most instances upon the development of local thrombosis or 
embolism, which commonly do not lead to infarction, together with gen- 
eral disturbances of the circulation which prevent the re-establishment 
of equilibrium in the hepatic vessels.1 
1 For a study of liver infarcts see summary of Baldwin, ref. footnote p. 711; also Steinhaus, Deut. 
Arch. f. klin. Med., Bd. Ixxx., p. 364, 1904. 714 
THE LIVER 
Rupture of the Portal Vein, with fatty degeneration of its walls, has 
occurred in a few instances. 
Chronic Endophlebitis, with atheroma and calcification, may occur in 
the walls of the portal vein, giving rise to thrombosis. 
Dilatation of the Portal Vein, either uniform or varicose, may occur in 
various parts of the vessel or its branches. It may be caused by destruc- 
tion of the liver capillaries in cirrhosis, or by occlusion of the vein by 
thrombi, tumors, etc. 
The Hepatic Veins. 
The hepatic veins present lesions similar to those of the portal vein 
and its branches, but they are much less frequent. The veins may be 
dilated by obstruction to the passage of venous blood into the heart. 
They may be the seat of acute and chronic inflammation, and soft thrombi 
and suppurative inflammation may be produced by abscesses in the 
liver. Rarely there is a localized obliterating phlebitis in the hepatic 
vein followed by chronic congestion, interstitial inflammation, and 
thrombosis.1 
ATROPHY OF THE LIVER. 
Atrophy of the liver may affect the entire organ or be confined to 
some part of it. General atrophy may occur in old age as a senile 
change, or may be induced by starvation or chronic exhausting diseases. 
The organ is diminished in size, is usually firm, and the acini appear 
smaller than usual. Microscopically the change is seen to be due to a 
diminution in size of the liver cells, and hand-in-hand with this there 
occurs frequently an accumulation of pigment granules within the atro- 
phied cells. The cells may entirely disappear over circumscribed areas, 
leaving only shrivelled blood-vessels and connective tissue; or, in some 
cases, there may be an increase of connective tissue associated with 
the atrophy of the cells. When much pigment is formed in the cells the 
lesion is often called pigment atrophy. 
Essentially the same changes may occur in circumscribed portions of 
the liver, as the result of pressure from new connective tissue in cirrhosis, 
from tumors, hydatids, amyloid degeneration, gall-stones, etc. In 
atrophy from pressure the liver cells are apt to become very much flat- 
tened and squeezed together as they diminish in size. 
NECROSIS. 
Necroses in the liver may occur under various conditions and in 
many forms.2 
Minute areas of necrosis of liver cells, focal necrosis (see p. 58), are 
1 Consult for obliterating phlebitis of the main trunks of the hepatic vein as a cause of death, 
Chiari, Ziegler's Beitr., Bd. xxvi., p. 1, 1899, bibl. 
2 For a study of necroses of the liver see Mallory, Jour, of Med. Res., vol. vi., 1901, p. 264. THE LIVER 
715 
found irregularly scattered through the organ in various acute infections, 
and may be artificially induced in animals by the injection of bacteria 
or other vegetable toxins, such as ricin and abrin.1 
More extensive necroses of liver cells, especially about the central 
vein, frequently occur, usually in acute infectious diseases-diphtheria, 
endocarditis, lobar pneumonia, peritonitis, cerebro-spinal meningitis.2 
This has been called central necrosis. 
Necrosis in the liver may, however, be limited to the peripheral 
zone of the lobule, peripheral necrosis. This condition has been described 
in a few instances, especially in connection with eclampsia. 
Finally, the necrosis of parenchyma cells in the liver may be limited 
to the middle zone of the lobule, "midzonal necrosis." 
In most of these forms of so-called " zonal necrosis"3 bacterial toxins 
or infections appear to be the chief determining factor. 
Many of the necroses of the liver are doubtless due to the action of 
bacteria or bacterial toxins. The focal forms may be determined by the 
local growth of bacteria, by the occlusion of capillaries by swollen and 
proliferated endothelial cells, as in typhoid fever, or by fibrinous or 
agglutinative thrombi. 
The reason for the topography of the lesion in the various forms of 
"zonal necrosis" has not yet been definitely determined. Nor is the 
relation of these to certain phases of so-called acute yellow atrophy of the 
liver, clear. 
Pearce has shown4 that by the injection into animals of hEemagglutinative sub- 
stances contained in various cytolytic immune sera, agglutinative thrombi may form 
in the capillaries and smaller branches of the portal vein, leading to necrosis of the 
liver. The position and extent of these areas of hyaline necroses vary with the amount 
of the serum administered. They are mostly superficial, and may be small and focal 
or involve nearly all the parenchyma of the lobule, except that in the vicinity of the 
portal spaces. 
Pearce and Winne5 have shown that similar lesions may follow the injection of 
haemagglutinins of bacterial origin. In these areas of hyaline necrosis the liver cells 
stain poorly with eosin; the nuclei do not stain and may be seen only as faint outlines, 
or they are shrunken. 
Oertel has described the occurrence of multiple circumscribed necrotic and atrophic 
foci in the liver not associated with local infective processes and without marks of 
inflammation or connective-tissue hyperplasia. These are associated with stasis in 
the blood, and bile capillaries, and local portal sclerosis. These areas contain bile 
pigment. This lesion is most marked about the central vein, and may vary in extent. 
It is associated with jaundice. The lesion is diffuse in the liver, often running in 
streaks which merge into normal liver tissue. Thus the liver becomes tough, pale, 
bile-stained, with obscured markings. The liver cells in the affected areas apparently 
lose their cytoplasm, leaving a well-preserved outline, and may contain fat. 
For this lesion the designation multiple non-inflammatory necrosis of the liver with 
jaundice is suggested.8 
1 Flexner, Johns Hopkins Hosp. Rep., vol. vi., p. 259, 1897; Mallory, Jour. Exp. Med., vol. iii., 
p. 611, 1898. 
2 Mallory, Jour. Med. Res., vol. vi., p. 264, 1901. 
3 For a study of "zonal necroses" of the liver see Opie, Jour. Med. Res., vol. xii., p. 147, 1904. 
4 Pearce, Jour. Med. Res., vol. xii., p. 329, 1904; also ibid., vol. xiv., p. 541, 1906. 
6 Pearce and Winne, Amer. Jour. Med. Sci., vol. cxxviii., p. 669 1904. 
6 Oertel, Jour. Med. Res., vol. xii., p. 75, 1904; Jour. Exp. Med., vol. vii., p. 103, 1906, and Berl. 
Klin. Wchnschr., 1912, xlix., 2019. For a study of changes in necrotic cells in cytolysis in the liver and 
elsewhere see Symmers, Jour. Exp. Med., vol. ix., p. 64, 1907. 716 
THE LIVER 
Howland and Richards1 have shown that chloroform anaesthesia in animals repeated 
on several successive days induces fatty degeneration or hyaline necrosis or both, of 
the liver cells in the central portion of the lobules. Whipple and Sperry2 found that 
animals may recover from the chloroform liver necroses with complete restitution of 
the cells after two or three weeks. 
The acute degenerations of the liver occurring in eclampsia, in which condition 
chloroform is often administered, require careful scrutiny in view of the striking lesions 
of necrosis induced by chloroform alone. 
DEGENERATION. 
Albuminous Degeneration.-In the infectious diseases and in certain 
cases of acute anaemia and phosphorus poisoning, the liver is swollen 
and, on section, of a dull yellowish gray color, looking as if it had been 
boiled. It contains less blood than usual, and the outlines of the lobules 
are indistinct. Microscopical examination shows the lesion to consist of 
a swelling of the liver cells and an accumulation in them of moderately 
refractile, finer and coarser albuminous granules. These granules may 
disappear and the cells return to their normal condition, or fatty degen- 
eration may follow. Fatty and parenchymatous degenerations are often 
associated. 
Acute Yellow Atrophy (Acute Parenchymatous Degeneration).-This 
rare condition is characterized anatomically by a rapid diminution in the 
size of the liver as the result of a granular and fatty degeneration, 
necrosis, and disintegration of the liver cells. It is frequently associated 
with the clinical condition called icterus gravis. The liver, sometimes 
within a few days, may be reduced to one-half its normal size. On open- 
ing the abdominal cavity the organ may be found lying, concealed by 
the diaphragm, close against the vertebral column. The amount of 
diminution and the general appearance of the affected organ depend to a 
considerable extent upon its previous condition-i.e., whether or not it 
was the seat of other lesions-as well as upon the duration of the process 
and the degree of degenerative change. In general, if the lesion is well 
marked, the liver is small, flabby-sometimes almost fluctuating-and 
the capsule wrinkled. On section the cut surface may show but little 
trace of lobular structure, but present an irregular mottling with 
gray, ochre-yellow, or red; sometimes one sometimes another color 
preponderating. 
Microscopical examination shows varying degrees of degeneration and 
destruction of the liver cells. Most evidently in those parts which have 
a grayish appearance, the outlines of the cells are preserved and the proto- 
plasm is filled with larger and smaller granules. In the yellow portions 
the outlines of the liver cells may be preserved, and they may contain 
varying quantities of larger and smaller fat droplets and granules of 
yellow pigment. Or the cells may be necrotic or disintegrated, and in 
their place are irregular collections of fat droplets, hyaline material, pig- 
ment granules, red and yellow crystals, and detritus; only the connective 
1 Howland and Richards, Jour. Exp. Med., xi., 344, 1909; see also Opie, ref. page 718. 
2 Whipple and Sperry, Johns Hop. Hosp. Bull., xx., 278, 1909. THE LIVER 
717 
tissue and blood-vessels of the original liver tissue remaining (Fig. 468). 
The red areas may show nearly complete absence of liver cells and cell 
detritus, and sometimes irregular rows of cells which are variously 
interpreted as being new-formed gall-ducts or proliferated liver cells, 
marking a reparative process which may be extensive.1 In these areas it 
appears to be, in part at least, the blood contained in the vessels which 
imparts the red color. Sometimes the interstitial tissue is infiltrated 
with small spheroidal cells resembling leucocytes. Crystals of leucin and 
tyrosin are sometimes found intermingled with the cell detritus. In 
some cases the liver is not diminished in size. In early stages it may 
even be larger than normal. 
These lesions of the liver are frequently associated with enlargement 
Fig. 468.-Acute Yellow Atrophy of the Liver. 
The liver cells in the periphery of the lobule are little changed; those toward the centre are 
largely destroyed. 
of the spleen and parenchymatous degeneration of the kidney and of the 
heart muscle. Multiple hemorrhages may occur in the gastro-intestinal 
canal, kidneys, bladder, and lungs. There is frequently marked jaundice. 
The condition above described as acute yellow atrophy of the liver 
sometimes occurs in persons previously apparently well, but may accom- 
pany infectious diseases-typhoid fever, diphtheria, puerperal infection, 
etc.-and may be seen in eclampsia and pernicious vomiting in preg- 
nancy. While the nature of the condition is not well understood it 
seems probable that the lesion is essentially a necrosis and degeneration 
resulting from toxic substances produced either in bacterial infection or 
through faulty cell metabolism and followed by more or less pronounced 
autolysis. It is probably erroneous to consider the lesions of the liver 
1 For a study of regenerative changes in the liver after acute yellow atrophy see MacCallum, 
Johns Hopkins Hosp. Rep., vol. x., 1902, p. 375; also Pearce, Jour. Med. Res., vol. xv., p. 99, 1906. 
See also for repair of liver, Muir. Jour, of Path., xii., 287, 1908 and Milne, Proc. N. Y. Path. Soc., 
Oct. and Nov., 1909. 718 
THE LIVER 
described under the name of acute yellow atrophy as marking a single 
disease process. 
As to the details of the pathogenesis of this condition, opinions differ, 
and the whole subject is in urgent need of more exact research. 
In the forms of this liver lesion which mark the toxaemia of pregnancy, 
whether these be clinically manifested in eclampsia, pernicious vomiting, 
or other less well marked abnormal conditions, there appears to be 
a disturbance of nitrogenous metabolism in the liver, associated with 
the characteristic rapid destruction of the parenchyma.1 
It should be borne in mind, finally, that while acute yellow atrophy 
of the liver has been regarded as an especially fatal lesion, there is abun- 
dant clinical and morphological evidence that various grades of the lesion 
may occur and that recovery from many forms with regeneration of liver 
tissue is not uncommon.2 
Fig. 469.-Fatty Infiltration of Liver. 
Portion of the periphery of a lobule, showing many liver cells distended with a single large drop of 
fat, while between these are liver cells with small fat droplets and others flattened by pressure. In 
this section, hardened by alcohol, the fat has been dissolved, leaving clear spaces. 
Experimental Studies.-The experiments of Opie3 in inducing in animals lesions 
comparable with those of acute yellow atrophy in man are very suggestive. Opie 
found that after the relatively slight injury of the liver parenchyma induced by re- 
peated doses of chloroform in dogs, the injection of Bacillus coli-not itself especially 
virulent for these animals-may be followed by changes in the liver which neither the 
chloroform (see p. 716) nor the bacteria alone can induce. For under these conditions 
he found that the liver cells may be largely destroyed by necrosis, the remainder be- 
ing fatty, while evidence of reparative changes-new fibrous tissue and new-formed 
gall-ducts, such as are often seen in acute yellow atrophy in man-was strikingly 
shown. In view of these experiments Opie calls attention to the possibility that 
some of the lesions of the toxaemia of pregnancy and acute yellow atrophy in man 
may in fact be due to the action of bacteria or their poisons on liver cells already 
vulnerable from metabolic or other forms of intoxication. 
1 For discussion and bibl. see White, Bost. Med. and Surg. Jour., 158, 729, 1908. 
2 For forms of acute yellow atrophy in the toxaemia of eclampsia and other disturbances of preg- 
nancy see Strauss, Amer. Jour, of Obstetrics, vol. liii., 1906, bibl.; Ewing, ibid., vol. li., 1905; and 
Proc. Path. Soc., Phila., xiii., 65, 1910. For acute yellow atrophy in children see Philips, Amer. Jour. 
Med. Sc., 1912, cxliii, 177, bibl. 
3Opie, Jour. Exp. Med., xii., 367, 1910. THE LIVER 
719 
Fatty Infiltration.-In the normal human liver there is usually a cer- 
tain amount of fat in the liver cells, and this amount varies considerably 
under different conditions. 
The gross appearance of pathological fatty livers varies a good deal, 
depending upon the amount and distribution of fat and its association 
with other changes. If the lesion is un- 
complicated and considerable, the organ 
is increased in size, the edges are rounded, 
the consistence is firm, the color yellow- 
ish, and the cut surface greasy. The 
lobules are enlarged and their outlines 
indistinct, and the blood content is 
diminished. The liver is increased in 
weight. The lesion may be uniform 
throughout the organ or it may occur 
in patches. In the latter case the liver 
has a mottled appearance, irregular yel- 
lowish patches alternating with the brownish red, unaffected portions. 
Fatty infiltration is often associated with chronic congestion (nutmeg 
liver), with cirrhosis and amyloid degeneration; the picture may then 
present considerable complexity. Fatty livers may be stained brown or 
greenish with bile pigment. 
Fig. 470.-Fatty Infiltration of 
Liver Cells. 
Fig. 471.-Fatty Degeneration of Liver Cells. 
Microscopically the liver cells are seen to contain larger and smaller 
droplets of fat (Fig. 469), and frequently large drops of fat occupy nearly 
the entire volume of the cell, so that the protoplasm may be visible only 
as a narrow, nucleated crescent at one side, or it may disappear alto- 
gether (Fig. 470). 
Fatty infiltration of the liver may occur as a result of excessive 720 
THE LIVER 
ingestion of oleaginous food; in chronic alcohol, phosphorus, and arsenic 
poisoning; in certain exhausting diseases accompanied by malnutrition, 
as in pulmonary phthisis, chronic dysentery, etc.; and under a variety 
of conditions which we do not understand. It is common in children, 
especially in acute infectious diseases.1 
Fatty Degeneration.-In this condition, which in many cases cannot 
be distinguished morphologically from fatty infiltration, the fat is 
believed to be formed by a transformation of the protoplasm of the liver 
cells (see p. 40). The fat droplets are, for the most part, very small and 
abundant (Fig. 471), though this is not constant. Fatty degeneration 
Fig. 472.-Amyloid Degeneration of Liver Capillaries. 
The capillaries are much enlarged and occluded by the amyloid material; the liver cells 
between them are atrophied. 
of the liver cells frequently follows, and is associated with, cloudy 
swelling under the varying conditions in which this occurs, or it may 
appear in profound anaemia and in acute phosphorus and arsenic 
poisoning.2 
Amyloid Degeneration.-In the liver amyloid degeneration may be 
general or local; so extensive as to give the organ very characteristic 
appearances, or so slight as to be unrecognizable without the aid of the 
microscope. It may be associated with other lesions. When the change 
is extensive and general the liver is enlarged sometimes to more than 
twice its normal size; the edges are thickened and rounded; the surface 
is smooth; the tissue tough, firm, inelastic, more or less translucent, and 
of a brownish yellow color. The lobular structure may be more or less 
indistinct, or it may become very evident by an associated fatty degen- 
1 See Freeman, Archives of Pediatrics, vol. xvii., p. 81, 1900. 
2 For a study of localization of fat in the liver see McCrae and Klotz, Jour. Exp. Med., xii., 746, 
1910. THE LIVER 
721 
eration of the peripheral or central cells of the lobules. The translu- 
cency and peculiar appearance of the tissue may be best seen by slicing 
off a thin section and holding it up to the light. When the lesion is less 
considerable the liver may be of the usual size, and may feel harder than 
normal, and here and there a translucent mottling may be evident, or 
the degeneration may be apparent only on the addition of staining 
agents. When, as is frequently the case, it is associated with cirrhosis, 
the liver may be small and nodular, and the appearance of the cut sur- 
face varies, depending upon the character of the cirrhotic change and 
the presence or absence of fat. 
This degeneration usually commences in the walls of the intralobular 
blood-vessels, causing them to become thickened and translucent (Fig. 
472). Their lumen may be nearly or entirely occluded. The liver cells 
may be squeezed by the thickening of the vessels and may become 
partially or completely atrophied, or they may be fatty. Amyloid 
degeneration may also involve the interlobular vessels, and in advanced 
stages larger and smaller areas of liver tissue may be almost completely 
converted into the dense, re- 
fractile substance in which 
here and there flattened liver 
cells may be seen. 
Amyloid degeneration of 
the liver is usually associated 
with a similar lesion of other 
organs. 
Glycogen Degeneration.- 
This may occur in the liver 
cells in diabetes. 
PIGMENTATION OF THE 
LIVER. 
Pigmentation of the liver 
cells, from bile and blood de- 
rivatives, is to a certain extent 
normal, but may be greatly 
increased as a result of atro- 
phy, of localized haemorrhage, 
and of obstructive jaundice. Pigmentation of the liver may be marked 
in haemochromatosis (see p. 54). 
As a result of severe malarial poisoning a variable amount of brown, 
black, or reddish pigment is often found in the blood. This is usually 
mostly taken up by the leucocytes and deposited in various parts of the 
body, chiefly in the liver, spleen, and marrow of the bones. In the liver 
it is usually found enclosed in the endothelial cells1 free or in place in the 
blood-vessels (see Fig. 473), but sometimes in the tissue between them. 
Fig. 473.-Malarial Pigmentation of the Liver. 
The pigment is largely in the exfoliated endothelium 
within the capillaries. Pigmented malarial parasites 
may be seen in some of the cells. 
1 For a study of the phagocytic powers of the endothelial cells of the blood-vessels of the liver 
see Heinz, Arch. f. mik. Anat., Bd. Iviii., 1901, p. 576. 722 
THE LIVER 
The liver cells frequently contain bile pigment, but usually are free from 
the melanotic pigment characteristic of this malarial condition. As the 
result of this accumulation of pigment the liver may have a dark reddish 
brown, an olive brown, or a black color (sometimes called bronze liver). 
Pigment similar in character to that which occurs in the lungs from 
the inhalation of coal dust may be found in the connective tissue along 
the portal vessels. Inhaled pigment particles may pass the lungs and 
bronchial lymph-nodes, and be deposited in the liver as they are in the 
spleen and hepatic lymph-nodes. 
CALCIFICATION. 
This lesion of the liver is rare. The deposit of lime may be in the 
vicinity of the arteries or the veins.1 
INFLAMMATION. (Hepatitis.) 
Acute Exudative Hepatitis (Purulent Hepatitis).-Purulent or suppura- 
tive inflammation of the liver may be the result of injury; it may be 
secondary to inflammation of the gall-ducts or the branches of the portal 
vein. It may occur as the result of the presence of tumors and parasites, 
or from propagation of an inflammatory process from without, as in ulcer 
of the stomach with adhesions to the liver and secondary involvement of 
the latter. It is often directly due to the introduction of bacteria into 
the organ, through the blood-vessels or gall-ducts or otherwise. Puru- 
lent inflammation in the liver almost always results in abscess. 
Large abscesses of the liver may be traumatic, but are often due to 
unknown causes. They are not infrequently associated with dysentery, 
and may then be due to the conveyance of micro-organisms through the 
veins, or lymph-channels, or peritoneum, or gall-ducts from the intestinal 
ulcers. Such abscesses may be due to the presence of the amoeba coli. 
They occur most frequently in tropical climates-hence the name tropical 
abscess-but are not very uncommon in the temperate zone. They are 
usually single, but there may be several of them. They are sometimes 
so large as to occupy a large part of the lobe. They are most frequent 
in the right lobe, but may occur in any part of the organ. They tend to 
enlarge, and as they do so they approach the surface of the liver. Here 
the contents of the abscess may be discharged into the peritoneal cavity. 
More frequently, however, as they approach the surface, a localized 
adhesive peritonitis ensues, so that the liver becomes bound to adjacent 
parts, and thus the abscess may open into the pleural cavity, or, owing 
to a secondary pleurisy with adhesions, into the lung tissue. They may 
open into the pericardium. They may open externally through the 
abdominal wall; into the stomach, duodenum, colon, or pelvis of the right 
kidney; into the hepatic veins, portal vein, vena cava, or gall-bladder 
or gall-ducts. 
The early stages in the formation of large abscesses of the liver are 
1 See Brill and Libman, Jour. Exp. Med., vol. iv., p. 541, 1899. THE LIVER 
723 
but little known. It is probable, however, that in many cases they are 
the result of the confluence of smaller abscesses (Fig. 488). Their con- 
tents, usually bad-smelling, may be thick and yellow like ordinary pus, 
but more commonly they are thin, reddish-brown, or greenish in color 
from admixture with the pus of blood, gall pigment, and broken-down 
liver tissue. Microscopical examination shows the contents to consist of 
fluid with pus cells, more or less degenerated blood, degenerated liver 
cells, fragments of blood-vessels, and pigment granules and crystals. 
The walls of the abscess are usually ragged, shreds of necrotic liver tissue 
hanging from the sides. Microscopical examination of the liver tissue 
Fig. 474.-Small Abscesses in the Liver Containing Bacilli. 
near the abscess shows infiltration with pus, flattening of the liver cells 
from pressure, cloudy swelling, and necrosis of those lying along the 
cavity.1 
The amoebic abscesses are usually free from bacteria. Other abscesses 
may contain the Bacillus coli communis or the Streptococcus pyogenes 
or Staphylococcus pyogenes. 
Not infrequently, however, especially in old abscesses, examination 
both morphological and cultural fails to reveal the presence of micro- 
organisms. 
After the discharge of the contents of the abscess or without this, if 
it be not very large, granulation tissue may form in the wall of the cavity 
and a fibrous capsule be produced, enclosing the contents, which become 
1 See for a study of tropical abscess of the liver Howard and Hoover, Am. Jour. Med. Sci., vol. 
cxiv., pp. 150, 263, 1897, bibl. 724 
THE LIVER 
thickened and often calcareous, and in this condition may remain for a 
long time. Or the connective-tissue walls may approach one another 
and join, forming a fibrous cicatrix at the seat of the abscess. 
Small multiple metastatic abscesses are not infrequent in pyaemia. In 
these abscesses we can readily study the various stages of formation. 
Suppurative processes in any part of the body-in the head, upper and 
lower extremities, etc.-may act as distributing centres for micro- 
organisms.1 These, entering the circulation, may pass the heart and 
pulmonary capillaries, with or without inducing lesions in the lungs, and, 
lodging in the vessels of the liver, induce circumscribed necrosis of the 
liver tissue (see Fig. 56, p. 89) and suppurative inflammation. Under 
these conditions we may find on section of the liver larger and smaller 
yellowish or grayish spots, the larger of which may be soft and present 
a, New-formed connective tissue; b, dilated blood-vessels of the new tissue; c, gall-duct. 
Fig. 475.-Chronic Interstitial Hepatitis-Cirrhosis. 
the usual characters of abscesses. The smaller, which may not be larger 
than a pin's head, may present the usual consistence of liver tissue with 
the lobular structure still evident; others may be softer, more yellow, 
and surrounded by a zone of hyperaemic liver tissue. Microscopical 
examination of the earlier stages often shows the blood-vessels filled with 
bacteria, scattered and in masses. Around these the liver cells are found 
in various stages of necrosis; in many the nuclei do not stain and the 
bodies are very granular, or the entire cell is broken down into a mass 
of detritus. About these necrotic islets of liver cells, pus cells collect 
and often form a zone of dense infiltration (Fig. 57, p. 90). Thus, by 
the increase of pus cells and the necrosis of liver tissue, small abscesses 
are formed whose contents are intermingled with greater or less num- 
bers of bacteria (Fig. 474), which seem to increase in number as the 
process goes on. By the confluence of small abscesses larger ones may 
1 Kruse and Pasquale, Zeitschr. f. Hygieneu k. Infr., Bd. xvi., p. 1, 1894. THE LIVER 
725 
be formed. Death usually ensues, however, before the abscesses attain 
a very large size. 
Chronic Interstitial Hepatitis (Cirrhosis).1-The most marked result of 
chronic interstitial hepatitis is the formation of new connective tissue in 
the liver. The character, amount, and distribution of the new tissue 
vary greatly in different cases. Secondarily there are usually marked 
changes in the liver cells and in the blood-vessels and gall-ducts. The 
new tissue is most commonly formed and most abundant in the periphery 
On account of the rough surface such livers are sometimes called "hobnail livers." This cut is 
a photographic reproduction of a cirrhotic liver of a child. 
Fig. 476.-Chronic Interstitial Hepatitis-Cirrhosis. 
of the lobules along the so-called capsule of Glisson, but it may extend 
into the lobules between the liver cells. It may surround single lobules, 
or more frequently larger and smaller groups of lobules (Fig. 475). It 
may occur in broad or narrow, irregular streaks or bands and is associated 
with the old fibrous stroma of the organ. It is frequently more abundant 
in one part of the liver than in another. The new-formed tissue tends 
to contract, and thus compromise by pressure the enclosed islets of liver 
1 Various names have been applied to the form of cirrhosis described under this head: Portal 
cirrhosis, fibrous liver, lacunar cirrhosis, hobnail liver, granular liver. See for details of liver lesions 
Rolleston, "Diseases of the Liver," 1905. 726 
THE LIVER 
tissue, causing them to project, in larger and smaller nodules, from the 
surface of the organ. The liver cells may be flattened or atrophied from 
pressure; or, from interference with the portal circulation, they may 
atrophy or become fatty; or they may become colored with bile pig- 
ment. This form of lesion is called atrophic cirrhosis. 
The varied appearances which cirrhotic livers present to the naked 
eye depend largely upon the amount and distribution of the new con- 
nective tissue and upon the secondary changes in the liver cells. The 
surface may be very rough and uneven from the projection of larger 
and smaller irregular-shaped nodules of liver tissue (Fig. 476) between 
which are the depressed contracted bands of new-formed connective 
Fig. 477.-Chronic Interstitial Hepatitis. 
Showing a portion of the section shown in Fig. 475, but more highly magnified, a, Portions of 
liver lobules; b, new-formed connective tissue; c, gall-ducts, apparently new-formed; d, blood-vessels 
in the new tissue. 
tissue. On the other hand, the surface of the liver may be smooth, when 
the new connective-tissue bands are small, evenly distributed, or little 
contracted. Again the liver may be greatly distorted and misshapen 
by the atrophy of the parenchyma and the contraction of large and 
irregular bands or masses of new connective tissue. In sections through 
cirrhotic livers the new tissue may not be visible to the naked eye, or it 
may appear as grayish, irregular streaks, or bands, or patches, often 
sharply outlined against the dark-red, or brown, or yellow, or greenish 
yellow parenchyma. When, as is often the case, fatty infiltration is 
associated with atrophic cirrhosis, the liver may not only not be dimin- 
ished in size, but may be larger than normal. THE LIVER 
727 
On microscopical examination the new connective tissue is found in 
some cases loose in texture and containing many variously shaped cells; 
or it may be dense and contain comparatively few cells; it is usually 
quite vascular and contains a relatively large number of elastic fibrils.1 
The connective tissue is most abundant between the lobular masses of 
liver parenchyma, but it may encroach more or less upon their periph- 
eries. Small gall-ducts, some of them at least apparently new-formed, 
are usually present in the connective 
tissue around the islets of parenchyma 
(Fig. 477). Some of these may usually 
be found continuous with the old 
ducts or gall capillaries. Sometimes 
rows of more or less cuboidal cells in 
the connective tissue appear to be 
liver cells which have reverted to a 
simpler type (Fig. 478).2 From the 
old liver cells or from the cells of the 
new-formed gall-ducts new liver cells 
are produced so that here as in certain 
cases of acute yellow atrophy a repar- 
ative process is initiated and a certain 
amount of new parenchyma may 
form.3 
The branches of the hepatic and 
portal veins, particularly the latter, 
often become obliterated by pressure 
from the new connective tissue or 
from chronic thickening of their walls, 
so as seriously to interfere with 
the functions and nutrition of the 
liver cells.4 The bile-ducts also may 
become obliterated, or there may be catarrhal inflammation, especially 
of the larger trunks. The branches of the hepatic artery are much less 
liable to alterations than the other vessels. The capsule of the liver is 
usually thickened, either uniformly or irk irregular patches; or its surface 
may be roughened by larger and smaller papillary projections. The 
liver is frequently bound to the diaphragm or other adjacent organs by 
connective-tissue adhesions. Amyloid and fatty degeneration may be 
associated with cirrhosis. Cirrhotic livers frequently show an unusual 
number of leucocytes in the blood-vessels. 
The obstruction to the portal circulation induced by cirrhosis usually 
gives rise to a number of secondary lesions, since collateral circulation 
is rarely established in sufficient degree to afford much relief. The 
haemorrhoidal and vesical veins may be greatly enlarged, and also veins 
Fig. 478.-New-formed Gall-duCts 
in Cirrhosis. 
The section shows the projection into the 
new connective tissue from the rows of old 
liver cells, of cell masses resembling gall-duct 
epithe-lium. This may be interpreted as an 
example of reversion of the differentiated liver 
cells to a simpler type. 
1For a study of the character of the new connective tissue in cirrhosis see Flexner, University 
Medical Magazine, vol. xiii., p. 613, 1900. 
2 For consideration of reversion see p. 63. 
3 See ref. Muir, p. 717. 
4 For a study of the increase of portal pressure in portal cirrhosis see Herrick, Jour. Exp. Med. 
vol. ix., p. 93, 1907. 728 
THE LIVER 
of communication between Glisson's capsule and the diaphragmatic 
veins. 
In rare cases a very peculiar dilatation of the cutaneous veins about 
the umbilicus is observed. The enlarged veins form a circular network 
around the umbilicus, or a pyramidal tumor beside it, or all the veins of 
the abdominal wall, from the epigastrium to the inguinal region, are 
dilated. This condition is said to be dependent upon the congenital 
non-closure and subsequent dilatation of the umbilical vein and its anas- 
tomoses with the internal mammary, epigastric, and cutaneous veins. 
According to Sappey, it is not the umbilical vein which is dilated, but a 
vein which accompanies the ligamentum teres. 
There is very frequently also a dilatation of the veins of the abdom- 
inal wall, which has a different origin. It is produced by the pressure of 
the fluid of ascites on the vena cava, and is found with ascites from any 
cause and with abdominal tumors. 
Ascites is the most common secondary lesion of atrophic cirrhosis. 
It usually begins at an early stage of the disease, and is apt to increase 
constantly. It generally precedes oedema of the feet, but both may 
appear at the same time. This fluid is of a clear yellow or brown, green 
or red; it is sometimes mixed with shreds of fibrin, and more rarely 
with blood. The peritoneum remains normal, or becomes opaque and 
thick, or there may be adhesions between the viscera. 
The spleen is very frequently enlarged, and the enlargement may be 
considerable. When it is not increased in size this seems usually due 
to previous atrophy of the organ, or to fibrous thickening of its capsule, 
or to haemorrhages from the stomach and bowels occurring just before 
death. 
The pancreas is usually the seat of more or less marked interstitial 
hyperplasia.1 
The stomach and intestines are often secondarily affected by the 
obstruction to the portal circulation. Profuse haemorrhage from the 
stomach and intestines may occur and sometimes cause sudden death. 
The mucous membrane is then found pale, or congested, or with haemor- 
rhagic erosions. The haemorrhage not infrequently results from rupture 
of oesophageal varices which are present, especially in the lower portion, 
in a noteworthy proportion of cases of atrophic cirrhosis.2 Sometimes 
the blood is infiltrated in the coats of the stomach and intestines. 
The mucous membrane of the stomach, and of the entire length of the 
intestines, is frequently the seat of chronic catarrhal inflammation, and 
is sometimes uniformly and intensely congested and coated with mucus. 
In other cases both the mucous and muscular coats are pale, but very 
markedly thickened. 
Cirrhosis of the liver is not infrequently accompanied by chronic 
diffuse nephritis. 
Hypertrophic Cirrhosis.-There is a form of interstitial hepatitis in 
1 For a study of pancreas lesions in hepatic cirrhosis see Lando, Zeits. f. Heilkunde, Abt. f. path. 
Anat., Bd. xxvii., p. 1, 1906. 
2 For a critical summary of gastro-intestinal hemorrhage in cirrhosis, with bibliography, see 
Preble, Am. Jour. Med. Sci., vol. cxix., p. 263, 1900. THE LIVER 
729 
which the growth of new tissue not only occurs between the lobules, but 
extends into the lobule between the liver cells (Fig. 479). Under these 
conditions even in advanced forms of the lesion the liver may be enlarged, 
the surface may be smooth or slightly roughened, the parenchyma is 
often bile-stained. This form of interstitial hepatitis is called hyper- 
trophic cirrhosis. There is a form of interstitial hepatitis, usually of the 
hypertrophic type, in which the growth of connective tissue is most 
marked in the vicinity of the smaller bile-ducts. This often occurs in con- 
nection with obstruction of the bile-ducts, and the lesion is called biliary 
cirrhosis. In "biliary cirrhosis" marked jaundice is a frequent symptom, 
while ascites is moderate or absent. In certain cases there is a marked 
difference in the gross and microscopic appearance in atrophic and hyper- 
Showing formation of connective tissue between the liver cells. 
Fig. 479.-Hypertrophic Cirrhosis of the Liver. 
trophic cirrhosis, but intermediate forms occur. The difference in the 
conditions which lead to these two forms of cirrhosis of the liver, the 
atrophic and the hypertrophic, is not yet clear, and the distinctions 
which have been made between them, in part clinical, in part morpho- 
logical, are often unsatisfactory. 
The causes of cirrhosis are imperfectly understood. It is a disease 
of adult life, but exceptionally occurs in children.1 Congenital cirrhosis 
with obliteration of the bile-duct is of occasional occurrence.3 In adults 
it seems in many cases to be directly dependent upon the continued 
ingestion of large quantities of strong alcoholic liquors. It very rarely 
occurs as a result of beer drinking. 
Doubtless many of the irregular cirrhotic lesions are the result of 
repair in antecedent necroses and profound degenerative processes like 
the so-called acute yellow atrophy of the liver. 
1 For a resume of cirrhosis in childhood see Morse, Boston Med. and Surg. Jour., September 11,1902. 
2 See Rolleston and Hayne, British Med. Jour., 1901, vol. i., p. 758, bibliography. 730 
THE LIVER 
There are many cases of cirrhosis for which no primary inciting 
condition can be discovered. 
The Nature of Cirrhosis.-Cirrhosis of the liver was formerly believed 
to be primarily a productive inflammation of the interstitial fibrous 
tissue with secondary atrophy of the parenchyma. It is now clear, 
however, that in most instances it is primarily due to atrophic or destruc- 
tive changes in the liver cells which precede or accompany the formation 
of the fibrous tissue, and the regenerative processes in the liver cells and 
gall-ducts. The lesion is thus more properly considered as a replace- 
ment hyperplasia. This marks cirrhosis of the liver as a reparative 
process.1 
EXPERIMENTAL CIRRHOSIS 
The attempt has often been made to induce cirrhosis of the liver in 
animals.2 Interstitial lesions have been secured in many ways, but in 
extent and character most of them differ widely from cirrhosis in man. 
Recently, however, chloroform has been used for this purpose. 
Among the most striking results of the action of this agent are those 
secured by Opie,3 who found that by the administration of chloroform 
to dogs by the stomach in small doses, frequently repeated so as to 
thwart the immediate restitution of liver cells (see p. 727), sclerotic 
changes presently set in, marked by new connective-tissue, new bile-duct 
formation, etc., so that the lesion is fairly comparable with that of 
cirrhosis in man. 
Opie further found that by associating with the chloroform admin- 
istration injections of Bacillus coli, lesions may be induced still more 
clearly resembling those of advanced cirrhosis in man, with active new 
formation of gall-ducts.4 
Welch5 has described the occurrence of small circumscribed areas of 
fibrous tissue in the liver, replacing liver cells and containing coal pig- 
ment. This rare lesion he has called cirrhosis hepatis anthracotica. 
Syphilitic Hepatitis.-Chronic interstitial inflammation of the liver 
very frequently results from syphilitic infection, either congenitally or 
in the later stages of the acquired form. It may occur in a diffuse man- 
ner, new connective tissue being formed either between the lobules, or 
within them between the rows of liver cells. The new tissue may be 
rich in cells, or dense and firm.6 This form is frequently seen in children, 
and cannot be distinguished, either macroscopically or microscopically, 
from similar forms of interstitial hepatitis from other causes. 
1 For genesis of liver cirrhosis see Ribbert, Deutsch Med. Wochenschr., 1908, No. 39. 
2 Grover, Jour. Amer. Med. Assn., 1913, Ixi., 458, risumi and bibl. . 
3 Opie, Jour. Exp. Med. xii., 367, 1910. 
4 For a further study of the reparative phases of cirrhosis see MacCallum, Jour. Am. Med. Assn., vol. 
xliii., p. 649, 1904. For a resume of nature and lesions of cirrhosis see Kelly, Am. Jour. Med. Sci., vol. 
cxxx., p. 951, 1905. See for studies on experimental cirrhosis of the liver Pearce, Jour. Exp. Med., 
vol. viii., p. 64, 1906. bibl.; also Jour. Med. Res., vol. xv., p. 99, 1906; Lissauer, Berl. klin. Wchnschr., 
1914, li., 114 and 159. For relation of cirrhosis to chronic protein intoxication see Longcope, Trans. 
Assn. Amer. Phys., 1913, xxviii, 427. 
6 Welch, "Cirrhosis hepatis anthracotica," Johns Hopkins Hosp. Bull., vol. ii., p. 32, 1891. 
6 For a description of congenital liver cirrhosis with giant cells see Binder, Virch. Arch., Bd. clxxvii , 
p. 44, 1904. THE LIVER 
731 
In other cases, particularly in children, there may be numerous small 
gummata (so-called miliary gummata} (Fig. 160, p. 274) scattered 
through the liver, together with more or less new connective tissue. 
An extensive formation of giant cells in the liver has been described 
in connection with congenital syphilis.1 In adults, gummata are usually 
larger, varying in size from that of a pea to a hen's egg, and may be 
surrounded by larger and smaller irregular zones of ordinary connective 
tissue (Fig. 480). In still other cases in adults there are larger and 
smaller dense, irregular bands or masses of connective tissue running 
through the liver, drawing in the capsule and often causing great defor- 
mity of the organ (Fig. 481). These bands and masses of new tissue 
a, Cheesy centre; b, fibrous periphery; c, small-celled peripheral infiltration; d, portions of liver lobules. 
The drawing is somewhat schematic. 
Fig. 480.-Gumma of Liver. 
may or may not enclose gummata, either large or small. These deform- 
ing cicatrices, either with or without gummata, are very characteristic 
of syphilitic inflammation of the liver. 
This, like the simple interstitial inflammation of the liver, may be 
associated with fatty and waxy degeneration, and with atrophy of the 
parenchyma from pressure. 
Tuberculous Hepatitis.-This lesion, which is usually secondary to 
tuberculous inflammation in some other part of the body, or a part of 
acute general miliary tuberculosis, is most frequently characterized by 
the formation of larger and smaller miliary tubercles, which may be 
either within or between the liver lobules or in the walls of the bile-ducts. 
Many of the tubercles are too small to be seen with the naked eye; 
1 See Lonicer, Ziegler's Beitr., Bd. xxxix., p. 539, 1906, bibl. 732 
THE LIVER 
others may be just visible as grayish points; still others may be from 1 
to 3 mm. in diameter, with distinct yellowish-white centres. Micro- 
scopical examination shows considerable variation in the structure of 
the tubercles in different cases, as well as in the same liver. Some of 
them, usually the smaller ones, consist simply of more or less circum- 
scribed collections of small spheroidal cells, which are not morphologically 
distinguishable, so far as the form and arrangement of the cells are 
concerned, from simple inflammatory foci, or from the diffuse masses 
of lymphatic tissue which occur normally in the liver. 
Fig. 481.-Syphilitic Hepatitis. 
The liver is greatly deformed by the contraction of new-formed connective tissue. The ragged surface 
is due to the tearing away of adhesions to surrounding parts. 
In other forms we find a well-marked reticulum with larger and 
smaller spheroidal and polyhedral cells, with or without giant cells. In 
still other forms there is more or less extensive cheesy degeneration 
(Fig. 482). The larger forms are conglomerate, being composed of several 
tubercle granula joined together to form a single nodular mass. The liver 
cells at the seat of the tubercle are destroyed, and the interstitial tissue 
and blood-vessels are either destroyed or merged into the tubercle tissue. THE LIVER 
733 
In the periphery of the tubercles the liver cells may be in a condition 
of coagulation necrosis, and the tissue round about may be infiltrated 
with small spheroidal cells. There is in some cases a new formation of 
gall-ducts or of structures which resemble these and which in transverse 
sections resemble giant cells. Tubercle bacilli, frequently in small 
numbers, but often in great abundance, may be found within the tubercles. 
Tuberculosis of the liver may be associated with cirrhosis, or waxy 
and fatty degeneration. 
Much more rarely than the above form there are found in the liver 
more or less numerous scattered tuberculous masses from the size of a pea 
to that of a walnut or larger, with cheesy centres and usually a new 
Fig. 482.-A Miliary Tubercle of the Liver. 
Shows a cheesy centre and giant cells. 
growth of connective tissue in the periphery. These so-called solitary 
tubercles of the liver may be softened at the centres. Tuberculous inflam- 
mation of the gall-ducts may give rise to numerous scattered, cheesy 
nodules, as large as a pea or larger, which may be softened at the centre 
and stained yellow with bile. Small cavities may thus be formed.1 
This lesion is rare and seems to be more frequent in children than in 
adults. 
Perihepatitis.-Acute exudative inflammation of the serous covering of 
the liver, with the formation of fibrin, may occur as a part of acute gen- 
eral or localized peritonitis, or over the surface of abscesses, tumors, 
hydatids, etc., of the organ, when these lie near or approach the surface; 
or it may be secondary to acute pleurisy. 
1 See for a study of tuberculous cavities in the liver Fletcher, Journal of Path, and Bact., vol. vi. 
p. 147, 1900, bibl. 734 
THE LIVER 
Chronic perihepatitis, resulting in the thickening of the capsule of the 
liver, and the formation of new connective tissue in and beneath it may 
be secondary to an acute inflammation of the capsule, or it may be 
chronic from the beginning and associated with chronic pleurisy, chronic 
peritonitis, and cirrhosis. In this way more or less extensive adhesions 
of the liver to adjacent structures may be formed; or, by contraction of 
the new-formed connective tissue, considerable deformity of the liver may 
be produced. The capsule is sometimes uniformly thickened, sometimes 
the new tissue occurs in more or less sharply circumscribed patches. The 
surface is sometimes roughened from little, irregular, projecting masses 
of connective tissue. Microscopically the new-formed tissue is usually 
dense and firm, but it may be loose in texture and contain many cells. 
Not infrequently bands or masses of connective tissue run inward from 
the thickened capsule between the superficial lobules, causing localized 
atrophy of the parenchyma. 
HYPERPLASIA OF LYMPHATIC TISSUE IN THE LIVER. 
In some forms of leukaemia and pseudo-leukaemia the liver is not 
infrequently enlarged and soft and besprinkled with small white spots, or 
streaked with narrow whitish, irregular bands, or it may be of a diffuse 
grayish color. Microscopical examination shows this change to be due 
to an accumulation of cells resembling leucocytes, either along the portal 
vein, or diffusely through the liver tissue, or in small circumscribed 
masses. The amount of accumulation of these small cells varies much, 
but is sometimes so great as seriously to compromise the liver cells. The 
origin of these new cells is not yet definitely known. They may be, and 
doubtless in part are, brought to the organ through the portal vein; but 
they may, in part at least, be formed in the liver itself, possibly from the 
capillary endothelium. (See Fig. 282, p. 477.) 
In typhoid fever, smallpox, scarlatina, diphtheria, and measles, small 
circumscribed masses of spheroidal cells are sometimes found in the 
liver. These nodules differ in character, some are due to focal necroses, 
such as occur in various toxa?mias with a later multiplication of cells or 
invasion of leucocytes. In some, as in typhoid fever, there is necrosis 
with proliferation of endothelium (see p. 241). Finally, some of the 
small masses of spheroidal cells encountered in the liver in infectious 
diseases are doubtless hyperplastic lymph-nodules.1 
TUMORS OF THE LIVER. 
Tumors of the liver may be primary or secondary; the latter are 
most common. 
Cavernous Angiomata.-These tumors, usually small, are most com- 
mon in elderly persons and are of no practical significance. They may be 
situated at the surface (Fig. 483) or embedded in the organ, and are of 
a dark red color; sometimes sharply circumscribed by a connective- 
1 For changes in the blood in diseases of the liver consult Ewing's "ClinicalPathology of the Blood.' THE LIVER 
735 
tissue capsule, sometimes merging imperceptibly into the adjacent liver 
tissue. Microscopically they consist of a congeries of irregular cavities 
(Fig. 239, p. 394) filled with blood and frequently communicating 
freely with one another. The walls of the cavities consist of connective 
tissue, often containing small blood-vessels, and are sometimes thick, 
sometimes thin. They are believed to be formed by dilatation of the 
liver capillaries, with subsequent thickening of their walls and atrophy 
of the adjacent liver cells. By the organization of clots within the blood 
cavities these tumors may be partially or entirely converted into masses 
of dense fibrous tissue.1 
Small fibromata and lipomata have been described, also fibro-neuro- 
mata of the sympathetic. Endothelioma and hypernephroma are 
recorded. 
Fig. 483.-Cavernous Angioma of the Liver. 
Adenomata of the liver are of not infrequent occurrence. They are 
sometimes small and circumscribed, sometimes very large and multiple. 
They present two tolerably distinct types of structure. In one form the 
tissue presents essentially the same structure as normal liver tissue, 
except that the arrangement of the cells is less uniform and the cells are 
apt to be larger. They look like little islets of liver tissue, sometimes 
encapsulated and sometimes not, lying in the liver parenchyma. In the 
other form the cells are less like liver cells, are frequently cylindrical, 
and are arranged in the form of irregular masses of tubular structures 
with more or less well-defined lumina. These tumors are sometimes 
large and multiple, and in one case described by Greenfield there were 
metastatic tumors in the lungs. These tubular adenomata are in some 
1 See Merkel, Ziegler's Beitr., Bd. xxxvi , p. 574, 1904. 736 
THE LIVER 
cases so closely similar to some of the carcinomata as to be scarcely dis- 
tinguishable from them, and seem, indeed, to merge into them.1 
Aberrant nodules of adrenal tissue have been found in the liver and 
may be mistaken for adenomata.2 Cysts may develop in adenomata.3 
Carcinomata are the most common and important of the liver tumors, 
and may be primary and secondary. Primary carcinomata derived either 
from the liver epithelium or from that of the gall-ducts, and in some 
cases are arranged along the larger trunks. The cells are usually poly- 
hedral, sometimes cylindrical, and may be arranged irregularly in alveoli 
or form more or less well-defined tubular structures.4 
Secondary carcinoma of the liver, which is by far the most common, is 
usually due to the dissemination in the organ of tumor cells from carci- 
Fig. 484.-Secondary Carcinoma of the Liver. 
The section is through the entire organ, showing carcinomatous tumors of various sizes and forms: 
some are white, some are dark red from haemorrhage. The larger tumor at the left is softening at the 
centre. 
nomata of the stomach, intestines, pancreas, or gall-bladder. But it 
may be the result of metastases from the mamma, oesophagus, uterus, 
and various other parts of the body. In secondary carcinoma the cells 
resemble more or less closely the type of those forming the primary tumor. 
The form in which the carcinoma in the liver occurs varies consider- 
ably. Sometimes the tumors are single, but more often multiple (Fig. 
484); they may be very large, or so small as to be scarcely visible to the 
naked eye; very frequently numerous small nodules are grouped in the 
periphery of a larger one. They are sometimes deeply embedded in the 
liver, sometimes they project from the surface. The liver is frequently 
and sometimes enormously enlarged. The nodules are usually whitish or 
1 Sokoloff has described an adeno-carcinoma of the liver with ciliated cells, Virchow's Arch., Bd. 
clxii., p. 1, 1900, bibl. of allied tumors. See also Herxheimer, Cbl. f. Path., Bd. xiii., 1902, p. 705. For 
a study of the origin and growth of liver adenoma see Wdtzold, Ziegler's Beitr., Bd. xxxix., p. 456, 
1906, bibl. 
2 See ref. Noyes and Beer, foot-note, p. 515. 
3 See for cyst formation in the liver Dmochowski and Janowski, Ziegler's Beitr. z. path. Anat., 
Bd. xvi., p. 102, 1894. 
4 For a study of retrograde metastases from the stomach see ref. Jacob, foot-note, p. 666. 
For a study of primary liver carcinoma see Herxheimer, Cbl. f. Path., Bd. xvii., 1906, p. 724. THE LIVER 
737 
yellowish or pink in color or bile-stained, and they are often the seat of 
haemorrhages, and may become softened at the centre, forming cysts filled 
with degenerated tumor tissue often mixed with blood. The nodules are 
sometimes hard, sometimes soft and almost diffluent. Fatty degenera- 
tion in the tumor is frequent, and may be recognized by yellowish streaks 
or patches on the sections. Owing to the degeneration and partial absorp- 
tion of the central portions of the tumors, the nodules on the surface of 
the liver frequently present a shallow depression at the centre. The 
tumors may be sharply outlined against the adjacent liver tissue, or may 
merge imperceptibly into it. They may be so large or numerous as to 
occupy the greater part of the enlarged organ. The neighboring liver 
cells may be flattened and atrophic. The tumors may press upon the 
portal vein or its branches, or upon the gall-ducts, and thus seriously 
interfere with the functions of the organ. Sometimes, however, the 
tumors are very large and numerous without apparent interference with 
the function of the liver. Melanotic carcinomata sometimes occur in the 
liver, most frequently as secondary tumors. 
In some cases, instead of forming separate, distinct nodules, the 
cancerous growth develops in the form of a diffuse infiltration of the organ, 
so that the often greatly enlarged liver is irregularly mottled with white 
and reddish brown masses, and may then somewhat resemble certain 
forms of chronic interstitial hepatitis. 
Sarcomata.-Spindle- and round-celled sarcoma and angio-sarcoma 
are among the more frequent types of the rarely occurring primary 
sarcomata of the liver.1 Spindle-celled, melanotic, and telangiectatic 
sarcomata may occur in the liver as secondary tumors.2 Secondary 
myxomata and chondromata have also been described, but they are very 
rare. Cavernous lymphangiomata have been described in a few cases. 
CYSTS OF THE LIVER. 
Cysts, usually of small size, may be formed by dilatation of the bile- 
ducts. They may be multiple and contain serum, mucus, and degener- 
ated epithelium. Single cysts, apparently unconnected with the gall- 
ducts, are occasionally found in the connective tissue of the liver. They 
may be lined with ciliated epithelium. 
The liver is sometimes the seat of larger and smaller single or multiple 
cysts, varying from microscopical size up to that of a pea, and sometimes 
larger. They are sometimes associated with multiple cysts of the kid- 
ney and with congenital anomalies in other parts of the body. They 
may be associated with aberrant bile-ducts within the liver in which 
the studies of Moschcowitz show that they probably originate.3 A 
teratoma of the liver has been described by Misick.4 
1 Arnold, Ziegler's Beitr. z. path. Anat., Bd. viii., p. 123, 1890; also, for later summary of primary 
liver sarcoma, Marx, Cbl. f. Path., Bd. xv., p. 433, 1904. 
2 See Hektoen and Herrick, Trans. Assn. Am. Phys., vol. xiii., p. 385, 1898. 
3 See for study of non-parasitic cysts of the liver, with bibl., Moschcowitz, Am. Jour. Med. Sci., vol. 
cxxxi., p. 674, 1906. See also "biliary angioma" of liver, Castelli, Arch. gen. de med., 1913, xxv.,623. 
4 Misick, Jour Path, and Bact., vol. v., p. 128, 1898. 738 
THE LIVER 
Foamy Liver.-Occasionally the liver is found at the autopsy, even 
if this be made but a few hours after death, more or less completely rid- 
dled with small, irregular-shaped cavities, from the size of a pin's head to 
that of a pea. These holes are due to the accumulation of gases in the 
liver, formed by the Bacillus aerogenes capsulatus. This is the so-called 
"foamy liver" (Fig. 485). 
Fig. 485.-"Foamy Liver." 
The liver is riddled with small holes formed by the accumulation of gas developed by B. aerogenes 
capsulatus-"gas bacillus." 
PARASITES. 
Echinococcus.-This parasite is the most common and important of 
those which occur in the human liver. It forms the so-called hydatids of 
the liver. These represent one of the developmental stages of the small 
tapeworm of the dog, Toenia echinococcus (see p. 125). The cysts in 
the liver may be very small and multiple, but they may be as large as 
a man's head or larger. The liver may be greatly increased in size, and 
the tissue about the cysts atrophied. The liver itself furnishes a connec- 
tive-tissue capsule, within which is the translucent, lamellated membrane 
furnished by the parasite. On the inside of this we may find a layer of 
cells, granular matter, and a vascular and muscular system belonging to 
the parasite. Projecting from this inner capsule are the brood capsules 
and heads or scolices of the immature tapeworm. The scolices may 
become detached from the wall and lie free in the cavity, which is filled 
with a transparent or turbid fluid. Not infrequently the cysts are 
sterile, and are then simply filled with clear or turbid fluid; or the embryos 
may have died and disintegrated, and their detritus, including the hook- 
lets, may be intermingled with the fluid contents of the cysts. The 
contents of the cysts may be mixed with fat, cholesterin crystals, pus, 
bile, or blood; or form a grumous mass, in which we may or may not 
be able to find the booklets of the scolices or fragments of the lamellated 
wall. The connective tissue of the walls of the cysts may be greatly 
thickened, or it may be calcified. 
In other countries the lesion is much more common and frequently THE LIVER 
739 
more formidable than in the United States. The cysts reach an enor- 
mous size, the veins of the liver may be compressed and filled with 
thrombi, the bile-ducts compressed and ulcerated. So much of the liver 
tissue may be replaced by the hydatids that the patient may die from this 
cause alone. Very frequently there is local peritonitis, and adhesions are 
formed between the liver and the surrounding parts. In some cases the 
cysts rupture, and their contents are emptied into the peritoneal cavity, 
the stomach, the intestines, the pleural cavity, or the lung tissue. Some- 
times the cysts perforate the bile-ducts, the vena cava, or some of the 
branches of the portal or hepatic veins; or the abdominal wall is per- 
forated and a fistula formed between the cavity in the liver and the 
surface. 
Echinococcus multilocularis (see p. 126), which is apparently an 
abortive form of the above species, is very rare in the United States 
(Fig. 486).1 
Distoma hepaticum, D. sinense, D. lanceolatum, may occur in the gall- 
ducts and gall-bladder. D. sinense occurs especially in the East, and has 
been found in great numbers in the bodies of Chinamen. D. haemato- 
bium is very common in Egypt and Abyssinia, occurring in the blood- 
vessels of the liver. 
A section of a small portion of the cystic and fibrous growth in the liver. There were no booklets 
within the cysts in this case, but the delicately lamellated character of the lining membrane sufficed 
for a diagnosis. 
Fig. 486.-Echinococcus Multilocularis of the Liver. 
Pentastoma denticulatum is the undeveloped form of Pentastoma 
taenioides, a parasite which inhabits the nasal cavity of dogs and some 
other animals. In the liver of man it usually occurs in the form of 
small, rounded, calcified cysts. The cysts may contain fat, calcareous 
matter, and the remains of the dead parasite, among which the booklets 
may be found. 
Ascaris lumbricoides sometimes finds its way from the intestines into 
the bile-ducts. It may cause no disturbance here, but in some cases the 
worms have been present in large numbers and caused occlusion, dilata- 
1 See Oertel, Yale Med. Jour., vol. v., p. 233, 1899; consult also monograph by Posselt, 1900. 740 
THE LIVER 
tion, and ulceration of the biliary passages, and have led to the formation 
of abscess of the liver. 
Coccidium oviforme, the very common parasite in the rabbit's liver, 
has been found a few times in the liver of man. 
LESIONS OF THE BILIARY PASSAGES AND THE GALL-BLADDER. 
Perforation and rupture of the gall-bladder may occur under various 
conditions and is usually followed by peritonitis.1 
Catarrhal inflammation of the 
gall-ducts (cholangitis) most fre- 
quently involves the lower por- 
tion of the common duct and 
the gall-bladder. In the acute 
form it usually leaves but few 
changes appreciable after death. 
An abnormal coating of mucus, 
and sometimes congestion of the 
blood-vessels, are almost the only 
post-mortem lesions. Owing to 
the swelling of the mucous mem- 
brane and the accumulation of 
mucus in the lumen, the ducts 
may be temporarily occluded, 
but this occlusion may not be 
evident after death. If, how- 
ever, the inflammation becomes 
chronic, the walls of the bile- 
ducts may become thickened and 
their lumina more or less perma- 
nently obstructed (Fig. 487). In 
consequence of this, dilatation 
or ulceration of the bile ducts 
may ensue. Temporary obstruc- 
tion of the bile ducts may pro- 
duce marked pigmentation of the 
liver, owing to the accumulation 
of pigment granules in the liver 
cells, particularly in the vicinity 
of the capsule of Glisson, and 
jaundice of the entire body. 
The gall-bladder may be in- 
flamed by itself-cholecystitis-or 
in connection with inflammation 
of the biliary passages. If the 
disease is chronic the wall of the bladder may be thickened and bound 
to adjacent parts by fibrous tissue; polypoid growths may occur in the 
Fig. 487.-Suppurative Inflammation in the Gall-ducts-Cholangitis. 
1 See Machard, Arch. gen. de m6d., t. iv., p. 159, 1900, bibl. THE LIVER 
741 
mucosa; the duct may be occluded; dilatation, ulceration, the forma- 
tion of gall-stones, calcification, and atrophy may ensue. 
Inflammation of the stomach and duodenum, hypersemia and inflam- 
mation of the liver, concretions, and parasites frequently accompany 
catarrhal inflammation of the biliary passages, but it may occur without 
these. 
Suppurative and Croupous Inflammation of the Bile-Ducts (Cholan- 
gitis) and Gall-Bladder (Cholecystitis).-The walls of the ducts may be 
covered or infiltrated with a fibrinous or a purulent exudate; they may 
ulcerate. 
These lesions occur most frequently in connection with obstruction 
of the bile-ducts by gall-stones or otherwise, and in typhoid and typhus 
Fig. 488.-Suppurative Inflammation of the Gall-ducts in the Liver-Cholangitis. 
The suppurative foci are almost coalescent in the infected region. This lesion was secondary to 
suppurative inflammation in the larger gall passages with the presence of gall-stones. 
fever, pyaemia, and cholera; or they may be due to the extension of 
inflammatory processes from without. They also occur under unknown 
conditions. 
In many cases of inflammation of the gall-ducts the Bacillus coli 
communis, in fewer the pyogenic streptococcus and staphylococcus, 
are apparently concerned. 
Suppurative inflammation may lead to perforations of the ducts or 
bladder, with escape of bile and peritonitis; or fistulous openings between 
the gall-bladder and the duodenum, colon, and stomach, or through the 
abdominal wall. Or the inflammation may extend to the liver tissue 
and produce abscesses. Under the latter conditions there may be a series 
of small abscesses ranged along the walls of the suppurating gall-ducts 742 
THE LIVER 
(Fig. 488). In more advanced stages the abscesses may become large 
and communicate with one another, so that a considerable portion of 
the liver may be occupied by a series of communicating cavities with 
ragged walls, containing pus and detritus of liver tissue more or less 
tinged with bile.' 
Such abscesses may become more or less completely enclosed by con- 
nective-tissue walls. The portal vein may also become inflamed, and 
perforations may be formed between it and the bile-ducts. The excitants 
of these inflammatory processes in the gall-ducts and gall-bladder are 
This section is from a small tumor growing within one of the gall-ducts in the liver. 
Fig. 489.-Adenoma of the Gall-Duct. 
probably usually bacteria. Those which have been most frequently 
found are the "pyogenic cocci,"1 the colon and typhoid bacilli, and the 
pneumococcus. It should be borne in mind that post-mortem invasion 
of the gall-bladder and passages by bacteria may take place early. 
Constriction and Occlusion of the Bile-Ducts.-This may be produced 
by inflammation of the ducts themselves, by new growths in their walls, 
by calculi or parasites in their lumina, by changes in the hepatic tissue 
in chronic and acute hepatitis, by aneurisms, or by pressure on the duct 
from without, as by tumors in the head of the pancreas, etc. 
The obliteration of the smaller bile-ducts produces no marked lesions. 
When the ductus communis of the hepatic duct is obstructed, the ducts 
throughout the liver are frequently dilated and the liver tissue is bile- 
stained. The liver may undergo atrophy and the whole body be intensely 
1For a study of gall-bladder infections consult Cushing, Johns Hopkins Hosp. Bull., vol. x., p 
166, 1899, bibl. Also Gilbert and Lippmann, Comptes rend, de la Soc. Biol.. Nov. 8th, 1902, p. 1189. THE LIVER 
743 
jaundiced. When the cystic duct is obstructed the gall-bladder is 
dilated.1 
Dilatation of the Bile-Ducts is usually produced by strictures in the 
ways just mentioned, or by calculi. When calculi have produced the 
dilatation this condition may sometimes continue after they have found 
their way into the intestines. Sometimes, however, there is very 
marked dilatation of the bile-ducts without evident present or past 
obstruction. The dilatation may affect only the common and hepatic 
ducts, or it may extend to the smaller ducts in the liver, which are then 
dilated uniformly or in sacculated forms. They may contain bile, mucus, 
or calculi. The liver is at first enlarged, but may afterward atrophy. 
The gall-bladder may be dilated in consequence of obstruction of the 
common or the cystic duct. In the latter case it may reach an immense 
size and form a large tumor in the abdominal cavity. The dilatation 
is generally uniform, the bladder retaining its normal shape; sometimes, 
however, there are diverticula, which are usually produced by calculi. If 
the obstruction to the hepatic duct is incomplete or movable the gall- 
bladder may contain bile, and often calculi. If the obstruction is 
complete the contained fluid may gradually lose its biliary character and 
become a serous or mucous fluid of a light yellow color-hydrops cystidis 
fellea. The walls of the bladder may be of normal thickness, or thinned, 
or thickened, or calcified. If the obstruction is due to a calculus, this 
may pass into the intestine and the gall-bladder be suddenly emptied. 
Usually the bladder fills again, owing to its loss of contractile power. 
TUMORS OF THE GALL-BLADDER AND LARGER GALL-DUCTS. 
Small fibromata have been described in the gall-bladder and in the 
common duct, but they are very rare. The most common tumors are 
carcinomata. These may be primary or secondary, and present the usual 
structural variations. The cells may be cylindrical or polyhedral; or 
they may present the characteristics of gelatinous cancer. Primary 
carcinomata and adeno-carcinomata of the gall-bladder and larger gall- 
ducts are not uncommon, and are frequently associated with calculi.2 
Not infrequently the pancreatic and common ducts are both involved, 
and it is difficult to say whether the tumor is primarily in the head of the 
pancreas or in the gall-duct. The bladder and ducts may also be second- 
arily involved in carcinomata of the stomach, liver, and duodenum. 
Adenoma and papilloma of the gall-ducts are of occasional occurrence 
(Fig. 489). 
BILIARY CALCULI. (Cholelithiasis.) 
These bodies are of common occurrence. They are found usually in 
the gall-bladder, sometimes in the hepatic, cystic, and common ducts; 
less frequently in the small ducts of the liver. In the gall-bladder from 
1 For a study of congenital obliteration of bile-ducts see Howard and Wolbach, Arch. Int. Med., 1911 
viii., 557. 
2 See Warthin, Phila. Med. Jour., vol. vi.; pp. 38, 82, and 120, 1900, bibl. 744 
THE LIVER 
1 to 7,800 calculi have been counted. They vary in size from that of a 
pin's head to that of a hen's egg, or they may be larger. Single gall- 
stones are usually spheroidal or ovoidal; when multiple they are usually 
flattened at the sides or faceted (Fig. 490). 
They may be composed: 
1. Principally of cholesterin, and may be of pure white color, or 
tinged with various shades of yellow or brown by bile pigment. The 
fractured surface shows a radiating crystalline structure. 
2. Of cholesterin, bile pigment, and salts of calcium and magnesium. 
These are usually dark colored, brown, reddish black, or green, and may 
be spheroidal or faceted, smooth or rough on the surface; the fractured 
surface is usually radiating crystalline. This is the most common form. 
3. Principally of bile pigment. Such calculi are rare, usually small, 
very dark colored, and not numerous. 
Fig. 490.-Biliary Calculi. 
The smaller calculi show the faceted character; the larger, cut across, show the lamellation. 
4. Of calcium carbonate. These are rare, have a nodular surface, and 
a clear crystalline, not radiating fracture. 
Most calculi are formed around a central mass, sometimes called the 
nucleus, which may consist of cholesterin, bile pigment, mucus, or epi- 
thelium, or more rarely of some foreign body. Thus a dead parasite, a 
needle, and fruit seeds may serve as nuclei. The body of the calculus 
may be homogeneous, or lamellated, or crystalline.1 
Biliary calculi in the gall-bladder may produce no symptoms and be 
discovered only after death. In the hepatic and common ducts they may 
obstruct the flow of bile and lead to fatal jaundice; or they may pass 
from time to time into the intestine, producing biliary colic. If they 
are impacted in the cystic duct they may lead to dilatation of the gall- 
bladder. They may get into the duodenum by ulceration through the 
walls of the ducts or gall-bladder, or in the same wray into the peritoneal 
1 On formation of gall-stones see Elsner, Interstate Med. Jour., 1913, Feb. THE LIVER 
745 
cavity. Gall-stones which get into the intestinal cavity usually pass off 
without doing any further injury, but very large calculi may cause 
occlusion of the gut with fatal results. The r61e of micro-organisms in 
the formation of gall-stones has been the subject of significant studies.1 
1 Consult Mignot, Arch. gen. de medecine, 1898, t. ii., p. 129 and 263; also Cushing, Johns Hopkins 
Hosp. Bull., vol. x., p. 166, 1899; also Mieczkowski, Mitth. a. d. Grenzgeb. d. Med. u. Chir., Bd. vi., 
p. 307, 1900. CHAPTER IX. 
THE URINARY ORGANS. 
The Kidneys. 
Malformations. 
Both kidneys may be absent in connection with extensive malformation in foetuses 
which are not viable. 
Absence of one kidney is not uncommon, the left kidney being more frequently 
absent than the right. The absence of the kidney may be complete, the ureter being 
also absent; there may be an irregular mass of much-atrophied kidney tissue with con- 
nective tissue and fat, or there may be only a little mass of connective tissue and fat 
representing the kidney, and a ureter running down to the bladder. The single 
kidney which is present is usually much enlarged. It may be in its natural position or 
displaced downward. When both kidneys are present one of them may be much 
larger than the other. One kidney may have two pelves or two ureters. 
A frequent malformation is the so-called horseshoe kidney (Figs. 183 and 491). 
The lower ends of the kidneys are joined together by a commissure. The commissure 
Fig. 491.-Horseshoe Kidney. 
is usually composed of kidney tissue, but sometimes of connective tissue. The two 
kidneys may be normal, except for the commissure; or their shape, the arrangement of 
the vessels and ureters, and the position may be unnatural. The two kidneys may be 
united throughout so as to look like a single misshapen kidney with two or more pelves 
746 THE URINARY ORGANS 
747 
and irregular blood-vessels. The united kidneys may be both situated on one side of 
the vertebral column or in the pelvis. 
The fcetal lobulation of the kidney frequently persists during adult life (Fig. 492). 
Changes in Position. 
The kidneys may be placed in an abnormal situation, in which they are either 
fixed or movable. 
The change in position is either lateral or downward. When displaced downward 
the kidney may be over the sacrum or below this in the cavity of the pelvis. The 
Fig. 492.-Fcetal Lobulation of Kidneys in Adult. 
The kidneys were of normal size. 
vessels also have an irregular origin and distribution. The kidney is firmly attached 
in its abnormal position. 
Movable or wandering kidneys are found in adult life as a result of tight lacing, of 
pregnancy, of overexertion, and of unknown causes. They are more common in 
females than in males, and the right kidney is most frequently involved. The blood- 
vessels become lengthened and the attachments of the kidneys longer and looser. 
COMPENSATORY HYPERTROPHY OF THE KIDNEY. 
In congenital absence of one kidney or in post-embryonal life when 
one kidney is involved in lesions which seriously interfere with its 
function, the other organ may increase in functional capacity through 
an hypertrophy and hyperplasia of its gland cells. A similar alteration 
may take place in the sound parts of an organ partially compromised by 
structural lesions.1 The marks of hypertrophy are not evident in the 
glomeruli and convoluted tubules. The epithelial cells are larger and 
increased in number; the tufts of the glomeruli are also enlarged. 
1 For a study of this condition see Sacerdotti, Virchow's Arch., Bd. cxlvi., p. 267, 1896, bibl. 
Consult also for general consideration of hypertrophy Thoma, "Text-book of General Pathology," 
vol. i., p. 448, Eng. trans. 748 
THE URINARY ORGANS 
DISTURBANCES OF CIRCULATION. 
Anaemia of the kidney occurs in general anaemia: it may be associated 
with various forms of diffuse nephritis. Local anaemia may be due to 
thrombosis or embolism. 
Acute Hyperaemia-Acute Congestion.-This may occur in early 
phases of an acute inflammatory process or after the ingestion of irritant 
poisons. The kidneys may be swollen, the vessels distended, and bloody 
fluid exude from the cut surfaces. There may be extravasation of red 
blood cells from diapedesis. 
Chronic Hyperaemia-Chronic Congestion.-This may occur in con- 
nection with a similar condition in the other viscera when the circulation 
is impeded through uncompensated lesions of the heart and lungs, such as 
chronic endocarditis involving the aortic and mitral valves, cardiac dila- 
tation, aortic aneurism, emphysema, large accumulations of fluid in the 
pleural cavities; or it may be associated with obstruction of the renal 
vein or inferior vena cava by thrombosis or pressure from tumors, etc. 
The kidneys in this condition are, when typical, slightly or considerably 
enlarged, increased in weight, hard, and dark red in color with capsule 
not adherent and surface smooth. The congestion is most marked in the 
capillaries of the glomeruli, which are widely dilated, often with thickened 
walls, in the interlobular veins, the vasa recta, and the stellate veins of 
the cortical surface. 
The epithelium of the convoluted tubules may be swollen; or it may 
be much flattened so that the lumen of the tubule is enlarged. If the 
congestion persists, there is hyperplasia of the interstitial tissue of the 
kidney with degeneration of the epithelium, the formation of casts, 
atrophy of the tubules, etc. Chronic congestion may lead to chronic 
diffuse nephritis.1 
Embolism, Thrombosis, and Infarction.-If the renal artery or one of 
its branches be plugged by an embolus or thrombus, an anaemic infarct 
of the region is the result. There may be one or several such infarcts 
which are usually more or less wedge-shaped, the apex directed inward 
corresponding to the vascular territory compromised. They are pale or 
yellowish, hard, and, as inflammatory reaction sets in, may be surrounded 
by a red hypersemic zone. 
Within the limits of the infarct, necrosis of epithelium or of the 
entire mass of involved tissue may take place with such subsequent 
alterations as have been already described on page 29. 
The seat of old and healed infarcts may be indicated by small fibrous 
cicatrices.2 
Haemorrhagic infarcts in the kidney are rare. Infarcts may become 
the seat of gangrene when putrefactive bacteria gain access to them; 
or suppurative inflammation with the formation of abscesses may occur. 
1 For a study of theories of renal secretion see Lamy and Mayer, Jour, de Phys, et Path, gen., t 
viii., p. 660, 1906. 
2 For a study of the regenerative capacity of the renal epithelium in infarcts see Thorel, Virchow's 
Arch., Bd. cxlvi., p. 297, 1896, bibl.; also Thorel, Deutsch. Arch. f. klin. Med., Bd. Ixxvii., 1903. THE URINARY ORGANS 
749 
Embolism of the renal artery may result in necrosis of the entire kidney. 
Thrombosis of the renal vein may be induced by the pressure of tumors, 
either on this vessel or on the vena cava; or it may occur in cachectic 
conditions. 
ALBUMINURIA AND CASTS. 
Albuminuria.-Albuminous material or serum not infrequently passes 
out of the blood-vessels of the kidneys, either through the glomeruli or 
the tubules, and mingles with the excreted substances. While this may 
occasionally occur under conditions which cannot be regarded as abnor- 
mal, it is common in many diseases of the kidney and is frequent 
without demonstrable kidney lesions in fevers, infectious diseases, 
abnormal conditions of the blood, various forms of poisoning, disturbances 
of the circulation, etc. Albuminous material may also be set free by 
abnormal metabolism or disintegration of the renal epithelium. 
In albuminuria with pronounced kidney lesions there are usually 
well-defined alterations in the capillaries of the tufts and in their epi- 
Fig. 493.-Hyaline Globules in Uriniferous Tubule. 
There are also degeneration and disintegration of the epithelium. 
thelial investment. There may be thrombi in the capillaries; their walls 
may be thickened; the flat epithelium covering them may be swollen or 
fatty, or may peel off, or it may proliferate. In the kidneys of cases of 
pronounced albuminuria, preserved in alcohol or other fixatives which 
coagulate albuminous material, this substance may be seen within Bow- 
man's capsule or in the lumina of the tubules as fine or coarse granules. 
Albuminous material in the tubules may form casts (see below), or when 
the conditions are favorable fibrillar fibrin may form. 
Casts.-Albuminous material which under various abnormal condi- 
tions has escaped from the blood-vessels in solution may coagulate, 
especially in the lumina of the tubules, forming the more or less cylin- 
drical or globular structures called casts. These may be homogeneous 
in structure-hyaline casts; or the albuminous material of which they 750 
THE URINARY ORGANS 
are formed may be mingled with the products of degeneration and disin- 
tegration of epithelial cells, either from the glomeruli or from the tubules; 
or with red blood cells, or leucocytes, or exfoliated epithelial cells. In 
this way granular casts, epithelial casts, blood casts, etc., are formed. The 
epithelium of the tubules may peel off in masses, forming cast-like cell 
structures. Homogeneous globules of various sizes may be formed in 
the tubular epithelium which is yet in place, and, as the cells degenerate 
Fig. 494.-Hyaline Casts in Uriniferous Tubule. 
The epithelium is flattened in the tubules containing the casts. 
and disintegrate, such homogeneous globules may collect in the lumina 
of the tubules (Fig. 493) or they may fuse to form hyaline casts (Fig. 
494). Homogeneous casts giving the micro-chemical characters of amy- 
loid are of occasional occurrence in the tubules. 
Casts and cell detritus may form both in the cortical and medullary 
tubules and may pass out of the organ with the urine. 
NECROSIS. 
Necrosis of the epithelium of the kidney of varying extent may 
occur in disturbances of the circulation by thrombosis, degenerations, 
etc., in acute infectious diseases, in various nutritional disorders, such 
as gout, diabetes, etc., or auto-intoxications, as well as in poisoning by 
various substances, cantharidin, sublimate,1 chromates, chlorates, etc. 
In sublimate and oxalic-acid poisoning, calcification (Figs. 30 and 31) 
may be associated with the necrotic process. 
The extent of the lesion varies greatly. In some instances a large 
part of the epithelium of the convoluted tubules may be necrotic without 
marks of inflammation. In other cases the lesion involves the tubules 
in limited regions. It is suggested that certain forms of extensive necro- 
sis of renal epithelium are the analogues of some forms of acute yellow 
1 For studies on sublimate poisoning see ref. to Neuberger and Elbe, foot-note, p. 753. THE URINARY ORGANS 
751 
atrophy of the liver.1 In fact the kidney lesion may accompany acute 
yellow atrophy. 
DEGENERATION. 
Albuminous Degeneration (Parenchymatous Degeneration-Acute 
Degeneration).-This form of degeneration is most common in the acute 
infectious diseases, such as diphtheria, scarlatina, measles, typhoid fever, 
yellow fever, and in many forms of septicaemia and toxaemia. It usually 
accompanies similar lesions in other viscera. In moderate degrees of 
the lesion, the epithelium, particularly of the convoluted tubules, is 
swollen and more coarsely granular than normal (Fig. 495). In more 
Fig. 495.-Albuminous Degenbration of the Kidney (Acute Parenchymatous Degeneration) 
From a case of yellow fever, a, The swollen and granular epithelium peeling off and disinte- 
grating; 6, hyaline material in the lumen of the tubule. 
pronounced lesions, in addition to simple albuminous degeneration, the 
epithelium may become more or less filled with minute fat droplets, or 
the cells may disintegrate and peel off, or they may become necrotic and 
the nuclei fail to stain. The cell body may then undergo coagulation or 
disintegrate. 
The gross appearance of the kidneys varies with the degree and 
extent of the degeneration. The kidney may be slightly or considerably 
enlarged. On section the cortex is usually thickened and pale with 
obliteration of the normal cortical markings. The capsule of the kidney 
1 For a resume of necrosis of renal epithelium see Hewitt, Johns Hopkins Hosp. Bull., vol. xvii., p. 
272, 1906. 752 
THE URINARY ORGANS 
is not abnormally adherent. When there are other associated or ante- 
cedent lesions in the kidney, the gross appearance of the organ varies. 
Fig 496.-Fatty Degeneration of the Epithelium in the Convoluted Tubules of the Kidney. 
The fat droplets are stained black by osmic acid. 
Fatty Degeneration.-This may occur in those diseases of the blood or 
circulatory system in which general nutrition suffers; in infectious dis- 
eases often associated with or following albuminous degeneration; in 
a, The tuft is completely transformed into a waxy mass; b, portions of tuft waxy; c, tuft capillaries 
normal; d, convoluted tubule with disintegrating epithelium. 
Fig. 497.-Amyloid Degeneration of Tuft Capillaries in the Kidney. 
various cachexias; in acute and chronic forms of diffuse kidney disease, 
and in poisoning by phosphorus, arsenic, sublimate, etc. 
The degeneration may be diffuse and widespread or it may occur in THE URINARY ORGANS 
753 
patches. If diffuse, the cortex in which it is most marked is usually 
more or less thickened, opaque, and yellowish; if in patches, there are 
opaque yellow streaks or spots in the cortex. But these appearances are 
often obscured by various other lesions. If the degeneration be moder- 
ate in degree, there are larger and smaller fat droplets, usually most 
abundant in the basal portion of the epithelium of the convoluted tubules 
(Fig. 496). In more marked degeneration, the cells of the convoluted 
tubules may be filled with fat droplets and may peel off, or they may 
disintegrate, setting the fat free in the lumen of the tubules. The 
degeneration may involve the tuft and capsule epithelium as well as 
Fig. 498.-Glycogen Degeneration of the Epithelium of the Kidney in Diabetes. 
that of the collecting tubes, and fat droplets may be found free or in cells 
in the interstitial tissue. 
Amyloid Degeneration.-This is usually associated with amyloid 
degeneration elsewhere in the body, and commonly occurs in kidneys 
which are already the seat of various forms of chronic lesion. Usually 
the kidney is enlarged, the section is shining or translucent, the cortex is 
thick and pale, the glomeruli are often unusually plain. The capillaries 
of the tufts (Fig. 497) and the vasa recta are most often involved. If the 
kidney be otherwise altered, the gross and microscopic appearances vary. 
Glycogen Degeneration of the epithelium may take place in diabetes 
mellitus. It is usually most marked in the cells of Henle's loops (Fig. 498). 
Calcification may occur in chronic inflammatory lesions or in old 
infarctions, in the intertubular tissue of the medulla in the aged, and in 
casts in the collecting tubes, and is especially well marked in degenerated 
and necrotic epithelial cells in sublimate poisoning (Figs. 30 and 31).1 
INFLAMMATION. 
General Considerations. 
Many of the alterations in the kidney which are commonly considered inflamma- 
tory are in fact degenerative, and these degenerative changes are often so important 
and so conspicuous in the lesions as fairly to dominate the gross and microscopic 
appearances. The processes in the kidneys which may be properly considered inflam- 
1 See Neuberger, Ziegler's Beitr., Bd. vi., p. 429, 1889; also Elbe, Virch. Arch., Bd. clxxxii., p. 445, 
1905. 754 
THE URINARY ORGANS 
matory are either exudative or productive, so that the apparently complex series of 
kidney changes which are grouped under the name nephritis, or Bright's disease, are 
really phases of exudative or productive inflammation, or both, associated with degenera- 
tive processes. 
Whether the kidneys be large or small, white or red or mottled, smooth or rough; 
whether the disease be acute or chronic, it is always these comparatively simple proc- 
esses, varying in extent, in duration, in intensity, and in relative predominance, 
which are to be taken into the account in the study of inflammation of this organ. 
There are perhaps no lesions whose classification has seemed beset with such diffi- 
culties as those of the kidneys. This is largely due to a failure to realize that the vari- 
ous phases of inflammation and degeneration do not stand apart as independent proc- 
esses or lesions, but are closely associated and often merge. It is difficult, perhaps 
impossible, to make a classification which shall meet the requirements of the clinic, 
the limitations of urinary tests, and at the same time accord with the revelations of 
the autopsy and the microscope. 
One of the difficulties in framing a classification of kidney lesions is that there are 
many and serious abnormalities in the function of the kidney which do not find expres- 
sion in such structural changes as we can at present recognize. Our knowledge of 
such of the minute structural lesions in the renal epithelium as are not manifested by 
alterations in the size and form and organic integrity of the cell is, in fact, very meagre, 
so that the attempt to classify inflammatory lesions of the kidney upon both clinical 
and morphological data often leads to conjecture or confusion, frequently to both. 
Considering the scope of this book and our present purpose, it seems wiser to set 
forth here as concisely as possible the essential character of the lesions in acute and in 
chronic phases of inflammation and degeneration in the kidney based upon morpho- 
logical rather than upon clinical data. 
It is convenient to divide the acute inflammatory processes of the 
kidneys into two forms, Suppurative Nephritis and Acute Diffuse Nephritis. 
Suppurative Nephritis. 
Suppurative inflammation of the kidney may follow injury with local 
infection. It is, however, most often due to the presence of bacteria, 
commonly the pyogenic cocci, which have been brought through the 
blood-vessels from a remote infective focus, as in ulcerative endocarditis, 
septic phlebitis, etc.-embolic infection. Or, on the other hand, the bac- 
terial excitant may be transmitted to the kidneys through the urinary 
passages-ascending infection. 
Traumatic lesions of the kidney may lead to suppurative nephritis 
either through direct infection of the wound or by the establishment of 
local vulnerability1 to the action of bacteria which may later gain access 
to the injured tissue through the circulation. After infected wounds or 
injuries of the kidney, large abscesses may develop, or nearly the whole 
organ may be converted into a mass of pus, blood, and disintegrated 
tissue. 
In the embolic type of suppurative nephritis, small abscesses are formed 
most frequently in the cortex. Where bacteria lodge and grow in the 
tissue there is at first circumscribed hypera?mia or haemorrhage and 
necrosis, with subsequent gathering of leucocytes and finally the disin- 
tegration of tissue and the formation of abscess. Such kidneys present 
to the naked eye on section small spots-or in the medulla, streaks- 
1 See ref. to Cheesman and Meltzer and to Brewer, foot-note, p. 152. THE URINARY ORGANS 
755 
which are red or gray or yellow, depending upon the degree of advance- 
ment of the lesion. In such areas the bacteria may be readily demon- 
strated, sometimes in early stages in dense masses in the capillaries and 
other smaller vessels, or later scattered through the necrotic and disinte- 
grating tissue (Fig. 119, p. 207). Embolic abscesses are commonly 
developed in both kidneys and by extensive coalescence may give rise to 
large abscesses. There is reason to believe that in certain forms of 
septicaemia bacteria may secure a foothold in the tubules, not as emboli, 
Fig. 499.-Suppurative Nephritis. 
Developed from infection by way of the urinary passages (so-called "surgical kidney"). 
but through excretion.1 In such cases the suppurative foci may be at 
first limited to the medulla. 
Ascending Infection.-In suppurative nephritis associated with a 
similar process in the ureter, bladder, etc., the medullary portion of the 
kidney is usually earliest involved, and then the elongated form of the 
suppurative areas (Fig. 499) corresponds to the grouping of the tubules 
in this region.2 
Whatever the form in which it may manifest itself, suppurative 
inflammation of the kidney is commonly induced by some one or combi- 
nation of the pyogenic micro-organisms which may lodge within it under 
favorable conditions. Thus Streptococcus pyogenes, Staphylococcus 
1For study of excretion of bacteria by kidney see Asch, Cbl. f. Kr. d. Ham- u. Sex.- Org., Bd. 
xiii., 1902, pp. 249 and 324. Also reference p. 151. 
For study of elimination of pigment by kidney see Carter, Jour. Am. Med. Assn., vol. xli., p. 1248, 
1903. 
2 For further details concerning suppurative nephritis consecutive to similar processes in adjacent 
organs see below. 756 
THE URINARY ORGANS 
pyogenes, Bacillus coli communis, Bacillus pyocyaneus, Bacillus proteus, 
the pneumococcus, the typhoid bacillus, and others, may be found in the 
suppurative foci. Sometimes, however, especially in the more chronic 
processes, micro-organisms are not demonstrable. 
Acute Diffuse Nephritis. 
This process may occur in acute infectious diseases; it is especially 
common in scarlatina and not infrequent in diphtheria, typhoid fever, the 
exanthemata, and malaria, and in septicaemia due to various bacterial 
excitants. 
The lesions of acute diffuse nephritis vary greatly in extent, in degree, 
in the relative involvement of one or other renal structure, as well as with 
the duration of the process. In this as in other forms of inflammation 
of the kidney, degeneration is an important and often predominant fac- 
tor in the morphology of the lesions. 
We shall now consider those lesions which in varying degrees are 
characteristic of an early phase of acute diffuse nephritis, such as fre- 
Fig. 500.-Acute Diffuse Nephritis. 
Showing swelling of the cells covering the capillary tufts and lining Bowman's capsule. 
quently occurs in the course of the acute infectious diseases. While 
changes in the different structural components of the kidney may occur 
simultaneously and are intimately related to each other, we shall study 
first the lesions of the glomeruli, second those of the tubules, third those 
of the interstitial tissue and its vessels. 
The Glomeruli.-One of the early alterations in the tufts of the glo- 
meruli is the swelling of the cells which cover the capillaries.1 These cells 
which in normal conditions are thin and scarcely visible, save by their 
nuclei, now project from the capillary loops, sometimes remaining closely 
apposed to the capillary walls, sometimes assuming polypoid shapes 
(Fig. 500), sometimes forming a continuous thick covering of cuboidal 
cells over the vessels. The nuclei are larger than normal and mitosis 
may be evident. Similar changes occur in the epithelium between the 
capillary loops. The capillaries are sometimes distended and plugged 
with cells; some of these are leucocytes; others are larger with large 
1 For a study of the development of the glomeruli and its relation to pathological changes see 
Herring, Jour. Path, and Bact., vol. vi., p. 459, 1900. THE URINARY ORGANS 
757 
nuclei and may be swollen endothelium. Hyaline thrombi are often 
found in these tuft capillaries. The swollen and proliferating tuft 
epithelia often undergo fatty degeneration and may peel off into the 
glomerular space. 
In some cases the proliferation and exfoliation are extensive and 
the cells may collect in crescentic masses within Bowman's capsule, 
crowding the tuft toward its hilus. The cells in these crescentic masses 
may be flattened from pressure and in profile appear fusiform (Fig. 501). 
The capsular epithelium may be swollen or remain apparently intact 
while there is a large cell accumulation from the tuft; or it may proliferate 
or become fatty or peel off. Swelling, exfoliation, and proliferation 
of the glomerular epithelium in some degree are of frequent occurrence 
Fig. 501.--Acute Diffuse Nephritis-Following Scarlatina. 
Swollen cells are seen upon the capillary tuft and lining Bowman's capsule. Polyhedral and 
flattened cells lie in masses between the capsule and the tuft; the latter has been pressed upon by the 
cells and other exudate within the capsule. 
in acute nephritis. They are sometimes so pronounced, especially in 
acute nephritis following scarlatina, either with or without extensive 
associated lesions, as to have suggested a name for one phase of the lesion 
-glomerulo-nephritis. There is sometimes a considerable accumulation 
of albuminous exudate between the tuft and capsule. Such albuminous 
material in specimens fixed by alcohol is in the form of fine granules and 
may be mingled with exfoliated and often fatty epithelium or cell 
detritus. 
Leucocytes and red blood cells may be present with other exudate 
within Bowman's capsule. 
The Tubules.-The lesions of the tubules of the kidney in the early 
phases of acute nephritis are largely degenerative; the epithelium, 
especially of the convoluted tubules, is swollen and coarsely granular 
(Fig. 495), or it may contain few or many fat droplets (Fig. 496)-albu- 
minous and fatty degeneration. The epithelium may become necrotic 
and may disintegrate or peel off over larger or smaller areas. Thus the 758 
THE URINARY ORGANS 
lumina of the tubules may contain fragments of epithelium or detritus 
mingled with albuminous fluid-serum-red blood cells and leucocytes, 
or hyaline or other forms of casts (Fig. 494). Red blood cells may be 
extravasated in considerable numbers and collect in the tubules or pass 
on with the exudates. The casts and other exudates may be present in 
the cortex or in the collecting tubes of the kidney. 
The Interstitial Tissue.-This in early phases of acute nephritis may 
be oedematous or it may be more or less infiltrated with leucocytes or 
Fig. 502.-Acute Diffuse Nephritis. 
Showing proliferation of cells on the tuft and lining the capsule of the glomerulus and the formation 
of new interstitial tissue with large polyhedral cells-glomerular and interstitial type. 
fibrinous exudate. Patches of new-formed small spheroidal cells, or 
larger cells with conspicuous excentric nuclei may be present either in 
the vicinity of the glomeruli (Fig. 502) or near the interlobular veins, 
or a general thickening of the interstitial tissue may occur even very 
early in some forms of acute diffuse nephritis, particularly in those fol- 
lowing scarlatina and diphtheria. 
We have thus seen that in the early phases of an acute inflammation 
of the kidneys, such as may occur independently or in connection with 
acute infective processes elsewhere, there is an involvement of all the 
structural units of the organ, the glomeruli, the tubular epithelium, and THE URINARY ORGANS 
759 
the interstitial tissue. Such a process involving the various kinds of 
tissue is called diffuse,1 and the process is therefore designated Acute 
Diffuse Nephritis. 
While both kidneys are involved in acute diffuse nephritis, the lesions 
in each are by no means uniform either in extent or advancement and 
are often patchy or irregular in distribution. 
Variations in Type in Acute Diffuse Nephritis.-There are many 
variations in the type of the lesions in acute diffuse nephritis, some of 
which seem to be directly dependent upon the character of the excitant, 
while in others the variations cannot as yet be associated with known 
determining conditions. 
If one guard himself against the notion of distinct species in the 
lesions it is convenient to recognize certain structural variants or types. 
Thus the changes in the glomerular capillaries and epithelium may, 
as above indicated, be prominent-glomerular type-(so-called glomerulo- 
nephritis') (Figs. 501 and 502); the degenerative process in the tubular 
epithelium may be extreme-parenchymatous or degenerative type; there 
may with other lesions be considerable heemorrrhage into the glomeruli, 
tubules, and interstitial tissue-haemorrhagic type. With or without 
marked structural involvement 
of the parenchyma and intersti- 
tial tissue there may be an exu- 
dative inflammation in which 
serum and leucocytes (Fig. 503) 
and more or less red blood cells 
may gather in the glomeruli or 
tubules and with various forms of 
casts pass off in the urine. This, 
which is common, has been called 
by Delafield the exudative type of 
acute diffuse nephritis. Finally, 
with any one or more of the 
above types of lesion there may 
be early and significant involve- 
ment of interstitial tissue of the 
kidney, so that new and often 
very cellular tissue, either in small patches or through a large portion 
of the organs, may lead to tubular atrophy and to serious and perma- 
nent structural alterations. This, which has been called by Delafield 
the productive type, by others the interstitial type, of acute diffuse 
nephritis (Fig. 502), is most frequent as a complication of scarlatina; 
it may follow diphtheria, or puerperal infections, and may occur as 
an apparently independent process? 
Between these types of lesion, largely based, as will be seen, upon the 
Fig, 503.-Acute Diffuse Nephritis. 
Showing pus cells and granular exudate in the 
tubules, with flattening of the epithelium; also mod- 
erate oedema of the interstitial tissue-exudative 
type. 
1 It should be understood that the word " diffuse " is not used in the sense of widespread or uniform, 
but as indicating involvement of the various structural units of the organ. 
2Consult for an interesting study of "acute interstitial nephritis," Councilman, Jour. Exp. Med., 
vol. iii., p. 393, 1898. Councilman regards the new cells in the interstitial tissue as largely "plasma 
cells" derived from lymphoid cells of the blood. 760 
THE URINARY ORGANS 
relative involvement of the structural units of the kidney, are many 
intermediate forms which the scope of this book does not permit us to 
consider. 
Kidneys which are the seat of acute diffuse nephritis sometimes 
appear almost normal on gross inspection. But in more typical forms 
they are slightly or considerably enlarged, the capsule is free, the cortex 
is thickened, and either reddened or pale or mottled red and gray. When 
the interstitial tissue is cedematous the cortex may appear translucent. 
The glomeruli may be red or pale and conspicuous or normal in appear- 
ance. The pyramids may seem unusually red by contrast with the 
thickened pale cortex. In haemorrhagic forms of acute nephritis in 
Showing an advancing lesion following an acute type. Note the formation of a patch of dense 
fibrous tissue, with thickening of the walls of the glomeruli and atrophy of the tubules. 
Fig. 504.-Diffuse Nephritis. 
which blood may collect in the glomeruli, in the interstitial tissue, and in 
the tubules, the cortex may be mottled with red. 
In many forms of acute diffuse nephritis, particularly if the inter- 
stitial tissue be not considerably involved, resolution may take place. 
The Excitants of Acute Diffuse Nephritis.-In many cases of acute 
diffuse nephritis, the process seems to be due to toxic substances which 
are formed under the influence of micro-organisms in other parts of the 
body and presumably excreted by the kidney with whose cells they come 
into intimate contact or in whose metabolism they may share. Acute 
nephritis is also induced by various exogenous poisons, such as corrosive 
sublimate, carbolic acid, cantharides, and many others; it may occur with 
extensive lesions of the skin and after exposure to cold. In the acute 
nephritis following extensive burns, exposure to cold, etc., it is probable 
that the poisonous products of abnormal body-cell metabolism are the 
direct excitants. THE URINARY ORGANS 
761 
Bacteria may be eliminated from the body through the kidney some- 
times without inducing lesions which are demonstrable with our present 
technique.1 The following bacteria have been found by numerous 
observers in the kidney and in the urine, in acute diffuse nephritis: the 
typhoid bacillus, pneumococcus, streptococcus and staphylococcus, the 
colon bacillus, and others. The Plasmodium malariae may be present in 
the kidney in large numbers.2 To what extent the kidney lesions are due 
to the presence of these organisms themselves and to what extent to 
eliminated toxins is not yet clear. 
Persistent and Advancing Lesions Following Acute Diffuse Nephritis. 
If we follow the alterations which the kidney in acute diffuse nephritis may un- 
dergo, if resolution do not occur, but the process continue, we find that in each of the 
three structural units of the kidney, the glomeruli, the tubules, and the interstitial 
tissue, with the blood-vessels, important changes take place which often lead to slight 
or to marked deformities of the organ, and to such minute changes as are in fact char- 
acteristic of what we are wont to call chronic diffuse nephritis. 
The capillaries of the tufts may become partly or wholly obliterated by a gradual 
thickening of their walls and an increase of the connective tissue between them, while 
at the same time Bowman's capsule is thickened and contracts upon the altered tuft 
(Fig. 504) with which it may unite so that the 
glomerulus may finally be represented by a small, 
dense spheroidal mass of fibrous tissue (Fig. 505). 
The interstitial tissue of the kidney may be in- 
creased in patches, most often at first near the 
glomeruli or along the interlobular veins. This 
tissue may at first be quite cellular, resembling a 
collection of small spheroidal cells or larger poly- 
hedral cells, among which new fibrillar stroma may 
develop; or there may be a more diffuse increase of 
connective-tissue cells and stroma. As this new- 
formed fibrous tissue grows less cellular it contracts, 
the tubules which it encloses are atrophied, the epi- 
thelium may undergo fatty degeneration and peel 
off or become flattened, casts may be present in the 
narrowed lumen, and the tubules may at last be 
represented by a small cluster of flattened cells with- 
out distinct tubular structure, or they may disap- 
pear altogether (Fig. 504). Such islets or masses 
of new-formed fibrous tissue enclosing variously 
altered and atrophied remnants of glomeruli and 
tubules vary greatly in size and usually merge 
gradually into less altered kidney tissue. When they are formed near the surface 
of the kidney, the shrinkage of the fibrous tissue, which is continuous with the 
inner layers of the capsule, may draw the surface inward, leaving between the irregu- 
lar depressions the areas of less altered, or otherwise altered, kidney tissue somewhat 
projecting in irregular knobs or granules. Thus arise the granular surface and the 
adhesion of the capsule which are frequent in some forms of persistent diffuse 
nephritis. 
Fig. 505.-Atrophied Glomerulus 
in Chronic Nephritis. 
The tuft is converted into a dense 
mass of fibrous tissue. 
1 See Biedl and Kraus, Arch. f. Exp. Path. u. Pnar., Bd. xxxvii., p. 1, 1896, bibliography; also v. 
Klecki, ibid., Bd. xxxix., p. 173, 1897; also Sittmann, Deut. Arch. f. klin. Med., Bd. liii., p. 323. 1894. 
See also references, page 151. 
2 For a study of malarial nephritis see Thayer, Am. Jour. Med. Sci., vol. cxvi., p. 560, 1898. 
See for the study of a case of acute malarial nephritis with large numbers of parasites in the kid- 
ney Ewing, Trans. Assn. Am. Phys., vol. xvi., p. 450, 1901 762 
THE URINARY ORGANS 
In the parts of the kidney less involved, or not at all involved in the production of 
new fibrous tissue, the tubules may undergo marked alterations. Thus the epithelium 
may be swollen and coarsely granular or fatty; it may become necrotic so that the 
nucleus fails to stain; it may, when necrotic or degenerated, peel off or disintegrate so 
that the tubules may be extensively denuded. On the other hand, the epithelium may 
remain in position but be much thinner than normal, while the lumen is largely dilated. 
This may take place by the blocking of the tubules below by desquamated cells or by 
compression of new-formed interstitial tissue. The whole tubule, not merely the 
lumen, may be dilated and irregular in shape, with well-preserved or fatty or other- 
wise altered epithelium. Casts of various forms may be present. 
Chronic Diffuse Nephritis. 
General Considerations.-We have seen that when the inflammatory 
process in the kidneys, at first acute, is protracted, both the degenerative 
and the productive lesions may become more marked and extensive. 
Thus with a preponderance now of the interstitial alterations and again 
of the degenerative or other changes in the parenchyma, the kidneys 
in a condition of chronic diffuse nephritis may present a considerable 
variety in gross as well as microscopical appearance. They are some- 
times larger than normal, as is often though not always the case when the 
parenchyma is more conspicuously involved; or smaller, as is usual when 
the interstitial lesions are widespread or advanced. 
Although there is no sharp line of separation, either clinical or mor- 
phological, to be drawn between acute and chronic diffuse nephritis, it 
is convenient to group kidney lesions in this way with the understanding 
that many intermediate forms exist, as must be the case, since, as we 
have seen, acute nephritis may pass gradually into the chronic form. 
While acute diffuse nephritis may be followed by the alterations 
which have just been summarized and which are characteristic of certain 
phases of chronic diffuse nephritis, the latter process, it should be remem- 
bered, is by no means always or usually preceded by an acute form of 
inflammation. 
In some phases of chronic diffuse nephritis, although interstitial 
alterations are present, the lesions of the tubules may be the most prom- 
inent feature; thus albuminous and fatty degeneration, disintegration, 
flattening and peeling of the epithelium, the formation of casts, the 
dilatation of the tubules, etc., may be most conspicuous. In another 
morphological group of kidneys in chronic diffuse nephritis, while there 
are many alterations in the tubules, the most marked change is the 
increase in amount and the subsequent contraction of the interstitial 
fibrous tissue with atrophy of the tubules and glomeruli and the conse- 
quent diminution in size and alteration in shape and consistence of the 
organ. Between these extremes of lesion there are all intermediate forms, 
in kidneys which are larger than normal, of normal size, or smaller than 
normal. 
In endeavoring to classify or group the lesions in chronic diffuse 
nephritis, one encounters difficulties similar to those which beset a like 
attempt in the acute forms of renal inflammation. But the difficulties 
are enhanced in the former case by the fact that the conditions under THE URINARY ORGANS 
763 
which the lesions develop are far more diverse and variable and at the 
same time are often much more obscure. 
If we leave out of sight for the moment the conditions under which 
chronic diffuse nephritis may arise and the direct excitants which with 
more or less certainty can be fixed upon as important, and confine our 
attention to morphology, it is at least convenient to place in one group 
as above indicated kidneys in which, while there may be important 
changes in the glomeruli and in the interstitial tissue, the most marked 
lesions are in the tubular epithelium. This may conveniently be called 
the parenchymatous or degenerative type of chronic diffuse nephritis. 
Fig. 506.-Chronic Diffuse Nephritis-Parenchymatous Type. 
At the left is a band of new-formed fibrous tissue with atrophy of tubules and swelling and pro- 
liferation of the capsule cells; in the central portions the tubular epithelium is disintegrating at the 
edges, while at the right the lumina of the tubules are dilated, with flattening of the epithelium. 
On the other hand, there is another large and important class of kid- 
neys which are characterized morphologically by a relatively prominent 
increase in the amount of interstitial fibrous tissue with associated destruc- 
tion by atrophy or otherwise of the tubular structures. This may be 
called the interstitial type of chronic diffuse nephritis. 
In considering this in many respects artificial grouping of persistent 
inflammatory kidney lesions, it should be remembered that while the 
parenchymatous and the interstitial types of lesion may originate as such 
and so persist, the lesion of the parenchymatous type may, as the disease 
progresses, assume the characters of the interstitial form.1 
Parenchymatous Type of Chronic Diffuse Nephritis.-This may origi- 
nate in an acute diffuse nephritis, but more frequently develops indepen- 
dently of this. As in other forms of diffuse nephritis, the tubules, the 
1 For a study of subacute and chronic nephritis see Ophuls, Arch. Int. Med., 1912, ix., 156; for a 
study of classification see Oertel, ibid., 1913, xi., 653. 764 
THE URINARY ORGANS 
glomeruli, and the interstitial tissue are more or less involved. The 
lesions are most marked in the cortex (Fig. 506), and here the epithelium 
may be swollen and coarsely granular or is often fatty. Droplets of clear 
fluid may form within the epithelium-so-called "vacuoles." The epi- 
thelium may be flattened or it may peel off or disintegrate and the cells 
and cell detritus together with leucocytes, red blood cells, and casts may 
collect in the irregular and often widened lumina. The casts may be 
hyaline or granular or epithelial, or they may be covered with leucocytes 
Fig. 507.-Chronic Diffuse Nephritis. 
Showing swelling of tuft and capsule epithelium; flattening of the tubular epithelium and slight increase 
in the interstitial tissue. 
or red blood cells. In the glomeruli, the tuft and capsule cells may 
swell and proliferate and peel off (Fig. 507); albuminous fluid which in 
specimens hardened in alcohol is represented by a granular precipitate 
may be present in the intracapsular space and in the tubules. The 
interstitial tissue may be increased in amount, usually in circumscribed 
regions, and here the enclosed tubules are atrophied. Not infrequently 
more or less extensive haemorrhages occur. 
If the disease have been of long standing the new-formed interstitial 
tissue may be present in considerable amount with much destruction of 
the tubules. The glomeruli may be compromised by the thickening of 
Bowman's capsule and the obliteration of the capillaries, so that at length THE URINARY ORGANS 
765 
the tuft and capsule may fuse and the glomeruli may be represented by 
dense fibrous nodules (Fig. 505). The growth of interstitial tissue in 
patches may, when near the surface of the organ, bind the capsule to the 
kidney so that in its removal small masses of the parenchyma may be 
stripped off, leaving a rough surface on which grayish depressed areas, 
corresponding to the interstitial growth, are intermingled with more 
projecting light or yellowish portions, in which albuminous or fatty degen- 
eration of the tubular epithelium may be marked and extensive. Very 
often the new fibrous tissue develops along the course of the interlobular 
vessels so that cylindrical or narrow, wedge-shaped areas are affected, 
extending inward from the capsule (Fig. 508). Amyloid degeneration 
Fig. 508.-Chronic Diffuse Nephritis-Parenchymatous Type. 
Showing a wedge-shaped mass of new-formed tissue extending inward from the capsule of the 
kidney, to which it is firmly attached. The tubules within the fibrous area are atrophied, while the 
tubules elsewhere show various degenerative epithelial changes. 
involving the capillary tufts, the vasa recta, and the larger arterial trunk 
is common. 
Such kidneys as have just been described present varying gross 
appearances which are dependent upon the character, extent, and dis- 
tribution of the lesions. Some are larger than normal with a thickened 
whitish or yellowish cortex. These are often called large white kidneys. 
But kidneys with essentially similar lesions are not always large, are often 
nearly normal in appearance, or may be smaller and with a cortex thinner 
than normal. If heemorrhage into the tubules or interstitial tissue be a 
marked feature of the lesion, the cortex may be reddish or mottled red 
and yellow. Such are the so-called large red kidneys. 766 
THE URINARY ORGANS 
Arterio-sclerosis and cardiac hypertrophy frequently accompany this 
type of kidney lesion. 
Interstitial Type of Chronic Diffuse Nephritis.-The type of chronic 
diffuse nephritis in which the growth of interstitial tissue is conspicuous, 
which may be called the interstitial or indurative type, apparently some- 
times represents a later phase of the parenchymatous type; or it may 
result from chronic congestion, or be associated with arterio-sclerosis; but 
it appears to be more frequently an independent process. As the new 
interstitial tissue which is formed in patches or streaks or large masses 
gradually becomes less cellular, more dense, and shrinks, the kidneys are 
usually smaller than normal and, owing to the uneven distribution of 
The capsule is thickened and adherent, especially to the dense mass of fibrous tissue at the left of 
the section in which the tubules are greatly atrophied. At the right the parenchyma is less atrophied, 
but here the lumina of the tubules are dilated, the epithelium is degenerating and flattened.. 
Fig. 509.-Chronic Diffuse Nephritis-Atrophied Kidney. 
the lesion, rough upon the surface when the thickened and adherent 
capsule is stripped off. The areas of the cortex in which the fibrous 
tissue is most abundant (Fig. 509) are grayish or translucent and depressed, 
while the parenchyma between, often fatty, projects as yellowish rounded 
knobs or granules. This condition is therefore sometimes spoken of as 
"granular atrophy," and such kidneys are often called "granular kid- 
neys" or "atrophied kidneys." The tissue is firm and resistant to the 
knife; and on section the cortex is seen to be in general thinned, often 
extremely so, some portions being much more atrophied than others. 
Small cysts of various sizes may be formed from dilatation and coales- 
cence of tubules. The cortex is usually more involved than the medulla. 
The fat with which the kidney is surrounded is often largely increased. THE URINARY ORGANS 
767 
On microscopical examination the new-formed interstitial tissue is 
sometimes in patches (Fig. 510) or streaks along the course of the inter- 
lobular vessels, with less affected regions between them. In these 
fibrous portions there may be flattening of the epithelium and various 
degrees of atrophy or complete destruction of the epithelium and the 
tubules. Between these fibrous regions, little altered tubules may be 
present, or those with granular and fatty degeneration, exfoliation, and 
disintegration of the epithelium. Various forms of casts may be present 
in the tubules; the epithelium mat be flattened with enlargement of the 
lumen. The glomeruli are variously altered; thus there may be thicken- 
ing of the capillary walls and of Bowman's capsule (Fig. 511), increase 
Fig. 510.-Chronic Diffuse Nephritis. 
Showing interstitial tissue, dense and fibrous in type, between the tubules. The epithelium is in part 
flattened; in places shows albuminous degeneration. 
and exfoliation of the tuft and capsular epithelium, or a more or less 
complete conversion of the glomerulus into a knob of dense fibrous tissue. 
Occasionally there is partial or complete atrophy of the tuft with more 
or less dilatation of the capsule. Thus small cysts are formed lined 
with flat cells and containing a homogeneous or granular fluid and 
sometimes small masses of calcium salts.1 
In advanced phases of the lesion the kidney may be very small; then 
a large part of the tissue is involved; and while the atrophy is always 
more marked in some places than in others, it is often difficult to find 
any normal structural elements.2 
Fibrous thickening of the walls of the arteries and veins of the kid- 
neys is usual in this type of chronic diffuse nephritis (Fig. 512). Amy- 
1 For a study of atrophic glomerular cysts see Beer, Amer. Jour. Med. Sci., vol. cxxvii., p. 611,1904. 
2 For a resume of views on the nature and origin of the contracted kidney see Aschoff, Cartwright 
Lectures, Arch. Int. Med., 1913, xii., 723. 768 
THE URINARY ORGANS 
loid degeneration of the vessels is not infrequent. The heart is often 
greatly hypertrophied, and general arterio-sclerosis is common.1 
Variations in Type in Chronic Diffuse Nephritis.-There are many 
variants in the two types of chronic diffuse nephritis which we have 
briefly described. It is possible to indicate in a general way morpho- 
logical appearances which are frequently present and more or less charac- 
teristic of each of the variants when the kidney lesions occur in connection 
with either gout or chronic visceral congestion or arterio-sclerosis or 
syphilis. But these variations in form cannot be further considered here. 
The diverse appearances which the kidneys present in chronic diffuse 
nephritis are, as we have seen, largely due to variations in local and 
Showing fibrous thickening of the glomerular tuft with a mass of dense fibrous interstitial tissue at 
one side (below) of the glomerulus. From an atrophied kidney. 
Fig. 511.-Chronic Diffuse Nephritis. 
general tissue vulnerability or to the rapidity and to the stage of develop- 
ment of the lesions as well as to the nature of the excitants. But acute 
inflammatory processes not infrequently supervene in kidneys which are 
the seat of slowly developed chronic processes; so that lesions typical of 
both acute and chronic nephritis are not infrequently associated. Finally 
it is evident that the grouping of the kidneys in chronic diffuse nephritis 
in accordance with the structural elements of the organ most conspic- 
uously involved is essentially artificial, since this in many cases is simply 
an indication of the period of the disease at which the patient died. 
The Excitants of Chronic Diffuse Nephritis.-The conditions under 
which chronic diffuse nephritis occurs are most diverse. Thus, judging 
from the clinical history, it may be a primary process; it may follow 
1 For an experimental study of the relationship between destruction of renal parenchyma and 
hypertrophy of the left ventricle see Passler and Heineke, Verhl. Deut. Path. Ges., Bd. ix., 1905, p. 99. THE URINARY ORGANS 
769 
infectious diseases either with or without a previous acute nephritis; it 
is not infrequently associated with gout and syphilis, with lead poisoning, 
with excessive use of alcohol, with arterio-sclerosis, with general chronic 
congestion of the viscera, with chronic suppurative and tuberculous 
processes, and appears in many cases to develop under the influence of 
dietetic excesses and protracted gastro-intestinal disorders. The nature 
of the excitants under these various con- 
ditions is most obscure. Although in 
gout, lead poisoning, alcoholism, etc., a 
fairly definite inciting toxic agency may 
be assumed, the exact mode of action of 
such extrinsic or intrinsic poisons is 
almost wholly unknown. In regard to 
other excitants of chronic diffuse nephri- 
tis, the prevalent views as to the impor- 
tance of disturbed metabolism in the 
body which may lead to the excretion 
of abnormal harmful products favor the 
conjecture that in many cases at least 
both the degenerative and the pro- 
ductive processes may be the marks of 
a persistent auto-intoxication. 
The relationship between arterio-sclerosis and chronic kidney lesions 
is not clear. Nor is it certain, assuming the initial importance of obstruc- 
tive vascular lesions, whether the new formation of fibrous tissue should 
be regarded as a primary productive inflammation or as replacement 
hyperplasia secondary to epithelial degeneration and tubular atrophy. 
The trend of opinion to-day is rather toward the belief that destructive 
changes in the epithelium are usually primary, while the new connective 
tissue formed is reparative. 
It should be remembered that in most cases the lesions of chronic 
diffuse nephritis are not independent, but are usually associated with 
those of other viscera. The significance of this association varies greatly. 
While the kidney lesions may be primary they are very often secondary 
to other visceral abnormalities, or the whole series of lesions may be 
dependent upon a common known or unknown etiological factor.1 
Fig. 512.-Chboni c Obliterating 
Endarteritis in an Atrophied Kidney 
with Chronic Diffuse Nephritis. 
Tuberculous Nephritis. 
Miliary tubercles may be present in the kidney in general acute mili- 
ary tuberculosis or in a localized tuberculous inflammation which is most 
marked elsewhere. Renal tuberculosis is, however, most often associated 
with tuberculous processes in other parts of the genito-urinary tract. It 
is not infrequently primary in the kidney and then is often unilateral. 
If only one kidney be involved the other may become the seat of chronic 
1 For studies bearing on experimental nephritis see Emerson, Arch. Int. Med., 1908, i., 485; Pearce, 
Hill and Eisenbrey, Jour. Exp. Med. xii., 196, 1910; Christian and O' Hare, Jour. Med. Res., 1913, N. S. 
xxiii, 227; and O'Hare, Arch. Int. Med., 1913, xii., 49 and 61. 770 
THE URINARY ORGANS 
diffuse nephritis with waxy degeneration of the walls of the arteries, 
Tuberculous inflammation may occur in a kidney already the seat of 
chronic inflammatory changes. 
The process is apt to begin in the mucous membrane of the pelvis and 
calyces, and extend from thence first to the pyramidal and afterward to 
the cortical portion of the kidney.1 In the mucous membrane of the 
pelvis and calyces there is a growth of new cellular tissue studded with 
tubercle granula, while the epithelial cells proliferate, become deformed, 
Fio. 513 -Tuberculous Nephritis. 
and desquamate. This process is often soon followed by cheesy degen- 
eration of the inflammatory products. Similar changes occur in the 
kidney which may become extensively involved and largely destroyed. 
The portions of the organ which do not share directly in the tuberculous 
process often develop lesions of the interstitial type of chronic diffuse 
nephritis or of suppuration. Thus the kidney may become hollowed out 
into a series of ragged cavities with caseous and disintegrating walls 
(Fig. 513). Sometimes the process comes to a standstill, and then the 
caseous portions may be infiltrated with salts of lime.2 
Syphilitic Inflammation. 
Gummata of the kidney are of occasional occurrence. A close rela- 
tionship between syphilitic arteritis and atrophied forms of chronic 
diffuse nephritis seems probable.3 
1 For a study of ascending urogenital tuberculosis see Baumgarten, Arbeiten Path. Anat. Inst. 
Tubingen, Bd. v., p. 372, 1906; also Kappis, ibid., p. 379. 
2 For a study of renal tuberculosis see Walker, Johns Hopkins Hosp. Rep., vol. xii., p. 455, 1904. 
3 For bibliography see Delamare, Gaz. des H6pitaux, May 12th, 1900. 771 
THE URINARY ORGANS 
SUPPURATIVE PYELITIS AND PYELO-NEPHRITIS. 
Suppurative Pyelitis is often associated with suppuration of the kid- 
ney substance, more frequently with a similar process in the bladder or 
ureters. But it may occur by itself. It is incited by the same micro- 
organisms as are concerned in the induction of the associated lesions in 
the kidney and bladder; in the latter case, it is most often the Bacillus 
coli communis, the Streptococcus pyogenes, and Staphylococcus pyogenes. 
The mucous membrane of the pelvis may be congested, thicker and 
more opaque than normal, and coated with pus or with patches of fibrin. 
The presence of pelvic calculi is to be regarded as a predisposing rather 
than as a direct inciting agent in suppurative pyelitis. 
Fig. 514.-Chronic Pyelo-Nephritis. 
Showing dilatation of the pelvis and calyces. 
Suppurative Ureteritis.-The conditions under which suppurative 
inflammation of the ureter occurs are similar, as is the general appearance 
of its mucous membrane, to those just indicated in the pelvis. 
Suppurative Pyelo-Nephritis with Cystitis.-In this association of 
lesions of the bladder and kidneys, which is usually initiated by the 
inflammation of the bladder, the affection of the kidneys is commonly 
bilateral. The suppurative areas in the kidney may be in the form of 
small abscesses scattered through the kidneys, or in the form of elongated 
whitish streaks or wedges between the tubules (see Fig. 499). The 
purulent foci are often surrounded by a red zone of congestion. 
The kidney tissue in the vicinity of the abscesses may be necrotic, the 
outlines of the cells being preserved but their nuclei absent or not revealed 
by the usual staining agents. 
The infective agent may traverse the ureters in passing from the 
inflamed bladder to the kidneys, leaving the mucous membrane of the 
ureter intact. 
Chronic Pyelo-Nephritis.-Chronic cystitis or calculi in the pelvis of 772 
THE URINARY ORGANS 
the kidneys may set up a chronic inflammation which involves both the 
pelvis and calyces and the kidney tissue. The mucous membrane of the 
pelvis and calyces is thickened, the epithelial layer is changed, there is a 
growth of granulation tissue beneath the epithelium, and there may be 
little polypoid outgrowths. The surface of the mucous membrane is 
coated with pus or fibrin, or the cavity of the pelvis and calyces is dilated 
and distended with purulent serum (Fig. 514). 
The kidney itself is the seat of a chronic interstitial inflammation 
with the production of new connective tissue, and sometimes of pus, 
with obliteration of the renal tubules. 
HYDRONEPHROSIS. 
Dilatation of the pelvis and calyces of the kidneys may be congenital 
and may be associated with other malformations. The pelves and caly- 
ces of both kidneys, and the ureters, are distended with urine; the bladder 
also may be distended and its wall hypertrophied. The urethra may 
be closed, or no obstruction can be demonstrated. 
In adults hydronephrosis may follow mechanical obstruction of the 
urethra or ureters (Fig. 515), from inflammation, tumors, or calculi. 
According to the position of the obstruction, either one or both kidneys 
are involved. 
The pelvis and calyces are dilated, sometimes enormously, and filled 
with urine alone or urine mixed with pus. The kidney tissue is flat- 
tened and thinned over the distended cavities. Its texture may remain 
unchanged, or there may be developed suppurative pyelo-nephritis or 
chronic diffuse nephritis. 
PERINEPHRITIC SUPPURATION. 
The loose connective tissue about the kidney may become the seat of 
suppurative inflammation. This may follow mechanical injury or may 
be secondary to suppurative or other inflammatory processes, such as 
caries of the spine, empyema, pelvic cellulitis, puerperal parametritis, 
perityphlitis, and suppurative nephritis. It may be associated with 
acute infectious diseases in children. The suppuration may extend back- 
ward through the muscles; downward into the iliac fossa, the perineum, 
the bladder, the scrotum, or the vagina; forward into the peritoneal 
cavity or the colon; or upward through the diaphragm. 
The kidney itself may be simply compressed by the abscess or become 
involved in the suppurative process. 
CYSTS IN THE KIDNEYS. 
Cysts are formed in the kidneys both during intra-uterine arid extra- 
uterine life. 
Congenital Cystic Kidneys are often striking objects. Either one or 
both kidneys may be greatly enlarged and converted into a mass of THE URINARY ORGANS 
773 
cysts (Fig. 516). The cysts are of various sizes and are separated from 
each other by fibrous septa or compressed kidney tissue. They may con- 
tain a clear yellow, acid fluid holding in solution the urinary salts; or 
the fluid is turbid and brown, and contains blood, uric-acid crystals, and 
cholesterin. The cysts are often lined with a single layer of flat, polyg- 
onal cells. Some of them seem to be formed by a dilatation of the 
tubules and of the capsules of the Malpighian bodies. As causes for such 
dilatations there may be found obliteration of the tubes in the papillte. 
Fig. 515.-Hydronephrosis. 
From obstruction of ureter. 
and stenosis of the pelvis, ureters, bladder, or urethra. Other congenital 
malformations are often associated with this. 
Cysts of the Kidney in the Adult may be single and occur in otherwise 
normal organs. There may be one or more cysts filled with clear or brown 
serum or gelatinous material (Fig. 517). These cysts do not appear to 
interfere with the function of the kidneys. 
In chronic diffuse nephritis, especially in the atrophic form, groups 
of tubes may be dilated. Apparently one or more of the larger tubes 
in the pyramids are obstructed, and this causes dilatation of a correspond- 
ing group of tubes. Such a dilatation may be moderate in size, or it 774 
THE URINARY ORGANS 
may form cysts visible to the naked eye. Very small cysts of Bowman's 
capsule may form with atrophy of the vascular tuft. 
Occasionally both kidneys are very much enlarged and converted 
into a mass of cysts containing clear or colored serum or gelatinous mate- 
rial. The nature of these cysts is uncertain; they may be congenital. 
They are sometimes associated with similar cysts in the liver.1 
Only very small portions of the kidney tissue remain, crowded between the cysts. 
Fig. 516.-Congenital Cystic Kidney. 
Small multiple cysts of the ureter, lined with flattened or cuboidal 
epithelium, are of occasional occurrence, and may be associated with 
similar cysts in the pelvis of the kidney. Such cysts in the ureter may be 
pedunculated.2 
RENAL CALCULI. 
In the kidneys of new-born children, from the first to the fourteenth 
day after birth, the large tubes of the pyramids often contain small 
brownish, rounded bodies composed of the urates of ammonium and 
sodium. Similar masses may also be present in the calyces and pelves. 
In still-born children these masses are usually absent. The carbonate 
1 For a study of cystic kidney with extensive bibl. see Ritchie, Laboratory Reports, Royal Coll, 
of Phys., Edinburgh, vol. iv.; also Braunwarth, Virch. Arch., Bd. clxxxvi., p. 341, 1906, bibl. 
2 For a resume of cysts of the ureter with bibl. see Harris, Am. Med., vol. iii., p. 731, 1902. THE URINARY ORGANS 
775 
Fig. 517.-Single Cyst of the Kidney. 
Fig. 518.-Calculus in the Pelvis of the Kidney. 776 
THE URINARY ORGANS 
and phosphate of lime may be deposited in the tubes of the pyramids, in 
the form of white linear masses, in the kidneys of old persons and of those 
who have suffered from destructive diseases of the bones. 
Urate of soda in the form of acicular crystals is deposited both in the 
tubes and stroma of the kidneys of gouty persons. 
Concretions of the urinary salts are often formed in the pelves of the 
kidneys. They may remain there as rounded masses (Fig. 518), or they 
may attain a large size and be moulded into the shape of the pelvis and 
calyces. Smaller calculi may pass into the ureter and either become 
impacted there or pass through it into the bladder. The most common 
form of calculus is that composed of uric acid. But they may also be 
formed of uric acid with a shell of 
oxalate of lime, or of oxalate of 
lime alone, or of the phosphates, or 
of cystin.1 
The most serious result of the 
presence of these calculi is the oc- 
clusion of the ureters or the incite- 
ment of pyelo-nephritis. 
TUMORS. 
Small fibromata, lipomata, myo- 
mata, and angiomata may occur in 
the kidney and with the exception 
of the fibromata are most common 
in the cortical portion. Papilloma 
may form in the mucous membrane 
of the pelvis. Sarcoma, myxo-sar- 
coma, and endothelioma, often of 
large size, may develop in the kid- 
ney. These tumors are frequently soft and vascular and are prone to 
haemorrhage. Primary sarcoma of the kidney is common in children. 
Secondary sarcoma of the kidney is not rare. 
There are mixed tumors of the kidney often occurring in childhood 
and having a sarcomatous and adenomatous character; or they may 
contain mucous or elastic or muscle tissue with structures suggesting 
glomeruli. These tumors are of doubtful origin.2 
Adenoma is of frequent occurrence in the kidneys. It usually origi- 
nates in the cortex and may be invisible to the naked eye (Fig. 519), or, 
in the form of a well-defined, circumscribed nodule (Figs. 520 and 521), 
it may invade the medulla or largely replace the kidney. The adeno- 
mata are usually light in color save when very vascular with haemorrhage, 
and they may be separated from the kidney structure by a fibrous capsule. 
Such tumors are not rare in children.3 
Fig. 519.-Small Adenoma of Kidney. 
Situated in the cortex. 
1 For a study of the composition of renal calculi see Kahn, Arch. Int. Med., 1913, xi., 92. 
2 See for a study of the mixed tumors of the kidney Hedren, Ziegler's Beitr., Bd. xl., p. i, 1906, 
bibl. 
3 See Engelken, Ziegler's Beitr., Bd. xxvi. p. 320, 1899, bibl. THE URINARY ORGANS 
777 
There are two principal varieties of these tumors, the papillary and 
the alveolar, which are, however, closely related. • 
1. Papillary Adenoma.-There are cavities of different sizes, from the 
walls of which spring branching tufts covered with cylindrical or cuboidal 
epithelium (Fig. 522). These tufts 
nearly fill the cavities. 
2. AIveolar Adenoma.-There is 
a connective-tissue framework en- 
closing small round, oval, or tubu- 
lar alveoli, lined or filled with cells 
(Fig. 523). The cells are usually 
large and may be cylindrical, cu- 
boidal, or polyhedral, and may be 
pigmented in a manner similar to 
the cells of the adrenals. 
Fatty degeneration of the epi- 
thelium may be excessive, and gly- 
cogen may form in the cells of these 
tumors. The stroma may be pres- 
ent in considerable quantity, the 
blood-vessels may form conspicuous 
features, or a cystic distention of the 
alveoli may occur. Large areas 
may become necrotic. 
Many of these tumors appear 
to have developed from adrenal 
cells astray in the kidneys, and are 
then called hypernephroma (Figs. 
520 and 524). Metastases of hy- 
pernephroma are not uncommon 
in the liver, lung, intestines, retro- 
peritoneal and other lymph-nodes 
(Fig. 525), bone and muscle. 
The relationship between true 
kidney adenomata, adenomata pos- 
sibly of adrenal elements, and 
tumors regarded by some as endotheliomata or angiosarcomata, is not 
yet clear. The view that the hypernephromata are of renal and not of 
adrenal origin is gaining ground.1 
Primary carcinoma of the kidney is rare, adenoma being frequently 
mistaken for it. Secondary carcinoma is not infrequent.2 
Fig. 520.-Adenoma of the Kidney. 
Hypernephroma.) 
A tumor of the kidney formed from 
aberrant adrenal tissue. 
iIpsen, Ziegler's Beitr., 1912, liv., 233; and Wilson and Willis, Jour. Med. Res., 1911, N. S. 
xix., 73. 
2 For a careful study of tumors and other growths in the kidney see Kelynack, "Renal Growths," 
1898, bibl.; also ref. to bibl. Busse, Virchow's Arch., Bd. clvii., pp. 346, 377, 1898. For a statistical 
study of malignant tumors of the kidney in children see Oshima, Wiener klin. Woch., p. 93, 1907. 778 
THE URINARY ORGANS 
Fig 521.-Adenoma of the Kidney. 
Showing encapsulation of the nodules. 
Fig. 522.-Adenoma of the Kilney 
Papillary variety. THE URINARY ORGANS 
779 
Fig 523.-Adenoma of the Kidney. 
Alveolar variety. 
Fig. 524.-Hypernephroma. 
The cells filling the alveoli are in part transparent, resembling those of the adrenal. 780 
THE URINARY ORGANS 
Fig. 525.-Hypernephroma. 
Metastasis in lymph-node of arm. Atypical form with multinucleated cells. 
Fig 526.-Diverticula of the Bladder. THE URINARY ORGANS 
781 
PARASITES. 
Echinococcus, in its ordinary form of mother and daughter cysts, is 
sometimes found in the kidney. The cysts may open into the pelvis of 
the kidney, into the pleura, or through the wall of the abdomen. 
Cysticercus cellulosae is of very rare occurrence. Filaria sanguinis 
hominis is found in the arteries, veins, lymphatics, and stroma, and may 
pass into the urine. Strongylus gigas has been found several times in the 
pelvis of the kidney. 
The Urinary Bladder. 
Malformations. 
Absence of the bladder is of rare occurrence. The bladder may be very small, 
the urine passing almost directly into the urethra. The bladder may be separated 
into an upper and a lower portion by a circular constriction. It may be completely 
divided by a vertical septum into two lateral portions. Diverticula of the wall of the 
bladder are sometimes found in new- 
born children. Partial or complete 
closure of the neck of the bladder may 
occur. This may lead to hydronephro- 
sis, or the urine may be discharged 
through the open urachus. 
Exstroversion of the bladder is 
one of the most frequent malform- 
ations, and may occur in either sex. 
It presents several varieties: 
1. The umbilicus is lower down 
than usual, the pubic bones are not 
united at the symphysis, the pelvis is 
wider and shallower than it should be. 
Between the umbilicus and pubes 
the abdominal wall is wanting. In its 
place is a projecting, ovoid mass of mu- 
cous membrane, in which may be seen 
the openings of the ureters. The penis 
is usually rudimentary; the urethra is 
an open fissure (epispadias); the clitoris 
may be separated into two halves. 
The ureters usually open normally; 
sometimes their openings are displaced 
or are multiple. They may be dilated. 
2. There may be a fissure in the 
abdominal wall, filled up by the per- 
fectly formed bladder. 
3. The umbilicus may be well 
formed, and there is a portion of ab- 
dominal wall between it and the exstro- 
phied bladder. 
4. The external genitals and ure- 
thra may be well formed, and the symphysis pubis united, while only the bladder is 
fissured. 
5. The genitals, urethra, and symphysis may be well formed, the bladder closed 
except at the upper part of its anterior wall. The bladder is entirely or in part in- 
verted and pushed through the opening in the abdominal wall. 
Fig. 527.-Hypertrophy of the Wall of 
the Bladder. 782 
THE URINARY ORGANS 
The urachus normally remains as a very small canal, 5 to 7 cm. long, with a 
small opening into the bladder, or entirely closed at that point. If there is a congen- 
ital obstruction to the flow of urine through the urethra, the urachus may remain open 
and the urine pass through it. Or the bladder may present, even in the adult, a 
slender distention reaching close to the umbilicus as the result of a persistent urachus. 
Changes in Size and Position. 
Dilatation.-This may be general or partial, leading to the formation of 
diverticula. 
General dilatation of the bladder is produced by the accumulation of urine in 
consequence of some mechanical obstacle to its escape, or of paralysis of the muscular 
walls of the organ. The dilatation is usually uniform and may be very great, so that 
the bladder may reach to the umbilicus. If the walls of the bladder are paralyzed, or 
the obstruction occurs suddenly or is complete, the wall of the bladder is thinned. 
When an incomplete obstruction exists for some time the walls of the bladder are apt 
to hypertrophy, so that, although the bladder is larger than normal, the walls may not 
only be of the usual thickness, but even very much thicker. In the foetus dilatation 
of the bladder may reach such a size as to interfere with delivery. 
The retained urine in dilated bladders is liable to decomposition, from the presence 
of bacteria, and this may lead to inflammation or gangrene of the mucous membrane. 
Diverticula of the bladder may be produced by the pouching out of circumscribed 
portions of the wall of the bladder, the wall of the pouch containing all the layers of 
the bladder wall. More frequently, however, they are produced by a protrusion of the 
mucous membrane between hypertrophied bundles of muscle fibre. They may be 
very small (Fig. 526), or they may be as large as a child's head. They may communi- 
cate with the bladder by a large or small opening. The decomposition of stagnant 
urine in diverticula is apt to induce inflammation. Calculi may be formed in them or 
may slip into them from the bladder. 
Hypertrophy of the muscular coat of the bladder is usually due to mechanical 
obstructions to the outflow of urine, such as stricture of the urethra, enlarged prostate, 
calculi, new growths, etc. The muscular coat is thickened uniformly or assumes a 
trabeculated appearance (Fig. 527). The organ retains its normal capacity, or is 
dilated, or becomes smaller. The mucous membrane is frequently the seat of chronic 
or acute inflammation. Dilatation of the ureters and hydronephrosis frequently 
accompany this condition. 
Hernial of the bladder sometimes accompany intestinal herniae through the ingui- 
nal and crural canals and the foramen ovale. The changes in position of the bladder, 
produced by displacements of the vagina and uterus, will be mentioned with the 
lesions of those organs. 
In the female the base of the bladder may press downward, causing protrusion of 
the vaginal wall (vaginal cystocele'); or there may be inversion and prolapse of the 
bladder through the dilated urethra. 
W OU NDS RUPTURE PERFORATION. 
Penetrating wounds of the bladder may permit escape of urine into 
the abdominal cavity, or infiltration into the surrounding connective 
tissue or permanent fistulae. Such wounds are always serious and fre- 
quently fatal, owing chiefly to the severe and often gangrenous inflam- 
mation which decomposing urine sets up in the connective tissue, or to 
the peritonitis induced by the same cause. 
Rupture of the bladder may be produced by severe blows and falls 
when the bladder contains urine. More rarely rupture takes place from 
overdistention. Death may occur from rupture of the bladder with 
escape of urine into the peritoneal cavity, without evidences of peritonitis. THE URINARY ORGANS 
783 
Perforations of the bladder may be due to ulceration and gangrene, 
to abscesses from without, and to cancerous ulceration from the adjoin- 
ing organs. Fractures of the pelvic bones may be accompanied by 
laceration of the bladder. Perforations of the bladder may lead to the 
establishment of fistulae, communicating with the rectum, vagina, uterus, 
or opening externally. 
DISTURBANCES OF CIRCULATION. 
Hyperaemia.-Aside from active hyperaemia of the mucous membrane 
in acute inflammation, the bladder is not infrequently the seat of chronic 
congestion from obstruction to the venous circulation. Under these 
conditions there may be- chronic catarrhal inflammation, or a marked 
dilatation of the veins (vesical haemorrhoids), which may give rise to 
haemorrhage or to obstruction of the opening of the ureters. 
Haemorrhage.-Extensive haemorrhages into the bladder are com- 
monly due to injury or to the presence of calculi or tumors. Small haem- 
orrhages into the substance of the mucous membrane may accompany 
inflammation, the haemorrhagic diathesis, scurvy, purpura, smallpox, 
etc. If the haemorrhage is considerable and occurs rapidly in an empty 
bladder, a clot is apt to form; but when the blood mixes with urine as it 
is extravasated it more commonly remains liquid and is discharged as a 
reddish brown fluid. 
There are exfoliation of epithelium and emigration of leucocytes from the submucosa. 
Fig. 528.--Acute Catarrhal Cystitis 
INFLAMMATION. (Cystitis.) 
Acute Catarrhal and Exudative Cystitis.-This may be incited by the 
presence of urine which has decomposed under the influence of bacteria; 
by cantharides or other drugs; by the presence of foreign bodies and 
calculi; or it may be due to an extension of gonorrhoeal urethritis or 
vaginitis; or it may occur with acute general infectious diseases. The 
mucous membrane is swollen and congested, although these alterations 
may not be very evident after death. There may be ecchymosis: the 
epithelium is granular and may proliferate and peel off. Leucocytes 
may infiltrate the submucosa and pass out between the epithelial cells 784 
THE URINARY ORGANS 
(Fig. 528). Mixed with the urine there may be shreds of mucus, pus cells, 
epithelial cells of various shapes, usually more or less swollen and granu- 
lar, or fragments of such cells; red blood cells, bacteria, and various 
urinary crystals; abscesses may form in the mucous membrane; or there 
may be phlegmonous inflammation in the submucosa and muscularis of 
the bladder with formation of abscesses. Thus perforations and fistulae 
may occur. Resolution may take place after acute catarrhal and exu- 
dative cystitis, but the inflammation very frequently assumes a chronic 
character. 
Chronic Cystitis.-In this form the mucous membrane may be swollen, 
succulent, grayish, or mottled with spots of congestion or extravasation, 
and covered with a layer of mucus and pus. Microscopically the mem- 
brane may be more or less infiltrated with pus cells, and pus may be 
Fig. 529.-Hyperplasia of the Bladder Epithelium. 
The hyperplastic epithelium is transparent and, dipping into the submucosa, forms gland-like structures. 
constantly produced and thrown off into the urine. Later the mucous 
membrane may become thickened either diffusely or in the form of tufts 
or polypi. In some cases it becomes atrophied. Owing to decomposi- 
tion of the haemoglobin in the extravasated blood the mucosa may 
become pigmented, brown, or slate-colored. The mucous membrane 
frequently becomes eroded, especially on the most elevated portions, or 
deep ulcerations may occur. The muscular coats may become paralyzed 
and the bladder dilated; or the submucosa or the muscularis, or both, 
may become hypertrophied. The mucous membrane may become 
encrusted with urinary salts. 
In another class of cases the inflammation assumes a necrotic charac- 
ter. Larger and smaller shreds and patches of the mucosa die, become 
brown or gray in color, loosen or peel off, and become mixed with the 
urine and exudations. The gangrenous process may extend to all the THE URINARY ORGANS 
785 
coats of the bladder, so that perforation and fatal peritonitis may occur. 
The gangrenous form of cystitis is more apt to occur in paralytics. 
In still another class of cases the inflammation is suppurative. The 
submucosa, the intermuscular connective tissue, and the adjacent parts 
become infiltrated with pus, either diffusely or in the form of larger and 
smaller abscesses, which may open externally or internally, forming deep 
ulcers. In all these cases the inflammation may extend to the ureters 
and kidneys; it may skip the ureters and involve the kidneys. 
The small nodules of lymphoid tissue in the mucous membrane of 
the bladder, especially near the neck, may become enlarged and promi- 
nent in cystitis, and may then be mistaken for miliary tubercles (nodular 
cystitis). 
Hyperplasia of the epithelium of the bladder sometimes occurs in 
chronic cystitis and under other conditions. This may be diffuse or cir- 
cumscribed and the epithelium may assume an epidermal character. 
Thus masses of transparent epidermis-like cells may lie between papillary 
projections of the submucosa, forming structures which resemble glands 
(see Fig. 529), or layers of flattened epithelium may cover or peel from 
the surface (see Fig. 530).1 
Fig. 530.-Hyperplasia of the Bladder Epithelium. 
The epithelium has assumed the squamous type and is exfoliating. 
A few cases have been described in which scattered over the mucous 
membrane of the bladder are small thickened areas, from two to fifteen 
millimetres in diameter, usually surrounded by a hypersemic zone, and 
frequently ulcerated. These areas of chronic inflammatory thickening 
are formed by hyperplasia of the connective tissue with small-cell infil- 
tration and by peculiar large cells which appear to be phagocytes con- 
taining red blood cells, fragments of other cells, bacteria, etc. The 
nature of this lesion is not yet clear. It has been called malakoplakie and 
cystitis en plaque.2 
Croupous Cystitis.-In connection with any of the above lesions the 
mucous membrane of the bladder may be covered, in patches or some- 
times over a considerable portion of its surface, with a layer of fibrin, 
1 For a study of regeneration in mucous membrane of the bladder see Lasio, Virch. Arch., Bd. 
clxxviii., p. 65, 1904. 
2 See for a description and discussion of this lesion Landsteiner and Stoerk, Ziegler's Beitr., Bd. 
xxxvi., p. 131, 1904. 786 
THE URINARY ORGANS 
either granular or fibrillar, enclosing pus and epithelial cells and bacteria. 
The mucosa may be infiltrated with fibrin. 
This form of inflammation may occur in connection with severe 
infectious diseases-measles, diphtheria, scarlatina, typhoid fever; in 
connection with similar inflammation of the external genitals, in puer- 
peral fever, noma, and sometimes in the presence of foreign bodies. It 
rarely occurs independently. 
In the so-called emphysematous cystitis, due to the presence of Bacil- 
lus aerogenes capsulatus, larger and smaller gas blebs may be present in 
the mucosa and underlying tissue.1 
The most common micro-organisms which act as excitants of acute 
catarrhal and exudative cystitis are Bacillus coli communis, Streptococ- 
cus pyogenes, and Staphylococcus pyogenes, the gonococcus and typhoid 
bacillus,2 Bacillus proteus, and Bacillus aerogenes capsulatus. Many 
other forms are of occasional occurrence.3 
Tuberculous Cystitis.-There may at first be miliary tubercles formed 
in the submucosa. By the coalescence of these and the degeneration of 
tissue about them, ulcers are formed, and it is most frequently in the 
ulcerative stage that the lesion is seen. The ulcers, which may be large 
or small, are usually most abundant at the base of the organ. Their 
edges may be cheesy, and miliary tubercles in greater or smaller num- 
bers are usually found in the mucosa about them. Not infrequently 
large shreds of tissue are loosened and cast off. The mucosa about the 
ulcers is apt to be infiltrated with small spheroidal cells. Tubercle 
bacilli are present in many of the tubercles and in the edges and base of 
the ulcers, and may be found in the urine. Catarrhal inflammation is 
a very constant accompaniment of this lesion. Tuberculous cystitis may 
occur in connection with tuberculous inflammation of the lungs and 
intestines, or of the kidney, uterus, prostate, etc. 
TUMORS. 
Small nodular fibromata may form in the submucosa. 
Aside from the polypoid thickenings of the mucosa occurring in 
chronic cystitis, soft vascular papillomata are of frequent occurrence. 
These tumors vary in size from that of a pea to that of a pigeon's egg or 
larger. They consist of a fibrous, often very vascular stroma, and are 
covered on the surface with numerous small, closely set, villous projec- 
tions, over which are irregular layers of elongated or cylindrical cells 
(Fig. 531). These tumors are very liable to bleed, are often accompanied 
by vesical catarrh, and may be covered by a precipitate of urinary salts. 
The epithelium is liable to peel off from the surface of the villi and 
appear in the urine. Sarcoma of the bladder has been described, but is 
rare.4 
1 See for bibliography Kedrowsky, Centralbl. f. Path., Bd. ix., p. 817, 1898. 
2 See Curschmann, Miinchener med. Wochenschr., Oct. 16th, 1900, bibl. 
3 For a study of bacteria of urinary passages see Faltin, Cbl. f. d. Kr. d. Ham- u. Sex.- Org., Bd. 
xiii., 1902, p. 130, bibl. 
4 See Wilder, Am. Jour. Med. Sci., vol. cxxix., p. 63, 1903. THE URINARY ORGANS 
787 
Fig. 531.-Papilloma of the Bladder. 
Fig. 532.-Carcinoma of the Bladder. 788 
THE URINARY ORGANS 
Myoma, adenoma, and angioma are recorded. 
Carcinoma.-Carcinoma of the bladder is most frequently secondary, 
and is then rarely due to metastasis, but to an extension of the growth 
from neighboring parts, as the uterus, vagina, or rectum. 
Primary carcinoma of the bladder may occur: 
1. As a diffuse scirrhous infiltration of the entire wall of the bladder, 
usually with ulcerations of its inner surface. 
2. As a circumscribed nodule (Fig. 532) which grows inward and out- 
ward, ulcerating on its inner surface, and sometimes producing perfora- 
tions. 
Fig. 533.-Papillary Carcinoma of the Bladder. 
3. As a villous or papillomatous growth. The tumor grows from one or 
more points of the inner surface of the bladder. It is formed of tubular 
follicles lined with epithelium (Fig. 533), while on its surface are tufts 
covered with cylindrical epithelium. The new growth may involve 
the entire thickness of the wall of the bladder. 
4. A few cases of carcinoma have been described in which the stroma 
contained a varying quantity of smooth muscle tissue.1 
Cysts.-Dermoid cysts of the wall of the bladder have been described, 
but are rare.2 Small cysts with serous contents sometimes occur in the 
1 For study of carcinoma of the ureter see Metcalf and Safford, Am. Jour. Med. Sci.t vol. cxxix., 
p.50, 1905. 
2 See case by Block and Hall, Am. Jour. Med. Sci., vol. cxxix., p 651, 1905. THE URINARY ORGANS 
789 
mucous membrane; a part of them, at least, are believed to be due to 
faulty embryonal development. 
PARASITES, FOREIGN BODIES, AND CALCULI. 
Among the animal parasites occasionally found in the bladder may 
be mentioned Echinococcus, Distoma haematobium, Filaria sanguinis, 
Ascarides, and Oxyurides. 
A great variety of foreign bodies may be found in the bladder, par- 
ticularly in the female. If their stay is long they are apt to become 
encrusted with urinary salts. 
Calculi. 
Vesical calculi may occur singly or in great numbers, and vary greatly in size, 
ranging from small, sand-like particles up to masses four or five inches in diameter; 
but the usual range is from the size of a pea to that of a hen's egg. They are usually 
oval, spheroidal, or elongated; or, when several are present, they are apt to be faceted. 
The surface may be smooth or rough. They are usually more or less distinctly lamel- 
lated, and are frequently formed around a central body called a nucleus, which may 
Showing lamellations indicating successive depositions of different texture and composition. 
Fig. 534.-Vesical Calculus. 
either be formed of urinary salts or some foreign body. Their most common con- 
stituents are phosphates, uric acid, and urates, and calcium oxalate, or various combina- 
tions of these. 
Uric-acid Calculi.-These are the most common of vesical calculi. In the form 
of small brownish red, crystalline aggregations they may be passed as "gravel." The 
larger uric-acid calculi are not commonly of very great size, are frequently finely 
nodulated on the surface, but may be smooth. The color varies from light yellow to 
dark reddish brown; they are usually dense and lamellated. 790 
THE URINARY ORGANS 
Calculi Formed of Urates.-Calculi composed of pure urates are rare, these 
salts being more commonly combined with uric acid and the phosphates to form the 
complex calculi. Sodium urate, in the form of small spined, more or less globular 
crystalline masses, forms one of the varieties of "gravel." 
Phosphatic Calculi.-Pure calcium-phosphate calculi are rarely found as whitish, 
usually smooth, and small lamellated concretions. 
Mixed or Triple Phosphate calculi are common, and frequently attain large 
size. These calculi are sometimes pure, but the deposit is more frequently associated 
with other salts, either as encrusting or intercalated lamellae. Triple-phosphate 
calculi are usually rough on the surface, of grayish white color, lamellated, and fre- 
quently very friable (Fig. 534). 
Calcium-caiubonate Calculi.-Small gray or white, hard, and usually smooth 
calculi of pure calcium carbonate occur rarely. Calcium carbonate is sometimes passed 
as gravel in the form of minute spheroidal bodies, either singly or in clusters. 
Calcium-oxalate calculi (mulberry calculi) are comparatively common, either pure 
or in combination with uric acid or the phosphates. Calcium oxalate may occur 
in the form of very small, hard, smooth concretions, or as larger, heavy, hard, finely or 
coarsely nodulated brown or blackish lamellated masses. The nucleus or some of the 
lamellae, or both, are often composed of uric acid. 
Cystin Calculi are usually ovoidal in shape, of waxy consistence, of clear or 
brownish or greenish yellow color, with mammillated surface and crystalline fracture. 
Cystin may be associated in a variety of ways with other calculi. 
Xanthin Calculi, which are very rare, are usually of moderate size, smooth, of a 
cinnamon or cinnabar-red color, lamellated, and oval or flattened in shape. 
Solid masses of fibrin and blood sometimes occur in the bladder, and may exist as 
independent structures, or form nuclei for the deposit of urinary salts. 
For a detailed account of calculi, the conditions under which they form, modes of 
analysis, etc., we refer to special works on this subject. 
The Urethra. 
Malformations. 
Some of the malformations of the urethra are described with those of the penis. 
The urethra may be impervious or may open at the root of the penis. More com- 
monly there is partial obliteration or stricture of some part of the canal. The entire 
urethra may be dilated into a sac. 
There may be a canal on the dorsum of the penis, formed by the fusion of the sper- 
matic cords, and opening in the glans above the urethra. 
There may be two or more openings of the urethra. The canal may be dislocated 
so as to open in the inguinal region. 
A number of cases have been reported in which a valve in the urethra has led to 
hypertrophy of the bladder, dilatation of the ureters, and hydronephrosis. 
Owing to its narrowness, greater length, and peculiar connections with the internal 
generative organs, the male urethra is much more liable to disease than the female. 
Changes in Size and Position. 
Dilatation of the urethra may be produced by strictures, or by calculi or other 
bodies fixed in its lumen. The dilatations are fusiform or sacculated in shape, and 
may reach the size of an orange or be even larger. 
Strictures of the urethra are usually due to inflammation of its walls. 
The stricture may be temporary, and due to a diffuse inflammatory swelling of the 
mucous membrane, or to the raising of the relaxed membrane into a fold or pocket. 
Permanent strictures are produced by structural changes in the walls of the urethra. 
1. The mucous membrane and submucous tissue become thickened in inflamma- THE URINARY ORGANS 
791 
tion or as the result of injury and the new-formed fibrous tissue which contracts and 
narrows the canal. 
2. Ulceration of the mucous membrane leaves cicatricial tissue, which contracts, 
and also produces adhesions and bands of fibrous tissue (Fig. 535). 
3. There is fibrous induration of the corpus spongiosum and consequent constric- 
tion of the urethra. 
The most frequent position of strictures is at the junction of the membranous and 
spongy portions of the urethra, or close to this point. They also occur at the fossa 
navicularis and meatus, but more frequently in the prostatic portion. There may be 
one stricture or several. The consequences of stricture are dilatation of the urethra, 
Fig. 535.-Stricture of the Male Urethra. 
the bladder, and the ureters, and hydronephrosis; inflammation and ulceration of the 
urethra behind the stricture, with perforation, infiltration of urine, or the formation of 
fistul®. 
The urethra may also be obstructed by folds of the mucous membrane; by muscular 
valves at the neck of the bladder; by wounds; by polypi and swollen glands; by new 
growths; by changes in the prostate and perineum; by calculi, mucus, blood, and 
echinococci coming from the bladder; by foreign bodies introduced from without. 
Prolapse and inversion of the mucous membrane occur occasionally in young 
girls and women. There is a bluish-red swelling, from the size of a pea to that of a 
walnut, at the meatus. In the male, invagination of the mucous membrane of the 
urethra has been seen after injuries of the perineum. 
INJURIES PERFORATION HEMORRHAGES. 
Wounds of the urethra are produced in many ways, but most com- 
monly by catheters and bougies. The wounds may cicatrize, or there 
may be infiltration of urine or the formation of fistulae or false passages. 
Ruptures of the urethra are produced by severe contusions and by 
fracture of the pelvic bones. Extravasations of blood and urine, and 
gangrenous inflammation of the surrounding soft parts, are the ordinary 
results. Urethral varices in the female may lead to haemorrhage. 
Ulceration and perforation of the urethra may lead to the formation 
of fistulae, which open in various directions through the skin. 
INFLAMMATION. (Urethritis.) 
Catarrhal Urethritis may be due to the action of chemical irritants, and 
to the extension to the urethra of inflammation from other parts; but its 792 
THE URINARY ORGANS 
most frequent excitant is the gonococcus. In its acute form it involves 
either a portion or the whole of the urethra. The mucous membrane 
is red, swollen, and covered with muco-pus. The epithelium may be 
loosened or exfoliated; pus cells are present in the submucosa between 
the epithelial cells. The gonococcus is present usually in considerable 
numbers in the exudate, both free and in the pus cells. It may pene- 
trate between the epithelial cells. 
Resolution may follow acute gonorrhoeal urethritis. But the condi- 
tion may become chronic and then is often confined to the posterior por- 
tions of the urethra. Here the gonococcus may persist for a long time 
and may be mingled with the exudate, which is now less purulent and 
consists very largely of mucus which in thread-like forms may be passed 
with the urine. 
Chronic Inflammation of the urethra may exist for a long time with 
the production of a muco-purulent exudation, but without the occur- 
rence of marked structural lesions. In other cases it leads to ulceration, 
to fibrous induration of the wall of the canal (see Fig. 535), to indura- 
tion and swelling of the mucous follicles, to polypoid thickenings of the 
mucous membrane. 
The inflammation may extend to the fibrous wall of the urethra, the 
corpora spongiosa and cavernosa. This may result in the formation of 
new connective tissue or of abscesses, especially near the fossa navicu- 
laris. There may be involvement of the bladder, the glands of Cowper, 
the prostate, the spermatic cord, and the testicles. The inguinal glands 
also may be swollen and inflamed, and the lymphatic vessels on the 
dorsum of the penis may be involved in the same process. 
Membranous Inflammation is sometimes seen in children. Fibrinous 
casts of a small or large portion of the canal may be formed. 
Tuberculous Inflammation occurs rarely in the mucous membrane of 
the urethra in connection with tuberculous inflammation of the bladder, 
prostate, or testicles. 
Syphilitic Ulcers may be situated at the meatus or as far back as the 
fossa navicularis. They are apt to produce strictures. 
TUMORS. 
Aside from the polypoid outgrowths from the mucous membrane of 
the urethra as the result of chronic inflammation, fibrous polyps may 
occur congenitally, or polyps containing glandular structures or cysts 
rarely occur. Carcinoma may occur as a result of local extension from 
adjacent organs or metastasis from the bladder. 
Cysts may occur in the membrane as a result of the dilatation of the 
mucous glands. Circumscribed masses of dilated veins occasionally 
occur in the urethra, forming the so-called urethral haemorrhoids. 
The sinus pocularis may be dilated in children by the retention of its 
secretion, so as to form a mass which may obstruct the exit of urine and 
lead to hypertrophy of the bladder and dilatation of the ureters. CHAPTER X. 
THE REPRODUCTIVE ORGANS OF THE FEMALE. 
The Vulva. 
Malformations. 
The external genitals may be entirely absent or imperfectly developed. The 
fissure between the labia may be unformed, or the labia may grow together, with or 
without obstruction of the urethra. The clitoris and nymphse may be abnormally 
large, or the nymphse may be increased in number. The clitoris may be abnormally 
long; at the same time the vagina is narrow, the uterus small and undeveloped or 
malformed; the ovaries are small, sometimes situated in the labia; the mammae small, 
and the body is of a masculine character. Such cases are sometimes called pseudo- 
hermaphrodites. The clitoris may be perforated by the urethra or may be cleft and 
apparently double. 
The hymen is subject to various anomalies. It may be entirely absent. The 
opening may be very large or in unusual places; there may be several openings; the 
free edge may be beset with papillary projections; there may be no opening at all. 
HEMORRHAGE, HYPEREMIA, ETC. 
Haemorrhage may take place from wounds or ulcers of the vulva, but 
the most important form of haemorrhage is that which occurs in the con- 
nective tissue of the labia majora. This may occur during labor or 
result from external injury. One of the labia may be much swollen and 
distended by the extravasated blood. The blood may be gradually 
absorbed, or it may decompose with suppuration or gangrene of the 
surrounding tissue. 
Varicose Veins in the labia are not infrequent. (Edema of the labia 
majora may occur in pregnancy or in labor. It frequently accompanies 
disturbances of the venous circulation, as in certain heart and lung dis- 
eases; or it may occur in chronic diffuse nephritis or other wasting dis- 
eases; or as a result of thrombosis or other disturbances of circulation in 
the uterine or perivaginal venous plexuses. The latter may be excessive, 
leading to the transudation of fluid through the skin, to the formation of 
vesicles, or superficial erosion, or even of gangrene. 
INFLAMMATION. (Vulvitis.) 
The skin, mucous membrane, connective tissue, and glands of the 
vulva may be the seat of inflammation. 
Acute Catarrhal Inflammation of the mucous membrane may be 
induced by a variety of substances, but is most frequently due to gonor- 
rhoeal infection. The mucous membrane is swollen and red and covered 
793 794 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
with a muco-purulent exudate. The labia may be swollen, the glands 
of Bartholin are liable to be involved, and abscesses of the labia may be 
developed. 
Chronic Catarrhal Inflammation may lead to superficial or deep ulcera- 
tion of the mucous membrane, or to papillary outgrowths, or to thickening 
of the labia. Suppurative inflammation of the tissue of the labia may 
occur with a similar process in neighboring parts. Erysipelatous Inflam- 
mation of the skin of the vulva is frequent in young children. In adults 
it is less common. Inflammation of the vulvo-vaginal glands may be 
acute and lead to abscesses, or chronic and produce induration of the 
gland. 
Gangrene may follow erysipelatous inflammation, or occur after par- 
turition; it may accompany severe exhausting and infectious diseases. 
It may follow bruises or other injuries. In some forms, such as those 
known as noma and hospital gangrene, the destruction of tissue proceeds 
with extreme rapidity.1 
Membranous Inflammation may occur, with or without diphtheria 
and a similar lesion of the fauces or elsewhere, and is frequently associ- 
ated with gangrene. 
Tuberculous Inflammation, usually with ulceration, occasionally 
occurs in the vulva. 
Syphilitic Inflammation and ulceration are of frequent occurrence on 
the vulva, particularly on the mucous surfaces, and may lead to consid- 
erable destruction of tissue and cicatricial contractions. 
In one form, the so-called mucous patch, there is an infiltration of the 
papillary layers of the skin or mucous membrane with variously shaped 
cells and fluid, so that the tissue has a gelatinous appearance. In other 
cases there is an hypertrophy of the papillae, so that larger and smaller 
wart-like excrescences are formed. This is called the pointed condyloma. 
TUMORS. 
Fibroma.-Circumscribed fibrous tumors are found in the connective 
tissue of the labia, mons veneris, perineum, clitoris, and entrance to the 
vagina. They may attain a large size, and, attached only by a pedicle, 
may hang far down between the legs. The skin is usually movable over 
the surface of these tumors. 
Fibroma diffusum (elephantiasis).-This usually involves the clitoris 
or the labia, or both, and may extend to surrounding parts of the skin. 
It consists essentially of a diffuse hypertrophy of the skin and subcuta- 
neous tissue, with or without involvement of the papillae and epidermis. 
The surface may be smooth or rough. When the papillae and epidermis 
are much involved, larger and smaller cauliflower-like excrescences may 
cover the hypertrophied parts, and the surface be very rough and scaly. 
Papillomata.-These growths consist of hypertrophied papillae covered 
with thick layers of epithelium. They vary in size from that of a pea to 
1 For a study of noma with bibl. see Blumer and MacFarlane, Am. Jour. Med. Sci., vol. cxxii., 1901, 
p. 527. THE REPRODUCTIVE ORGANS OF THE FEMALE 
795 
that of an apple, and have a cauliflower appearance. Lipoma, fibroma, 
fibro-sarcoma, and angioma are of occasional occurrence in the vulva. 
A few cases of melano-sarcoma are recorded. Chondroma of the clitoris 
has been described. Carcinoma of the vulva may be primary, usually in 
the form of epithelioma of the clitoris or labia, or it may be secondary to 
cancer of the uterus, vagina, etc. Adenoma of Bartholin's glands is noted. 
Cysts are found in the connective tissue of the labia majora and 
minora. They are from the size of a pea to that of a child's head. 
They may contain serum, colloid material, purulent or bloody fluid, or 
they may have the characters of dermoid cysts or atheroma cysts. Their 
origin is in many cases obscure. In some cases they are doubtless due 
to dilatation of lymph-vessels. Cysts may be formed by a stoppage and 
filling with fluid of the canal of Nuck, or by a dilatation of the ducts or 
acini of the vulvo-vaginal glands.1 
The Vagina. 
Malformations. 
The vagina may be entirely absent, and the internal organs of generation also 
absent or imperfectly developed. Either the upper or the lower portion of the canal 
may be absent while the remaining portion is present. 
The vagina may be closed by an imperforate hymen or by fibrous septa at any part 
of its canal. The canal may be abnormally small without being occluded. 
The vagina may be double, in connection with a double uterus; or, while the uterus 
is normal, the vagina may be incompletely divided by a longitudinal septum. 
Changes in Size and Position. 
Dilatation of the vagina is produced by tumors, by the prolapsed uterus, and by 
the accumulation of blood and mucus behind constrictions or obliterations of the canal. 
Lengthening of the vagina is produced by any cause which draws the uterus 
upward. Narrowing occurs as a senile change, is produced by the pressure of tumors, 
or may follow ulceration of the wall of the canal through cicatricial contraction. 
Prolapse of the vagina occurs independently, usually as a result of thickening 
or laxity of its walls, or in connection with prolapse of the uterus. It may occur soon 
after parturition. A larger or smaller portion of the canal is inverted and projects 
through the vulva. The entire circumference of the canal may be inverted and pro- 
lapsed, or only the anterior or posterior wall. The prolapse, at first small, may after- 
ward gradually increase in size and drag down the uterus with it. In other cases pro- 
lapse of the uterus is primary, and the vagina is inverted by the descent of that organ; 
or the body of the uterus may retain its normal position, while an hypertrophy and 
lengthening of the cervix alone drags down the vagina. 
Hernia Vesico-vaginalis-Cystocele-may be either the cause or effect of a 
prolapse of the vagina and uterus. If the cystocele be the primary lesion, it begins as 
a small projection of the wall of the bladder into the anterior part of the vagina. As 
the urine accumulates in this sac it increases in size, projects through the vulva, draws 
down the vagina and the anterior lip of the cervix, and finally the entire uterus. If 
the cystocele be the secondary lesion, it is produced by the dragging down of the pos- 
terior wall of the bladder by the inverted vagina. 
Hernia Intestino-vaginalis.-A portion of the intestines may become fixed in 
Douglas' cul-de-sac between the rectum and the uterus. This portion of intestine 
gradually becomes larger, pushes forward the posterior wall of the vagina, inverts and 
'For a study of cysts of Bartholin's glands see Cullen, Jour. Am. Med. Assn., vol. xliv., p. 204, 
1905. 796 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
fills up that canal, and finally projects through the vulva. It may drag with it the 
posterior wall of the vagina and the uterus. 
Rectocele Vaginalis.-A sac is formed by the projection of the anterior wall 
of the rectum and the posterior wall of the vagina. This lesion is of rare occurrence 
and does not reach a large size. 
When the vagina is prolapsed there is usually inflammation of the lining membrane 
or a thickening of the epidermis. 
WOUNDS-PERFORATIONS. 
Wounds of the vagina are made by penetrating instruments, by for- 
ceps and other obstetrical weapons, by the foetus during delivery, or may 
result from coitus. Such wounds may heal, or give rise to large haemor- 
rhages, or suppurate, and lead to abscesses in the surrounding tissue, or 
leave fistulous openings into the vagina; or they may by cicatricial con- 
traction in healing lead to constriction or obliteration of its canal. 
Vesico-vaginal Fistulae are usually produced by injuries from instru- 
ments or from the foetus during delivery; less frequently by ulceration 
of the vagina, bladder, or adjacent connective tissue, or by abscess in 
the surrounding parts. The fistulae form an opening between either the 
bladder or the urethra and the vagina. They allow the urine to pass 
into the vagina. Spontaneous cure does not take place. 
Recto-vaginal Fistulae are formed in the same way as the last-men- 
tioned. They allow the passage of gas or faeces into the vagina. They 
sometimes heal spontaneously. 
Catarrhal Inflammation of the vaginal mucous membrane may be 
acute or chronic. It is most frequently induced by the gonococcus, but 
may be due to local irritation or accompany active infectious processes. 
It not infrequently occurs in the new-born. In the acute form the mucous 
membrane is swollen and frequently covered with a muco-purulent or a 
purulent exudation. In the chronic form the mucous membrane may be 
swollen, covered with a purulent exudation; there may be an exfoliation 
of epithelium, shallow or deep erosions, or ulcers. 
Sometimes large shreds or membranes are cast off from the vagina 
which consist wholly of exfoliated, flat epithelium.1 In other cases the 
mucous membrane is thickened, dense, and sometimes pigmented, or 
it may be roughened, covered with papillae, or it may be relaxed and 
prolapsed. 
Membranous Inflammation may occur after parturition, in dysentery, 
typhus and typhoid fevers, diphtheria, scarlatina, measles, and other 
infectious diseases. The mucous membrane is swollen and covered with 
a grayish layer of fibrin and pus. The mucosa and submucosa may be 
infiltrated with fibrin and pus. The infiltrated portions of the mucosa 
and submucosa may die and become gangrenous, and thus deep and 
extensive ulcers be formed. 
INFLAMMATION (Vaginitis.) 
1 Consult McFarland, Proc. Phiia. Path. Soc., N. S., vol. ii., p. 115, 1899. THE REPRODUCTIVE ORGANS OF THE FEMALE 
797 
Suppurative Inflammation of the fibromuscular coat of the vagina may 
occur after injuries or in pregnant and puerperal women. Abscesses 
may be formed which penetrate into the labia or into the pelvic connec- 
tive tissue. In other cases the intense phlegmonous inflammation may 
lead to the death and casting-off of portions of the vaginal wall, or even 
of the entire wall. 
Emphysematous Vaginitis.-Anaerobic bacilli developing in the vag- 
inal wall may give rise to small cysts or blebs. 
Gangrene of the vagina may occur as a result of croupous or intense 
suppurative or syphilitic inflammation, or from unknown causes. In 
the form of noma it may be very extensive and rapidly destructive. 
Tuberculous and Syphilitic Inflammation, usually leading to more or 
less extensive ulceration, may occur in any part of the vagina. Tuber- 
culous inflammation is usually secondary to tuberculosis of other parts. 
Syphilitic ulcers may heal, sometimes leaving marked cicatrices, and 
sometimes not. 
TUMORS. 
Fibroma, fibro-myoma, sarcoma, myoma laevicellulare, are of occa- 
sional occurrence in the vagina. Myoma striocellulare is of rare occur- 
rence. A teratoma has been described and a few cases of endothelioma.1 
Papillomata are of frequent occurrence as a result of chronic inflam- 
mation. Carcinoma of the vagina is usually secondary to cancer of the 
uterus. It may be primary and nodular, or more often it is papillary 
and ulcerating and spreads to adjacent parts. 
Cysts.-These are not very common and may be small or as large as 
a hen's egg. They may be lined with flattened epithelium, and contain 
serous or viscid, dark-colored or transparent fluid.2 
PARASITES. 
Among the animal parasites Oxyuris and Trichomonas vaginalis are of 
occasional occurrence. Among the vegetable forms Oidium albicans and 
Leptothrix are occasionally seen, while various forms of bacteria are com- 
mon. Staphylococcus and Streptococcus pyogenes have been found 
many times in the normal vagina. While these and other bacteria may 
be harmless in the normal vagina, should conditions favoring their growth 
or an increase in their virulence occur, as after delivery for example, 
serious infectious processes may follow. The rdle of the gonococcus as an 
excitant of catarrhal inflammation is well established. 
The Uterus. 
The uterus, tubes, and vagina may be entirely absent, with or without absence of 
the external genitals. Or the uterus alone, or the upper part of the vagina also, may 
be absent. 
Congenital Malformations. 
1 See Raschkes, Cbl. f. Path., Path., Bd. xiv., 1903, p. 657. 
2 Consult Stokes, Johns Hopkins Hosp. Rep., vol. vii., p. 109, 1899, bibl.; also Cullen, Johns Hop- 
kins Hosp. Bull., vol. xvi., p. 207, 1905. 798 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The uterus may be only rudimentary while the vagina is normal. It then appears 
as a flattened solid body with solid cornua. Or there are two cornua joined at their 
lower extremities so as to form a small double uterus (Fig. 536). Or the uterus is 
represented by a small sac, which may or may not communicate with the vagina. Or 
there is a very small uterus, with thin muscular walls and two large cornua. 
Only one of the cornua which should form the uterus may be developed while the 
other is arrested in its growth. The uterus is then a long, cylindrical body, termi- 
nating above in one tube. On the side where the horn should have been developed 
there is no tube, or only a rudiment. Both ovaries are usually present. 
The two cornua may be fully developed, but their lower ends remain separated 
and form a double uterus. An entire separation into two distinct uteri and vaginae is 
Fig. 536.-Uterus Bicornis. 
rare. More frequently the uterus consists of one body, divided by a septum into two 
cavities. There are then two cervical portions of the uterus projecting into a single 
vagina, or each into a separate vagina. Or there is only a single cervix. The septum 
in the uterus may be complete or only partial. 
The uterus may be abnormal in size or be variously flexed; the cervix may be 
solid or may be closed by the vaginal mucous membrane. Or the cervix may have an 
abnormal form with a small opening or canal. 
Changes in Size. 
In the new-born infant the uterus is small, the body flattened, the cervix dispro- 
portionately large. During childhood the organ increases in size, but the body THE REPRODUCTIVE ORGANS OF THE FEMALE 
799 
remains small in proportion to the cervix. At puberty the shape changes and the 
body becomes larger. 
At every menstruation the uterus is somewhat swollen and congested. After 
pregnancy it does not return to its virgin size, but remains somewhat larger. In old 
age it gradually becomes smaller; its walls are harder and more fibrous. 
Abnormal Smallness of the uterus is sometimes found as an arrest of develop- 
ment. It may result, however, from chronic endometritis, from repeated pregnancies, 
from old age, or from chronic exhausting diseases. Its cavity may be smaller than 
normal, or distended with mucus. Large myomata sometimes induce atrophy of the 
uterine wall. Atrophy of the vaginal portion of the uterus is sometimes observed 
after repeated pregnancies. Narrowing and obliteration of the cavity of the uterus 
and of the cervix are usually produced by chronic inflammation. 
Enlargement of the Uterus may be due to too early development. It is 
accompanied by abnormally early development of all the sexual organs and functions. 
The uterus may be enlarged in connection with heart disease, prolapse and abnormal 
flexions and versions, chronic inflammations, repeated pregnancies, myomata, and 
accumulations of blood or mucus in the uterine cavity. Enlargement of the vaginal 
portion alone may occur. One or both lips of the cervix may be uniformly increased 
in size, or they may be lobulated. 
Dilatation of the uterus is produced by accumulations of blood, mucus, or pus in 
consequence of narrowing or obliteration of the cervix or vagina. The uterine walls 
Fig. 537.-Hour-glass Uterus. 
Showing a small uterus with distention of the cavities of the body and cervix from fibrous-tissue con 
traction at the os externum and the os internum. 
may retain their normal thickness, be thickened or thinned. The most frequent posi- 
tion of the stenosis is the os internum. The retained contents after a time change in 
character, forming a thin, serous fluid-hydrometra-or they may be mixed with blood 
The dilated uterus may be of enormous size. If both os internum and os externum 
are closed the cervical cavity may be also dilated and the uterus have an hour-glass 
shape (Fig. 537); or the dilatation may be limited to the cervix. If the obstruction is 
not complete, the retained fluid may escape into the vagina and be followed by a fresh 
accumulation. If the obstruction be in the vagina, the uterus and vagina may form 
a large, flask-shaped body, and the line of demarcation between cervix and vagina 
be lost. 800 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Accumulation of menstrual blood in the cavity of the uterus-hoematometra-is 
usually due to congenital stenosis of the cervix or vagina, and may be very great. If 
the fluid is not evacuated by surgical interference there may be either rupture or ulcer- 
ative perforation of the uterus. The blood may escape into the abdominal cavity, or 
be shut in by adhesions, or perforate into the bladder or intestines. Sometimes the 
blood passes into the Fallopian tubes, dilates them, and escapes through their abdomi- 
nal ends. 
Changes in Position. 
The body of the uterus may become fixed in an abnormal position, while the situa- 
tion of the cervix is unchanged. 
Flexion.-The body may be bent forward-anteflexion; backward-retroflexion 
(Fig. 538); or sideways-lateral flexion. The flexion may be slight, or so great that 
the neck and body form an acute angle. Anteflexion is the most common variety, 
Small cysts may be seen in the mucous membrane of the body. 
Fig. 538.-Retroflexion of the Uterus. 
and that in which the flexion is greatest. Peritoneal adhesions, flaccidity of the 
uterine walls, particularly after delivery, atrophy of the walls, ovarian and other 
tumors, etc., are the usual causes of flexion. 
Version of the uterus consists in an abnormal inclination of the long axis of the 
organ to that of the vagina. The uterus may be inclined backward, forward, or to 
one side. THE REPRODUCTIVE ORGANS OF THE FEMALE 
801 
Retroversion is the most common. The fundus uteri is directed backward and 
downward, the cervix forward and upward. This condition is found in various 
degrees; in the highest the fundus lies in Douglas' cul-de-sac with the cervix upward, so 
that the axis of the uterus is parallel to that of the vagina, but in a direction nearly 
opposite to the normal. Abnormal looseness of the uterine ligaments, abnormally 
large capacity of the pelvis, enlarge- 
ment or tumors of the uterus, and 
pregnancy during the first four 
months, are some of the more com- 
mon conditions under wrhich this 
lesion occurs. 
Anteversion.-Inclination of the 
fundus forward and downward, and 
of the cervix backward and upward, 
is not common and seldom reaches a 
high degree. It occurs under the 
same general external conditions as 
anteflexion. 
Lateroversion is not very common 
as a simple lesion, but is not infre- 
quently combined with other displace- 
ments. It may be produced by con- 
genital shortening of one of the broad 
ligaments, by adhesions, or by the 
pressure of tumors. 
The greater degrees of version 
may produce very grave lesions. The 
urethra and rectum may be com- 
pressed. Cystitis, perforation of the 
bladder, dilatation of the ureters and 
hydronephrosis, and fatal obstruction 
of the bowels may follow. If preg- 
nancy exist abortion may take place, 
or the inverted uterus may be forced 
through the peritoneum and posterior 
wall of the vagina and project through 
the vulva. In the non-pregnant 
uterus pressure on the veins and con- 
sequent chronic inflammation of the 
organ may follow. 
Prolapsus uteri consists of a de- 
scent of the uterus into the vagina. 
The uterus may be only slightly 
lowered or it may project at the vulva (Fig. 539). In complete prolapse we find a 
tumor projecting through the vulva, partly covered by the distended vagina, and 
presenting the opening of the os externum near its centre. The bladder and rectum 
may be drawn down with the vagina or may remain in place. The exposed cervix 
and vagina usually become inflamed and sometimes ulcerated, or the mucous mem- 
brane may become thickened. The lesion is frequently complicated by hypertrophy 
of the cervix. 
Gradual prolapse, ■which is most frequent, may be due to an increased weight of the 
uterus, as in pregnancy, inflammatory enlargement, the presence of tumors, etc.; or to 
some abnormal condition of the uterine supports. It is frequently due to a vaginal 
cystocele or rectocele. Sudden prolapse is most apt to occur in an enlarged uterus or 
one unduly heavy by reason of tumors connected with it. It is most common in 
subinvolution after parturition. 
Elevation of the uterus is produced by mechanical causes crowding or dragging 
it upward, as adhesions, tumors, etc. The vagina is drawn up and lengthened, and 
the vaginal portion of the cervix may be obliterated. 
Fig. 539.-Prolapse of the Uterus. 
The cervix projects from the vulva and there are 
small ulcerations about the os externum. 802 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
[ Inversion of the uterus consists of an invagination of the fundus. The fundus 
may be invaginated in the body, the fundus and body in the cervix, or the entire 
organ in the vagina. It usually occurs when the uterine walls are relaxed, and may 
be^due to traction on the placenta during parturition. It may take place spontane- 
ously after parturition. It may be produced by intra-uterine tumors. The mucous 
membrane of the inverted organ is frequently inflamed, particularly when the inver- 
sion is complete. The epithelium may become squamous and lamellated in type. 
Hernia of the uterus are rare. Ventral hernice may occur during the latter months 
of pregnancy, the peritoneum, aponeurosis, and skin being forced outward to form a 
sac in which the uterus lies. Crural hernia are produced by the drawing down of the 
uterus and ovaries into the sac of an intestinal hernia. Inguinal hernia may be pro- 
duced in the same way or be congenital. Ischiatic hernia has been seen. Pregnancy 
may occur in the uterus while it is within a crural or inguinal hernia. 
RUPTURE AND PERFORATION. 
Rupture of the unimpregnated uterus is rare. It may, however, 
occur when the uterine cavity is distended with blood or serum, or in 
connection with large myomata of the uterine walls. 
In the gravid uterus ruptures have been seen in nearly every month 
of pregnancy, but most frequently toward the end. The rupture may be 
due to a thinning of the uterine wall by tumors or by violent contusions, 
or as the result of cicatricial contraction of the os. 
It most frequently takes place in parturition. Malpositions of the 
foetus, narrowing of the pelvis, protracted labor, thinning of the uterine 
wall from tumors, forcible use of the forceps and other instruments, are 
the ordinary causes. The rupture may be in the body of the uterus or 
the cervix, or both; it may be large or small; it may extend completely 
or only partly through the uterine wall. The consequences of partial 
rupture are haemorrhage, gangrenous inflammation of the edges of the 
rupture, peritonitis, and usually death. In rare cases the rupture cica- 
trizes and the patient recovers. Complete rupture usually leads to death 
in a short time. The foetus may escape partly or completely into the 
abdominal cavity. If the patient survive the immediate shock, fatal 
peritonitis usually soon ensues. In rare cases the foetus is shut in by 
adhesions and the patient survives. 
Perforations of the uterus may be produced by carcinoma, by abscesses 
in its neighborhood, and by ovarian cysts. 
HYPEREMIA-UTERINE AND PERI-UTERINE HEMORRHAGE. 
Hyperaemia.-Aside from the active menstrual hyperaemia, the uterus 
may be hyperaemic in acute and chronic inflammation, as a result of 
displacement of the organ, and in certain forms of heart disease. The 
organ is usually enlarged, the mucous membrane swollen, ana the 
veins are more or less evidently dilated. (Edema may be associated 
with hyperaemia. 
Haemorrhage.-Effusion of blood into the cavity of the uterus occurs 
normally at the menstrual periods. For the abnormalities to which this 
function is subject we refer to works on gynecology. Effusions of blood 
at other than the menstrual periods may be associated with mechanical THE REPRODUCTIVE ORGANS OF THE FEMALE 
803 
hyperaemia, haemorrhoids, acute hyperaemia, intrauterine polypi and 
other tumors, acute and chronic inflammation, typhus fever, scurvy, etc., 
ulcerating carcinoma, abortions, and miscarriage. 
A peculiar form of haemorrhage results in the so-called polypoid haema- 
toma, or fibrinous polyp. It occurs after parturition and after abortions. 
The portions of the uterine wall where the placenta was attached, with or 
without a portion of retained placenta, forms the point of attachment of 
the pedicle of the thrombus. A bloody mass is firmly attached by a 
pedicle to the uterine wall; the uterus enlarges with its formation, the 
cervix is dilated, and the thrombus may project into and fill the vagina. 
The formation of such a thrombus is accompanied by repeated haemor- 
rhages. 
Haemorrhage in the substance of the uterus occurs in arterio-sclerosis. 
The mucous membrane and uterine wall or the cervix are infiltrated with 
blood, and there may be blood in the uterine cavity. 
Peri-uterine or Retro-uterine Haematocele consists in an accumulation 
of blood around the uterus or in Douglas' cul-de-sac. The haemorrhagic 
mass may become encapsulated with fibrous tissue, or may soften or 
suppurate and perforate into rectum or vagina, or may be absorbed. 
A form of extraperitoneal haematocele is described in which the blood 
lies between the folds of the broad ligament. The extravasation may 
proceed from haemorrhage of any of the abdominal viscera or rupture of 
aneurisms; from vascular new-formed false membranes; from rupture of 
the varicose veins of the broad ligaments; from rupture of haemorrhagic 
cysts of the ovaries; from rupture of the Fallopian tubes in tubal preg- 
nancy or in haematometra; or from general causes, such as scurvy, 
purpura, etc. In some cases the extravasation begins at a menstrual 
period, and increases at the succeeding periods. 
Ante-uterine Haematocele is of occasional occurrence, either in con- 
nection with the retro-uterine form or when the posterior cul-de-sac is 
obliterated. 
ATROPHY, DEGENERATION, ETC. 
Atrophy of the uterus occurs as a physiological process in old age. 
It may be associated with severe general or infectious diseases or follow 
removal of the ovaries. It may follow pregnancy apparently as an 
excessive involution process. 
Fatty Degeneration.-This may occur in connection with inflam- 
matory changes, in acute infectious diseases, and in phosphorus poisoning. 
Amyloid Degeneration in the uterus is of rare occurrence. It may 
affect the muscle fibres or the walls of the blood-vessels. 
Phagedenic or Corroding Ulcer.-This rare and little understood form 
of ulceration usually occurs in old age. It begins in the cervix and 
gradually extends until it may destroy the greater part of the uterus or 
even invade the bladder and rectum. The ulcer is of irregular form; 
its base is rough and blackish, its walls are indurated. It should not be 
confounded with carcinomatous ulcer, which it considerably resembles. 804 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
INFLAMMATION. (Metritis and Endometritis.) 
I. Inflammation of the Unimpregnated Uterus. 
Acute Catarrhal Endometritis.-In this disease, which in its lighter 
grades may leave but little alteration after death, the mucous membrane 
is swollen, hyperaemic, and sometimes the seat of punctate haemorrhages. 
The epithelium may be degenerated and may desquamate, and the 
mucosa contain an undue quantity of polynuclear leucocytes. The sur- 
face is more or less thickly covered with muco-purulent exudate. In 
severe cases shreds of mucous membrane may be exfoliated. The lesion 
is usually most marked in the mucous membrane of the body, but may 
involve the cervix at the same time, or the cervix alone. The body of 
the uterus may be soft, swollen and hyperaemic. 
In endometritis exfoliativa (membranous dysmenorrhoea) there may 
be an expulsion, with more or less blood, of membranous masses consisting 
of fibrin mingled with blood and pus cells, or consisting of exfoliated 
superficial layers of endometrium. The exfoliated epithelium is fre- 
quently much flattened so as to resemble the vaginal epithelium.1 
The decidual reaction in interstitial tissue is occasionally very consider- 
able, so that pregnancy may be suspected; but the cells never reach the 
size of those seen in pregnancy. 
Acute catarrhal inflammation of the uterus may be due to injury, 
exposure during menstruation, gonorrhoeal infection, local infection with 
other bacteria,2 or it may ac- 
company the general acute 
infectious diseases. 
Chronic Endometritis.- 
This may be a continuation 
of an acute inflammation or 
begin as a chronic process. 
There may be a general atro- 
phy of all the elements or, on 
the other hand, the mucous 
membrane may be swollen, 
hyperaemic, and covered with 
muco-purulent exudation. In 
other cases there is more or 
less well-marked thickening 
of the mucous membrane, 
which may present a smooth 
or a rough papillary surface of 
polypoid outgrowths. 
The thickened mucous membrane shows on microscopical examina- 
tion a diffuse hyperplasia of the uterine glands. These may be fairly 
Fig. 540.-Chronic Endometritis, showing Glandular 
Hyperplasia of the Mucous Membrane. 
The stroma of the mucosa is increased in amount and is 
dense and fibrous in texture. 
1 See DeWitt, Am. Jour, of Obstetrics, vol. xlii., 1900, bibl. 
2 For an account with bibl. of the bacteria of the vagina see Williams, Am. Jour, of Obstetrics, 
vol. xxxviii., No. 4, 1898; for bacteria of non-pregnant uterus see Miller, Johns Hopkins Hosp. Bull., 
vol. x., p. 29, 1899, bibl.; also ref. to Wadsworth, p. 809. THE REPRODUCTIVE ORGANS OF THE FEMALE 
805 
normal and regular in type; or the epithelial cells may be much increased 
and irregularly massed within the tubules; the hyperplastic glands are 
often contorted, forming irregular spirals. The interglandular stroma of 
the mucosa may be little changed or much thickened; it may be dense or 
very loose in texture and formed largely of small fusiform and plasma 
cells. It is often extremely vascular and may be the seat of interstitial 
haemorrhage. If there be considerable growth of new gland structure the 
condition is called " glandular hyperplasia" of the mucous membrane. 
It is difficult from the microscopical examination of curetted fragments to 
decide whether the lesion is a hyperplasia or chronic inflammation or 
Fig. 541.-Chronic Endometritis. 
Showing glandular hyperplasia of the mucous membrane. The stroma of the mucosa is increased 
in amount and is loose in texture. The glands are contorted. 
merely a phase of the cyclic menstrual alterations which occur in the endo- 
metrium. The glandular and interstitial changes shown in Figs. 540 and 
541 are equally representative of chronic endometritis and the resting 
and premenstrual stages of the endometrium, respectively. 
Sometimes a thick layer of new-formed, very vascular tissue develops 
over the surface of the mucous membrane, largely covering in the uterine 
glands (Fig. 542). From the decomposition of extravasated blood in 
the mucous membrane the latter may be mottled with brown or black. 
The glandular elements of the mucosa may be partially or almost entirely 
destroyed. Occasionally the glands are dilated, forming numerous small 
cysts which may project from the surface. The papillae of the cervix 
may be hypertrophied, the mucous follicles swollen and their outlets 
obstructed, leading to the formation of the so-called ovula Nabothi. The 
uterine wall becomes flaccid and atrophied, or it may be hyperplastic 
especially in the cervical portion. Ulceration of the mucous membrane, 
especially of the cervix, may occur. There may be contraction or obliter- 
ation of the cervical canal. 
Fibrous hyperplasia of the cervix with ectasia of the Nabothian 
glands and thickening and erosion or ulceration of the mucous membrane 806 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
is a frequent condition at the climacteric period (Fig. 543). Under these 
conditions both the clinical manifestations and the general appearance 
of the cervix on inspection often suggest the existence of cancer. 
Chronic endometritis may occur at any age, but is most frequent 
after puberty, and is due to a great variety of conditions. It may occur 
in ill-nourished persons or in those suffering from exhausting diseases. 
Fig. 542.-Chronic Endometritis with the Formation of a Thick Layer of New-formed, very 
Vascular Tissue over the Surface of the Mucous Membrane. 
a, Uterine muscle tissue; b, mucous membrane of uterus; c, new-formed vascular tissue. 
It may follow displacements and tumors of the uterus, subinvolution, 
injuries, etc. 
Membranous Endometritis.-This form of inflammation is not very 
common. It occasionally occurs in the puerperal uterus, and in acute 
infectious diseases. It sometimes involves the vulva, vagina, and Fallo- 
pian tubes. It may coexist with membranous inflammation of the 
colon. 
Tuberculous Endometritis.-This is rare and usually occurs as part of 
tuberculous inflammation of the genito-urinary tract. A part or the 
whole of the cavity of the uterus may be lined with a rough, yellowish 
or gray, caseous mass, which may deeply involve the muscular walls of 
the organ. At the edges of the ulcerating caseous areas there may be 
miliary tubercles, or these may be scattered through the otherwise 
intact mucosa.1 
'For bibl. see Cullen, Johns Hopkins Hosp. Rep., vol. iv., p. 441, 1895. THE REPRODUCTIVE ORGANS OF THE FEMALE 
807 
Syphilitic Endometritis.-This is usually confined to the cervical por- 
tion, and is characterized by shallow or deep ulcerations and condylomata 
of the mucous membrane; or there may be a diffuse thickening of the 
mucosa. 
Acute Metritis is usually associated with acute catarrhal endometritis. 
The organ is swollen, succulent, congested; the mucous membrane cov- 
The figure shows one side of the cervix in longitudinal section. The fibrous tissue of the cervix 
is very dense and the walls of the blood-vessels are thickened. There is hyperplasia of the glands of 
the cervical canal with erosion of the surface epithelium. The Nabothian glands are distended with 
clear, glairy fluid (ovula Nabothi). There is erosion of the epithelium at the os externum, and this, 
with the congestion of the small superficial vessels here, gave a rough red appearance to the os, suggestive 
of a malignant growth. 
Fig. 543.-Fibrous and Glandular Hyperplasia of the Cervix Uteri. 
ered with muco-pus; the peritoneal coat congested. There may be small 
extravasations of blood in the wall or cavity of the uterus. The inflam- 
mation, in rare cases, becomes suppurative, and abscesses are formed in 
the uterine wall; these may perforate into the peritoneal cavity or into 
the rectum. 808 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Perimetritis.-The peritoneal coat of the uterus may be inflamed, with 
the production of membranous adhesions or of pus. The adhesions may 
be small or very extensive, and, owing to their contractions, may cause 
various distortions and displacements of the pelvic organs. The inflam- 
mation is usually an accompaniment of chronic metritis and endometritis. 
In prostitutes such adhesions are of very common occurrence. 
Parametritis.-The connective tissue about the uterus, between that 
organ and the reflexions of the peritoneum, may be the seat of suppura- 
tive inflammation. It most frequently ends in death, but may result in 
the formation of dense connective tissue about the uterus. 
Chronic Metritis may follow acute metritis or accompany acute or 
chronic endometritis, and is dependent upon similar conditions: subin- 
volution, displacements, tumors, active irritants, etc. The uterus is 
enlarged, the wall congested, thickened, and soft, or, owing to the new 
formation of connective tissue, hard and dense. The lesion is usually 
accompanied by chronic peri- and parametritis; in fact, a separation of 
the three conditions is somewhat artificial. 
The forms of inflammation which have just been described may also 
occur in the pregnant uterus. Catarrhal endometritis may lead to effusion 
of serum, extravasations of blood, and abortions. Metritis may lead to 
softening of the uterine wall, so that rupture takes place during labor. 
Perimetritis and parametritis produce adhesions and abscesses about the 
uterus. 
Infectious Inflammation (Puerperal Fever).-For a week or more after 
delivery the inner surface of the still dilated uterus is rough, especially 
at the insertion of the placenta, and covered with dark shreds of blood, 
mucous membrane, and placenta. This condition should not, as is some- 
times the case, be mistaken for inflammation or gangrene. 
As a result of injury to the uterus or vagina during or after delivery, 
and the action of bacteria which may gain access to the tissues in this 
vulnerable state, the puerperal uterus is liable to become the seat of a 
series of severe and often destructive inflammatory and necrotic changes. 
These may be confined to the uterus; they may induce serious alterations 
in surrounding parts; they may lead to an involvement of the peritoneum 
or to septicaemia or pyaemia and its accompanying lesions in the most 
distant parts of the body. In some cases a more or less extensive gan- 
grenous inflammation of the mucous membrane and the underlying parts 
may lead to the casting-off of larger and smaller shreds of necrotic tissue 
and the formation of deep and spreading ulcers, which may be accom- 
panied by severe parametritis and fatal peritonitis. In other cases the 
inflammation is membranous, and may affect the vagina, leading to 
necrosis, gangrene, ulceration, or peritonitis. 
In connection with either of the above forms of inflammation, or 
without them, there may be thrombosis of the uterine sinuses, purulent 
inflammation of the veins, suppuration and abscess in the uterine wall, 
suppurative inflammation of the ovaries and tubes, and, owing to the 
II. Inflammation of the Pregnant Uterus. THE REPRODUCTIVE ORGANS OF THE FEMALE 
809 
generalization of the infectious material, metastatic abscesses in the lungs, 
spleen, kidneys, etc. Or acute pleurisy, ulcerative endocarditis, ery- 
sipelas, purulent inflammation of the joints, hyperplastic swelling of the 
spleen and lymph-nodes, thrombosis or thrombo-phlebitis of the saphen- 
ous veins, etc., may follow. In some cases which rapidly pass to a fatal 
termination the local lesions may be but slightly marked, and general 
alterations characteristic of pyaemia, such as metastatic abscesses, etc., be 
Fig. 544.-Uterine Phlebitis following Delivery; with Retained Placenta. 
Death nine days after delivery. Micrococci in the walls of the inflamed veins stained violet. 
entirely wanting. Death is in such cases apparently clue to toxaemia or 
septicaemia. 
Bacteria are usually present in the exudate, in the lymph-vessels, 
veins, and inflamed tissue of the uterus (see Fig. 544); often in enormous 
quantities in the peritoneal exudation and in the metastatic inflammatory 
foci. Streptococcus pyogenes, the gonococcus, B. aerogenes capsulatus, 
and the colon bacillus are the most frequent excitants of the lesion.1 
TUMORS. 
Fibromata.-Dense nodular fibromata of the uterus are rare, the 
so-called fibromata being in most cases myomata or fibro-myomata. 
Fibroma papillare, on the other hand, is a common form of growth from 
the mucous membrane. It consists of a more or less vascular connective- 
tissue stroma covered with epithelium. The surface may be smooth or 
villous. It may contain very numerous gland follicles, and then ap- 
proaches the type of adenoma, or even carcinoma. The stroma may be 
1 Consult Wadsworth, "On Puerperal Infection," Am. Jour, of Obstetrics, vol. xliii., 1901. 810 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
loose and succulent, and resemble mucous tissue, forming the so-called 
mucous polypi. In any of these forms the blood-vessels may be abundant 
and dilated, forming telangiectatic or cavernous polypi. The adenoma- 
tous polypi may become cystic from the dilatation of the gland follicles. 
Polypi of the uterus may be multiple or single, small or large. Numer- 
ous smaller and larger papillary outgrowths from the mucous membrane 
may occur in chronic endometritis. Single polypi may grow from the 
mucosa of the body of the uterus 
or from the cervix, and hang by 
a long pedicle down into the 
vagina. 
The large number of glandu- 
lar structures in many of these 
chronic inflammatory, papillary, 
and polypoid outgrowths (Fig. 
545) often justifies the name of 
adenomatous hyperplasia of the 
mucous membrane or of adeno- 
matous papillomata or polyps. 
Syphilitic papillary growths 
in the form of pointed condylo- 
mata may form finely papillary, 
wart-like excrescences of vari- 
able size, particularly on the 
cervix. 
Myomata. - These tumors, 
whose characteristic structural 
elements are smooth muscle 
cells (Fig. 232), are the most 
common of uterine tumors and 
while frequently of little prac- 
tical importance are sometimes 
of serious import. They are 
especially common in negroes. 
They are most frequently composed of both muscular and fibrous tissue 
-fibromyomata-but the relative amount of the two kinds of tissue is 
subject to great variation. They are most apt to occur after puberty, 
and usually in advanced life. They may be single or multiple, small or of 
enormous size; are usually sharply circumscribed, whitish or pink, dense 
and hard, or sometimes soft, and present on section interlacing bands 
or irregular masses of glistening tissue. Their favorite situation is in 
connection with the body of the uterus, but they may occur in the cervix 
or in the folds of the broad ligaments. According to their position we 
may distinguish subserous, submucous, and intraparietal forms. 
The subserous myomata, often multiple, grow from the outer muscular 
layers of the uterus in the form of little nodules. As they increase in 
size they may become separated from the uterine wall and remain 
attached only by a narrow pedicle or by a little connective tissue; or may 
Fig. 545.-Uterine Polyp-Adenomatous or 
Glandular Polyp of the Uterus-Polypoid 
Hyperplasia of the Mucous Membrane in 
Chronic Endometritis. THE REPRODUCTIVE ORGANS OF THE FEMALE 
811 
even be entirely free. They may work their way between the folds of 
the broad ligament until they are at some distance from their point of 
origin. The tumors may become very large, but remain firmly attached 
to the uterus; this organ may then be drawn upward, the cervix and 
vagina being elongated and narrowed. The traction may be so great that 
the body of the uterus is entirely separated from the cervix. The bladder 
may also be drawn upward. But subserous myomata of considerable 
size may interfere but slightly with the function of the uterus (see 
Fig. 546). 
Fig. 546.-Extramural Myomata. 
Shows the uninvolved interior of the uterus containing a well-formed foetus. 
The submucous myomata grow from the inner muscular layers of the 
uterine wall, most frequently in the fundus. They may project into 
the uterine cavity and remain sessile or become pediculated; the uterus 
dilates with the growth of the tumor, and its wall may also be thickened. 
They are usually single, although there may be at the same time 
subserous and intraparietal tumors.. They are frequently soft. If 
they are of large size and polypoid in form, they may project through 
the cervix and drag down the fundus of the uterus, producing inversion. 
The mucous membrane covering them may be atrophied or hyperaemic, 
with dilated blood-vessels, and may thus give rise to severe and repeated 
haemorrhages. In some cases the pedicle of a tumor is destroyed and it 
is spontaneously expelled. 812 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The intramural myomata grow in the substance of the uterine wall, 
but, if they attain a large size, project beneath the serous or the mucous 
coat (Fig. 547). They are found in every part of the uterus, but are 
most frequent in the posterior wall. 
The shape of the uterus is altered in a great variety of ways by the 
presence of these tumors; its cavity is narrowed, dilated, or misshapen; 
it undergoes flexion or version. The tumors may sink downward and 
become attached to the posterior wall of the vagina. 
Myomata may undergo a variety of secondary alterations. The mus- 
cle fibres may undergo fatty degeneration and the tumor diminish in size. 
Fig. 547.-Intraparietal Myomata of the Uterus. 
or may even, it is said, be entirely destroyed. Calcification may occur, 
converting a part or the whole of the tumor into a stony mass. The 
intra-parietal and submucous myomata may give rise to profuse haemor- 
rhages; they may suppurate and become gangrenous. 
Sometimes the tumors or circumscribed portions of them are very 
vascular, constituting the telangiectatic or cavernous variety. These 
tumors, which possess some of the characters of erectile tissue, may sud- 
denly change in size from a variation in the amount of blood which they 
contain. Larger and smaller cysts may develop within these tumors 
-fibro-cystic tumors. These may be multiple and may communicate; 
they may be filled with a clear or bloody fluid. These cystic myomata 
may reach an immense size and fill the abdominal cavity. The cysts THE REPRODUCTIVE ORGANS OB' THE FEMALE 
813 
may be lined with ciliated epithelium.1 Combinations of myoma and 
sarcoma sometimes occur-myo-sarcoma. These tumors are sometimes 
called malignant myomata. Such tumors may form metastases.2 Lipo- 
myoma has been described.3 
Myomata of the cervix are rare. They may grow as polypi beneath 
the mucous coat, or produce enlargement of the anterior or posterior 
lips, or may grow outward into the abdominal cavity. 
Myomata of the uterus, either subserous, intraparietal, or submucous, 
containing glandular structures of the type of those in the uterine mucosa, 
are of occasional occurrence (Fig. 548). These glandular or adenoma- 
tous myomata are sometimes 
directly connected with the 
uterine mucous membrane, but 
are often so distant and so en- 
tirely separated from it as to 
justify the conjecture that they 
are derived from some embryonal 
abnormality associated with, the 
development of the Wolffian 
body.4 Similar tumors have 
been described in the round liga- 
ment.5 
Sarcomata may occur as pri- 
mary tumors in the mucous 
membrane of the uterus, either 
in the form of a diffuse infiltra- 
tion or as a circumscribed nodular or polypoid mass. They frequently 
involve the muscular wall, are liable to haemorrhage and gangrene, and, 
particularly in the diffuse form, are liable to recur after removal. They 
may consist largely of spindle or spheroidal cells, or both. It is said that 
sarcoma of the uterus is more liable to occur at an advanced age than at 
an early period, as is the rule with sarcomata of other organs. Giant- 
celled sarcomata have been described. 
A few cases have been described in which, situated usually in the 
upper cervical region, there were lobed or "grapelike" tumors, fibro- 
sarcomatous in character. Some of these contained striated muscle 
fibres. These tumors are malignant.6 
Angioma.-Cavernous angiomata of the wall of the uterus have been 
described. Endothelioma is of rare occurrence in the cervix.7 Myoma, 
lipoma, and chondroma are recorded. 
Fig. 548.-Adenomatous or Glandular Myoma 
of the Uterus 
1 Consult monograph by Breus, "Ueber wahre Epithel fiihrende Cystenbildung d. Uterus-myo- 
men," Leipsic, 1894. 
2 For references to the occurrence of sarcomatous changes in myomata see Cullen, Jour. Am. Med. 
Assn., vol. xlvi., p. 695, 1906. 
3 See Knox, Johns Hopkins Hosp. Bull., vol. xii., p. 318. 
4 Cullen, Johns Hopkins Hospital Reports, vol. vi., p. 133, 1897, bibl.; also Cullen, monograph as 
supplement to Orth's "Festschrift," 1903. 
5 Cullen, Johns Hopkins Hosp. Bull., vol. ix., p. 142, 1898, bibl.; also Blumer, Am. Jour Ob- 
stetrics, vol. xxxvii., p. 37, 1898. 
9 For a study of these tumors see Lawen, Ziegler's Beitr., Bd. xxxviii., p. 177, 1905. 
7 Hurdon, Johns Hopkins Hosp. Bull., vol. ix., p. 186, 1898. bibl 814 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Adenoma.-Between a simple adenomatous hyperplasia of the mucous 
membrane of the uterus, on the one hand (see Figs. 540 and 541), and 
carcinoma on the other,' there is no absolutely sharp morphological dis- 
tinction. But there is a considerable group of growths, to which the 
name adenoma is properly applied, which lie on the border zone between 
the distinctly benign and the definitely malignant new epithelial-tissue 
growths. 
Many epithelial cell growths of the uterus, while adenomatous in 
structure, are so distinctly malignant, and are so liable to develop that 
structural lawlessness characteristic of carcinoma, that it has seemed wise 
to many observers to avoid the name adenoma altogether and class all 
Fig. 549.-Adenoma of the Uterus. 
the epithelial tumors of the uterus among the carcinomata. Others, 
recognizing the benign character of many of the epithelial tumors, make 
a sharp distinction between benign and malignant adenomata. 
It seems to the writer wise to preserve here, as elsewhere in the body, 
the morphological distinction between adenoma and carcinoma. But 
in doing this it should always be borne in mind that the adenomata of the 
uterus, as those of the gastro-intestinal canal, may not only be extremely 
malignant as adenomata, but that the more benign forms are extremely 
prone to develop, both in structure and malignancy, into carcinomata. 
In fact, in many cases we can express the peculiarities of structure in these 
tumors only by calling them adeno-carcinoma. 
The adenomata of the uterus may begin in a simple hyperplasia of the 
mucous membrane, in which glandular development is preponderant (see 
above). When the tumor character becomes established this new gland- 
ular growth is commonly in the form of irregular, often dilated follicular 
structures with a well-marked lumen lined with cylindrical or cuboidal 
cells. It may develop in irregular papillary masses (Fig. 549), the more 
or less abundant fibrous stroma being covered with irregular layers of THE REPRODUCTIVE ORGANS OF THE FEMALE 
815 
epithelium (Figs. 550 and 551). The new growth may project from the 
inner surface of the uterus in the form of ragged lobular masses (Fig. 552), 
or it may infiltrate the submucous tissues (Fig. 553). Or growth in 
both directions may occur at once. 
Fig. 550.-Adenoma of the Uterus. 
Showing a small portion of a glandular and papillary growth. 
The topographical features and clinical stories of many adenomata 
of the uterus are identical with those of the infiltrating and ulcerating 
carcinomata. 
Carcinoma.1-The carcinomata of the uterus commence most fre- 
quently in the cervix and portio vaginalis, and the most common form 
is the epithelioma. The growth of epithe- 
liomata of the cervix uteri proceeds under 
three tolerably distinct forms, which, how- 
ever, frequently merge into one another. 
1. The fiat, ulcerating epithelioma. This 
form of cancer commences as a somewhat 
elevated, flat induration of the superficial 
layers of the cervix, sometimes circumscribed, 
sometimes diffuse. This induration is due to 
the growth of plugs and irregular masses of 
epithelial cells into the underlying tissue (Fig. 
554). Ulceration usually commences early 
and may proceed slowly or rapidly. The 
edges of the ulcer are irregular, indurated, and 
somewhat elevated. The ulceration of the 
new-formed cancerous tissue at the edges is 
usually progressive, so that the vaginal por- 
tion of the cervix, the cervical canal, the 
vagina, and even the bladder and rectum may be involved. More or 
less extensive haemorrhages and necrosis of the base of the ulcer are 
liable to occur. The entire cervix may be destroyed. 
Fig. 551.-Adenoma of the 
Uterus. 
Showing a small portion of the 
epithelium in Fig. 550 more highly 
magnified. Mitotic figures are 
seen in the deeper layers. 
1 Consult for details Cullen, "Carcinoma of the Uterus," 1900. 816 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
2. In another class of cases the carcinomatous growth develops under 
the form of papillary or fungous excrescences, which may form larger or 
smaller masses composed of epitheliomatous tissue. Hand-in-hand with 
this projecting growth there may occur an epithelial infiltration of the 
underlying tissue of the cervix. These growths are often quite vascular 
and may give rise to severe haemorrhages. They may ulcerate and thus 
produce great destruction of tissue. 
3. In still another class of cases there is a more or less deep infiltration 
of the submucous tissue, either diffuse or in circumscribed nodules, 
Fig. 552.-Adenoma of the Uterus. 
Showing the gross appearance of the interior of the uterus with an adenomatous involvement of the 
entire mucosa. 
with epithelial cell masses. We find at first, in the vaginal portion of 
the cervix, in the submucous connective tissue, either nodules or a gen- 
eral infiltration of a whitish new growth. The cervix then appears large 
and hard. Very soon the mucous membrane over the new growth degen- 
erates and falls off; the superficial layers of the new growth undergo 
the same changes. After this the formation of the new growth and its 
ulceration go on simultaneously, producing first an infiltration and then 
destruction of the cervix and often of a part of the body of the uterus. 
The growth frequently extends to the vagina, the bladder, and the rectum 
with the same destructive character, so that we often find the cervix and 
upper part of the vagina destroyed, and in their place a large cavity with 
ragged, gangrenous, cancerous walls (Fig. 555). Less frequently the 
pelvic bones are invaded in the same way. Not infrequently the ureters THE REPRODUCTIVE ORGANS OF THE FEMALE 
817 
are surrounded and compressed by the new growth, so that they become 
dilated. The dilatation may extend to the pelves and calyces of the 
kidneys. The new growth may begin in the cervix and extend uniformly 
over the internal surface of the cervix and of the body of the uterus. The 
entire uterus is converted into a large sac, of which the walls are infil- 
trated with the new growth, while the internal surface is ulcerating and 
gangrenous. In some cases there is a considerable formation of new, 
dense connective tissue, so that the growth has a scirrhous form. 
Fig. 553.-Adenoma of the Uterus. 
Showing the extension of the new growth into the deeper portions of the cervix. The section 
shows one side of the cervix. The epithelium over the portio vaginalis is intact; in the right upper 
region in the figure is seen a ragged erosion of the epithelium lining the cervical canal, and the exposure 
of a portion of the tumor growth upon the free surface. 
In rare cases the growth begins in the upper part of the cervix or in 
the body of the uterus, while the lower part of the cervix is not involved. 
In all of these cases the epithelial cells of the new growth follow more 
or less closely the type of the epithelial cells of the part from which they 
spring. But it has been observed that carcinoma developing from the 
mucous membrane of the body of an inverted uterus, or rarely without 
inversion, may be of the squamous-celled type. 
In still another class of cases, in which the new growth may be in the 
form of nodules, or diffuse infiltrations, or polypoid masses, or may pre- 
sent more or less extensive alterations, the cells are irregular, polyhedral 
in shape, the tumor belonging to the class of glandular or medullary 818 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
carcinomata (Fig. 550). These also usually commence in the cervix, 
and, according to the views of many writers, probably in the mucous 
glands. 
In rare cases the entire wall of the uterus is infiltrated with the new 
growth and the organ is much enlarged. Gelatinous carcinoma some- 
times occurs, but is rare. 
While we may for convenience recognize the above types of carcinoma 
of the uterus, it should be borne in mind, as above stated, that they are 
Fig. 554.-Carcinoma (Epithelioma) of the Uterus. 
Showing ramifying epithelial cell masses. 
often not distinct, and may merge into one another or exist simultane- 
ously. Exudative inflammation is of frequent occurrence in these as in 
other tumors of the uterus. 
As a result of the ulceration of these various forms of carcinoma, recto- 
vaginal fistula? may be formed; the lumbar lymph-nodes may be involved 
and metastases in distant organs are occasionally, though not often, 
formed. Frequent and profuse haemorrhages, gangrenous destruction of 
tissue, the absorption of deleterious materials, etc., are apt to lead to the 
development of a more or less profound anaemia and cachexia. THE REPRODUCTIVE ORGANS OF THE FEMALE 
819 
Fig. 555.-Carcinoma of the Cervix Uteri. 
The infiltrating and ulcerating type. 
Fig. 556.-Carcinoma of the Uterus. Medullary type. 820 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Chorionepithelioma of Pregnancy.1 (Deciduoma Malignum.) 
Malignant tumors derived from chorionic villi or from some abnormal 
form of these, as hydatid moles (see p. 824), and composed of cells more 
or less closely resembling the various types of chorionic epithelium, are 
known as chorionepitheliomata of pregnancy.2 
Characters of the Chorionic Villi.-In order to understand the struc- 
ture and biological characters of these tumors, one must bear in mind the 
Fig. 557.-Chorionepithelioma. 
A mediastinal tumor showing the syncytial cells and the Langhans' cells in characteristic relationship 
to each other. 
nature of the normal chorionic villi. These consist of a vascular con- 
nective-tissue framework which is covered with two layers of epithelial 
cells. The inner layer is formed in general of a single layer of sharply 
defined, polyhedral, transparent cells with oval nuclei. These cells con- 
tain glycogen. They are called Langhans' cells. The outer layer is 
composed of a mass of cells whose outlines are in general indistinct, with 
many nuclei of various shapes, the whole resembling masses of giant cells. 
This outer layer of cells is called the syncytium, and from it small pro- 
toplasmic, bud-like processes-syncytial buds-project. In the later 
1 For an admirable summary of these tumors, with a study of new cases and bibl., see Frank, Jour. 
Amer. Med. Assn., vol. xlvi., p. 248, 1906. 
2 This specific designation is necessary because tumors of similar morphological characters, but 
differently derived occur in non-pregnant individuals, in the testicle, and elsewhere as parts of terato- 
mata. THE REPRODUCTIVE ORGANS OF THE FEMALE 
821 
periods of pregnancy the cell layers are as a rule less distinct than at an 
earlier time. The cells covering the chorionic villi penetrate the maternal 
decidua, mingling with its cells, and may pass into the structures of the 
uterine wall. Certain of the covering cells of the chorionic villi have 
remarkable powers of penetrating the maternal tissues, their invasion 
being apparently secured through lytic action. These are called chori- 
onic wandering cells. They may erode blood-vessels, causing haemor- 
rhage and thrombosis, and may enter the maternal circulation and be 
carried as emboli into the viscera-liver, lungs, etc.1 
It is cells of these three types-Langhans' cells, the syncytium, and 
the chorionic wandering cells-invading the tissues of the uterus, from 
Fig. 558.-Large Cells from Chorionepithelioma of the Uterus. 
Vaginal curettings. 
which they directly derive their nourishment, without the development 
of a special stroma, as is the case of most tumors, that give character and 
malignancy to chorionepitheliomata when they have become freed from 
the restraints of normal growth. 
In typical cases the chorionepitheliomata of pregnancy (Fig. 557) are 
formed: first, of large polynuclear cells or cell masses-syncytial masses 
-appearing in irregular multinuclear strands or branching protoplasmic 
structures; and, second, of more transparent, sharply circumscribed, 
polyhedral cells with single oval nuclei, with glycogen-containing proto- 
plasm. They often contain free blood and fibrin, and the stroma is 
largely made up of the tissue which they invade. 
In many instances these tumors are less typical in structure, depart- 
ing more from the character of the chorionepithelium. The delicately 
outlined transparent cells may be absent; the syncytial masses may 
fail; the whole growth being made up of irregularly shaped cells of 
1 See for a study of embolism of chorionic cells Schmorl, Verb, deutsch. path. Ges., 1904, Bd, viii., 
p. 39; also ibid., Centrbl. f. Gynakol., Bd. xxix., 1905, p. 129. See also Veit, Zeit, f. Geburtshilfe u. 
Gynakol., Bd. xlix., p. 210 822 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
various sizes with nuclei varying in size, but often very large (Fig. 558). 
The cells are sometimes multinuclear. 
Chorionepitheliomata were at first regarded as sarcomata, but are 
now known to be derived from cells of the chorionic villi. In many 
cases they bear an intimate relationship to hydatid moles. 
The development of these tumors often follows the discharge of an 
hydatid mole. In the malignant types there may be invasion of the wall 
of the uterus and the pelvis with repeated haemorrhages and cachexia. 
Vaginal metastases are common and develop early, and there may be 
general metastasis with secondary tumors, most often in the lungs and 
liver. They may develop as a sequel to ectopic gestation, but this is 
rare: they may follow retained placenta.1 
CHORIONEPITHELIOMA WITH TERATOMA. 
Several cases are recorded in which females whose age or condition 
precluded the possibility of pregnancy have developed tumors having 
the characters of the chorionepitheliomata. These it is believed are 
all instances in which teratomata furnished the embryonal ectodermal 
tissues in which the tumors originated. Similarly the so-called chorion- 
epitheliomata of the testicle (Fig. 601), of which several cases have been 
described, are derived from teratomata. 
PARASITES AND CYSTS. 
Echinococcus has been found in the body and neck of the uterus, and 
may rupture into the peritoneal cavity or into the vagina. 
Cysts.-Aside from the cysts which develop in tumors of the uterus, 
the mucous follicles in the cervix are frequently so dilated as to form 
cysts filled with a gelatinous material and more or less epithelium. 
These cysts may be large or small, and are frequently called ovula Nabothi 
(Fig. 543). Sometimes there is an inflammatory growth of new connec- 
tive tissue about these cysts. In other cases the cysts may project 
from the mucous membrane in the form of polypi. Similar changes 
are infrequently found in the body of the uterus from the dilatation of 
occluded uterine glands. Dermoid cysts are rarely found in the walls 
of the uterus. 
Lesions of the Placenta.2 
Aside from the variations from the normal in size, shape, and posi- 
tion, for a description of which we refer to the works on obstetrics, we 
1 For a study of clinical and microscopical variations of these tumors, with suggestions for diagnosis 
see Frank, N. Y. Med. Jour., vol. Ixxxiii., p. 793, 1906. For experimental studies of Leo Loeb on 
the sensitizing of the uterine mucous membranes in animals by the corpus luteum secretion and the 
subsequent production through traumatic stimuli of new tissue growths in the submucosa-"decid- 
uoma, see Loeb, Jour. Am. Med. Assn., 1., 1897, 1908; Ibid, lii., 1471, 1909, and Arch. f. Entwick- 
lungsmech d. Organen, xxvii., No. 1, 1909; also for bibl. of secretion of corpus luteum with exp. study 
see Frank, Arch. Int. Med., vi., 314, 1910. 
2 For a study of the placenta, normal and pathological, see Eden, Journal of Path, and Bact., vol. 
iii., p. 449, 1896, and vol. iv., p. 265, 1897, bibl. THE REPRODUCTIVE ORGANS OF THE FEMALE 
823 
may briefly mention here some of the more important structural changes 
which the placenta may undergo. 
DEGENERATION. 
Fatty and amyloid degeneration and calcification of the placental 
tissue are of not infrequent occurrence. 
HAEMORRHAGE. 
This may occur either on the maternal surface in the decidua, or 
between the foetal surface and the membranes, or in the substance of the 
placenta. The latter form of haemorrhage constitutes the true placental 
apoplexy. This may occur as the result of rupture of a placental sinus. 
The placental tissue is crowded apart, and a blood-clot, often infiltrating 
the parenchyma, is formed. This may lead to abortion, or the blood 
may undergo disintegration and absorption and its place be occupied by 
a cicatrix. The placental tissue in its vicinity may undergo fatty degen- 
eration. Under other conditions, without evidence of rupture of the 
vessels, the placental tissue may become infiltrated with blood in the 
form of an infarction. In this, degenerative changes similar to the above 
may occur, leading to fibrous induration of the placenta. 
The so-called "infarctions" of the placenta vary in size, appearance, 
structure, and origin. They are most frequently due, according to 
Williams, to an endarteritis of the vessels of the chorionic villi. They 
appear to be of little significance when of moderate size.1 
INFLAMMATION. (Placentitis.) 
Suppurative Inflammation of the placenta, with the formation of 
abscesses, is of rare occurrence as the result of injury. 
Chronic Indurative Inflammation of the placenta may result in the 
formation of circumscribed masses of cellular and loose, or dense and 
cicatricial, connective tissue, or in a diffuse formation of connective tissue 
which may interfere with the nutrition of the foetus and cause abortion. 
The new-formed connective tissue may undergo fatty degeneration or 
calcification. 
In another class of cases the new connective tissue is formed mainly 
in the walls of the vessels, particularly the arteries. This may occur in 
circumscribed portions of the vessels, leading to nodular growths around 
the arteries, or it may occur extensively along the various ramifications 
of the vessels, converting them into thick fibrous cords. The change is 
primarily in the adventitia, but all the coats of the vessel may become 
involved, leading to more or less complete obliteration of the lumen. 
Various proliferative and indurative changes in the placenta may 
occur as the result of syphilitic inflammation. 
Tuberculous Inflammation of the placenta may occur in connection 
with other tuberculous processes in the mother. 
1 For a study of placental infarcts see Williams, "Welch Anniversary Contr. to the Science of 
Medicine," 1900, p. 431, bibl. 824 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Moles.-Under various conditions interfering with its nutrition the 
foetus may die and be cast off. The placenta and membranes may 
then dry, forming a fibrous or fleshy or bloody mass-fibrous mole; 
fleshy mole; bloody mole. These are not genuine tumors. 
TUMORS. 
Fig. 559.-Fragment of Decidua in Curettings from the Uterus. 
Fig. 560.-Curettings from the Uterine Cavity showing Portion of Retained Placenta, 
AND OF THE MUCOUS MEMBRANE SHOWING GLANDULAR HYPERPLASIA. 
Placental Polyps.-Not infrequently, especially after abortions, por- 
tions of the placenta (Fig. 559) remain attached in the uterus and may 
undergo various phases of hyperplasia forming polypoid outgrowths 825 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
or diffuse thickening of the mucous membrane, resembling some of the 
forms of moles in character. This condition is often associated with 
Showing a small portion of the mass. 
Fig. 561.-Hydatid Mole. 
Fig. 562.-Hydatid Mole. 
Section of a small portion showing mucous and slightly fibrous tissue covered with a layer of 
epithelial cells. 
glandular endometritis, and curettings of the uterus may then show 
both placental structures and glandular hyperplasia of the mucous 
membrane (see Fig. 560). 826 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Sometimes, however, the placenta, or some part of it, is transformed 
into an irregular mass of rounded pink or colorless transparent or trans- 
lucent bodies, from two to ten millimetres in diameter-hydatid moles 
(Figs. 561 and 562). These bodies, attached to the elongated chorionic 
villi, consist of loose, vascular connective tissue resembling mucous 
tissue and are covered with chorionic epithelium. The cause of this 
transformation of the placenta is unknown. It may be cast off with 
the foetus or there may be no trace of the embryo. But the hydatid mole 
may remain after the foetus is discharged, and through the growth of the 
chorionic epithelium may give rise to chorionepithelioma1 (see p. 821), 
or to chorionepithelial emboli in various parts of the body,2 with meta- 
static growths having the characters of hydatid moles.3 
Cysts of the placenta are of occasional occurrence; their origin is in 
most cases obscure.4 
The Ovaries. 
Malformations. 
One or both ovaries may be absent, the other organs of generation being also absent 
or undeveloped; or they may be only partially developed. Absence or arrest of 
development of one ovary occasionally occurs in otherwise well-formed individuals, 
and is sometimes accompanied by a low position of the kidney on the same side. The 
ovaries may pass into the inguinal canal or into the labia majora, and remain 
fixed there through life. Less frequently they are found in the crural canal or the 
foramen ovale. 
Changes in Size and Position. 
The ovaries may become larger than normal by chronic inflammation, by the 
formation of cysts and tumors. They may become atrophied in old age, the Graafian 
follicles disappearing and the organ shrivelling into a small, irregular, fibrous body. 
Atrophy may be produced by ascites, by chronic inflammation, or from unknown 
causes. As the result of the maturing and rupture of the Graafian follicles, with and 
without pregnancy, the surface of the ovary, which before puberty is smooth, may 
become roughened by irregular cicatricial depressions. 
In adult life the ovaries may pass as herniae into the inguinal or crural canal, the 
foramen ovale, or the umbilicus. Their position in the abdomen may be changed by 
the pressure of tumors, the traction of false membranes, etc. This may occur in 
enlarged ovaries or in those of normal size, and by the compression of the veins may 
lead to congestion and chronic inflammation of the organs. 
HYPERaEMIA AND HaEMORRHAGE. 
Aside from the normal hyperaemia of the ovaries during various sexual 
functions, the vessels may be congested in inflammation, in displacements 
with interference with the venous circulation, in certain diseases of the 
heart, etc., and this may then be followed by chronic inflammation. 
1 See Pick, Berl. klin. Woch., 1897, pp. 1069 and 1097. 
2See Schmorl, Verb. d. deut. Naturf. u. Aerzte, Bd. ii., 1897, part 2, pp. 21 and 111; also ibid., 
Verh. d. deut. Path. Ges., Bd. viii., p. 39, 1904. 
3 For pathology of hydatid mole and chorionepithelioma see Frank, Amer. Jour. Obstet., 1911, 
Ixiv., 435. 
4 See Biland, Ziegler's Beitr., Bd. xl., p. 195, 1907, bibl. THE REPRODUCTIVE ORGANS OF THE FEMALE 
827 
The menstrual periods are accompanied by the effusion of blood into 
a Graafian follicle. Normally the amount of blood is small, becomes 
solid, is decolorized, and then gradually absorbed. Sometimes the effu- 
sion of blood is much greater; the follicle filled with blood is as large as 
a pigeon's egg. The blood may remain in the follicle, and be absorbed 
and replaced by a serous fluid, or through rupture it may escape into the 
peritoneal cavity. Death may ensue from the haemorrhage, or the blood 
may collect in Douglas' cul-de-sac and become encapsulated. Haemor- 
rhages also occur in follicles which have become cystic. Interstitial 
haemorrhage in the ovary sometimes occurs without known cause. 
INFLAMMATION. (Oophoritis.) 
Acute Exudative Inflammation of the ovaries occurs most frequently 
in the puerperal condition, either as part of a general peritonitis or as a 
primary affection. 
With puerperal peritonitis both ovaries are usually inflamed; they 
are swollen, congested, soft, infiltrated with serum or pus, or gangrenous. 
The lesion may involve principally the capsule, the stroma, or the 
follicles. Inflammation of the capsule results in adhesions and collections 
Fig. 563.-Chronic Oophoritis with Dilated Blood-vessels and Cysts. 
1, Dense connective-tissue stroma; b, dilated veins; c, cysts; d. cyst with granular contents; e, cortical 
zone of immature Graafian follicles. 
of pus, shut in by false membranes; of the stroma, in abscesses and 
fibrous induration; of the follicles, in their dilatation with purulent 
serum. 
If the inflammation of the ovary be the primary lesion, it is usually 
confined to one organ. The stroma of the ovary is infiltrated with serum 
and pus, and may contain abscesses of large size. In other cases the 
ovary itself is but little changed, but is surrounded by a mass of fibrinous 828 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
and purulent exudation. Such independent forms of ovarian inflam- 
mation may terminate in recovery; or the abscesses may perforate into 
the rectum and vagina; or the ovary is left indurated and bound down 
by adhesions; or the patient may die. 
Acute exudative inflammation of the ovaries unconnected with the 
puerperal condition is not common, but it may occur in connection with 
acute or chronic peritonitis or perimetritis, with various infectious dis- 
eases, pyaemia, etc. It is usually confined to one ovary. 
Chronic Interstitial Oophoritis is not infrequently preceded by an 
acute inflammation, or it may gradually develop as an independent con- 
dition, often determined by some mechanical interference with the blood 
current. The organ may be increased in size, owing to the formation of 
loose, cellular, or of dense, firm, new connective tissue. Under these 
Fig. 564.-Chronic Oophoritis with Atrophy. 
From a case of valvular disease of the heart with chronic metritis and endometritis, a, Thickened 
and dense interstitial tissue; b, old corpora lutea; c, arteries with greatly thickened walls; d, dilated veins. 
conditions the blood-vessels, especially the veins, may be widely dilated, 
and cysts in varying number and size may be present (Fig. 563). Some- 
times the new-formed dense connective tissue may be largely limited to 
the surface of the organ, so that the albuginea may become dense and 
thick. Under these conditions the surface of the ovary may be smooth 
or rough. 
On the other hand, the organ may be smaller than normal as the 
result of the formation of dense new interstitial connective tissue, and its 
surface greatly roughened and distorted (Fig. 564). Sometimes the for- 
mation of new dense tissue may be largely confined to the walls of the 
arteries, which become prominent and tortuous. Obliterating endarter- 
itis is not infrequent. The atrophied ovary may be largely made up of 
thick-walled arteries and of fibrous masses which are the result of incom- 
plete resolution of the corpora lutea. 
Occasionally a more or less extensive hyperplasia of cells in the corpus THE REPRODUCTIVE ORGANS OF THE FEMALE 
829 
luteum leads to the development of larger or smaller new-formed, convo- 
luted, nodular masses in the ovary, which are sometimes regarded as 
tumors.1 Sarcomata of the ovary appear to originate in such a hyper- 
plasia (see Fig. 567). 
Tuberculous Inflammation of the ovaries is rare, and may accompany 
tuberculous inflammation of other organs, particularly the peritoneum 
and Fallopian tubes. It usually results in the production of dense 
caseous nodules of considerable size. 
Syphilitic Inflammation in the form of gummata is uncommon. 
TUMORS. 
Fibroma is not common nor usually of great importance. Such 
tumors may be small or large. They are usually dense in texture, and 
seem often to originate in the tissue formed in the closure of the ruptured 
Graafian follicle. They may contain cysts or be accompanied by cysts of 
the surrounding stroma. Papillary fibromata of the surface of the ovary 
are not infrequent (Fig. 565). They may contain cysts (Fig. 566), and 
the growth may be transplanted from this situation to the general perit- 
oneal surfaces. Angioma is described. 
Fig. 565.-Papilloma of the Ovary. 
Chondroma of the ovaries is described, but is rare; cartilage not infre- 
quently occurs, however, in dermoid cysts. 
Leiomyoma containing more or less fibrous tissue is of occasional 
occurrence. 
Sarcoma of the ovaries is not common. It is usually primary, and 
may apparently develop from the new-formed cells of the corpus luteum 
(Fig. 567), but may be metastatic. It is usually of the spindle-celled 
variety, but may contain areas of spheroidal-celled tissue or more or less 
1 For a resume of recent studies on the nature of the corpus luteum and its internal secretion see 
Frank, Arch. Int. Med., vi., 314, 1910, with bibl. 830 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
fibrous tissue. The tumors may be hard or soft, and are apt to involve 
both ovaries. Endotheliomata may be found in the ovaries (Fig. 568), 
though tumors of this morphology are now more usually classed as 
carcinomata. 
Carcinoma, usually of the medullary variety, may occur as a primary 
tumor of the ovary. It may be due to a continuous extension from 
neighboring organs, or more rarely it is of metastatic origin. Although 
the medullary carcinomata are the most common, scirrhous, melanotic, 
and gelatinous forms sometimes occur. 
Fig. 566.-Papilloma of the Ovary. 
Shows cyst with papillary growth within. 
Adenoma (Cystic Adenoma; Compound Ovarian Cyst).-These 
growths, which may occur in one or both ovaries, form one of the most 
common and important classes of ovarian tumors. They probably 
originate in the gland epithelium of the ovary either before or after the 
formation of the Graafian follicles. Some of their most noteworthy and 
important features depend upon their tendency to the formation of cysts. 
It should be remembered, however, that the primary lesion is a true new 
formation of glandular tissue, and not, as in the case of most cysts, a 
transformation, by retention or otherwise, of pre-existing structures. 
The growth primarily consists of a fibrous stroma in which are tubu- 
lar follicles lined with cylindrical epithelium-glandular type. Or, in 
some cases, it consists of papillary outgrowths from a fibrous stroma, 
which are covered with cylindrical epithelium-papillary type. THE REPRODUCTIVE ORGANS OF THE FEMALE 
831 
Fig. 567.--Commencement of Sarcomatous Growth in the Ovary. 
From hyperplastic cells of corpus luteum. 
Fig. 568.-Endothelioma of the Ovary. 832 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Glandular Cystadenoma.-There is, as above stated, a marked tend- 
ency, in this form of adenoma, to dilatation of the follicles by a semi- 
fluid material, and the formation of cysts. There may be a number of 
follicles equally dilated, so as to form a number of cysts of moderate size 
(Fig. 559); or a few follicles are greatly dilated to form a large multilocu- 
lar cyst with but few compartments (Fig. 570). The walls of the cysts 
may fuse together and be absorbed, so as to form one large cyst divided 
by incomplete septa-unilocular cysts. The stroma in which the follicles 
and cysts are embedded may be largely developed or very scanty. 
The walls of the larger cysts are composed of fibrous tissue which is 
dense in the outer layers, more cellular in the inner, upon which the 
epithelium is placed. They may be thin and membranous, or there is 
Fig. 569.-Cyst adenoma of the Ovary-(Multilocular Ovarian Cyst-Adeno-Cystoma). 
This photographic reproduction is about four-fifths natural size. 
upon their internal surfaces an intracystic growth composed of a fibrous 
stroma and tubular follicles. These secondary follicles may also be filled 
with fluid and form larger and smaller cysts. The intracystic growths 
may be so large as to fill up the original cysts. Sometimes the intracys- 
tic growth presents very little dilatation of its follicles, so that the entire 
tumor has more the character of a solid growth than of a cyst. 
The cylindrical epithelium lining the cysts usually forms a single layer 
(Fig. 571), but several layers often irregular in thickness may form, and 
owing to the accumulation of fluid the cells may become flattened and 
atrophied, or they may be fatty or desquamated. The contents of the 
cysts differ considerably in different cases, and even in different cysts in 
the same case. They may be tough and ropy, or gelatinous or serous; 
transparent and colorless, or yellow or reddish, or reddish brown; or 
they may be turbid and colorless, or variously colored-red, brown, or 
chocolate. THE REPRODUCTIVE ORGANS OF THE FEMALE 
833 
Chemically the cyst contents, when thick and ropy, include mucin or 
paralbumin, and perhaps other less well-known compounds belonging to 
the same class. It is probable that the contents of these cysts are, so far 
as the mucin and paralbumin are concerned, produced by a metamor- 
Fig. 570.-Cystadenoma of the Ovary. 
Showing large cysts, with a glandular mass within one of the cysts. 
phosis of the protoplasm of the lining cells, similar to that by which the 
mucin is produced in the mucous glands and in mucous membranes. 
The cylindrical cells often present the form of the so-called " beaker 
cells," and in some cases the mucous contents of the cysts are seen to be 
continuous with the similar contents of the beaker cells. It is probable 834 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
that much of the fluid contents of the cysts comes from simple transu- 
dation. 
Microscopically the contents of these cysts present also considerable 
Fig. 571.-Cyst adenoma of the Ovary-Glandular Type. 
variation. We may find almost no structural elements, or there may be 
red blood cells in variable quantity, and leucocytes in various stages 
of granular or fatty degeneration or of disintegration. There may be 
Fig. 572.-Cystadenoma of the Ovary-Papillary Type. 
cylindrical, or flattened, or polyhedral cells, either well preserved, swol- 
len, or in a state of fatty degeneration, or fragments of these cells. It 
is these various forms of cells, often more or less swollen and in a con- THE REPRODUCTIVE ORGANS OF THE FEMALE 
835 
dition of more or less well-marked granular and fatty degeneration, which 
have been considered characteristic of the ovarian cysts and are some- 
times called Drysdale's corpuscles. While, however, they are of frequent 
occurrence under these conditions, they are by no means pathognomonic, 
since we find them in the contents of various kinds of cysts and cavities 
where the cells are undergoing degeneration. In addition to the above 
structural elements we may find free fat droplets, cholesterin crystals, 
pigment granules, and more or less granular detritus. The gelatinous 
material filling these cysts is sometimes called colloid, and the cysts are 
frequently called colloid cysts. 
Numerous secondary changes are liable to occur in these cysts. The 
cells may peel off, the walls of the cysts atrophy or become calcified. 
Fig. 573.-Multiple Papillary Cysts of the Omentum, Secondary to a Similar Growth 
in the Ovary. 
The papillary outgrowths are themselves becoming softened at their centres, forming 
accessory cysts. 
Suppurative inflammation, perforation into the peritoneum, bladder, 
vagina, or rectum; haemorrhage, gangrene, etc., may occur. As a result 
of chronic productive processes, the cyst walls may become thickened 
and extensive adhesions form. Carcinoma may develop from these 
tumors. 
Papillary Cystadenoma.-This type of cystadenoma was formerly 
regarded as but a variety of the form above described-a variety charac- 
terized by papillary outgrowths in cauliflower-like tufts from the walls 
of the cysts, which often in large degree fill the cyst spaces (Fig. 572). 
There appears, however, to be sufficient evidence, both anatomical and 
clinical, to justify the separation of the papillary from the glandular 
form of cystadenoma. . . 
The papillary cystadenomata are not, as a rule, as large as the gland- 
ular form. The cysts are fewer and they do not contain colloid material. 
The papillary outgrowths often break through the cyst walls, and may 836 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
be transplanted to the peritoneal or other surfaces in the form of multiple 
cystic or papillary tumors (Fig. 573). The papillae and cyst walls may 
be lined by cylindrical and often by ciliated epithelium.1 
Follicular Cysts of the Ovary.-The Graafian follicles may be dilated 
so as to form cysts. This may occur in one or both ovaries, and the cysts 
may be small or large, single or multiple (Fig. 574). They are usually 
found after middle life, but may occur during youth, childhood, or 
even in the foetus. The follicles dilate from the accumulation of fluid 
within them; the ovum is destroyed, the epithelium flattened. The con- 
tents are usually serous and colorless, but may be viscid, turbid, purulent, 
or variously colored, red, yellow, or brown. The ovary may be crowded 
Fig. 574.-Follicular Cysts of the Ovary. 
These cysts are associated with chronic inflammation. At the right an old corpus luteum is visible. 
with numerous cysts of moderate size, whose adjacent walls may coalesce 
and atrophy, forming communications between them.2 
A variety of this type of cyst is formed by the dilatation of a corpus 
luteum either with or without the hyperplasia of the wall. 
Dermoid Cysts (Teratomata).-These cysts may be uni- or multilocu- 
lar, are usually of moderate size, but sometimes become as large as a 
man's head or larger. Their fibrous walls may be thick or thin, and 
portions of the internal surface may present more or less completely 
developed cuticular structures, such as corium, papillae, epidermis, hairs 
and hair follicles, sebaceous glands, etc. The cavity may contain a 
thick, whitish, greasy material composed of flattened epithelium, fat, or 
cholesterin crystals. Or the cavity or walls may contain masses of 
irregularly formed hair (Fig. 575), teeth, bone, cartilage, striated muscle, 
thyroid gland,3 and nerve fibres and cells.4 Such embryonal growths, 
1 For reference to bibliography of these ovarian cysts see Russell, Johns Hopkins Hosp. Bull., 
vol. x., p. 10, 1899. 
2 v. Kahlden, Ziegler's Beitr., Bd. xxvii., p. 1, 1900, bibl. . 
3 For a resume with case of thyroid tissue in the ovary (struma ovarii) see Frank, Am. Jour. Obstet., 
lx., No. 3, 1909. 
4 For a study of the origin of dermoid cysts of the ovary see Arnsperger, Virchow's Arch., Bd. 
clvi., p. 1, 1899, bibl; also Askanazy, Bibliotheca Medica, Heft 19, 1905. THE REPRODUCTIVE ORGANS OF THE FEMALE 
837 
may exist for many years without causing inconvenience; but inflamma- 
tory changes may occur in them, 
leading to adhesions and per- 
forations into adjacent organs. 
They may form the nidus for 
the development of carcinoma, 
chorionepithelioma (see p. 820), 
and other tumors, or they may 
calcify. 
In addition to the above- 
described adenoid, dermoid, 
and simple follicular cysts, 
there are a number of com- 
posite forms of not infrequent 
occurrence. Thus, in connec- 
tion with dermoid cysts or 
separately, there may be simple 
ciliated cysts or those which 
partake of the characters of 
both adenoid and dermoid 
cysts. These may be multi- 
locular and be lined with flat- 
tened, cylindrical, or ciliated 
epithelium, and may contain 
epidermal cells, cholesterin or mucin, etc. 
Small cysts, sometimes pedicu- 
lated, sometimes not, of doubtful 
origin and usually of no special sig- 
nificance, are frequently found grow- 
ing from the broad ligament near 
the ovary. The walls are usually 
very thin, lined with flattened epi- 
thelial cells, and the contents serous 
(Fig. 576). 
Teratomata not cystic are of oc- 
casional occurrence in the ovary.1 
Cysts of the Parovarium, lying 
between the peritoneal layers of the 
broad ligament, are usually small, 
but may be as large as a man's head. 
They are usually lined with ciliated 
epithelium, but sometimes with flat- 
tened non-ciliated cells. The con- 
tents may be serous, or may be thick 
and contain mucin and paralbumin. 
One of the cysts contains a mass of hair and 
sebaceous material. 
Fig. 575.-Dermoid Cyst of the Ovary. 
Fig. 576.-Small Pediculated Cyst Grow- 
ing from the Broad Ligament. 
1 Consult Wilms, Ziegler's Beitr., z. path. Anat., Bd. xix., p. 367, 1896; for a summary of views 
see Anspach, Bull. Univ. Pa., xvi., 1903, p. 337 838 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The Fallopian Tubes. 
Malformations. 
Absence of both tubes occurs with absence of the uterus. One tube may be absent, 
with arrested development of the corresponding side of the uterus. Both tubes may 
be imperfectly developed; either of their ends may be closed; they may be inserted 
into the uterus at an abnormal place; they may terminate in two or three abdominal 
ostia. 
Changes in Position and Size. 
The Fallopian tubes may participate in the various malpositions of the uterus and 
ovaries; but they are most frequently displaced by the contraction of adhesions 
formed in perimetritic and periovarial inflammations. 
The lumen of the tube may be partially or completely closed as the result of 
inflammation of the mucous membrane; of peritonitis about the fimbriated extremity; 
The tube at the left is much distended, but still tubular. The tube at the right is dilated to cystic 
form. Between the distended tubes is the fundus of the uterus. 
Fig. 577.-Hydrosalpinx. 
of tumors or inflammation of the uterus; or by pressure from without, or by adhesions, 
tumors, etc. It may become stopped by plugs of mucus or pus. 
Dilatation of the tubes may be produced by an accumulation of catarrhal or other 
exudation, when there is partial or complete stenosis at some portion of the tube. 
The dilatation may be moderate, converting the tube into a tortuous, sacculated canal 
containing mucous or serous fluid; or, more rarely, large cysts may form containing 
several pounds of serous fluid-hydrosalpinx1 (Fig. 577). As the fluid collects the 
1 For a study of hydrosalpinx with full bibliography see Cullen, Johns Hopkins Hosp. Rep., vol. 
iv., p. 351, 1895. THE REPRODUCTIVE ORGANS OF THE FEMALE 
839 
epithelium may become flattened or fatty or may desquamate. Inflammation may 
take place in the walls of the dilated tube and the contents may be mixed with pus or 
blood. Rupture of the dilated tube sometimes occurs; or severe and even fatal 
haemorrhage may take place into its cavity. Papillary growths are sometimes found 
springing from the inner wall of the cyst. 
HAEMORRHAGE. 
Haemorrhage into the tube may occur in puerperal women with retro- 
version of the uterus, with abortions; haematometra and tubal preg- 
nancy; in acute infectious diseases. The blood may undergo degenera- 
tive changes and be largely absorbed, or it may escape into the peritoneal 
cavity and incite peritonitis. 
INFLAMMATION. (Salpingitis.) 
Catarrhal Inflammation of the mucous membrane of the Fallopian 
tubes commonly occurs in connection with endometritis, frequently in the 
puerperal condition. In the acute stage the mucous membrane is hyper- 
semic and swollen, and covered with a mucous or muco-purulent, often 
The distended tube containing pus is attached to the ovary. 
Fig. 578.-Pyosalpinx. 
bloody exudate. The inflammation may subside, leaving no lesions, but 
it more frequently becomes chronic, and may then result in peritoneal 
adhesions, thickening of the walls, obliteration of the tubes, dilatation, 
etc.; or the mucous membrane may undergo hyperplasia with papillary 
outgrowth. Such papillary masses may partially coalesce, forming, on 
the accumulation of fluid, cyst-like cavities lined with epithelium. 
Hyperplasia of the muscle wall of the tube may be associated with these 
conditions.1 
1 Consult Ries, Jour. Exp. Med., vol. ii., p. 347, 1897, bibl. 840 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Suppurative Salpingitis.-Catarrhal inflammation of the mucous mem- 
brane may assume a suppurative character, sometimes in connection 
with puerperal metritis and peritonitis, and often as a result of gonorrhoeal 
infection.1 Under these conditions the wall of the tube may be involved 
and pus may exude from the abdominal ends. It is difficult, in many 
cases of suppurative salpingitis associated with peritonitis, to say which 
is the primary lesion. 
If the abdominal end of the tube be closed by adhesions or otherwise 
there may be a considerable collection of pus in the tubes, causing dila- 
tation-pyosalpinx (Figs. 578 and 579). Such a collection may rupture 
into the peritoneal cavity, or the pus may escape into a cavity shut in by 
Showing a cyst-like distention of the occluded tube. 
Fig. 579.-Pyosalpinx. 
adhesions, or may perforate into the intestine or bladder. Or it may 
dry and finally become calcified. 
Suppurative salpingitis is most commonly incited by the gonococcus 
or the pyogenic bacteria. 
Tuberculous Salpingitis.-The lesions are most frequently seen in the 
later stages of the process, when the mucous membrane is partially or 
entirely converted into a thick, caseous, often ulcerating layer (Fig. 580). 
The lumen of the tubes may be dilated, and the walls thickened from 
chronic inflammation. This lesion may occur by itself, or may be asso- 
ciated with tuberculous inflammation of the lungs, or of the other genito- 
urinary organs, or of the peritoneum. It usually commences at the 
abdominal ends of the tubes, and both tubes are apt to be involved. 
Syphilitic Inflammation, manifested by a diffuse fibrous thickening of 
the wall, has been described. 
1 For a study of gonorrhoeal salpingitis, see Gurd, Jour. Med. Res. xxiii., 151, 1910. THE REPRODUCTIVE ORGANS OF THE FEMALE 
841 
Small fibromata and fibro-myomata sometimes occur in the wall of the 
tubes or in the fimbrise. Small lipomata have been seen between the 
folds of the broad ligament in close connection with the tubes. Papillo- 
mata are rare. Myxoma is recorded. Sarcoma is rare. 
Carcinoma of the tubes is usually, if not always, secondary to carci- 
noma of the uterus or the ovaries. 
Cysts, usually of small size, sometimes pediculated and with thin 
TUMORS. 
Fig. 580.-Tuberculous Salpingitis. 
The wall of a portion of the tube is converted into a dense mass of fibrous and necrotic tissue which 
is disintegrating. 
walls, are frequently seen in the peritoneal covering of the tubes or in 
the fimbrise. They are believed to be of embryonal origin. Combina- 
tion cysts of the tubes and ovaries are of occasional occurrence-retro- 
ovarian cysts.1 
Dilatation of the tubes, as above described, may convert them into 
cyst-like structures. 
Extra-uterine Pregnancy. 
Tubal Pregnancy.-The impregnated ovum, in some way hindered from passing 
into the uterus, may become fixed in the tube, and there develop. The villi of the 
chorion grow into the mucous membrane of the tube, forming an incomplete placenta. 
1 See Orthmann, Virch. Arch., Bd. civ., p. 220, 1899, bibl. 842 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Rare cases are recorded in which the placenta was situated in the uterus while the 
foetus was developed in the tube. The embryo and its membranes are developed until 
they reach such a size that the tube surrounding them ruptures. This may occur in 
the first month or not until much later. In rare cases, when the wall of the tube was 
extensively involved in the formation of the placenta, the development has gone on 
until term. The ovum may remain in the tube after the rupture, or may escape into 
the peritoneal cavity, still enveloped in its membranes; or the membranes may be 
ruptured and left in the tube. The rupture is generally attended with fatal hajmor- 
rhage. In some cases death is caused by the rupture of a dilated vein while the tube 
is still intact. Haemorrhage into the sac may occur before its rupture. 
In rare cases death does not take place and the foetus is shut in by adhesions and 
false membranes. The embryo soon dies. There may be a slow absorption of the 
soft parts of the foetus, the bones are separated and left embedded in a mass of fibrous 
tissue, fat, cholesterin, and pigment; or the foetus retains its shape and becomes 
mummified, and may then be encrusted with the salts of lime (lithopedion). 
On the other hand, degeneration and gangrene of the foetus may take place rapidly, 
with inflammation and suppuration of the surrounding tissue. There may be perfora- 
tion and escape of the broken-down foetus through the rectum, vagina, bladder, or 
abdominal wall. In some cases the foetus may escape through a rupture of the tube 
into the space between the folds of the broad ligament. 
In tubo-abdominal pregnancy the development of the ovum is in the fimbriated 
extremity of the Fallopian tube. Adhesions are formed, so that the foetus is partly in 
the end of the tube and partly in the abdomen. 
Interstitial Pregnancy.-The ovum in these cases is arrested and developed in 
the portion of the tube which passes through the wall of the uterus. 
Abdominal Pregnancy.-The ovum, after escaping from the ovary, may not 
enter the Fallopian tube, but may become fixed to the peritoneum, usually near the 
ovary, and develop in that position. 
Ovarian Pregnancy.-The existence of this form of pregnancy is doubtful and 
difficult to prove, but there are some cases in which it seems probable that the ovum 
develops in its Graafian follicle. The placenta may be attached to the tube or to the 
abdominal wall. 
The Mamma. 
Malformations. 
Arrest of development of the mammae occurs with arrest of development of the 
other reproductive organs, and less frequently alone. 
One or both mammae may be absent. Absence of the nipple is more common. 
Supernumerary mammae and nipples have been observed in a number of cases; the 
glands may all secrete milk during lactation. 
Too early development of the mammae is sometimes found in young children in 
connection with abnormal development of the organs of generation.1 
HEMORRHAGE. 
In young women who suffer from amenorrhoea or dysmenorrhoea, 
small haemorrhages sometimes occur in the mammae at the time of men- 
struation. The blood may find its way into the milk ducts and exude in 
small quantities at the nipple. 
Contusions of the breast may produce extravasations of blood in the 
mammary gland or the surrounding connective tissue. This may 
become absorbed, or may remain and be surrounded by fibrous tissue or 
be converted into cysts. 
1 See Frank and Unger, Arch. Int. Med., 1911, vii., 812. THE REPRODUCTIVE ORGANS OF THE FEMALE 
843 
INFLAMMATION. (Mastitis.) 
During lactation the nipple is liable to become inflamed, and ulcers 
and fissures may form. 
There is a form of eczematous inflammation of the nipple and areola 
a, Milk duct; b, interstitial tissue: c, dense collections of pus; d, diffuse infiltration of lobule with pus. 
Fig. 581.-Suppurative Mastitis in the Non-functionating Gland. 
which tends to ulcerate and in which carcinoma may originate. This 
is known as Paget's disease, and was at one time thought to be due to the 
presence of coccidia. 
Fig. 582.-Chronic Inflammation of Mammary Gland. 
Acute Exudative Inflammation (Mastitis).-This occurs most fre- 
quently during lactation; it also occurs during pregnancy, and occasion- 
ally in women who are neither pregnant nor nursing. 844 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The process may involve the subcutaneous connective tissue, the 
gland itself, or the connective tissue between the gland and the wall of 
the thorax. The inflamed tissues are at first congested, swollen, hard, 
and painful. The inflammation may stop at this point and resolution 
may take place, but more frequently it is succeeded by suppuration. If 
the inflammation involves the subcutaneous connective tissue the abscess 
may be superficial and may soon open through the skin. If the gland be 
involved one lobule after another may become affected (Fig. 581), so that 
Fig. 583.-Carcinoma and Tuberculosis of the Mamma. 
The occurrence of these lesions together is unusual. 
successive abscesses are formed. If the connective tissue beneath the 
gland be inflamed a deep abscess of large size may be formed, which usu- 
ally perforates through the skin, but sometimes into the pleural cavity. 
In both these latter forms of abscess there is apt to be necrosis of large 
portions of tissue. These abscesses may cicatrize, or they may pass into 
a chronic condition and remain for a long time as suppurating, fistulous 
tracts. Suppurative mastitis is usually due to the presence of Strepto- 
coccus and Staphylococcus pyogenes. 
In new-born children there is often a painful swelling of the breasts, 
which usually subsides in a few days, but may go on to suppuration. 
Epidemic parotitis is sometimes complicated by mastitis. THE REPRODUCTIVE ORGANS OF THE FEMALE 
845 
Chronic Inflammation of the interstitial connective tissue of the 
mammary gland may result in the formation of dense connective tissue 
(Fig. 582), with or without cystic dilatation of the milk ducts and atrophy 
of the glandular elements. Acute exudative inflammation may occur in 
a gland which is the seat of chronic inflammation, and abscesses may be 
formed. 
Cystic Hyperplasia.-About the time of the menopause, when the 
mammary gland undergoes involution, the fibrous tissue is apt to increase. 
This fibrous hyperplasia may be excessive, and is then frequently asso- 
Fig. 584.-Hypebtbophy of the Mamma. 
dated with a cystic dilatation of the smaller ducts. The epithelium may 
become atrophied or it may proliferate, and frequently forms papillary 
projections into the dilated ducts. This cystic hyperplasia of the 
mamma, when the epithelial changes are marked, is scarcely to be differ- 
entiated from adenoma, to which indeed it probably frequently leads.1 
Tuberculous Inflammation of the mammary gland and its excretory 
ducts is of occasional occurrence. It may manifest itself in the form of 
miliary tubercles, larger and smaller caseous masses of new-formed tissue, 
1 For a study of this lesion with bibliography see Greenough and Hartwell, Jour, of Med. Res., vol, 
ix., p. 416, 1903. 846 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
or cold abscesses.1 The association of tuberculosis with carcinoma of 
the mamma (Fig. 583) is rare. 
From case shown in Fig. 584. Low power showing topography. 
Fig. 585.-Hypertrophy of the Mamma. 
Showing structure of the enlarged breasts of Fig. 584. 
Fig. 586.-Hypertrophy of the Mamma 
Syphilitic Ulcers may occur in the nipple either as primary chancres or 
as mucous patches. Gummy tumors have been observed in the mamma. 
1 See a bibliographic summary of tuberculosis of the breast by Scudder, Am. Jour. Med. Sei., vol. 
cxvi.. p. 75, 1898. THE REPRODUCTIVE ORGANS OF THE FEMALE 
847 
Hypertrophy.-There may be a general hypertrophy of one or both 
breasts. This is usually found in young, unmarried women, but some- 
times in women in advanced life. The glands may be symmetrically 
and excessively enlarged (Fig. 584). There is an increase in both the 
glandular and the connective-tissue elements of the organ1 (Figs. 585 
and 586). 
TUMORS. 
Fibroma.-Circumscribed tumors composed of connective tissue are 
sometimes found in the breast. They are dense and hard, and may 
enclose some of the gland ducts and acini. 
Fig. 587.-Intracanalicular Fibroma of the Mamma. 
Intracanalicular Fibroma.-These tumors are formed by a diffuse 
growth of connective tissue, and a growth of polypoid fibrous tumors 
from the walls of the milk ducts into their cavities leading to dilatation. 
1 For a study of hypertrophy of the breast see Kirchheim, Arch. f. klin. Chir., Bd. Ixviii., 1903, bibb 848 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
The glandular acini may be atrophied, or enlarged, or cystic. A section 
of such a tumor looks like a solid mass of fibrous tissue, divided by clefts 
and fissures lined with cylindrical or cuboidal epithelium (Fig. 587), or 
fibrous tissue containing cysts into which project polypoid fibrous out- 
growths from the walls. Sometimes, the new-formed fibrous growths 
into the dilated ducts are adenomatous in character, containing many 
new-formed irregular acini (Fig. 588). Such tumors may be called intra- 
canalicular fiibro-adenomata. These tumors grow slowly, but if left to 
themselves may reach an enormous size. The skin over them may ulcer- 
ate and the tumor project through the opening in fungous masses. They 
may be associated with interstitial fibrous hyperplasia of the gland. 
Pericanalicular Fibroma.-Sometimes the new connective tissue forms 
a more or less thick cylindrical investment of the duct without growing 
Showing new-formed gland acini in the fibrous-tissue mass growing into a duct. 
Fig. 588.-Intracanalicular Fibro-Adenoma of the Mamma. 
into its lumen. This formation, which is shown in Fig. 589, is some- 
times called pericanalicular fibroma. 
Myxoma.-This may be a circumscribed growth replacing part of 
the mamma, or it may form in the same way as the intracanalicular fibro- 
mata. It is not uncommon in these intracanalicular tumors to find a 
combination of fibrous, mucous, and sarcomatous tissue in the same 
tumor. 
Osteoma and Chondroma are rare forms of tumor in the mamma. 
A few cases have been described in which they were combined with car- 
cinoma or with sarcoma. Osteochondroma is described.1 
Lipoma, myoma, and angioma are described. 
1 For a study of the cartilaginous and bony tumors of the breast see St. Arnold, Virch. Arch., Bd. 
cxlviii., p. 449, 1897. 849 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Adenoma.-Tumors composed of glandular acini and ducts surrounded 
by connective tissue are of frequent occurrence in the mamma (Fig. 
Fig. 589.-Pericanalicular Fibroma of the Mamma. 
These new-formed acini, while maintaining the gland character, are still quite atypical in form and 
grouping and in the irregularity of the epithelium. 
Fig. 590.-Adenoma of the Mamma. 
590). They are either single or multiple, or several may be developed 
successively in the same breast. They grow, as a rule, at first slowly, 850 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
afterward more rapidly. Their structure may be further complicated 
by the dilatation of one or more of the ducts which compose the tumor 
into cysts, and the ingrowth of connective tissue from the walls of these 
cysts. This growth is often in papillary form-papillary cystadenoma- 
(Fig. 591). A case of cystic adenoma with ciliated epithelium has been 
described.1 
While preserving the gland type the adenomata present great varia- 
tion in the form and grouping of the epithelial cells of the ducts and acini, 
so that here as elsewhere various intermediate forms may be found be- 
tween adenoma and carcinoma.2 The new-formed glandular epithelium 
often presents two types, one in which the cells are fairly distinct and 
cuboidal or cylindrical (Fig. 592), and the other in which the cells pro- 
ject into the lumina in irregular masses (Fig. 593). 
Fig. 591.-Papillary Cystadenoma of the Mamma. 
Sarcoma.-These tumors may develop in a nodular or diffuse form 
and may largely replace the gland, or may form intracanalicular growths. 
They may be of the round or spindle-cell type; they often become very 
large, and ulcerate. Metastasis in the axillary lymph-nodes is usual.3 
Primary Carcinoma of the mamma is most common in women be- 
tween the ages of thirty-five and fifty-five, but it sometimes occurs in 
women not over twenty, and sometimes in old persons. It occurs in 
either breast, in the right rather more frequently than in the left, but 
sometimes in both. The growth begins more frequently at the periphery 
of the gland than at its centre, and more frequently in the upper edge of 
the gland than in any other place. 
The growth most frequently begins as a small, circumscribed nodule, 
1 Buday, Virchow's Arch., Bd. clvi., p. 395, 1899. 
2 See Cystic hyperplasia, p. 845. 
3 For a case of giant-celled sarcoma and carcinoma in the same breast see Schlagenhauf er, Cbl. f. 
Path., Bd. xvii., 1906, p. 385. THE REPRODUCTIVE ORGANS OF THE FEMALE 
851 
which enlarges and involves more and more of the breast; sometimes, 
however, it is diffuse from the first, and sometimes it begins in the nipple. 
It may infiltrate the adjacent tissues and the axillary and cervical 
glands, and form metastatic tumors in different parts of the body.1 
The local extension of carcinoma often takes place through the lymph- 
vessels which pass along the fibrous trabeculae of the periglandular fat; 
Fig. 592.-Adenoma of the Mamma. 
Type of acini lined with duct epithelium. 
so that bands of fibrous tissue harboring tumor cells, with their active 
capacity for growth, may extend far from the central mass (Fig. 594). 
Fibrous bands of such significance are, in the early stages of extension, 
not to be differentiated from the normal, either by the touch or by the 
eye. Even with the microscrope it is often impossible to determine 
whether small spheroidal or polyhedral cells w'hich are not character- 
istically grouped in these fibrous bands are epithelial in character or not. 
Type of acini lined with irregular epithelial cell masses. 
Fig. 593.-Adenoma of the Mamma. 
It is such cells, frequently left behind in other than thorough operations, 
which give rise to local recurrence. 
The medullary and fibrous types are most common; the gelatinous is 
rare. In any of these forms of cancer there may be cystic dilatations of 
the ducts and acini. Epithelioma may form at the nipple. Secondary 
carcinoma of the mamma is rare. Retraction of the nipple is common in 
later stages of fibrous types of mammary cancer (see Fig. 594). 
1 For a study of dissemination of carcinoma of the breast see Stiles, Brit. Med. Jour., vol. i., p. 1452, 
1899. 852 
THE REPRODUCTIVE ORGANS OF THE FEMALE 
Cysts of the mamma seem to be for the most part retention cysts, 
formed by the dilatation of the gland ducts or acini. During lacta- 
tion such retention cysts are sometimes formed, and then contain milk. 
They may reach an enormous size. At other times retention cysts are 
formed containing serous or viscid, brownish fluid, which often exudes 
Fig. 594.-Carcinoma of the Mamma-Fibrocs Type-Scirrhus. 
The nipple is retracted by the shrinkage of the fibrous tissue. The growth is extending along 
the fibrous bands of the mammary fat and at the left has reached the plane of excision The darker 
portions in the figure are lobules of fat. 
through the nipple. These cysts may be large or small, single or multi- 
ple. There are usually at the same time some growth and induration of 
the connective tissue of the gland. In some cases there are polypoid 
outgrowths of connective tissue from the wall of the cyst. These cysts 
are not to be confounded with the cysts which are developed with the 
intracanalicular tumors, described above. CHAPTER XL 
REPRODUCTIVE ORGANS OF THE MALE. 
The Penis. 
Malformations. 
The penis may be absent with great defects of development of the rest of the body. 
The urethra then usually opens into the rectum. 
An abnormally small penis may be associated with absence or arrested develop- 
ment of the testicles. The prepuce may be rudimentary or absent. 
Congenital phimosis is not uncommon. 
Hypospadias is an arrest of development of the penis and scrotum. In its high- 
est degree the penis is short, the glans penis small. On the lower side of the penis is a 
deep cleft lined with mucous membrane. Into this cleft the urethra opens at the root 
of the penis. The scrotum remains separated into two halves, resembling labia 
majora. The testes may descend into their proper position on each side or remain in 
the abdomen. If the testicles continue to develop normally the individual has the 
appearance and capacities of a man; if their development is arrested the individual 
is apt to be of feminine type. 
In lesser grades of hypospadias the two halves of the scrotum are joined and the 
penis is larger, but a part of the urethra remains open as a cleft at some point of the 
penis. 
Epispadias is an opening of the urethra on the upper side of the penis. It pre- 
sents various grades and forms. 
Hermaphroditism.-This is a union of two sexes in the same person, the test of 
which is the presence of the secreting organs, the ovaries and testicles. True her- 
maphroditism is rare, but it does occur, while most of the conditions called her- 
maphroditism are in reality due to varying malformations of the external generative 
organs. 
Pseudo-hermaphroditism.-In the male, normally, the greater part of Muller's 
canal disappears and its lower end forms the vesicula prostatica. In this malforma- 
tion Muller's canal is changed, as it is in the female, into Fallopian tubes, uterus, and 
vagina, while at the same times the testes, epididymides, vesicula; seminales, and 
spermatic cord are formed as usual. In the lesser degrees of this malformation we 
find, in the place of the vesicula prostatica, a pear-shaped sac as large as a pigeon's egg, 
with muscular walls and an epithelial lining. This sac may be incompletely divided 
into a uterus and vagina, and it opens into the urethra. In the higher grades we find 
a well-formed vagina and uterus. The uterus may or may not have Fallopian tubes. 
The testicles are usually retained in the abdomen or inguinal canals, and are small. 
The spermatic ducts run on the sides of the uterus and open into the urethra or are 
closed. The penis and scrotum appear as in hypospadias, or are well formed. The 
appearance of the individual varies with the development of the testicles. 
True hermaphroditism may be lateral. In this condition there is hypospadias; a 
vagina and uterus and a Fallopian tube and ovary are on one side, and a testicle and 
spermatic cord on the other. 
In certain cases, which may be called bilateral hermaphroditism, there is a testicle 
on one side and an ovary on the other.1 
Enlargement of the penis is sometimes caused by venous congestion from 
1 For a detailed consideration of the malformations of the male and female generative organs 
consult Klebs, "Handbuch der pathologischen Anatomie," and more recent cases of hermaphroditism 
by Heppner, Arch. f. Anat. u. Physiol., 1870, and by Hofmann, Wien. med. Jahrb., 1877. 
853 854 
REPRODUCTIVE ORGANS OF THE MALE 
heart disease; by long-continued masturbation, as a result of which the corpus caver- 
nosum may lose its contractility; and in rare cases by hyperplasia of the stroma of the 
corpus cavernosum. 
INJURY AND HAEMORRHAGE. 
Injuries to the penis are liable to give rise to severe haemorrhage on 
account of its peculiar vascular character; suppurative inflammation, 
gangrene, infiltration with urine and its consequences, are also liable to 
occur. The contractions of the cicatricial tissue by which wounds are 
healed frequently give rise to various distortions of the organ. 
INFLAMMATION. 
Balanitis-inflammation of the glans penis and the prepuce-is 
usually due to gonococcal or syphilitic infection, or it may be incited by 
foul accumulations of smegma. The parts are red and swollen and may 
ulcerate. Condylomata may be formed, and adhesions between the pre- 
puce and glans. The glans may ulcerate and the prepuce may be much 
thickened. If the prepuce be long, phimosis may occur with the accumu- 
lation of exudate beneath. The prepuce may become gangrenous. 
Paraphimosis is produced by the retraction of a narrow prepuce be- 
hind the glans, with consequent stricture, inflammation, and sometimes 
gangrene. 
Inflammation of the Corpora Cavernosa may be the result of injury, 
may follow fistulse, may occur in connection with inflammation of the 
connective tissue of the penis, and may accompany the acute infectious 
diseases. It may result in fibrous induration of portions of the corpora 
cavernosa; rarely in abscess or diffuse purulent infiltration; sometimes 
in gangrene. Larger and smaller masses or plates of very dense fibrous 
tissue sometimes form in the sheath of the corpora cavernosa without 
history of antecedent lesion.1 
Tuberculous Inflammation of the penis has repeatedly followed cir- 
cumcision performed by uncleanly tuberculous persons. 
Syphilitic Ulcers frequently occur in the glans penis and prepuce. 
The indurated chancre is formed either from an excoriation in which 
a pustule is formed or from a little nodule. The pustule breaks and 
its walls are infiltrated with small round cells. The nodule softens, 
breaks down, and forms an ulcer whose walls are infiltrated with cells. 
Syphilitic condylomata are of frequent occurrence on the glans. 
Herpes of the prepuce occurs in the form of small vesicles, which may 
later become ulcers. Erysipelatous and furuncular inflammation some- 
times involves the skin of the penis. 
TUMORS. 
Papilloma is found on the prepuce and glans penis. It occurs in the 
form of little warty growths, or of composite, cauliflower masses, even 
as large as a fist. In either case the structure is the same-hypertro- 
1 For a study with bibliography of indurations in the corpora cavernosa penis see Sachs, Wiener 
klin. Wochenschr., Jan. 31st, 1901. REPRODUCTIVE ORGANS OF THE MALE 
855 
phied papillee covered with epithelium. Sometimes the epithelial layers 
become thick and horny, forming large, dense projections. 
Fibroma diffusum, or elephantiasis of the prepuce, may occur, leading 
to great thickening. It is due to a diffuse growth of fibrous tissue in the 
cutis. Lipoma, angioma, circumscribed fibroma, and sebaceous cysts may 
occur in the penis. Carcinoma is usually of the epitheliomatous type. 
It is most frequent in the prepuce and glans penis. It may have the form 
of a flat ulcer, or of infiltrating, ulcerating nodules, or it may be papil- 
lary. Such growths may attain great size, ulcerate, or undergo a variety 
of inflammatory changes. Carcinoma may involve the entire skin of the 
penis or may invade deeper parts. The inguinal glands may be involved. 
Distant metastases are not frequent. Medullary or glandular carcinoma 
of the penis is not common. It may be secondary to carcinoma in some 
other part of the body. 
Sarcoma is described. 
Dermoid tumors of the penis are of occasional occurrence.1 
Calcification and ossification of the connective tissue of the corpora 
cavernosa sometimes occur. Large and small preputial calculi are occa- 
sionally found between the prepuce and the glans. These may be formed 
in situ, may come from the bladder or from without, and may later 
increase in size. 
The Scrotum 
The skin of the scrotum is subject to the various forms of lesions 
which may occur in any part of the integument. 
Elephantiasis of the scrotum consists in the main of a development of 
new connective tissue in the cutis, which is sometimes accompanied by 
dilatation of the lymph-vessels; thus the thickened scrotum may form a 
large tumor, often rough upon the surface, which may entirely cover in 
the penis. 
TUMORS. 
Lipoma and fibroma occur. Epitheliomata, in the form of flat or 
papillary ulcerating tumors, are of frequent occurrence among chimney 
sweepers, and may lead to extensive ulcerations of the adjacent parts and 
involvement of neighboring lymph-nodes. 
Dermoid Cysts and Teratomata of the scrotum are not uncommon. In 
very rare cases tumors containing a considerable portion of a foetal skele- 
ton have been found in the scrotum. Occasionally the skin of the scro- 
tum is beset with numerous larger and smaller sebaceous cysts, which 
raise the surface into little globular or wart-like projections. 
The Testicles. 
Malformations. 
Absence of both testicles, either with or without absence of the epididymides, 
spermatic cords, and vesicuke seminales, occurs in rare cases. The scrotum is only 
1 Gerulanos, Deut. Zeits. f. Chir., Bd. lv., p. 326, 1900. 856 
REPRODUCTIVE ORGANS OF THE MALE 
indicated or may contain the epididymides. The penis is small, and the individuals 
are small and poorly developed. 
The testes may be imperfectly developed. The individuals are effeminate. 
Absence of one testicle with healthy development of the other, is more frequent. 
The corresponding epididymis and cord may be absent or present. 
The spermatic cords and vesiculae seminales may be absent or imperfectly devel- 
oped on one or both sides, while the testes are normal. 
Cryptorchismus.-Either one or both testicles may remain permanently in their 
foetal position, or may not descend into the scrotum for several years after birth 
(cryptorchismus), or not at all. This condition may be due to an arrest of develop- 
ment in the testes or the gubernaculum testis; adhesions produced by antenatal perit- 
onitis; narrowing of the inguinal canal; nar- 
rowing or shortening of the vaginal process 
of the peritoneum; or to abnormal size or 
position of the testicle. Usually the mal- 
formation is confined to one testicle, and 
then is more frequent on the left side. The 
testicle is usually found in the abdomen close 
to the mouth of the inguinal canal, or in the 
inguinal canal just below the external ring; 
but it may be beneath the skin in the peri- 
neum, or in the crural canal with the femoral 
vessels, or elsewhere. The retained testis is 
usually not fully developed, or undergoes 
fatty degeneration or fibrous hyperplasia. 
The retention of one or even of both testicles 
does not preclude the possibility of procrea- 
tion. Retained testicles are prone to inflam- 
matory changes and liable to become the 
seat of malignant tumors.1 
Sometimes, while the testis is retained, the 
epididymis and spermatic cord descend into 
the scrotum. In rare cases the position of 
the testis may be changed so that the epi- 
didymis and cord are in front. The occur- 
rence of supernumerary testicles is described. 
Varicocele. 
In varicocele the veins of the spermatic 
cord are dilated, often forming tortuous 
masses of considerable size (Fig. 595). 
In hydrocele of the tunica vaginalis there 
is an accumulation of fluid in the cavity of 
the sac. It is usually unilateral and is com- 
monly associated with acute or chronic in- 
flammation of the tunica vaginalis, vari- 
cocele, or general dropsy. The serum is 
present in small or in large quantity; it is usually transparent, may contain choles- 
terin, or be purulent or mixed with blood. The tunica vaginalis remains unchanged, 
or is thickened, or contains plates of bone, or is covered with polypoid fibrous bodies 
which may fall off and be found free in the cavity of the sac. There may be adhesions 
between the layers of the tunica vaginalis, and in this way the fluid becomes sacculated. 
The testis is pushed downward and backward; it remains unchanged or is atrophied. 
In hydrocele of the processus vaginalis there is an accumulation of serum in the 
cavity of the vaginal process of the peritoneum, which remains open after the descent 
of the testicle. There are several varieties. 
Hydrocele. 
The distended and tortuous vessels have 
been filled with wax. 
Fig. 595.-Varicocele. 
1 For histology of undescended testicle see Unffreduzzi, Arch. Klin. Chir., 1913, c., 1151; and ci., 150. 857 
REPRODUCTIVE ORGANS OF THE MALE 
(a) The vaginal process is entirely open and there is a free communication with 
the peritoneal cavity. The serum may originate in the cavity of the peritoneum or 
of the vaginal process, and passes freely from one to the other. 
(b) The processus vaginalis is closed in the inguinal canal, while its lower portion 
is filled with serum. 
(c) The processus vaginalis is closed about the testis and the visceral layer of the 
tunica vaginalis is formed. The serum accumulates in the upper part of the vaginal 
process which communicates with the peritoneal cavity. 
(d) The vaginal process is closed in the inguinal canal and over the testis; the 
serum accumulates so as to form one or more sacs between these two points. Inguinal 
hernia may complicate this form of hydrocele. 
In hydrocele of the spermatic cord there is general oedema or the development of 
circumscribed cysts in the connective tissue of the cord. 
A peculiar type of hydrocele is formed by the accumulation of serum in the sac of 
an inguinal hernia from which the intestine has become retracted. 
In hsematocele of the tunica vaginalis there is an effusion of blood into the cavity 
of this sac. It may occur in injury; in scurvy, or with the haemorrhagic diathesis; or 
it may complicate a pre-existing hydrocele. The effused blood usually soon degen- 
erates, and the sac is filled with a brownish fluid or a thick, grumous mass. The 
tunica vaginalis may be thickened. The testis remains normal or is atrophied. 
Effusion of blood into the loose connective tissue of the scrotum is often called 
extravaginal hamatocele. 
Haematocele of the spermatic cord occurs in rare cases as a diffuse infiltration of 
blood in the connective tissue of the cord. Or blood may be effused into a hydrocele of 
the cord. 
Haematocele. 
Cysts containing spermatic fluid not infrequently arise from the epididymis or 
from the rete testis. These sometimes acquire a large size and crowd the tunica vag- 
inalis before them, so that they simulate a collection of fluid in the cavity of the latter. 
The wall of the cyst may be lined with ciliated or with flattened epithelium. The 
contents are sometimes simply serous, but more frequently opalescent, and may con- 
tain spermatozoa. 
Spermatocele. 
ATROPHY. 
Atrophy of the testicle may occur in old age or in persons who are in 
a condition of premature senility; or as the result of injury or of pressure 
from hernise, hydrocele, or inflammatory products. Fatty degeneration 
and the accumulation of various degeneration products in the lumen of 
the tubules may accompany atrophy. 
INFLAMMATION. (Orchitis.) 
Inflammation of the testicles may follow injuries, exposure to cold, 
and inflammation of the urethra; it may occur in parotitis or with 
syphilis and various other infectious diseases. The testes, epididymis, 
or tunica albuginea may be principally involved. Usually only one 
testicle is inflamed, sometimes both. The inflammation may extend to 
the vas deferens. 
Acute Exudative Orchitis is most frequent in the epididymis and tunica 
albuginea. When the testis is involved the organ is congested and infil- 
trated with serum or pus. From this condition it may return to the 
normal state; or small abscesses may form which may be absorbed, or 858 
REPRODUCTIVE ORGANS OF THE MALE 
increase in size so as to involve nearly the entire organ. They may 
perforate externally, and then healing may occur by means of granula- 
tion tissue; or extensive gangrenous destruction of the scrotum may 
occur. Abscesses may become enclosed in a fibrous capsule, when the 
contents may dry and become caseous or calcified, and so persist for a 
long time. The acute inflammation may become chronic. 
Acute epididymitis is frequently the result of gonorrhoeal infection, 
and may or may not be associated with inflammation of the testis. The 
products of inflammation may collect in varying quantity in the lumina 
of the seminiferous tubules and in the ducts of the epididymis, and the 
epithelium of these structures may degenerate. 
Chronic Orchitis occurs as a sequel of acute inflammation or as an 
independent process. It may involve the testis, the epididymis, or the 
Fig. 596.-Chronic Interstitial Orchitis with Atrophy of the Seminiferous Tubules. 
a, Thickened interstitial tissue; c, thickened membrana propria of the tubules; d, separated epithelial 
cell mass in the lumen of the tubules. 
spermatic cord. The seminiferous tubules may be filled with desqua- 
mated and degenerated epithelium; they may be atrophied, or their walls 
may be greatly thickened so that they are converted into dense fibrous 
cords, with partial or complete obliteration of their lumina. There is 
usually a marked increase in the interstitial tissue, which causes atrophy 
of the tubules (Fig. 596). The albuginea may be greatly thickened. In 
some cases the testis is converted into a mass of dense fibrous tissue, in 
which but little trace of the original structure can be made out. The 
new-formed fibrous tissue may become calcified. A periorchitis may 
lead to thickenng and union of the layers of the tunica vaginalis testis. 
Abscesses are not infrequent in connection with chronic orchitis. 
Tuberculous Orchitis may occur in connection with tuberculosis of the 
other genito-urinary organs or the lungs, in acute general miliary tuber- 
culosis, or independently. It usually originates in the epididymis, and 
may extend from there to the testis; or it may commence in the testis. REPRODUCTIVE ORGANS OF THE MALE 
859 
The appearance which the testicles present, when they are the seat of 
this form of inflammation, are exceedingly varied and often difficult of 
interpretation. This is partly due to the complex structure of the organ, 
partly to the varied complicating simple inflammatory changes which 
the different parts of the organ undergo in connection with the tuber- 
culous lesion. 
We may find in the testicle small circumscribed masses of cells, visi- 
ble to the naked eye as whitish spots, which are sometimes composed of 
small spheroidal cells or of larger polyhedral or fusiform or round cells. 
These occur in the walls of seminiferous tubules and blood-vessels, and 
in the interstitial tissue. Sometimes associated with these smaller nod- 
ules, and sometimes not, we find larger, irregular, yellowish or gray 
cheesy masses, which may be formed by the confluence' and degeneration 
Fig. 597.-Tuberculous Orchitis. 
of the smaller nodules (Fig. 597). The cheesy masses may break down 
and open externally, giving rise to fistula, gangrenous inflammation, etc. 
Hand-in-hand with this distinctly tuberculous nodular formation of 
tissue, which is disposed to degenerative changes, there are various more 
or less diffuse alterations of the parenchyma and interstitial tissue of 
the organ which often constitute a most prominent feature of the lesion. 
The interstitial tissue may be more or less densely and diffusely infil- 
trated with small spheroidal cells. The arteries are often the seat of 
obliterating endarteritis. The walls of the seminiferous tubules may be 
very much thickened, so that the lumen may be entirely obliterated. 
The epithelium lining the tubules may be fatty, disintegrated, and peeled 
off, or it may have largely disappeared. The lumen of the tubules may 
be filled with a granular, nucleated mass which in transverse sections 
looks like a giant cell. The thickened walls of the tubules may be infil- 860 
REPRODUCTIVE ORGANS OF THE MALE 
trated with small spheroidal cells, so that the underlying stroma is 
scarcely visible. When this occurs in connection with a similar infiltra- 
tion of the interstitial tissue and the formation of giant cells in the lumina, 
we have structures which present the greatest resemblance to some forms 
of tubercle granula (Fig. 598). 
Tuberculous inflammation may extend from the testis to the vas 
deferens, vesiculae seminales, and prostate. 
Syphilitic Orchitis.-This may occur in the form of a diffuse new for- 
mation of connective tissue, which may be localized or be widely dis- 
Fig. 598.-Chronic Orchitis with the Formation of Structures Resembling Miliary Tubercles 
a, Thickened interstitial tissue; b, mass of granular cells in the interstitial tissue; c, thickened 
membrana propria of seminiferous tubule; d, mass of separated epithelium in tubule; e, accumulation 
of small spheroidal cells around tubules; /, thickened membrana propria enclosing g, a multinuclear mass 
resembling a giant cell. 
tributed. This organ becomes dense and firm. Morphologically there 
is no difference between this form of orchitis and chronic indurative 
orchitis from other excitants. It may occur in children affected with 
congenital syphilis. Gummata may form in connection with the 
interstitial induration. These may disappear, leaving irregular cicatrices. 
In leprosy, inflammatory foci in the testicle are common.1 
TUMORS. 
Fibromata occur in the form of small dendritic or polypoid growths of 
the visceral layer of the tunica vaginalis. These sometimes become free 
and are found in the sac, usually in connection with hydrocele. Small 
nodular fibromata occasionally occur in the albuginea and in the sper- 
matic cord. 
Lipoma, either pure or in combination with myxoma and sarcoma, 
may arise from the connective tissue of the spermatic cord or from the 
tunica albuginea. 
Chondroma, sometimes in a pure form, but more frequently combined 
with myxoma and sarcoma, occurs in the testicles and may attain a large 
size. Osteoma has been described. 
1 For a summary of orchitis, consult Sebileau, Arch. gen. de med., t. i., pp. 636 757, 1899, bibl. REPRODUCTIVE ORGANS OF THE MALE 
861 
Sarcomata occur in the testes and epididymis, most frequently in the 
former. They may be composed of spheroidal or spindle-shaped cells; 
they may be soft or contain much fibrous tissue; they are very frequently 
combined with myxoma, chondroma, lipoma, etc. Owing to the occlu- 
sion of the seminiferous tubules, cysts may be formed in these sarcomata. 
In such cysts sarcomatous tissue may occur in the form of intracanalicular 
polypoid growths. Thus the so-called cystosarcomata of the testicle 
are formed. The wralls of these cysts may coalesce, so that large, 
irregular cavities may be formed. When the cysts are not filled by 
polypoid outgrowths from their walls they may contain a mucous, serous, 
or bloody fluid, or masses of flattened cells, fat, and cholesterin. The 
cysts may be lined with cylindrical, ciliated, or flattened cells. 
Imperfect striated muscle fibres lie in an embryonal connective tissue. 
Fig. 599.-Rhabdomyoma of the Testicle. 
Rhabdomyoma has been several times observed, frequently in com- 
bination with cysts.1 
Myoma and angioma are described. 
Adenoma is occasionally found, usually in combination with sarcoma 
or carcinoma, or with cyst formation. 
Carcinoma of the testicle is commonly of the soft medullary form, of 
rapid growth, and usually primary. It may commence in the testis or 
epididymis. Usually only one testicle is involved. Frequently the 
entire glandular portion of the organs is replaced by the new growth. 
The albuginea expands with the growth of the tumor, and may continue 
to enclose it even when of large size. The tissues are often very vascular, 
and haemorrhages, areas of softening, fatty and mucous degeneration are 
frequent. The inguinal and lumbar lymph-nodes are apt to become 
involved, and distant metastasis may occur. Rarely the growth assumes 
a scirrhous form. 
1 For study of rhabdomyoma see Becker, Virchow's Arch., Bd. clxiii., p. 244, 1901, bibl. 862 
REPRODUCTIVE ORGANS OF THE MALE 
Masses of hyaline cartilage at the left; new-formed atypical glandular structures at the right. 
Fig. 600.-Teratoma of the Testicle. 
Fig. 601.-Chorionepithelioma of the Testicle. 
Showing syncytium and Langhans' cells and their relation to blood sinuses. REPRODUCTIVE ORGANS OF THE MALE 
863 
Cysts.-Aside from the above-mentioned cysts, which occur in con- 
nection with tumors and spermatocele, cysts may be formed from per- 
sistent remnants of Muller's canal in the epididymis, or from obstruction 
of the seminiferous tubules or ducts by inflammatory products or tissue. 
Teratomata of various kinds, with or without cysts, are of infrequent 
occurrence, and are sometimes quite complex in character (Fig. 600). 
They may be embedded in the substance of the gland.1 Probably some 
of the above-mentioned cystic rhabdomyomata belong here. 
Chorionepithelioma.-Several cases of chorionepitheliomata of the 
testicle have been described. These tumors (Fig. 601) resemble those 
occurring in the uterus and elsewhere (see p. 820), the various forms of 
cells, syncytium, Langhans' cells, and wandering chorionic forms, being 
in some instances typical in character. They are malignant and form 
metastases. They are associated with teratomata.2 
PARASITES. 
Echinococcus may occur in the testis or epididymis. 
The Seminal Vesicles. 
The seminal vesicles may be the seat of acute or chronic infammation, 
which is most frequently associated with inflammatory changes in adja- 
cent parts, prostate, urethra, etc. As a result of chronic inflammation 
the vesicles may be atrophied, or they may be greatly dilated, forming 
cysts due to constriction of the ducts. Tuberculous inflammation is 
usually secondary. 
TUMORS. 
Carcinoma of the rectum or other genito-urinary organs may second- 
arily involve the seminal vesicles. Small concretions, sometimes con- 
taining masses of spermatozoa, are occasionally found in the seminal 
vesicles. 
The Prostate. 
DEGENERATION, ATROPHY, AND HYPERTROPHY. 
Fatty and hyaline degeneration of the muscle may occur in the prostate, 
with or without hypertrophy. Atrophy of the prostate may follow 
lesions or removal of the testicle, inflammation of the prostate itself, and 
may occur as a senile process. Dilatation of the ducts may accompany 
the atrophic process. 
Hypertrophy.-Enlargement of the prostate-so-called hypertrophy 
-is of frequent occurrence in advanced years. It may involve the entire 
1 Consult for teratoid tumors of the testicle Wilms, Ziegler's Beitr. z. path Anat., Bd. xix., p. 233, 
1896. 
2 See for a summary and discussion of these tumors Frank, Jour. Amer. Med. Assn., vol. xlvi. 
p. 248, 1906. 864 
REPRODUCTIVE ORGANS OF THE MALE 
organ or be partial; it may be nodular (Fig. G02) or diffuse. The middle 
lobe is most frequently involved, and this may press upon the urethra, 
leading to difficult urination and such secondary alterations in the blad- 
der as are associated with this, i.e., hypertrophy and dilatation of the 
bladder, or cystitis, not infrequently with involvement of the ureter and 
kidneys. 
Hypertrophy of the prostate may be due to hyperplasia of the muscle 
and fibrous tissue of the organ; at the same time the gland tissue may 
be increased (Fig. 603), or the latter may be alone involved. The 
increase in gland tissue has usually the character of glandular hyperplasia. 
Fig. 602.-Hypertrophy of the Prostate. 
But genuine adenomata may form both with and without hyperplasia 
of the connective tissue, muscle, and glands. 
In partial hypertrophy there are circumscribed nodules of muscle 
tissue or of muscle and gland tissue. These are usually situated at the 
periphery of the organ and project into the bladder. They may become 
detached from the prostate, and be found as small, movable tumors 
beneath the mucous membrane of the bladder. 
Acute Exudative Inflammation of the prostate is induced by gonorrhoea, 
by injuries, or, more rarely, is independent. It may be acute or chronic. 
The gland may after a time return to its normal condition, or be gradu- 
INFLAMMATION. (Prostatitis.) REPRODUCTIVE ORGANS OF THE MALE 
865 
Fig. 603.-"Hypertrophy"-Hyperplasia-or the Prostate. 
There is a glandular hyperplasia as well as hyperplasia of the fibro-muscular stroma. 
In the upper portion of the cut, at the right, are three nearly normal acini of the prostate, while 
the remainder shows various phases of new gland formation. The prostate, in addition to the circum- 
scribed tumor growth, was the seat of the usual glandular and interstitial hyperplasia. 
Fig. 604.-Adenoma of the Prostate. 866 
REPRODUCTIVE ORGANS OF THE MALE 
ally converted into a mass of fibrous tissue filled with abscesses. The 
abscesses may perforate into the bladder, urethra, vesiculse seminales, 
rectum, or peritoneum. Or the inflammation may extend to the connec- 
tive tissue of the scrotum or beneath the pelvic peritoneum. The pus 
may become thickened and cheesy, or even calcified. 
Tuberculous Inflammation of the prostate usually accompanies a sim- 
ilar lesion of some of the other genito-urinary organs. Large cheesy 
masses are often formed, which may break down and open into the 
bladder or rectum. 
TUMORS. 
Sarcoma of the prostate has been described. Adenoma (Fig. 604) 
occurs either with or without an increase in the fibro-muscular interstitial 
tissue and gland hyperplasia. 
Carcinoma is of occasional occurrence, and may be primary or sec- 
ondary. 
Fig. 605.-Glandular Hyperplasia of the Prostate with Cystic Dilatation. 
Some of the dilated glands contain corpora amylacea. 
Cysts of the prostate (Fig. 605) are sometimes found either as a 
result of occlusion of the ducts by hypertrophy of the interstitial tissue, 
tumors, etc., or as a result of faulty development.1 
PARASITES AND CONCRETIONS. 
Echinococcus of the prostate has been described, but is rare. 
Concretions.-Small ovoidal or spheroidal, often brown or black 
bodies, having the characters of corpora amylacea (Fig. 606), are of very- 
frequent occurrence in the alveoli of the prostate, particularly in old per- 
sons. We find a certain number of them in the prostate of nearly all old 
men, but they are sometimes present in great numbers. Larger, irreg- 
1 The occurrence of squamous epithelium in the ducts and sinuses of the prostate has been described 
see Schmidt, Ziegler's Beitr., Bd, xl., p. 120, 1906. REPRODUCTIVE ORGANS OF THE MALE 
867 
ular concretions, apparently formed by the coalescence or growth of the 
smaller ones, are less frequently found, and may be encrusted with lime 
salts. These concretions may give rise to ulceration of the ducts of the 
gland or to interference with the passage of urine, but usually they are 
of no practical importance. 
Fig. 606.-Corpora Amylacea in Glandular Hyperplasia of the Prostate. 
Cowper's Glands. 
Inflammatory processes, acute or chronic, may occur in these organs 
in connection with urethritis or prostatitis. Abscesses may form; the 
glands, either in acute or chronic inflammation, may become enlarged 
and encroach upon the lumen of the urethra. Retention cysts formed by 
the closure of the excretory ducts may also project into the urethral 
canal. 
The Male Mamma. 
There may be an abnormal number of mamms. In boys, at about 
the time of puberty, the mammae may be swollen and inflamed or they 
may secrete milk. Cases are recorded in which adult males possessed 
large mammae which secreted milk. The breasts may be enlarged from 
an increase of fat or of connective tissue. 
Fibroma, sarcoma, cysto-sarcoma, myxoma, and various forms of 
carcinoma1 may occur. 
Cysts of the male breast are not very infrequent. 
1 For bibliography of carcinoma of the male breast see Warfield, Johns Hopkins Hosp. Bull., vol 
xii., p. 305, 1901. CHAPTER XII. 
VOLUNTARY MUSCLE. 
NECROSIS. 
Necrosis of muscle may be the local result of mechanical or chemical 
injury; it occurs in inflammatory foci, and may follow serious local dis- 
turbances of the circulation, as from pressure by tumors or cicatrices, etc. 
The muscle fibres may gradually lose their striations, become granular 
and disintegrate, or the muscle substance may become homogeneous and 
strongly refractile and break into irregular masses. Necrotic muscle 
fibres are finally removed by the direct action of phagocytes or after 
various transformations leading to their solution. 
ATROPHY AND HYPERTROPHY. 
Simple Atrophy.-This may occur in old age, in prolonged exhausting 
diseases, or as a result of pressure from a foreign body, tumors, etc. 
The muscle fibres grow narrower, the degree of narrowing frequently 
Fig. 607.-Progressive Muscular Atrophy (Soleus muscle, longitudinal section). 
a, Atrophied muscle fibre; 6, degenerated muscle fibre; c, interstitial tissue; d, clusters of proliferated 
muscle nuclei. 
varying considerably in different parts. They usually retain the stria- 
tions, but these may be obscured by degenerative changes. The sarco- 
lemma may become thickened, and there may be a considerable increase 
in connective tissue between the muscle fibres and bundles. Brown pig- 
ment particles may accumulate in the atrophied fibres. 
868 VOLUNTARY MUSCLE 
869 
Progressive Muscular Atrophy.-This lesion consists essentially in a 
combination of simple or degenerative atrophy of the muscle fibres with 
chronic interstitial inflammation, and is sometimes associated with 
proliferative changes in the muscle nuclei. In the earlier stages of the 
disease the muscles may be pale and soft, but exhibit otherwise to the 
naked eye but little alteration. Gradually, however, the muscle sub- 
stance becomes replaced by connective tissue, so that in marked and 
advanced cases the muscles are converted into fibrous bands or cords, 
whose cicatricial contraction may induce great deformities. 
Fig. 608.-Progressive Muscular Atrophy (Soleus muscle, transverse section). 
a, Increased interstitial tissue; b, nearly normal muscle fibres; c, degenerated muscle fibres; d, atrophied 
muscle fibres; e, clusters of proliferated muscle nuclei. 
Microscopical examination shows in the early stages of the disease a 
proliferation of cells in the interstitial tissue, so that this may have the 
appearance of granulation or embryonal tissue; also in some cases marked 
proliferative changes in the muscle nuclei (Fig. 607), leading to the for- 
mation of new cells which may more or less replace the contractile 
substance within the sarcolemma. The new interstitial tissue increases 
in quantity and grows denser, and may crowd the muscle fibres apart 
(Fig. 608). The walls of the blood-vessels may also become thickened. 
Hand-in-hand with these interstitial alterations the atrophy of the muscle 
fibres proceeds. These may simply grow narrower, retaining their 
striations; or they may split up into longitudinal fibrillae, or transversely 
into discoid masses, and in this condition disappear. In other cases a 
certain amount of fatty or hyaline degeneration may be present. These 870 
VOLUNTARY MUSCLE 
degenerative and proliferative changes do not, as a rule, occur uniformly 
in the affected muscles, but some parts are affected earlier and more 
markedly than others. The atrophied muscle may be replaced by fat. 
Progressive muscular atrophy is apt to commence in the small muscles 
of the extremities, in many cases in the muscles of the ball of the thumb. 
It may commence in the muscles of the shoulder, the arms, or the back. 
It may have a continuous extension, or it may jump single muscles or 
groups of muscles. Death may be induced by the affection of the 
muscles of respiration or deglutition. 
The causes of this lesion are in many cases unknown, and there is 
considerable lack of unanimity of opinion as to whether it is primarily a 
Fig. 609.-Pseudo-hypertrophy of Gastrocnemius Muscle (Fatty Infiltration). 
The specimen is from the case mentioned on page 871, accompanying multiple neuroma. 
disease of the muscles or of the nervous system. In a considerable 
proportion of cases the muscle lesion is associated with atrophy of the 
ganglion cells in the anterior cornua of the spinal cord and the develop- 
ment of connective tissue about them. See for the relationship between 
nerve lesions and special groups of muscle the chapter devoted to Dis- 
eases of the Nervous System. In other cases these changes in the cord 
may apparently be absent. 
Muscle atrophy is sometimes accompanied by atrophy of the nerves 
which are distributed to the muscles, and atrophy of the anterior roots 
has been described. 
It is probable that there are several varieties of progressive muscular 
atrophy, which our present knowledge does not enable us clearly to dis- VOLUNTARY MUSCLE 
871 
tinguish. Muscular atrophy in some cases follows overstraining of groups 
of muscles, or injuries, and may occur as one of the sequelae of typhoid 
fever and diphtheria. 
Hypertrophy.-True hypertrophy of muscle as a pathological con- 
dition is rare, but it has been described in a few cases. It is usually 
confined to circumscribed groups of muscles. On microscopical exam- 
ination the diameter of the fibres is increased, sometimes considerably, 
though not uniformly. The transverse striation is unaltered and the 
muscle nuclei are in some cases enlarged. The cause of the change is 
unknown. 
Atrophia Musculorum Lipomatosa (Pseudo-hypertrophy of the Muscles). 
-In some cases, hand-in-hand with the production of new connective 
tissue in the muscles and the atrophy of the muscle fibres, or after these 
changes have made considerable progress, there occurs a development of 
fat tissue between the fibres (Fig. 609) which may prevent any apparent 
diminution in the size of the muscles, or in some cases may even give 
them the appearance of a great increase in size. This condition is of 
most frequent occurrence in children, and is most apt to appear in the 
gastrocnemii muscles. In the upper extremities the deltoid and triceps 
are most frequently involved. The lesion may be symmetrical, affecting 
similar muscles on both sides of the body, or it may be unilateral. Parts 
of muscle bellies may be affected. 
The cause of this form of atrophy is not definitely known. Various 
lesions of the spinal cord have been described as occurring with it; but, 
in many cases at least, alterations of the nervous system cannot be 
detected. The writer has described a case1 in which this lesion was 
marked in the gastrccnemii in connection with multiple false neuromata. 
DEGENERATION. 
Albuminous Degeneration of striated muscle occurs as a mark of toxae- 
mia in acute infectious diseases, and may lead to fatty degeneration. 
Fatty Degeneration, with greater or less destruction of the muscles, 
may commence with a simple swelling and fine granulation of the fibres. 
As the process goes on, smaller and larger fat droplets appear in the con- 
tractile substance, which loses its striations and becomes friable, and may 
be entirely destroyed, leaving within the sarcolemma a mass of fatty 
detritus which may finally be absorbed and disappear. This alteration 
may occur in acute parenchymatous myositis in connection with various 
forms of atrophy, in prolonged exhausting diseases, and in phosphorus 
poisoning. 
Fatty Infiltration of the muscle may occur in obesity and in alcoholics. 
Hyaline Degeneration.-Under a variety of conditions the muscle 
fibres undergo a series of changes, leading to their conversion into a trans- 
lucent, highly refractile material, somewhat resembling amyloid, but not 
giving its microchemical reactions, and apparently more nearly allied to 
hyaline material. The lesion in the, muscle which we are considering is 
1 Prudden, Am. Jour, of Med. Sei., July, 1880, p. 134. 872 
VOLUNTARY MUSCLE 
often called waxy degeneration, from the peculiar appearances which the 
muscles present.1 When the lesion is far advanced and extensive the 
muscles are brittle and have a grayish-yellow, translucent appearance. 
Microscopical examination of various stages of hyaline degeneration of 
muscle shows that the contractile substance of the fibres becomes at first 
swollen and granular, and gradually converted into hyaline material 
which may present the outlines of the swollen fibres, but is more fre- 
quently broken into larger and smaller shapeless clumps (Fig. 610), 
which may disintegrate and finally be absorbed. Hand-in-hand with 
these changes there usually occurs an increase in the interfibrillar con- 
nective tissue, and in certain cases there may be a proliferation of the 
muscle nuclei and a new formation of variously shaped cells within the 
sarcolemma which lead to the regeneration of the fibres. As a result of 
Fig. 610.-Hyaline Degeneration (So-called Waxy Degeneration) 'of Abdominal Muscle 
in Typhoid Fever. 
the brittleness of the degenerated muscles they are apt to rupture, and in 
this way haemorrhage may occur. 
This form of degeneration may occur in progressive muscular atrophy, 
in various infectious diseases, in trichinosis, with local inflammation, 
injuries, freezing, etc. It is, however, most marked and frequent in 
typhoid fever. In this disease the rectus abdominis and the abductors 
of the thigh are most frequently affected. 
Experimental investigations have shown that, under certain condi- 
tions, very similar appearances may be produced in the muscles by post- 
mortem changes. Various changes-some of them necrotic-are at 
present included under the name "hyaline degeneration of the muscles." 
True amyloid degeneration is rare. 
Hoen has described a peculiar degeneration with atrophy of the stri- 
ated muscle of the uvula, in which a series of bleb-like structures form 
along the fibres, which they may finally replace.2 
Calcification of muscle is of rare occurrence. 
Serous or Hydropic Infiltration of muscle fibres occurs under various 
conditions in association with other lesions. Larger and smaller spaces 
filled with clear fluid are present between the fibres and often over small 
areas largely replacing them. Such fluid-filled spaces are often called 
vacuoles. 
■For a study of the so-called waxy or Zenkenfe degeneration of muscle see Thoma, Virch. Arch. 
Bd. clxxxvi., p. 64, 1906. 
2 Hoen, Jour. Exp. Med., vol. iii., p. 549, 1898. VOLUNTARY MUSCLE 
873 
INJURIES, HAEMORRHAGE, AND INFARCTION. 
Wounds and Rupture.-When the muscle fibres are severed by wounds 
or rupture there is more or less degeneration of the divided fibres, and 
the wound may heal by the production of granulation tissue, which 
gradually becomes converted into cicatricial tissue, thus binding the 
severed parts together. In some cases there is a moderate new formation 
of muscle fibres (see p. 70). When the wound does not gape, so that 
the severed ends are not much separated, there may be, it would seem, 
a direct re-establishment of muscular continuity by new development 
of muscle, without the formation of much new connective tissue. 
Haemorrhage.-This may occur as a result of mechanical injury; from 
rupture of the fibres by convulsive contraction, as in tetanus; or it may 
occur when the muscle fibres are degenerated, as in typhoid fever; or in 
connection with certain general diseases, as scurvy, purpura, haemor- 
rhagic diathesis, septicaemia, etc. The blood is usually readily absorbed. 
Embolic Infarction of Muscles in connection with heart disease has been 
described in a few cases, but it is rare. 
INFLAMMATION. (Myositis.) 
Suppurative Myositis.-In the early stages of this lesion the muscle is 
hyperaemic and cedematous, and the interstitial tissue more or less infil- 
trated with small spheroidal cells. If the inflammation becomes intense 
there may be an excessive accumulation of pus cells, either diffusely in 
the interstitial tissue or in larger and smaller masses. Hand-in-hand 
with this cell accumulation occur degenerative changes in the muscle 
fibres. By pressure their nutrition is interfered with and they undergo 
granular, fatty, or hyaline degeneration and necrosis. They may com- 
pletely disintegrate; or gangrene may occur, so that larger and smaller 
masses of the infiltrated muscle tissue become soft, foul-smelling, and 
converted into a mass of detritus in which but little muscle structure can 
be detected and which is intermingled with bacteria. In other cases 
there may be larger and smaller abscesses formed in the muscle, the 
muscle tissue itself degenerating and disintegrating and mixing with the 
contents of the abscess, or being pressed aside and undergoing atrophy 
and degeneration. In some cases, when the formation of pus is moderate 
in amount, there may be restoration by formation of granulation tissue 
between the muscle fibres. This becomes gradually dense and firm, and 
leads to more or less atrophy of the muscle fibres by pressure. 
Acute suppurative myositis may accompany wounds; it is very com- 
mon in acute phlegmonous inflammations of the skin and subcutaneous 
tissue, and often accompanies acute infectious diseases, such as pyaemia, 
erysipelas, etc. In most cases the "pyogenic" cocci are present in the 
inflammatory foci. Suppuration not infrequently occurs in the muscles 
adjacent to the inflamed mucous membranes in diphtheria. 
Chronic Interstitial Myositis.-In this lesion there is a new formation 
of connective tissue between the muscle fibres or bundles of fibres. This 874 
VOLUNTARY MUSCLE 
new tissue is sometimes very cellular, resembling granulation tissue, and 
this probably represents an early stage of the disease. In other cases 
(Fig. 611) dense cicatricial tissue crowds the muscle fibres apart, inducing 
atrophy in them, and sometimes leading to their complete destruction. 
This lesion, the analogue of chronic interstitial inflammation of the 
internal organs, may occur in muscles which are adjacent to other parts 
which are the seat of chronic inflam- 
matory processes. It may occur in 
muscles which are not used. The 
new formation of fibrous tissue seems 
in some cases to be secondary to 
atrophy of the muscle fibres. In this 
case it would more appropriately be 
called replacement fibrous hyperplasia. 
Primary Acute Polymyositis. - 
Several observers1 have described an 
affection involving swelling of the 
muscles of the tongue, back, and ex- 
tremities, with local pain and fever. 
Voluntary movement is lost, and 
various rashes of the skin may occur. 
The muscles are brownish red in color, with yellowish spots, haemor- 
rhages and foci of haemorrhagic exudates. There is degeneration of the 
muscle fibres. The disease may become chronic and may be fatal. It 
is believed to be due to some form of auto-intoxication and may be 
associated with some infective focus in the body. 
Myositis Ossificans.-Under conditions and for reasons which we do 
not understand, there occasionally occurs, usually in young persons, a 
new formation of bone in the interstitial tissue of muscles, and in ten- 
dons, ligaments, fasciae, and aponeuroses. This sometimes apparently 
starts as outgrowths from the periosteum, sometimes not. The bone for- 
mations are apt to commence about the neck and back, and may become 
very widespread over the body. So far as the muscles are concerned, 
there is usually an increase of connective tissue between the fibres and 
bundles, in which new bone is formed, usually in elongated and some- 
times in spicula-like masses. The muscle fibres undergo secondarily a 
greater or less degree of atrophy or degeneration. There may be fatty 
infiltration between the fibres, and various deformities are produced by 
the shortening and progressive immobility of the affected parts. 
While the above disease is a progressive and frequently a general one, 
there may be new formation of bone in muscle as a result of prolonged 
or repeated mechanical irritation. Thus in the adductors of the thigh 
in persons who are constantly in the saddle, or in the deltoid muscle of 
soldiers who strike this part with their weapons in drill, there may be a 
formation of bone.2 
Fig. 611.-Chronic Interstitial Myositis. 
1 See v. Strumpet, Deutsch Zeits. f. Nervenkr. i., 479, 1891. 
2 Consult for a study of myositis ossificans De Witt, Am. Jour. Med. Sci., vol. cxx., p 295, 1900, 
bi bl. Also Gruber, Path. d. circ. Muskelverknocherung, Jena, 1913. VOLUNTARY MUSCLE 
875 
Tuberculous and Syphilitic Inflammation in the muscle is of occasional 
occurrence; the active processes are in the connective tissue and blood- 
vessels, the muscle fibres being secondarily involved in various phases 
of atrophy and degeneration. 
TUMORS. 
Tumors of muscles usually develop in the connective tissue. Fibroma, 
chondroma, lipoma, myxoma, sarcoma, angioma, may occur as primary 
tumors. Carcinoma and sarcoma may occur secondarily in the muscles 
as a result of local extension from adjacent parts. 
Rhabdomyoma has been described. Teratomata and dermoid cysts 
are recorded in various parts of the body. 
The muscle fibres are, as a rule, only secondarily affected by pressure, 
etc., in tumors of the muscles, but there exist observations which point 
to the possibility of a proliferation of the muscle nuclei and the new 
formation from them of cells which may take part in the growth of the 
tumor. 
PARASITES. 
Trichina spiralis is the most common parasite in the muscles. 
Cysticercus cellulosae and echinococcus occasionally occur. CHAPTER XIII. 
THE BONES AND JOINTS. 
The Bones. 
General Considerations. 
It is not possible to understand the changes which the bones suffer under various 
abnormal conditions unless one hold in mind the physical peculiarities of this form 
of connective tissue and the ways in which the dense and solid structure is formed and 
dissolved and re-formed in the processes of development and growth. 
The striking character of bone, adapting it to serve as the supporting framework 
of the body, is the association with its organic tissue of the inorganic salts to which its 
hardness and solidity are due. But it is through connective tissue and blood-vessels 
and under the agency of highly specialized connective-tissue cells-osteoblasts, the 
"bone-builders," and osteoclasts, the "bone-destroyers"-that bone is formed and 
during development ceaselessly remoulded. 
The general pathological processes to be observed in bone are fundamentally 
similar to those in the soft tissues of the body. Disturbance of circulation, necrosis, 
degenerations, inflammation, tumors, etc., are common. But their manifestations 
are modified and often complicated and obscured in part by the hardness of texture 
and durability of bone tissue, but especially by the frequent participation in the proc- 
esses of the osteoblasts and osteoclasts. Thus it is that many abnormalities of the 
circulation and their sequelae are less obvious than in other parts of the body; necrosis 
is masked by appearances due to the inorganic elements; while many of the inflamma- 
tory processes and tumors are regularly associated with the formation of new bone in 
such mass and measure as often to distort the bone and greatly complicate the 
picture. 
We have seen repeatedly, in studying the lesions of the viscera, that the primary 
pathological processes are modified by the tissues in which they are active. Attention 
is called to this feature in bone only because the regional modification is here so con- 
spicuously marked that one is liable to lose sight of the unity of the fundamental proc- 
esses and erroneously to conceive that the pathology of bone is a subject especially 
obscure, complex, and difficult. 
ATROPHY. 
In old age or in senile conditions the bones may become atrophied by 
the absorption of the hard tissue; the medullary spaces are enlarged, the 
marrow tissue contains less fat and is often gelatinous in appearance. 
As the result of the lack of use, or from any cause which interferes with 
the nutrition, of the bone, such as paralysis of the muscles or diseases of 
the joints, the bones may atrophy. In connection with atrophy there 
may be an ossifying periostitis, which results in making the bone look 
even larger than normal. Many of the conditions commonly called 
atrophy, such as the erosions of bones from tumors, etc., pressing upon 
them, are really due to a rarefying osteitis. 
The bones, sometimes as the result of atrophy and sometimes from 
876 THE BONES AND JOINTS 
877 
causes which we do not understand, are unusually brittle and liable to 
fracture. This disposition is sometimes hereditary. 
DISTURBANCES OF CIRCULATION. 
Hyperaemia.-The evidences of this condition are most marked to the 
naked eye in the periosteum and marrow, particularly the latter. It 
should be remembered that the color of the marrow varies considerably 
under normal conditions, depending upon age and situation. In the 
bones of the foetus and new-born, and near the areas of ossification in the 
young, the marrow is normally red in color. In adults the marrow of 
the sternum, vertebrae, and to a certain degree that of the ribs, pelvic 
and cranial bones, and the cancellous tissue of the ends of the long bones, 
is red or reddish in color. But most of the marrow, particularly in long 
bones of the extremities, is of a yellowish color from the presence of fat 
cells. In old age the marrow of all the bones is apt to become pale, and 
to assume a more or less translucent or gelatinous appearance. 
Hyperaemia usually occurs as an accompaniment of inflammatory 
processes in the bone, and, when marked, the periosteum is swollen and 
red; the compact bone tissue may appear of a pink color, while the mar- 
row, either by an increase in the amount of blood or absorption of its fat, 
or both, may be of a uniform dark red color or mottled with red and red- 
dish yellow. 
Haemorrhage.-This may be due to wounds and injuries and to inflam- 
matory and necrotic processes; and small haemorrhages often accompany 
scurvy, purpura, haemorrhagic diathesis, and leukaemia. Clots of con- 
siderable size between the periosteum and bone may lead to serious 
consequences, by cutting off the blood supply to the superficial layers of 
bone and thus inducing necrosis. But when not infected through con- 
tact with the air or by micro-organisms brought in the circulatory chan- 
nels, they are not usually of serious import, and are readily absorbed. 
The smaller haemorrhages of the medulla are not usually of much impor- 
tance. The decomposition of the extravasated blood may lead to exten- 
sive pigmentation of the marrow. 
HEALING OF WOUNDS AND FRACTURES OF BONE. 
The process of healing in bone after fracture is, when uncomplicated, 
at first similar to that in ordinary healing by second intention in fibrous 
tissue. The blood and other exudates and the tissue detritus are gradu- 
ally absorbed or disposed of by phagocytes. By a proliferation of con- 
nective-tissue cells of the region a larger or smaller mass of granulation 
tissue is formed. This granulation tissue does not at first differ in 
appearance from similar tissue formed elsewhere in the body in the 
reparative phase of exudative inflammation. 
But soon, under the influence of the specially endowed cells of car- 
tilage or bone or periosteum, but especially of the latter, the granulation 
tissue becomes partially replaced either by cartilage or by a substance 878 
THE BONES AND JOINTS 
resembling bone in general appearance but containing no lime salts. 
This is called osteoid tissue. These new cartilaginous and osteoid tissues, 
which are apt to occur together, form irregular masses or interlacing 
trabeculae in the stroma of granulation tissue. This constitutes the 
so-called callus of a uniting fracture (Fig. 612). 
i Gradually the osteoid tissue becomes osseous, and the masses of car- 
tilage and bands of periosteal and other fibrous tissue, under transfor- 
mations practically identical with those seen in normal development, are 
Fig. 612.-New-formed Cartilage and Osteoid Tissue from Callus after Fracture 
of the Femur. 
converted into bone. Thus by gradual absorption and re-formation of 
bone in the usually redundant provisional bony mass, and by the re- 
adjustment of its vascular channels, the healing, with more or less per- 
manent deformity, is accomplished (Fig. 613). 
If the conditions be not favorable, the healing of fractures may occur 
only by fibrous-tissue formation, so that so-called ''false joints" may 
result. The healing of other injuries and losses of substance occurs by a 
process similar to that described in Fractures. 
The periosteum, bone tissue, and marrow are so intimately connected 
that in most cases they all share to a greater or less degree in the patholog- 
ical alterations of the bones. But as sometimes one, sometimes another 
is most markedly involved, it is convenient to consider separately here 
the inflammatory changes by which they are respectively affected. 
INFLAMMATION. 
Periostitis. 
Exudative inflammation in the periosteum is essentially similar to 
this form of inflammation in other parts of the body, except as it is THE BONES AND JOINTS 
879 
modified by the relationships of the connective tissue and blood-vessels 
to the hard bone and by the presence and performances of the osteoblasts 
and associated cells peculiar to bone. 
We may distinguish several forms of periosteal inflammation. 
Simple Exudative Periostitis.-This is 
apt to occur in children and ill-nourished 
persons after comparatively slight injuries 
or from unknown causes. The periosteum 
is thickened, succulent, congested, and more 
or less abundantly infiltrated with leuco- 
cytes. It becomes less firmly adherent to 
the bone, and the cells of the inner layers 
are increased in number. This form of in- 
flammation may terminate in resolution, or 
it may lead to other phases of inflamma- 
tion. 
Suppurative Periostitis may begin as a 
simple or as a purulent, inflammation. The 
pus is formed in the inner layers of the 
periosteum, and between it and the bone. 
The outer layers of the periosteum may for 
a long time resist the suppurative process. 
The accumulation of pus may dissect up 
the membrane from the bone and leave the 
latter bare. The pus thus formed may 
remain in this position for a long time, 
or be absorbed, or become dry and cheesy, 
or it may burst through the periosteum 
and lead to abscesses in the soft parts. The 
bone, if separated from its nutrient mem- 
brane, may remain unchanged, but more 
frequently necrosis or inflammation of the 
bone itself is set up. Such a periostitis 
may run an acute or a chronic course. 
Sometimes suppurative periostitis takes 
on a very malignant character. Pus is 
developed not only beneath, but in the 
periosteum, forming abscesses filled with 
foul pus. The periosteum breaks down 
into a gangrenous, foul-smelling mass, and 
the same change may affect the neighbor- 
ing soft parts. The medulla may take 
part in the process and break down into 
a purulent, gangrenous mass. Hsemor- 
rhages may complicate the process. The 
lymph-nodes are enlarged and swollen; 
abscesses may form in different parts of the body, and the patient 
may die with the symptoms of pyaemia. The Streptococcus and 
Fig. 613.-Healed Bone after 
Fracture. 
Shows redundant hard bone about 
seat of fracture. 880 
THE BONES AND JOINTS 
Staphylococcus pyogenes are the most common excitants of suppurative 
inflammation. 
Fibrous Periostitis.-This is a chronic form of inflammation, resulting 
Fig. 614.-Ossifying Periostitis. 
An irregular layer of new bone is forming between the periosteum and the old bone. 
in the development of new connective tissue in the periosteum, which 
becomes thickened and dense and usually adherent to the bone. It 
may accompany necrosis, chronic arthritis, chronic ulcers of adjacent soft 
Fig. 615.-Ossifying Periostitis-Tibia. 
Large exostoses at the end of the bone. The process involves the joint, and the bone is enlarged. 
parts, etc., or follow simple acute periostitis. It may in many instances 
be regarded as a conservative process of a reparative character. 
Ossifying Periostitis results in the formation of new bone from the 
inner layers of the periosteum. The masses of new-formed bone, called THE BONES AND JOINTS 
881 
osteophytes, are of variable shape. They may form a thin, velvet-like, 
villous layer (Fig. 614); or they are little spicula; or form larger, rounded 
masses (see Figs. 615, 616), or a thick, uniform layer extending over a 
large part of a bone. They may have at first a loose, spongy character, 
and be loosely connected with the old bone. But layers of compact 
bone tissue are formed within their medullary spaces, which are thus 
gradually filled, and they join the old bone so that they may finally 
become as compact as or even more compact and dense than normal bone 
to which they are firmly joined. The hyperostoses and exostoses thus 
formed may remain indefinitely, or they may gradually become smaller 
and finally disappear by absorption. 
The formation of new bone in osteophytes, or in dense masses beneath 
and in the periosteum, occurs as a result of the same process by which. 
A large part of the shaft is thickened and covered with ragged platelets of new-formed bone 
while above large rough exostoses project. This bone has been the seat of rarefying and formative 
osteitis. 
Fig. 616.-Ossifying Periostitis With Large Exostoses-Femur. 
bone tissue is normally formed. Certain large cells, called osteoblasts, 
which are developed along the blood-vessels, possess the power of deposit- 
ing osseous basement substance about themselves and so forming bone. 
Pathological new formation of bone differs from the normal mainly in 
the conditions under which it occurs. The blood-vessels around which 
the pathological bone develops, which grow out of the old vessels, as in 
the formation of granulation tissue, are irregularly arranged and subject 
to a variety of abnormal nutritive and mechanical conditions, so that the 
new bone is usually formed, not in a series of definite systems of lamellae, 
but, as above described, in a series of irregular spicula or masses. More- 
over, as will be seen further on, the conditions under which it is formed 
being liable to change, and itself serving no definite purpose in the econ- 
omy, as does normal bone, pathological new bone is often an evanescent 
structure. The details of its disappearance will be considered below. 
Syphilitic Periostitis.-Syphilitic infection may excite simple, purulent, 
fibrous, or ossifying periostitis. In addition to these, gummata (see p. 
273) may be developed in the periosteum in long bones, most frequently 
on the shaft, where they cause a more or less fusiform enlargement. The 882 
THE BONES AND JOINTS 
bone tissue is usually more or less involved. The gummata may be 
absorbed or undergo cheesy degeneration, or be converted into fibrous 
tissue, or they may suppurate. 
Tuberculous Periostitis.-In badly nourished persons, particularly in 
children suffering from scrofula, chronic purulent periostitis is frequently 
associated with the formation of miliary tubercles. Abscesses are apt 
to form in and about the periosteum, and when these are evacuated gran- 
Shows caries with extensive destruction of the bone. 
Fig. 617.-Tuberculosis of the Joint. 
ulation tissue may develop, which contains miliary tubercles. The bone 
is apt to be involved to a greater or less extent in simple imflammatory 
changes or caries (Fig. 617). 
Osteitis. 
Inflammation in bone tissue is dependent upon the same general con- 
ditions and presents essentially the same series of phenomena as inflam- 
mation in other kinds of connective tissue. But it is variously modified 
in detail by the peculiar dense and unyielding character of the basement 
substance, and by certain peculiarities of the blood supply and the 
nutritive conditions under which the cells are placed. In simple exuda- 
tive inflammation the same series of phenomena occur in connection with 
the blood-vessels as in other tissues, resulting in the production of serum, 
fibrin, and pus; but the extent to which these changes occur is limited 
and constantly associated with striking alterations in the basement 
substance. It is these secondary alterations in the basement substance 
which lend to inflammations of the bone their most peculiar characters, 
and in the prominence which these assume the fundamental alterations THE BONES AND JOINTS 
883 
are often overlooked. The most common of these secondary alterations 
are the absorption of the hard basement substance of the bone and 
its replacement by, or conversion into, young cellular forms of fibrillar 
connective tissue or marrow tissue, and the new formation, in a more or 
less typical manner, of new bone. The active phenomena of inflamma- 
tion in bone are processes of the blood-vessels and the fibrillar connective 
tissue as in other parts of the body, the hard bone substance being in a 
certain sense only secondarily involved. 
As a result of these changes the bone in simple inflammation becomes 
more vascular, and, with an increase of spaces filled with granulation or 
marrow tissue, more porous at the expense of the dense basement sub- 
stance. Or the new-formed spaces or the marrow cavities may be con- 
stantly encroached upon by the new-formed bone lamellae on their walls, 
so that the bone becomes more compact. Or, as is frequently the case, 
both series of changes occur either simultaneously in different regions, 
or follow each other, or are variously associated together. Very fre- 
quently one or the other of the opposing forms of alteration predominates, 
or one may occur to the exclusion of the other, and we thus have two 
prominent forms of inflammation, which are called rarefying osteitis 
or osteo-porosis, and condensing osteitis or osteosclerosis. The exact 
nature of the conditions under which in one case the bones become 
more, in another less dense, we do not understand. Nor is the exact way 
in which the osteoclasts dissolve hard bone, or the osteoblasts secure and 
deposit inorganic salts and become bone cells as yet clear. Furthermore, 
more or less characteristic forms of inflammation may occur in syphilitic 
and tuberculous infection-syphilitic and tuberculous osteitis. Suppura- 
tive osteitis may further complicate the process. 
In addition to these phases of inflammation in bone, and in frequent 
and varied association with them, there are alterations leading to death 
and destruction of bone tissue in greater or less amount, which are called 
caries and necrosis. Finally, any of these forms, and commonly several 
of them at once, are variously associated with more or less marked 
inflammatory or degenerative alterations of the periosteum on the one 
hand, or the marrow tissue on the other, or of both combined. 
Rarefying Osteitis consists essentially in the formation in the marrow 
spaces, Haversian canals, or beneath the periosteum, of new, very cel- 
lular and vascular tissue, resembling granulation of young marrow tissue, 
under whose influence the basement substance of the bone is absorbed. 
This absorption of the bone takes place largely as bone is absorbed in 
normal growth, namely under the influence of certain large cells, which 
are grouped around the blood-vessels. If a thin section of bone which 
is undergoing absorption be examined (Fig. 618), the edges of the bone 
which border on the vascular surfaces are found irregularly indented by 
deep or shallow depressions, sometimes simple, sometimes quite complex. 
These are called Howship's lacunce and are usually filled or lined by larger 
and smaller granular, frequently multinuclear cells-the so-called osteo- 
clasts. In the larger lacuna there may be granulation tissue with loops of 
blood-vessels, with or without osteoclasts. Under the influence of the 884 
THE BONES AND JOINTS 
osteoclasts or of the new vascular tissue, the bone is gradually ab- 
sorbed. 
On the other hand, there may be irregular branching channels through 
the bone across the lamellae, which appear to be due to the enlargement 
and coalescence of the lacunae and canaliculi, without the direct influence 
of blood-vessels or other cells than the fixed cells of the bone. 
The tissue which replaces the absorbed bone may be very rich in 
small spheroidal cells, or it may be more or less fibrillar. 
As a result of this process irregular islets of bone tissue may be 
entirely separated from adjacent bone and surrounded by a more or less 
a, Isolated bone fragment with rough edges; b, marrow tissue; c, Howship's lacunae with osteoclast. 
Fig. 618.-Rarefying Osteitis in Ulna of Child. 
fibrillar vascular tissue; this is most apt to occur in the cancellous tissue. 
Or the originally compact bone may become traversed by a series of larger 
and smaller irregular branching, communicating channels with ragged 
walls. These progressive alterations may cease, and be succeeded by a 
new formation of bone along the edges of the channels or cavities. 
Rarefying osteitis may occur as an independent process from unknown 
causes; it is often associated with scrofula, with diseases of the joints, 
with fractures or other injuries to the bone; it often forms a predominant 
feature in tuberculous inflammation of the bones. It is chiefly by a 
rarefying osteitis that bone tissue is eroded and destroyed in the vicinity 
of tumors, aneurisms, etc., which exert pressure on the bones. By the 
same process the sharp ends of fractured bones may be rounded off as 
healing proceeds. 
When this form of inflammation occurs in cancellous bone tissue the 
marrow is red or gelatinous, and the bony septa may disappear altogether, 
so that in extreme cases there may be, instead of cancellous bone, a mass 
of granulation tissue. When the process occurs in the articular extrem- THE BONES AND JOINTS 
885 
ity of a bone the granulating medulla may send little offshoots through 
the articular cartilage. These may become fused together and inflam- 
mation of the joint may follow. The walls of the shafts of the long 
bones may be converted into spongy tissue. If, as is sometimes the case, 
an ossifying periostitis occurs at the same time, the bone is thickened but 
spongy; or sometimes there are concentric layers of compact bone tissue, 
separated by rarefied bone. 
Condensing Osteitis (Osteo-sclerosis).-This lesion is characterized by 
the new formation of bone in the walls of the marrow cavities or Haver- 
sian canals. The bone is formed under the influence of the blood-vessels 
and osteoblasts, as in normal bone formation, but with less regularity. 
It may result in the conversion of cancellous tissue into compact bone, 
in the filling up of the medullary cavity of long bones with more or less 
dense bone tissue. The compact bone, owing to the filling of its Haver- 
sian canals, may become very dense and ivory-like. When the medullary 
Fig. 619.-Condensing Osteitis, or Osteo-sclerosis, in Ulna of Child. 
a. Fragment of old bone with roughened, sinuous edges; b, old Howship's lacunae covered with more 
recently formed bone lamellae; c, d, new Haversian canals. 
cavities of long bones are involved the yellow marrow is converted into 
red marrow by the absorption of fat and increased vascularity. 
Osteo-sclerosis is frequently associated with ossifying periostitis. It 
often follows rarefying osteitis, and then the Howship's lacunae resulting 
from the original absorption process may be filled and covered in with 
new bone lamellae (Fig. 619). It is apt to occur in connection with 
necrosis or chronic inflammation of adjacent soft parts, and is then a 
reparative and conservative process, but it sometimes occurs independ- 
ently under unknown conditions. 
Suppurative Osteitis (Abscess of Bone).-This process occurs usually in 
the ends of the long bones, and is associated with rarefying osteitis. As 886 
THE BONES AND JOINTS 
the bone tissue is absorbed, a circumscribed cavity may be formed in the 
bone, filled with pus and lined with granulation tissue. 
Less frequently abscesses are formed in the shaft of a long bone by 
circumscribed suppuration of the medulla. Such abscesses may occur in 
old people and may be of long duration. They may gradually enlarge 
and be accompanied by an ossifying periostitis, so that the bone is ex- 
panded. The abscesses in suppurative osteitis sometimes develop rapidly 
and may perforate. On the other hand, instead of abscesses, there may 
be a diffuse infiltration with pus of the Haversian canals or of the spaces 
formed by rarefying osteitis (see Osteomyelitis, below.) 
Osteomyelitis.-The tissues of the medulla so frequently share in the 
inflammatory processes in bone that many conditions described as osteitis 
are really osteomyelitis. It is customary, however, to reserve the latter 
name for those cases in which the medulla is primarily or chiefly involved. 
Acute Infectious Osteomyelitis.-This may occur as the result of 
a local injury which permits the access, or favors the development, of 
pyogenic micro-organisms; it may be metastatic, resulting from the 
transportation of infectious material from other parts of the body in septi- 
caemia and pyaemia, in typhoid fever, in the exanthematous fevers, and 
under other conditions; or it may occur without evidence of local predis- 
position or of infectious processes in other parts of the body. 
The lesions of acute infectious osteomyelitis are, in the large majority 
of cases at least, due to the presence and action of the pyogenic cocci, 
the Staphylococcus pyogenes and the Streptococcus pyogenes, and in 
many of its forms it may be regarded as one of the phases of septicaemia 
or septico-pyaemia. 
While the lesions vary widely, the following general description is 
applicable to a considerable proportion of the cases: 
At the commencement of the disease, which usually begins in the shaft 
of one of the long bones, there are hyperaemia and oedema of the medulla, 
so that if the bone be opened the marrow is soft and of a dark red color. 
A diffuse suppuration now rapidly ensues, and the marrow becomes 
streaked or mottled with gray. Occasionally, though not often, larger 
and smaller abscesses may form in the marrow. The inflammatory areas 
may be circumscribed; or, in the more malignant cases, the entire mar- 
row may become rapidly involved. The cancellous tissue of one or both 
of the epiphyses usually becomes affected. The disease, however, is 
not commonly confined to the medullary spaces. The periosteum 
becomes oedematous and infiltrated with pus, and the surrounding soft 
parts may become the seat of intense inflammatory changes. Abscesses 
of the periosteum or surrounding tissues are apt to form. As a result of 
these changes, necrosis of greater or less portions of the bone may ensue 
with the formation of larger or smaller sequestra (see p. 890). The 
medullary cavity may become enlarged as pus accumulates, and the wall 
of the bone may be broken through, permitting the discharge of pus 
outward. Sometimes several bones are involved at once. Secondary 
involvement of the joints is very frequent. Here there may be only a 
serous or purulent exudation; or the acute and destructive inflammatory THE BONES AND JOINTS 
887 
process may extend beneath the joint and produce extensive alterations. 
In young persons the epiphyses very frequently become separated from 
the shaft by the destruction of the cartilage which binds them together. 
In the severer cases, which are often called, par excellence, malignant 
osteomyelitis, the changes may be very rapid and destructive. The 
medulla is disintegrated and gangrenous; the joints are soon involved; 
necrosis of large portions of the bone, sometimes of the whole shaft, 
occurs, the periosteum and surrounding parts become gangrenous; the 
veins contain thrombi, and pyaemic infarctions and abscesses may form 
in various parts of the body.1 
Chronic Osteomyelitis.-In prolonged cases of osteomyelitis there 
is apt to be more or less ossifying periostitis and osteo-sclerosis, and 
fistulae may form in the bone, through which the exudates are discharged.2 
A miliary tubercle formed in the cancellous tissue near the joint in tuberculous arthritis. 
Fig. 620.-Tuberculous Osteitis. 
Tuberculous Osteitis is primarily a tuberculous inflammation of the 
soft parts of bone with associated rarefying and formative processes in 
the hard bone. The tubercles are sometimes small and scattered (Fig. 
620), sometimes they unite to form larger foci or large diffuse caseous 
masses. There may be extensive involvement of the medulla. Rare- 
fying and condensing osteitis and necrosis often accompany the tuber- 
culous process. Thus the bone frequently becomes spongy or fragile 
(Fig. 617). Much of the new tissue formed in tuberculosis of the bones 
is simple granulation tissue or fibrous tissue of reparative character. 
1 Consult for an elaborate treatment of acute osteomyelitis in its relationship to other forms of 
inflammation, with bibl., Jordan, Beitr. z. klin. Chir., Bd. x., p. 587. For a study of this condition in 
childhood see Koplik and Van Arsdale, Am. Jour. Med. Sci., vol. ciii., pp. 422 and 535, 1892. 
2 For a resume of the deformities resulting from osteomyelitis consult Park, Medical Record 
Nov. 2, 1895. 888 
THE BONES AND JOINTS 
Not infrequently an exudative inflammation occurs with the for- 
mation of the so-called cold abscesses. This abscess formation in bone 
as well as in soft parts may be due to the tubercle bacillus alone. But 
concurrent infection of tuberculous areas often takes place, the pyogenic 
or other organisms gaining access to the involved region either through 
the blood channels or by surface openings, fistula?, sinuses, etc. 
Tuberculous inflammation is most frequent in early life and, save 
for the smaller bones, such as the phalanges, metacarpal, metatarsal, it 
rarely involves the shafts of bones.1 It is often associated with tuber- 
culous involvement of the joints (Fig. 617). 
Syphilitic Osteitis.-Syphilitic infection may lead to one or other of the 
forms of osteitis just described, or gummatous nodules may form. Syph- 
ilitic osteitis usually commences in the periosteum, which becomes 
thickened and infiltrated with cells, so that there may be a circumscribed 
thickening of the periosteum, with or without distinct gummata. The 
vessels which extend from the periosteum into the bone become sur- 
rounded by new cellular tissue, which causes an enlargement of the 
canals. At this stage, if the periosteum be stripped off, it drags with it 
the vessels surrounded by the new cell growth, leaving the bones beneath 
with numerous small perforations extending inward. As the disease 
progresses the channels in the bone enlarge by a rarefying osteitis and 
coalesce, forming large, irregular defects filled with new fibrous tissue. 
In these masses of new tissue, cheesy degeneration may occur, so that the 
new growth has more or less of the character of a gumma. In the vicin- 
ity of these gumma-filled spaces a condensing osteitis may occur, both in 
the substance of the bone and on the surface, in the form of osteophytes, 
so that the opening in the bone may be surrounded by an elevated, irreg- 
ular ring of bone tissue. All this may occur beneath the uninvolved 
skin, or the skin may participate by a suppurative inflammation, result- 
ing in ulceration. These processes may be circumscribed or involve a 
large part of a bone. It is not infrequently associated with necrosis of 
larger and smaller portions of bone. The syphilitic tissue may be 
absorbed and its place be more or less filled with fibrous tissue. Syphilitic 
osteitis is most frequent in the cranial bones, but may occur elsewhere, 
as in the sternum, clavicle, tibia and fibula, the ribs, etc. 
Congenital Syphilis.-The bones of young children in this condition 
may show increased density or evidences of periostitis, or irregular thick- 
enings, particularly of the skull. Characteristic lesions are frequently 
found in the long bones in still-born or young children who are the vic- 
tims of hereditary syphilis. These lesions are found for the most part 
along the border zone between the epiphysis and diaphysis. In normal 
ossification of the long bones, the border line between the calcification 
and ossification zones is narrow, sharply defined, and straight, or lightly 
and evenly curved. In the syphilitic bones, on the contrary, this line is 
broader, uneven, and presents various modifications, which merge into 
one another, so that all intermediate forms may be seen. In a lesion of 
1 For a study of the relative prevalence of human and bovine types of tubercle bacilli in bone and 
joint tuberculosis of children see Fraser, Jour. Exper. Med., 1912, xvi., 432, bibl. THE BONES AND JOINTS 
889 
moderate grade there may be, between the cartilage and the new-formed 
spongy bone, a white or reddish-white zone, about two millimetres in 
breadth, with very irregular borders, consisting of calcified cartilage, in 
which the linear groups of cartilage cells are more abundant than normal. 
In more pronounced lesions the calcified zone, still containing an unusual 
number of cartilage cells, is broader and still more irregular and less 
sharply outlined against the ossification zone. The cartilage just beyond 
it is softer and almost gelatinous, and may contain numerous blood-ves- 
sels, islets of connective tissue or of calcification, or irregular ossification. 
Finally the bone may be pouched out at the sides around the ossification 
and calcification zones, and the perichondrium and periosteum thickened. 
The whitish, irregular calcified zone is hard and friable. Between this 
and the new-formed bone there is an irregular, soft, gray or grayish 
yellow zone, from two to four millimetres in thickness, which forms a loose, 
readily separated connection between the cartilage and the diaphysis. 
The white, friable zone consists mainly of irregular rows of degenerated 
and distorted cartilage cells lying in a calcified basement substance, of 
irregular masses of atypical bone tissue, and of blood-vessels surrounded 
by variously shaped cells. The soft zone consists of more or less vascular 
tissue with homogeneous basement substance, and round and spindle- 
shaped cells. This soft zone is not sharply outlined against the adjoining 
new-formed spongy bone, which, instead of consisting of the normal 
marrow spaces with bony lamellae between them, is largely composed of 
granulation tissue. 
Different phases of this faulty development may be seen in different 
bones in the same individual. According to Wegner the lesion is usually 
most advanced in the lower end of the femur, then in the lower ends of 
the leg bones and of the forearm, then in the upper ends of the tibia, 
femur, and fibula. 
Not infrequently there is fatty degeneration of the marrow cells and 
blood-vessels giving the marrow a reddish yellow color. These altera- 
tions of the bones may occur, not only in children who have gummata in 
other parts of the body, but also in those in whom other evidences of 
syphilitic infection are absent. So uniform is their occurrence that their 
presence alone suffices for the establishment of a diagnosis. 
NECROSIS. 
Necrosis is the death of a larger or smaller portion of bone. This 
may be induced by conditions which deprive the bone of its proper vas- 
cular supply from the periosteum and medulla. It may be associated 
with suppurative periostitis, osteomyelitis, and osteitis, traumatic sepa- 
ration of the periosteum, ulcers of neighboring soft parts, emboli, the 
action of phosphorus vapor, and exhaustive infectious diseases. Necro- 
sis is a pure form of gangrene, differing from gangrene of soft parts in 
that the dead bone has at first, and may retain for a long time, the general 
outward characters of the normal bone; while in dead soft parts rapid 890 
THE BONES AND JOINTS 
absorption may occur, or, should bacteria of various forms be presenter 
gain access to the dead tissue, putrefaction, with complex changes, may 
ensue. 
When a portion of bone has died, inflammation occurs at the dividing- 
line between the dead and living bone. This inflammation has the char- 
acters of a rarefying osteitis (see above), and finally separates the dead 
from the living bone. The dead bone, or sequestrum, may remain smooth 
and unaltered (Fig. 621), or it may be eroded by the influence of sur- 
rounding pus or granulation tissue or osteoclasts. In this way it is pos- 
sible for the sequestrum, if it be small, to be entirely absorbed. More 
frequently there is a production of new bone around the sequestrum, 
Fig. 621.-Necrosis of Bone. 
Showing sequestrum of dead bone partially surrounded by new-formed subperiosteal bone, 
with thickening of the shaft. 
either beneath the periosteum or in the substance of the bone, and this 
becomes lined with granulation tissue, from which pus may continue to 
be formed, bathing the sequestrum. 
Necrosis may involve the superficial layers, or the entire thickness of 
the wall of a long bone, or only the spongy tissue and inner layers, or an 
entire bone, or a number of different portions of the same bone, but it is 
most apt to occur in compact bone. 
The death and separation of the bone may be soon followed by the 
growth of new bone to repair the loss. The periosteum, the medulla, 
and the surrounding soft tissues may all take part in this new grow'th. 
The new bone is usually irregular, rough, and perforated with openings 
through which pus formed around the sequestrum may be discharged. 
If the sequestrum be removed, healing may occur by the formation of 
new bone; but the bone is usually more or less distorted by the irregular 
new ossification. 
Phosphorus Necrosis.-Under the influence of phosphorus vapor, 
periostitis and osteitis, particularly of the jaw, are apt to occur, which 
usually lead to more or less extensive necrosis, generally associated with 
prolonged and often extensive suppuration. THE BONES AND JOINTS 
891 
CARIES. 
Caries of bone is essentially an ulcerative osteitis resulting in progres- 
sive molecular destruction of the bone tissue. It differs from necrosis in 
that, in the latter, larger and smaller masses of bone die, while in caries the 
destruction is molecular and gradual 
(Fig. 622). It may occur in connec- 
tion with any form of osteitis, with 
periostitis and osteomyelitis, or it 
may be secondary to inflammatory or 
destructive processes in the joints or 
adjacent soft parts. The depressed 
surfaces of bones in which caries is 
progressing are rough and more or 
less finely jagged, and may be covered 
with granulations. The minute 
changes by which ulceration and 
destruction of the bone are pro- 
duced in caries are somewhat analo- 
gous with those in rarefying osteitis, 
but there are marked degenerative 
changes in the bone cells, which may 
become fatty or converted into a 
granular material. Moreover, the 
basement substance of the bone, in- 
stead of being absorbed, may disin- 
tegrate, with the formation of larger 
and smaller masses of detritus. 
Sometimes the lime salts are re- 
moved from the basement substance, 
which is converted into atypical 
fibrillar tissue and fatty and granu- 
lar detritus. Very extensive sup- 
purations and necrosis may be asso- 
ciated with caries. 
Long-continued caries, especially 
in badly nourished individuals, is apt 
to become complicated with tubercu- 
lous inflammation. 
There is very little tendency to spontaneous healing in caries, but it 
may occur, and the defects produced may be more or less supplied by 
means of new-formed bone. 
Fig. 622.-Caries of the Vertebra. 
Rickets is a developmental disease of bone, in which the proper 
ossification does not take place. The disease usually occurs during the 
first two years of life, but may be congenital,1 or may occur as late as 
the twelfth year. 
RACHITIS. (Rickets.) 
1 Salvetti, Ziegler's Beitr. z. path. Anat., etc., Bd. xvi., p. 29, 1894, bibl. 892 
THE BONES AND JOINTS 
The physiological growth of bones presents three phases. They 
grow in length by the production of bone in the cartilage between the 
epiphysis and diaphysis; in thickness, by the growth of bone from 
the inner layers of the periosteum. At the same time the medullary 
canal is enlarged, in proportion to the growth of the bone, by the disap- 
pearance of the inner layers of bone. 
In rickets these three phases of growth are abnormal. The carti- 
laginous and subperiosteal cell growth, which precedes ossification, goes 
on with increased rapidity and exuberance and in an irregular manner, 
both between the epiphyses and diaphyses and beneath the periosteum, 
while the actual ossification is imperfect, irregular, or wanting. At the 
same time the dilatation of the medullary cavity goes on irregularly 
and often to an excessive degree. 
Fig. 623.-Rachitic Bone. 
Showing ossification zone in a longitudinal section of a rib. 
If one examine microscopically in a rachitic bone the region between 
the epiphysis and diaphysis (Fig. 623), he finds that the cartilage cells 
are not regularly arranged in rows along a definite zone in advance of the 
line of ossification, as in normal development, but that there is an irreg- 
ular heaping-up of cartilage cells, sometimes in rows, sometimes not, 
over an ill-defined and irregular area. The zone of calcification also, 
instead of being narrow, regular, and sharply defined, is lacking in uni- 
formity. Areas of calcification may be isolated in the region of prolifer- 
ating cartilage cells, or calcification may be altogether absent over con- 
siderable areas. 
Corresponding to these irregularities the ossification zone is also irreg- 
ular. New-formed bone and marrow cavities containing blood-vessels 
may lie in the midst of the cartilage, or masses of cartilage may lie deep 
in the region which should be completely ossified. In other places it THE BONES AND JOINTS 
893 
seems as if the cartilage tissue were directly converted into an ill-formed 
bone tissue by metaplasia or direct transformation. It will readily be 
seen from this that the medullary spaces of the new-formed bone are 
irregular, and this abnormality is enhanced by the premature intra- 
medullary absorption of the bone. 
Similar irregularity in the bone formation may be seen beneath the 
periosteum. An excessive proliferation of cells in the inner layers of 
Fig. 624.-Rickets. 
Showing irregular ossification and bending of the long bones. 
the periosteum, the irregular calcification which occurs about them, and 
the absence of uniformity in the elaboration of ill-structured bone, con- 
spire to produce an irregular, spongy bone tissue instead of the compact, 
lamellated tissue which is so necessary here for the solidity of the struc- 
ture. The increased cell growth between the epiphyses and diaphyses 
produces the peculiar knobby swellings which are characteristic of 894 
THE BONES AND JOINTS 
rickets. At the same time the medullary cavity increases rapidly in 
size and the inner layers of the bone become spongy. The medulla may 
be congested, and fat, if it has formed, may be absorbed, and a modified 
form of osteitis may ensue. 
The result of these processes is that the bones do not possess solidity 
and cannot resist the traction of the muscles or outside pressure. The 
epiphyses may be displaced or bent, especially in the ribs, less frequently 
in the long bones. The long bones and the pelvic bones may be bent 
into a variety of forms (Fig. 629). Incomplete fractures are not infre- 
quent. Complete fractures do not usually occur until the later stages of 
the disease, when the bones have become more solid. In the head, the 
Fig. 625.-Craniotabes. 
This skull of a child is large, its bones are thin, with holes due to faulty development and 
covered only by a thin, fibrous membrane. 
cranium may be unnaturally large for the size of the face; the fontanelles 
and sutures may remain open; the bones may be soft, porous, and 
hyperaemic, while at their edges there may be rough, bony projections 
beneath the pericranium. Sometimes, especially in the occipital bone, 
there are rounded defects in the bone, filled only with a fibrous mem- 
brane; this constitutes one of the forms of so-called Craniotabes (Fig. 
625). 
It does not fall within the scope of this work to describe the various 
deformities which may occur as a result of this disease. The familar 
pigeon breast; the rows of knobs along the sides of the chest from bend- 
ing and dilatation of the ribs at the point of junction of cartilage and 
bone (Fig. 626); the knock-knees, bow-legs, spinal curvatures, etc., may 
all be the result of rachitic weakening of the bones. THE BONES AND JOINTS 
895 
After a time the rachitic process may stop and the bones take on a 
more normal character. The porous bone tissue becomes compact and 
View of interior of chest showing knobs on the ribs projecting inward. (Photograph by Dr. Northrup.) 
Fig. 626.-Thorax of Rachitic Child. 
Showing shortened and deformed arms and legs, the trunk and head being approximately normal. 
Fig. 627.-Achondroplasia. 
even unnaturally dense; the swellings at the epiphyses disappear; many 
of the deformed bones may become of a normal shape. In severe cases, 896 
THE BONES AND JOINTS 
however, the deformities continue through life; especially there is a ces- 
sation of the growth of the bones in their long axis, so that the persons 
affected are dwarfed. 
The disease may have an acute or a chronic character. The acute 
form begins usually during the first six months of life. The children are 
apt to suffer from vomiting, diarrhoea, profuse sweating, chronic bron- 
chitis and pneumonia, general anaemia, and wasting. They either die or 
the rachitic process is gradually developed. The chronic form is seen in 
older children, and often in those apparently healthy. The changes in 
the bones may take place without constitutional symptoms, though there 
are often catarrhal bronchitis, pneumonia, and anaemia. 
Achondroplasia (Foetal Rickets).-This disease of foetal life is of 
obscure nature, perhaps allied to rickets. 
Showing characteristic deformity of the hands. (Photograph by Dr. Northrup.) 
Fig. 628.-Achondroplasia. 
Bones which are of intra-membranous origin, or which in late foetal 
life are chiefly cartilaginous are least involved, while the long bones chiefly 
suffer, through failure in ossification at their ends, together with various 
defects in their cartilage. 
This condition is marked (see Fig. 627) by abnormalities in the 
length, shape, and consistency of the bones of the limbs, which in general 
are short and thick. The head may be normal or rachitic in type. 
The trunk may be of normal size. The fingers are often stumpy (Fig. 
628). These with other bone changes lead to the characteristic " dwarf" 
type of body. 
The characteristic lesions of achondroplasia are often associated 
with various developmental malformations of ordinary type. 
OSTEOMALACIA. 
This lesion consists in the softening of fully formed hard bone tissue 
by the removal of its inorganic salts. It is to be distinguished from 
rickets, whose lesions are due to a faulty development of bone, although 
in certain external characters the two diseases sometimes present consid- THE BONES AND JOINTS 
897 
erable similarity. Osteomalacia usually occurs in adults, most fre- 
quently in females during pregnancy and after parturition; more rarely 
it occurs in males, and in females unassociated with the above conditions. 
Microscopical examination shows that the decalcification occurs first 
in the periphery of the Haversian canals and in the inner layers of the 
walls of the marrow spaces. As the salts of lime are removed-the base- 
ment substance at first remains as a finely fibrillated material, gtilj :pre- 
serving the original lamellation. The bone cells may be changed in shape 
or degenerated. After a time the decalcified tissue may disintegrate, and 
be absorbed, and its place occupied by new-formed marrow or granula- 
tion tissue. As the disease goes "on, the marrow tissue is congested and 
red, the fat absorbed, and there is a great accumulation of small sphe- 
roidal cells; or the marrow may assume a gelatinous appearance. The 
decalcification and absorption of the bone from within may proceed so 
far that the bony substance in the cancellous tissue almost entirely dis- 
appears, and the compact bone is reduced to a thin, soft, decalcified tis- 
sue. The disease is not always continuously progressive, but may be 
subject to temporary cessation. 
As a result of this softened condition of the bones, the weight of the 
body and the actions of the muscles may induce a series of deformities 
which are sometimes excessive: curvatures of the spine, complete and 
incomplete fractures of the bone, distortions of the pelvis, sternum, etc. 
There ig.a tendency in this disease to a general involvement of the hones, 
but the changes are sometimes confined to single bones or groups of 
bones. The cranium is rarely much affected. 
This is a chronic bone disease resulting in the formation of cysts and tumor-like 
structures. The softening of the bone permits of spontaneous fractures and curvatures. 
The disease is localized chiefly in the extremities, most frequently in the diaphyses, 
but may occur in any of the bones of the body. Microscopical examination shows 
extensive absorption of bone with disappearance of the lime salts and a very large 
number of giant cells and new formed granular tissue which often lead to the errone- 
ous diagnosis of sarcoma.1 
Osteitis Fibrosa. 
ALTERATIONS OF THE EONE MARROW IN LEUKEMIA AND ANAEMIA. 
In certain forms of leukaemia the marrow of the bones is very mark- 
edly altered. The change consists mainly in an accumulation in the 
marrow tissue of spheroidal cells, often in a condition of fatty degen- 
eration, which lie in the meshes of reticular connective tissue and in and 
along the walls of the blood-vessels. The new cells which accumulate in 
the marrow under these conditions are of various forms. Most character- 
istic are cells which considerably resemble the large lymphocytes of nor- 
mal blood and are called myelocytes. In addition to these the marrow may 
contain, mingled with its usual elements, nucleated red blood cells, spher- 
oidal cells containing red blood cells, and not infrequently considerable 
numbers of small octahedral crystals (called Charcot's crystals). 
The degree to which this accumulation of cells occurs varies much in 
'See v. Recklinghausen, Untersuchungen uber Rachitis und Osteomalacie, Jena, 11910; and 
Michaelis, M., Uber Ostitis fibrosa, Inaug, Diss., Berlin, 1913. 898 
THE BONES AND JOINTS 
different cases, and the gross appearances of the marrow.are consequently 
very diverse. In some cases the marrow is soft and has a uniform red 
appearance, or it is variously mottled with gray and red. Occasionally 
circumscribed haemorrhages are seen. In another class of cases, in which 
Fig. 629.-Hyperplastic Bone Marrow of Rib. 
From a case of purpura haemorrhagica. 
The marrow shows little but fat tissue with occasional darker patches containing either a few red 
cells, often nucleated, or one of the characteristic megalokaryocytes of the marrow. 
Fig. 630.-Normal Bone Marrow from Shaft of Femur. 
the cell accumulation is more excessive, the marrow may be gray, 
grayish yellow, or puriform in appearance (Fig. 629). 
These changes may occur in the central marrow cavity, as well as in 
the marrow spaces of the spongy bone. They may be present in several 
or many of the bones. They are usually accompanied by analogous 
changes in the spleen and lymph-nodes (Fig. 630). THE BONES AND JOINTS 
899 
In certain cases of acute and chronic anaemia, particularly in the perni- 
cious and progressive varieties, the marrow, especially of the larger long 
bones, may lose its yellow color from absorption of the fat, and become 
red. Microscopical examination of the marrow under these conditions 
may show myelocytes and sometimes an abundance of developing nucle- 
ated red blood cells and Charcot's crystals. 
In many of the acute infectious diseases, typhus fever and typhoid 
fever, ulcerative endocarditis, recurrent fever, etc., the bone marrow has 
been found hyperaemic, and may, it is asserted by Ehrlich, contain mye- 
locytes in increased numbers. 
All these lesions of the marrow, although our knowledge of them 
is still very incomplete, together with what is known of the physiological 
functions of the marrow, point to a close relationship between the mar- 
row and the spleen and lymph-nodes as blood-producing organs. 
TUMORS. 
Tumors of the bone may involve either the periosteum, or the com- 
pact bone, or the medulla; or, as is more frequently the case, two or 
more of these structures may be involved at once. Tumors of the bone 
are usually accompanied by various secondary and sometimes very 
marked alterations of the bone tissue, osteo-porosis, osteo-sclerosis, ossi- 
fying periostitis, etc. The new growths are very apt to undergo calci- 
fication and ossification. 
Fibromata may grow from either the periosteum or the medulla. 
Their most common seat is in the periosteum of the bones of the head and 
face. They are apt to form polypoid tumors projecting into the posterior 
nares, pharynx, mouth, and antrum of Highmore. Central fibromata, 
i.e., those growing from the medulla, are rare. They usually occur in 
the lower jaw, but have been found in the ends of the long bones, the 
phalanges of the fingers, and the vertebrae. The fibromata may calcify 
or ossify, contain cysts, and not infrequently occur in combination with 
sarcoma. 
Myxomata are of occasional occurrence in bone. 
Osteomata.-New formations of bone as a result of inflammatory proc- 
esses are, as we have already seen, of frequent occurrence in bone, and 
although not, strictly speaking, tumors, some of their forms are very 
closely allied to them, and they may therefore be conveniently mentioned 
here. New growths of bone which arise from the surfaces are called 
exostoses (see Fig. 616) or enostoses, according to their origin from the 
external surface or from the interior of the bone. They may contain all 
the constituents of normal bone: bone, medulla, vessels, periosteum, 
and cartilage. The new bone may be compact and like ivory, or spongy, 
or contain large cavities filled with marrow. 
The shape of exostoses varies greatly; they may be in the form of 
sharp, narrow spicula and processes, and, occurring in connection with 
periostitis, are called osteophytes. They may be polypoid in shape, or 
form rounded tumors with a broad base. They may form a general 900 
THE BONES AND JOINTS 
enlargement of the bone with much roughening of the surface; this con- 
dition is often called hyperostosis. 
The bone, beneath these new growths may be normal, or sclerosed, or 
rarefied, or the medullary cavity of the bone may communicate with that 
of the exostosis. Exostoses are usually developed from the periosteum, 
sometimes in the insertion of tendons and ligaments. They are very 
frequently multiple, and may occur at all ages, even during uterine life. 
Enostoses are developed in the interior of bones from the medulla. 
They may increase in size, with absorption of the surrounding bone, un- 
til they project from the surface like exostoses. Their most frequent 
situation is in the bones of the cranium and face. 
Chondromata.-These tumors may be single or multiple, and most fre- 
quently grow from the interior of the bone, but sometimes from the 
periosteum. They are prone to form various combinations with other 
forms of tumors, as fibroma, myxoma, sarcoma, etc. They are frequently 
congenital, and are most common in young people. They occur most 
frequently in the bones of the hand and foot. 
There is a form of chondroma, called osteoid chondroma, which de- 
velops beneath the periosteum, most frequently in the femur and tibia 
near the knee-joint, forming a club-shaped enlargement of the bone. The 
characteristic of the tissue composing these tumors is that it resembles 
somewhat the immature bone tissue which is seen beneath the periosteum 
in developing bone. It differs from cartilage in the irregular shape of 
its cells, in the fibrillation and density of the basement substance, and in 
its general vascularity. On the other hand, it has not the inorganic con- 
tents or appearance of true bone. It resembles considerably the callus 
tissue forming about fractures of the bones. It may, however, and most 
frequently does, become converted, in some parts of the tumor, into true 
bone. On the other hand, combinations with sarcomatous tissue are of 
frequent occurrence (see below). 
Sarcoma is especially common in the bones. It grows from the inner 
layers of the periosteum or from the medulla, so that we may distinguish 
a periosteal and a myelogenic sarcoma. Sometimes the tumor involves the 
bone itself so early that it is impossible to say whether the tumor began 
in the periosteum or in the medulla. There is also a variety which grows 
close to the outside of the periosteum and becomes connected with it- 
parosteal sarcoma. 
The periosteal sarcomata usually belong to the varieties fibro-, myxo-, 
chondro-, and osteo-sarcoma, more rarely to the medullary variety. 
They commence in the inner layers of the periosteum, pushing this mem- 
brane outward. After a time the periosteum is involved and the tumor 
invades the surrounding soft parts. The bone beneath may remain nor- 
mal, or may be eroded and gradually disappear until the tumor is con- 
tinuous with the medulla. Portions of the tumor may be calcified, or a 
growth of new bone may accompany its growth. The new bone usually 
takes the form of plates, or spicula, radiating outward (Fig. 631). The 
minute structure of these tumors is very variable. The simplest-the 
fibro-sarcomata-are composed of fusiform, round, stellate, and some- THE BONES AND JOINTS 
901 
times giant cells (myeloplaxes), in varying proportions, packed closely 
in a fibrous stroma. In the medullary form the stroma is diminished 
to a minimum and the round cells are most numerous. In the chondro- 
and myxo-sarcoma the basement substance may be hyaline or mucous, 
and the cells follow the type of cartilage and mucous tissue more or less 
closely. There is a mixed form of tumor, called osteoid sarcoma, which 
is very apt to spread and to form metastases. The growth consists in 
part of tissue corresponding to fibro-sarcoma and round-celled sarcoma. 
In addition to this there occurs, in greater or less quantity, immature 
bone tissue, called osteoid tissue, which may in part become calcified, the 
calcification usually occurring in the central portions, leaving a softer 
peripheral zone. This form of tumor is most apt to occur at the ends 
of the long bones, and may form tumors of large size. It is often called 
Fig. 631.-Sarcoma of the Bone-Periosteal. 
The growth has invaded the shaft of the bone, which is fractured. Spicula of bone, new 
formed in the tumor, may be seen below, passing outward from the periosteum. 
on account of its tendency to extend and to form metastases, malignant 
osteoma or osteoid cancer. Angio-sarcomata are of frequent occurrence 
in bone. 
Sarcomata may originate in the medulla-myeloid sarcoma-and 
may grow rapidly. The bone surrounding them is destroyed and 
they project as rounded tumors. Most frequently new bone is formed 
beneath the periosteum, so that the tumor is enclosed in a thin, bony 
shell (Fig. 632); sometimes there are also plates of bone in the tumor; 
sometimes the periosteum is unaltered; sometimes it is perforated and the 
tumor invades the surrounding soft parts. The tumors are frequently 
very soft, vascular, and haemorrhagic in parts, or may enclose cysts filled 
with tumor detritus and blood. They are usually of the spindle- or 
round-celled variety, and not infrequently contain giant cells. 
Sarcomata may originate in the outer layers of the periosteum-par- 
osteal. They may be as firmly connected with the bone as is the peri- 
osteal form. The periosteum may remain intact between the tumor and 
the bone, or it may disappear and leave them in apposition. Endo- 
thelioma of bone is not uncommon. Lipoma is rare. 902 
THE BONES AND JOINTS 
Myeloma.-Under this name is included a peculiar group of tumors, 
which, while they resemble the sarcomata in many respects, are distinct 
from them in their histogenetic relationships; that is, they are derived 
from the special cells of the bone marrow, and not from the periosteum. 
These tumors are usually multiple, appearing simultaneously in many 
parts of the bony structures.1 They form grayish or reddish masses in 
the spongy bone or in the medullary canal 
and as they grow excite active resorption 
of the bone. Spontaneous fractures are 
frequent and bending of the bone from 
loss of lime salts is occasionally seen. 
Metastases in other organs are extremely 
rare. Another interesting point is the pres- 
ence in the urine in many of these cases 
of a peculiar proteid called Bence Jones' 
proteid, which coagulates on heating, and 
dissolves on further heating in the boiling 
liquid, only to reappear again as it cools. 
This proteid is not absolutely characteristic 
of myeloma as it has also been found in 
some of the leukaemias. 
Microscopically, the tumors are com- 
posed of three varieties of cells: myelo- 
cytes, or myeloblasts, red cells, and plasma 
cells. In the first type of tumor, which 
may very well be designated myelocytoma, 
the cells are large, with oval or irregular 
nuclei, and many of them show character- 
istic granulations of the neutrophile my- 
elocytes. Tumors formed largely of red 
cells (erythrocytoma or erythroblastoma) 
are extremely rare,2 while new growths 
largely composed of plasma cells are the 
most frequent variety. In such cases the 
plasma cells often appear in the circulating 
blood during life. 
Angioma.-A very large number of the 
tumors which have been described under 
this name are really very vascular sarco- 
mata. Cavernous angiomata may form 
between the periosteum and bone and be intimately connected with the 
latter. There are several cases described of cavities filled with blood in 
the interior of bones, which it is difficult to interpret. They have 
mostly been found in the head of the tibia. They are said to have 
consisted of single sacs composed of thickened periosteum, lined with 
Fi g. 632.-Myelogenic Sarcoma 
of the Sternum. 
1 Wright, "Multiple Myeloma," Trans. Assn. Am. Phys., 1900, xv., 137; Hoffmann, Ziegler's Beitr., 
1904, xxxv., 317; Jellinek, Virchow's Arch., 1904, clxxvii., 96 (bibliography); Christian, Jour. Exper 
Med., 1907, ix„ 325. 
2 Norris, Proc. N. Y. Path. Soc., 1906, vi., 128. THE BONES AND JOINTS 
903 
plates of bone, and filled with fluid and clotted blood. No large vessels 
communicated with the sacs, but their walls were covered with a rich 
vascular plexus, branches of which opened into the cavity of the sac. 
Carcinoma.-Primary carcinoma is of doubtful occurrence in the 
bones. Most of the structures thus named have doubtless been sar- 
comata or endotheliomata. Secondary carcinoma, on the other hand, 
as a result of metastases or local extension, is not infrequent. Metas- 
tatic carcinoma may occur in the bones of various parts of the body 
at the same time, and are most apt to be secondary to carcinoma of the 
mamma. 
Cysts.-These most frequently occur in the maxillary bones (p. 415) 
in connection with the teeth. They may be unilocular or multilocular, 
and contain clear serum or a mucous or brown fluid, and sometimes 
cholesterin. They may be lined with epithelium. They begin in the in- 
terior of the bone, and, as they increase in size, expand it until they may 
be covered with only a thin shell of bone. They may reach a large size, 
even as large as a child's head. 
Dermoid cysts are occasionally found in connection with the bones, 
particularly of the skull.1 
The Joints. 
For a description of the dislocations, misplacements, and injuries of 
the joints we refer to works on surgery. 
DEGENERATION. 
Fatty degeneration of the cartilage cells, mucous degeneration, and 
fibrillation of the stroma with softening, and often roughening, of the 
joint surfaces, calcification and amyloid degeneration, may occur in 
inflammation, or as a senile alteration, or under other conditions. The 
cartilage is usually, under these conditions, whiter and more opaque 
than normal. 
Exudative Arthritis.-The earlier stages of acute inflammation of the 
synovial membranes are better known from experiments on animals than 
from post-mortem examinations. Among the early changes are swelling 
and congestion of the membrane, with increased growth and desqua- 
mation of the lining cells, and infiltration of the membrane with lymphoid 
cells. These conditions are soon followed by an exudation. The exact 
origin of much of the exudate is not clear. 
In Serous Arthritis the accumulation of serum within the synovial sac 
is the most prominent lesion. The disease may terminate in recovery, or 
become chronic, or pass into the suppurative form. It may be incited 
INFLAMMATION. (Arthritis.) 
1 For a resume and bibl. of the pathology of bone see Schmidt in Lubarsch and Ostertag's "Ergeb- 
nisse," Jahrg. iv., for 1897, p. 531; also Jahrg. v. for 1898, p. 895. 
For a resume of cysts of bone see Bloodgood, Progressive Med., vol. vi., p. 181, 1904. 904 
THE BONES AND JOINTS 
by contusions, penetrating wounds, gonorrhoea, rheumatism, or it may 
occur without evident cause. 
Sero-fibrinous Arthritis may occur under the same conditions as those 
which lead to simple serous inflammation. The fibrin may be present 
largely as flocculi in the serum, or it may form false membranes over the 
surfaces of the joint. 
Suppurative Arthritis may follow or be associated with the above forms 
of inflammation. The synovial membrane is thickened and cloudy, and 
there may be but a moderate amount of pus in the joint, and a slight 
degree of infiltration of the synovial membrane with pus cells. Under 
these conditions resolution may occur. 
In other cases the accumulation of pus in the cavity may be great, 
the synovial membrane and its surrounding tissue densely infiltrated 
with pus cells. Under these conditions granulation tissue is apt to 
form and the cartilages of the joints are apt to become involved. There 
are swelling and proliferation or degeneration of the cartilage cells; the 
basement substance becomes disintegrated, ulcerates, and exposes the 
bone, in which osteitis, caries, rarefaction, etc., may occur. The new- 
formed granulation tissue may penetrate the cartilage, absorbing the base- 
ment substance, and by metaplasia the cartilage tissue may be converted 
into embryonal or granulation tissue. The pus may break through 
the capsule of the joint and form large abscesses in the adjacent soft 
parts. Sometimes the inflammation is not only suppurative but gan- 
grenous, and runs a rapidly fatal course. The synovial membrane, artic- 
ular cartilages, and ends of the bone all undergo a rapid suppuration 
and gangrene. Acute arthritis may be incited by trauma, or it may 
be associated with pyaemia, smallpox, measles, scarlet fever, pneumonia,1 
gonorrhoea,2 diphtheria, mumps, typhus fever, glanders, the puerperal 
condition, or other infectious diseases. In these cases the process is apt 
to be suppurative, and is induced by various forms of bacteria. 
Chronic Arthritis may begin as such, or it may be the result of previous 
acute inflammation. There is an increase of fluid in the joint. This 
fluid is thin and serous, or is thickened with flocculi of fibrin and epi- 
thelial and lymphoid cells, or is thick, syrupy, or even gelatinous. The 
synovial membrane is at first congested, its tufts are prominent. Later it 
becomes thickened, sclerosed, and anaemic; the lining cells are destroyed, 
and the tufts become large and projecting. From the distention of the 
capsule there may be subluxations or luxations of the joint, or the cap- 
sule may be ruptured. 
Rheumatic Arthritis.-An acute inflammation, usually exudative in 
character and involving one joint after another, is characteristic of acute 
articular rheumatism. The exudate is usually serous. 
A chronic form of so-called rheumatic arthritis is most common in 
elderly persons, usually affecting several joints and advancing slowly and 
steadily. There is a fibrous thickening of the synovial membrane and 
1For bibliography of pneumococcic arthritis see Cave, Lancet, 1901, vol. i., p. 82. 
2 See bibliography, p. 223. For chronic streptococcus arthritis see Davis, Jour. Amer. Med. Assn., 
1913, Ixi, 724. THE BONES AND JOINTS 
905 
the adjacent tissue. Fluid accumulations are not common. The artic- 
ular cartilages are apt to degenerate or ossify, or become softened and 
fibrillated, and they may disappear. The contracting synovial mem- 
branes and fibrous tissue render the joints stiff and may cause consider- 
able deformity. Not infrequently fibrous and bony ankyloses are formed 
between the ends of the bones. 
Arthritis Deformans.-This name has been applied to a variety of 
chronic inflammation of the joints which, combined with degeneration of 
parts of the joint and the new formation of bone, may result in marked 
deformities of the part. The disease usually occurs in elderly persons and 
is apt to involve several joints, most frequently the hip, knee, fingers, and 
feet. It may be idiopathic, or due to rheumatism or to injuries, or follow 
an acute arthritis. The capsules of the affected joints are thickened and 
sclerosed. The synovial fluid is at first increased in quantity; later, 
diminished and thickened. The tufts of the synovial membrane become 
much enlarged and vascular; they may be converted into cartilage. 
Sometimes the capsule becomes ossified. The new bone grows from the 
edge of the cartilage within the capsule and its articular surface is covered 
with cartilage. The articular cartilages are much changed. The base- 
ment substance splits into tufts, while the cartilage cells are increased in 
number. Or the basement substance becomes fibrous; or it is split into 
lamellae and the cartilage cells are multiplied; or there are fatty degener- 
ation and atrophy. 
As a result of these changes, larger or smaller portions of the cartilage 
are destroyed and the bone beneath is laid bare. The exposed bone may 
become compact and of an ivory smoothness. The ends of the bones are 
much deformed. They are flattened and made broader by irregular new 
growths of bone, while at the same time they atrophy. The new growth 
of bone starts from the articular cartilages. The cartilage cells increase 
in number and the basement substance grows in quantity. This growth 
is most excessive at the edge of the cartilage, so that a projecting rim is 
formed there. This projecting rim may ossify next the bone, and at the 
same time new cartilage may form on its surface, so that we may find 
large masses of bone covered with cartilage. All these changes occur in 
various combinations and sequences, so that joints in this condition pre- 
sent the greatest variety of appearances.1 
Arthritis Uratica (Gouty Arthritis).-This lesion is characterized by the 
deposit of salts of uric acid in the cartilages, bones, and ligaments, and 
also in the cavities of joints. The deposits may be in the form of stellate 
masses of acicular crystals in and about the cartilage cells or in the base- 
ment substance; or they may be deposited in the fibrillar connective- 
tissue structures of the joint in single crystals, or in the subcutaneous 
tissue about the joint as white concretions. The deposits may occur in 
repeated attacks of the disease, and are accompanied by acute inflam- 
matory changes. They may lead to various forms of chronic inflamma- 
tion of the joints. 
1 For a valuable study of arthritis deformans see Nichols and Richardson, Jour. Med. Res., xxi., 
149, 1909. 906 
THE BONES AND JOINTS 
Tuberculous Arthritis.-This process may commence in the synovial 
membrane of the joint, or may extend to the joint from adjacent bone. 
It is characterized by the formation of tubercle tissue and granulation 
tissue, sometimes in great quantity, and is usually associated with second- 
ary inflammatory and degenerative changes of surrounding parts. 
According to the prominence of one or other of these secondary altera- 
tions, several forms of tuberculous arthritis may be distinguished. If 
there is an excessive growth of granulation tissue without much suppura- 
tion, this constitutes a fungous form. Sometimes there is extensive 
suppuration, so that the cavity of the joint may be filled with pus, which 
may be discharged through openings in the skin; or there may be more 
or less extensive formation of abscesses, or infiltration of the soft parts 
about the joint with pus. In other cases there is disintegration of the 
new-formed tuberculous tissue and of the tissues of the joint-ulcerative 
form. The cartilage basement substance may become split into frag- 
ments and the cells degenerate, and thus deep and destructive ulcers 
of the cartilage may be formed. Or the new tissue may work its way 
through the cartilage into the bone beneath, by absorption of the base- 
ment substance of the cartilage, with or without proliferation of its cells. 
Caries and necrosis of the underlying bone may lead to extensive de- 
struction. Hand-in-hand with these alterations subperiosteal new 
formation of bone may occur, or sclerosis of the adjacent bone tissue. 
There may also be a great increase of fibrous tissue about the joint. 
The type of lesion depends in considerable degree upon the joint 
involved. 
This disease is most common in children and young persons. The 
so-called scrofulous diathesis is said to foster it, but local injuries are 
frequently the predisposing factors. It is most common in the large 
joints. It may occur in connection with tuberculous inflammation in 
other parts of the body, but it is frequently quite local, and may remain 
so for a very long time or permanently, since general infection from tuber- 
culous arthritis is comparatively infrequent. 
The process is usually slow, and may end in death. If recovery takes 
place before the cartilages and bones are involved, the topography of the 
joint is maintained; but it may be stiffened, or even immovable, from 
the contraction of the new fibrous tissue around it. If the cartilages and 
bones are diseased the joint is destroyed, and either bony or fibrous 
ankylosis results. Sometimes, from the change in the articulating sur- 
faces and the contraction of the muscles and the new fibrous tissue, 
partial or complete dislocations are produced. 
Occasionally miliary tubercles occur in the synovial membranes in 
cases of general miliary tuberculosis, with but little accompanying simple 
inflammatory change. 
TUMORS. 
Secondary tumors of the joints as a result of local extension from the 
adjacent parts are not uncommon, and the tumors may be of various THE BONES AND JOINTS 
907 
kinds. Primary tumors of the joints, on the contrary, are not very 
common. 
Lipoma.-A new growth of fat tissue may begin in the other portions 
of the synovial membrane, push this inward, and project into the joint 
in a mass of tufts-lipoma arborescens. 
Fibroma occurs as a hypertrophy of the little tufts and fringes of the 
synovial membrane. In this way large polypoid and dendritic bodies 
are formed. The pedicles of these growths may atrophy and even dis- 
appear, so that the growths are left free in the cavities of the joints. 
Corpora aliena Articulorum (Loose Cartilages in the Joints).-This 
name is given to bodies, of various structure and origin, which are found 
free or attached by slender pedicles in the cavities of the joints. They are 
most frequently found in the knee; next in order of frequency in the 
elbow, hip, ankle, shoulder, and maxillary joints. They may be single 
or in hundreds. Their size varies from that of a pin's head to that of 
the patella. They are polypoid, rounded, egg-shaped, or almond- 
shaped; their surface is smooth or faceted, or rough and mulberry-like. 
They are composed of fibrous tissue, cartilage, and bone in various 
proportions. 
These bodies are formed by hyperplasia of the synovial tufts and 
the production in them of cartilage and bone. 
More frequently the small plates of cartilage form on the inner surface 
of the synovial membrane, which increases in size while their outer layers 
ossify. These may remain fixed in the synovial membrane; or they pro- 
ject and become detached from it, and they then appear as flattened, 
concave bodies composed of bone covered with cartilage on one side. 
On the other hand, cartilage and bone may form outside the synovial 
membrane from the periosteum or the edges of the articular cartilages, 
and, pushing inward, may later become detached. 
Rarely portions of the articular cartilages may be detached by vio- 
lence or disease; or fibrinous and other concretions may form in arthri- 
tis, or under conditions which we do not understand.1 
'For a detailed consideration of lesions of the bones and joints consult Ziegler, "Lehrbuch der 
Pathologic," vol. ii. CHAPTER XIV. 
THE NERVOUS SYSTEM. 
The Membranes and the Ventricles. 
The Dura Mater Cerebralis. 
The dura mater is a dense connective-tissue membrane which serves the double 
purpose of a periosteum for the inner surface of the cranial bones, and of an investing 
membrane for the brain. It is itself but poorly supplied with blood-vessels, but it con- 
tains the large venous sinuses which carry the blood from the brain. Lesions of the 
dura mater, therefore, are apt to be associated with lesions of the cranial bones, of the 
pia mater, or of the venous sinuses. 
In young children the dura mater adheres closely to the inner surface of the cranial 
bones, in adults it is more readily detached, and in old persons it is again more adher- 
ent. Chronic inflammation of the external layers of the dura mater also renders it 
more adherent to the bones. 
HAEMORRHAGE. 
Extravasated blood may lie between the dura mater and the cranial 
bones, in the substance of the membrane, or between the dura mater and 
the pia mater. 
Haemorrhages between the dura mater and the cranial bones are usu- 
ally due to blows and injuries of the head, are often of considerable size, 
separating the membrane from the bones, and may compress the brain. 
They are often associated with laceration of the brain, and with haemor- 
rhages between the dura mater and pia mater. 
Haemorrhages between the dura mater and the pia mater may take 
place from the vessels of either membrane. Those from the vessels of 
the dura may result from chronic pachymeningitis. 
Hemorrhages into the substance of the dura mater are not frequent 
and are usually small. 
Pressure on the head of the infant in delivery may cause extravasa- 
tions of blood between the bones and the dura mater, as well as between 
the bones and the pericranium. 
THROMBOSIS. 
Thrombosis of the venous sinuses is not uncommon. It is often associ- 
ated with inflammation of the dura mater and with injuries and inflam- 
mations of the brain and pia mater, of the cranial bones, of the middle 
ear, and of the scalp. Like thrombosis in other parts of the body, it 
may occur in the infectious and exhausting diseases. It may occur in 
apparently healthy persons without discoverable cause. The thrombi 
may be red or white, and firm. They may induce no secondary changes, 
908 THE NERVOUS SYSTEM 
909 
or they may extend into the veins and induce haemorrhagic softening of 
the involved areas of the brain. 
INFLAMMATION. (Pachymeningitis.) 
This may involve the external layers of the membrane, pachymenin- 
gitis externa, or the internal layers, pachymeningitis interna. It may be 
either acute or chronic. The tissues of the substance of the dura mater 
participate to a greater or less degree in these changes, but the chief 
lesions are upon the surfaces. 
Acute Pachymeningitis Externa is usually secondary to injuries or dis- 
eases of the cranial bones; thus it may be incited by fractures of the 
skull, either depressed or not, osteitis, caries, suppurative inflammation 
of the internal and middle ear and of the mastoid cells. The dura mater 
At the left near the vessels are connective-tissue cells containing blood pigment. 
Fig. 633.-Pachymeningitis Interna Hemorrhagica-Chronic. 
is commonly congested and swollen, and may contain small ecchymoses. 
The inflammation is usually suppurative, and pus may accumulate be- 
tween the membrane and the bone, or in the substance of the membrane. 
The areas of inflammation are not usually extensive. It sometimes 
leads to thrombosis of the venous sinuses, and sometimes gangrene of the 
dura mater occurs. The inflammation may extend to the inner surface 
of the dura mater, to the pia mater and brain, or it may remain localized 
and undergo resolution. 
Acute Pachymeningitis Interna may be secondary to inflammation of 
the external surface, or it may occur as a complication in pyaunia, puer- 
peral fever, chronic diffuse nephritis, in the exanthemata and erysip- 
elas, or independently. There is a general or circumscribed production 
of fibrin and pus, so that the internal surface of the membrane is lined 
with a layer of soft, yellow exudate. 
Simple Chronic Pachymeningitis consists in the formation of new con- 
nective tissue in the dura mater, by which it becomes thicker and in 910 
THE NERVOUS SYSTEM 
many cases abnormally adherent to the bones of the skull. This thick- 
ening may be general or circumscribed, and may involve the entire 
thickness of the membrane. Not infrequently, when the external layers 
are especially involved, firm adhesions to the skull occur, with ossifi- 
cation of the outer layers, so that shreds of the membrane containing 
little - masses of bone (osteophytes) remain sticking to the skull when 
the membrane is stripped off. 
Pachymeningitis Interna Haemorrhagica.-This is an important form 
of chronic inflammation of the internal layer of the dura mater, character- 
ized by the formation of layers of new delicate 
connective tissue with numerous very thin-walled 
blood-vessels from which the blood is prone to 
escape. The membrane may at first appear as 
a delicate fibrinous pellicle, with small red spots 
scattered through it, or it may look like a simple 
reddish or brown staining of the inner surface of 
the dura mater. Microscopical examination 
shows this membrane to consist of numerous 
blood-vessels, mostly capillaries with very thin 
walls, which may be distended or pouched, and which have grown out 
from the vessels of the dura mater (Fig. 633). Between the vessels is a 
homogeneous or slightly differentiated basement substance, containing a 
variable number of spheroidal, fusiform, or branching cells. Red blood 
cells in variable quantity, blood pigment in various forms, frequently en- 
closed in the new cells, and small calcareous concretions (brain sand) (Fig. 
634), also lie in the intervascular spaces. In more advanced stages the 
new membrane may become greatly thickened, its outermost layers being 
changed into dense fibrous tissue with obliteration of the vessels; while 
the more recently formed layers are similar in structure to those at first 
developed. Considerable blood usually escapes by diapedesis from the 
vessels of the new membrane in all stages of its formation. The vessels 
are also very liable to rupture, giving rise to extensive haemorrhages 
either into the substance of the membrane or between it and the pia mater. 
Sometimes masses of new tissue and blood, from half an inch to an inch 
or more in thickness, are formed in this way, greatly compressing the 
brain. These new membranes are most frequently formed over the 
convexity of the brain, but may extend over nearly the entire surface 
of the dura mater. Sometimes, when old, the entire membrane, densely 
pigmented and firm, lies loosely beneath the dura mater without com- 
pressing the brain or giving any clinical indication of its presence. The 
membrane may induce chronic changes in the pia mater, with or without 
accompanying changes in the cortical portion of the brain. 
Rarely, serum accumulates between the layers of the new membranes 
and in this way cysts of large size may be formed. In rare cases diffuse 
suppuration of the entire new membrane occurs. 
The slighter degrees of this form of inflammation may occasion no 
symptoms during life. They are not infrequently found in persons suf- 
fering from various chronic brain lesions and from chronic alcoholism, 
Fig. 634.-Brain Sand from 
Pachymeningitis Interna. THE NERVOUS SYSTEM 
911 
but they may occur unassociated with complicating lesions. The more 
advanced forms of the lesions are frequently found in idiots, epileptics, 
etc. 
Tuberculous Pachymeningitis may occur secondarily to that form of 
inflammation in the pia mater or the bones, or as a part of general miliary 
tuberculosis. The tubercles may be situated on either surface of the 
membrane or in its substance, and may be single, or aggregated forming 
large masses. 
Syphilitic Pachymeningitis manifests itself by the formation of so-called 
gummy tumors upon either the external or internal surface of the dura 
mater. These tumors may be single or multiple, and vary greatly in 
size. They may be accompanied by simple inflammatory changes in the 
dura mater in their vicinity. They may undergo suppuration with the 
formation of abscess. The inflammation may extend to the pia mater, 
inducing simple or syphilitic meningitis and adhesions between the dura 
mater and pia mater. The gummata may, on the other hand, when 
occurring on the outer surface of the membrane cause absorption and 
perforation of the bones of the skull. 
TUMORS. 
Fibromata and lipomata occur rarely in the dura mater and are of 
small size. 
Small chondromata are sometimes found connected with the dura 
mater at the base of the brain. 
Osteomata.-In addition to the formation of osteophytes in chronic 
external pachymeningitis, plates and, more rarely, globular masses of 
bone may be formed in the dura mater, unconnected with the bones 
of the skull. They are most frequently found in the falx cerebri, but 
may occur elsewhere. The new bone may be dense or loose in texture, 
and usually produces no symptoms. 
Endotheliomata.1-These tumors may grow inward or outward, caus- 
ing pressure on the brain or absorption and perforation of the bones; they 
often attain considerable size. Some of these tumors somewhat resemble 
certain forms of epithelioma, and have often been described as primary 
carcinomata. They vary in character, being sometimes formed of 
densely packed masses of flattened cells with little fibrous stroma (Fig. 
219), sometimes lobulated with considerable dense stroma in narrow or 
broad bands. In other cases, the polyhedral or cuboidal cells are con- 
spicuously grouped around blood-vessels. Again, the cells form con- 
centric, densely packed masses, either around vessels or around a central 
cell group (Fig. 220). These form one of the types of psammoma, and 
the concentric borders are often calcified. 
Sarcomata are the most common tumors of the dura mater, and of 
these the spindle-celled forms are of more, the round- and polyhedral- 
celled forms of less, frequent occurrence. They may grow from either 
1 For a consideration of tumors of the dura mater allied to the endotheliomata consult Dagonet, 
Arch, de med. exp., t. iv., p. 361, 1892. 912 
THE NERVOUS SYSTEM 
surface of the membrane. Some of the round- and polyhedral-celled 
forms are soft and very vascular, and are apt to involve the neighboring 
pia mater and brain tissue, or the bones of the skull, which they may 
perforate. They sometimes project through the opening in the skull 
in fungous, bleeding masses. 
Fig. 635.-Psammoma of the Dura Mater. 
Psammomata are small globular tumors, often multiple and pedicu- 
lated, growing from the inner surface of the dura mater. They are 
usually composed of tissue, fibrous, sarcomatous, or endotheliomatous 
in character, and contain variously shaped calcareous concretions similar 
in appearance to the so-called brain sand1 (Fig. 635). 
The Pia Mater Cerebralis 
General Characters of the Pia Mater. 
The external surface of the brain is invested by a connective-tissue membrane 
which covers the convolutions, dips down into the sulci, and extends into the ventricles. 
This membrane is abundantly supplied with blood-vessels, and from it numerous ves- 
sels extend into the brain, so that any disturbance in the circulation of the blood in 
the pia mater involves a disturbance in the circulation of the blood in the brain also. 
The connective tissue which makes up the pia mater is arranged in a series of 
membranes and fibres reinforced by elastic tissue, so arranged as to form a spongy 
membrane containing numerous cavities more or less filled with fluid. These cavities 
are continuous with the perivascular spaces which surround the vessels that pass 
from the pia mater into the brain. The outer layers of the pia mater are the most 
compact, and are covered on their outside surface by a continuous layer of endothelial 
cells. This external layer of the pia mater is often described as a separate membrane 
called the "arachnoid," but it is really only part of the pia. The deeper layers of the 
pia contain the blood-vessels. The membranes and fibres which compose the pia 
mater are partly coated with cells which have irregular and delicate cell bodies and 
large, distinct nuclei. 
Along the borders of the longitudinal fissure, and, more rarely, on the under sur- 
face of the brain, are a number of small, white, firm, irregular bodies, the Pacchionian 
bodies. They vary in size, number, and in the extent of the surface of the hemispheres 
which they cover. They may perforate the dura mater, or, more rarely, the wall of 
the longitudinal sinus, and may produce erosions of the skull bones. They are com- 
posed of fibrous tissue and may undergo fatty or calcareous degeneration. We are 
ignorant as to their origin, and as to the causes of their variations in size and number. 
1 For a study of psammoma consult Ernst, "Ueber P ammome," in Ziegler's Beitrage zur path. 
Anatomie, Bd. xi., p. 234, 1892. 913 
THE NERVOUS SYSTEM 
The frequency of their occurrence, and the absence of any known pathological 
significance, warrant our regarding them as essentially normal structures. 
The pia mater is frequently thickened, opaque, and white, either in diffuse patches 
or, more commonly, along the course of the vessels. In other cases single or multiple 
small white spots, of the size of a pin's head or smaller, may be seen in the membrane, 
not appreciably elevated above the surface, but due to localized thickening. These 
slight opacities of the pia mater are commonly believed to be dependent upon repeated 
congestions of the membrane or upon chronic meningitis, but there is no evidence that 
this is always the case. They are most frequently found in old persons, but may exist 
at any age, and do not necessarily indicate the pre-existence of disease. 
The amount of blood contained in the vessels of the pia mater after death varies 
greatly, and is by no means a reliable indication of the amount present during life. In 
general anaemia the vessels of the pia mater may contain little blood, but, on the other 
hand, they sometimes seem to contain a relatively larger amount than other parts of 
the body. In oedema of the brain and pia mater the vessels of the latter may contain 
but a small amount of blood. 
(EDEMA. 
The quantity of serum beneath the pia mater and infiltrating its 
tissue is very variable in amount. It may accumulate as a result of 
atrophy of the brain substance or of venous hyperaemia, and sometimes 
is, and sometimes is not, accompanied by oedema of the brain substance. 
It may be diffuse or localized. It is not infrequent to find in hospital 
patients suffering from chronic nephritis, cardiac or pulmonary disease, 
or chronic alcoholism, a very considerable amount of serum in this situa- 
tion, though the patient has been free from cerebral symptoms. In 
other cases a serous effusion may accompany grave cerebral symptoms. 
It is necessary to be very careful in judging of the importance of this 
accumulation of fluid, especially in determining the cause of death in 
the absence of other marked lesions. 
It should always be borne in mind that an accumulation of fluid 
beneath the pia mater and in its meshes may occur as a result of post- 
mortem changes.1 
HYPEREMIA AND HAEMORRHAGE. 
Hyperaemia.-The pia mater may be hyperaemic in early stages of 
meningitis, in delirium tremens, in epileptic convulsions, in infectious 
diseases, and in poisoning. It may be due to the pressure of exudates or 
tumors on the veins, or to general or local lesions of the circulatory 
system. The time which elapsed between death and the autopsy, the 
position in which the body has lain, the coagulability of the blood, may 
have an important bearing upon the amount and situation of blood in 
the pia. 
Haemorrhage.-This may occur either into the space between the dura 
mater and the pia mater-inter meningeal hemorrhage-or in the meshes 
of the pia or between the latter and the brain. It may be due to injury, 
to rupture of aneurisms or otherwise diseased blood-vessels, to throm- 
boses of the venous sinuses, or to conditions which we are unable to 
ascertain. Haemorrhages without known cause not infrequently occur in 
1 For study of oedema of the pia arachnoid see Stillman, Arch. Int. Med., 1911, viii-., 193. 914 
THE NERVOUS SYSTEM 
the substance of the pia mater in young children, but in adults they are 
apt to be the result of injury. Multiple ecchymoses, however, in the 
substance of the pia mater sometimes occur in infectious diseases and 
also in acute inflammation of the pia mater. Haemorrhages in the brain 
substance may lead to the accumulation of blood beneath or in the 
meshes of the pia mater. Intermeningeal haemorrhage in infants as a 
result of injury during birth is not uncommon. Small, or sometimes 
considerable, extravasations of blood may occur from diapedesis, and 
sometimes, as a result of chronic congestion, degenerated blood pigment 
collects along the walls of the vessels. The extravasated blood in menin- 
geal haemorrhage, if small in quantity, may be largely absorbed, leaving 
a greater or smaller accumulation of pigment at the seat of the -haemor- 
rhage. Such pigmentations may last for a long time. 
INFLAMMATION. (Meningitis-Leptomeningitis.) 
We distinguish acute, chronic, tuberculous, and syphilitic meningitis. 
Acute Meningitis may occur as the characteristic lesion of epidemic 
cerebro-spinal meningitis; it is a not very infrequent complication of 
pneumonia, typhus and typhoid fever, the exanthemata, and of chronic 
diffuse nephritis; it may be secondary to injuries and inflammation of 
the cranial bones, of the dura mater, and of the middle ear, and it some- 
times occurs as an independent infectious process. 
In acute meningitis the inflammatory process is apt to extend down- 
ward and involve the pia mater of the cord. It may also involve the 
ependyma of the ventricles, and cause the distention of these cavities 
with serum. This latter condition is especially frequent in young 
children. 
It is convenient to consider two varieties of acute meningitis, one in 
which there is cell proliferation with little or no exudate, the other in 
which exudate is present. In many cases at least, the first may be the 
early stage of the latter form. 
1. Acute Cellular Meningitis.-The pia mater is congested, its 
surface is dry and lustreless, and it is somewhat opaque. The changes 
in the gross appearance of the membrane are not marked and are easily 
overlooked, but the minute changes are more decided. There is a pro- 
liferation of the endothelial and connective-tissue cells of the pia, and 
often a moderate collection of fluid and leucocytes in the meshes of the 
pia. This cell proliferation may involve the pia mater over most of the 
surface of the brain. This form of meningitis is of frequent occurrence 
and is attended with the ordinary clinical symptoms of acute meningitis. 
2. Acute Exudative Meningitis is characterized by the accumu- 
lation, chiefly in the meshes of the pia mater and along the walls of the 
blood-vessels, of variable quantities of serum, fibrin, and pus. Some- 
times one, sometimes another of these preponderates, giving rise to 
serous, fibrinous, or purulent forms of the inflammation. The absolute 
quantities of the exudations also vary greatly. In some cases death 
may occur with so slight a formation of exudate that to the naked eye THE NERVOUS SYSTEM 
915 
the pia mater may look quite normal or perhaps only moderately hyper- 
aemic or cedematous; the microscope, however, in these cases will reveal 
pus cells in small numbers, newly formed connective-tissue cells (Fig. 636 
and Fig. 637), and sometimes flakes of fibrin in the meshes of the pia and 
along the walls of the vessels. In other cases turbid serum in the meshes 
of the membrane is all that can be seen and the microscope shows the 
Showing distention of the meshes of the pia mater of the brain with fluid, in which are 
leucocytes and exfoliated endothelium, the latter undergoing proliferation. 
Fig. 636.-Acute Exudative Meningitis. 
turbidity to be due to pus cells or to a small amount of fibrin. Again, 
either with or without marked oedema of the pia mater, yellowish 
stripes are seen along the sides of the veins, sometimes appearing like 
faint turbid streaks, at other times dense, opaque, thick, and wide, and 
almost concealing the vessels. These are due to the accumulation of 
pus cells and fibrin in large quantities along the vessels, and are best 
Proliferation of connective-tissue cells and extravasation of leucocytes in the adventitia of a 
small blood-vessel of the pia mater. 
Fig. 637.-Acute Exudative Meningitis. 
seen and most abundant around the larger veins which pass over the 
sulci. In still other cases the infiltration with pus and fibrin is so dense, 
thick, and general, that the brain tissues, convolutions, and most of 
the vessels of the pia mater themselves are concealed by it. This pus is 
usually of a greenish yellow color, and is sometimes so thick as to form 
a sort of cast of the brain surface at the seat of the lesion (Fig. 638). 916 
THE NERVOUS SYSTEM 
Sometimes extravasated red blood cells are mingled with the other exu- 
dations, as the result of diapedesis. Microscopical examination shows 
numerous white blood cells sticking in the walls of the veins and capil- 
laries, or the vessels may be blocked with them. It is evident that a large 
part of the pus cells accumulate as the result of emigration. The 
connective-tissue cells of the pia mater may be detached from their 
places or degenerated. The endothelial cells and other connective- 
tissue cells may proliferate. In some cases there are considerable accu- 
mulations of pus between the pia mater and the brain substance and 
along the vessels which enter the latter. More rarely pus is found upon 
the free surface of the membrane. The brain substance may be com- 
Fig. 638.-Acute Exudative Meningitis. 
a, Convolutions of cerebrum; b, pia mater thickly infiltrated with pus; c, blood-vessels entering 
brain from pia apd surrounded by a zone of pus cells; d, congested blood-vessels of pia mater; e, smaller 
|>lood-vessels of pia, around which pus cells are collected in dense masses. 
pressed by the accumulated exudate, so that the convolutions are flattened. 
The cortical portion of the brain may be simply infiltrated with serum 
-cedematous-or it may undergo degenerative changes, or it may be 
the seat of punctate haemorrhages. Not infrequently the inflammation 
extends to the ventricles which may contain purulent serum, and to the 
pia mater of the cord. This form of inflammation is most frequent on 
the convexity of the brain, but may extend or even be confined to the 
base. It may be localized, but frequently extends widely over the sur- 
faces of the hemispheres. 
When recovery from acute exudative meningitis occurs there may be 
fatty degeneration of the cells which have accumulated in the pia mater, 
particularly along the vessels (Fig. 639), and this may produce white 
patches in the membrane and threads along the blood-vessels, which 
resemble the appearance of an accumulation of exudate in the acute 
stage. Fatty degeneration of the blood-vessels and cells of the pia 
mater may also occur without acute inflammatory changes. 
Sometimes, in children and young adults, inflammatory changes in THE NERVOUS SYSTEM 
917 
the ventricles persist for days and weeks after the subsidence of the 
inflammation of the pia mater. 
For a discussion of the bacterial excitants of exudative meningitis 
see page 223.1 
Chronic Meningitis.-The entire pia mater may be involved or the 
inflammation may be confined to the base alone (basilar meningitis), or to 
the convexity alone, or to circumscribed patches of the membrane. The; 
pia mater is thickened and opaque, the thickening being sometimes very 
considerable. There is a formation of new connective tissue and this 
may be associated with accumulation of pus, fibrin, and serum; the rela- 
tive quantity of these inflammatory products varies in different cases. 
Fig. 639.-Fatty Degeneration of Cells Along the Blood-vessels of the Pia Mater 
after Exudative Meningitis. 
From the pia mater of a child five years old. 
Firm and sometimes extensive adhesions may be formed between the 
dura mater and the pia mater. Not infrequently the cortical portions 
of the brain participate in the process, and there is an infiltration of small 
spheroidal cells around the blood-vessels, thickening of the walls of the 
vessels, and degenerative changes and atrophy of the nerve tissue. New 
connective tissue may also form in the brain substance, which may 
become closely adherent to the pia mater. The ventricles of the brain 
also may contain an increased amount of serum and may be dilated, 
the ependyma may be thickened and roughened. This form of inflam- 
mation may be the result of injury or disease of the cranial bones, or 
secondary to chronic pachymeningitis or to inflammation of the brain 
substance. It may occur in the vicinity of tumors of the brain or menin- 
ges. It may be a complication of chronic diffuse nephritis or the result 
of chronic alcoholic poisoning. It may occur in marked form in general 
paresis of the insane. 
1 The close topographic relationships which the nasal cavities and the middle ear bear to the 
meninges are significant in this connection on account of the possibility of the transmission to the 
brain membranes of bacteria not uncommonly present and usually harmless in the former situations. 918 
THE NERVOUS SYSTEM 
Tuberculous Meningitis.-This is especially characterized by the for- 
mation in the pia mater of miliary tubercles, associated with more or less 
well-marked exudative inflammation. It may occur in adults or in 
children, but is more common in the latter. The dura mater may be 
unchanged, or its inner surface may be sprinkled with miliary tubercles. 
The pia mater may or may not be congested; it may look dry on the sur- 
face or it may be cedematous. Usually the brain seems to fill the cere- 
bral cavity to an unusual degree, and the convolutions are flattened. If 
the pia mater be cedematous the serum may be clear, or turbid with pus 
and fibrin. The membrane may present any of the general appearances 
of exudative meningitis, but always in addition to these, and sometimes 
without them, are found miliary tubercles. These may be few and widely 
scattered, or present in great numbers. They are most numerous along 
the blood-vessels, but may occur anywhere. They are usually abundant 
at the base of the brain. On the convexity they are most common along 
the surfaces of the sulci. Some of the tubercles are so small as to be 
scarcely visible or entirely invisible to the naked eye; others are as large 
as a pin's head or larger. They may be formed in the membranous 
prolongations of the pia mater which dip into the sulci, around the ves- 
There is an area of caseation at the centre; on the right of this are two giant cells; there is 
a peripheral zone of small cells. The leucocytes are increased in the meshes of the pia. 
Fig. 640.-Miliary Tubercle of the Pia Mater of a Child. 
seis which enter the brain substance, in the choroid plexus and ependyma 
of the ventricles, and may exist in the spinal cord. 
The miliary tubercles have the usual structural characters of focal 
tuberculosis in connective tissue (Fig. 640). 
In children the ventricles are usually more or less distended by an 
accumulation of transparent or turbid serum, and the walls of the ven- 
tricles may be studded with miliary tubercles (see Fig. 641). In adults 
the ventricles are less frequently involved. The brain tissue around 
the ventricles is often softened. The central canal of the spinal cord 
may also be dilated. It is the dilatation of the ventricles which causes 
the flattening of the convolutions, and the flattening is usually in direct 
proportion to the amount of accumulated fluid. 
Owing to the frequency of the dilatation of the ventricles with serum 
in children, the disease is often called acute hydrocephalus. 
In both children and adults the tuberculous inflammation may pro- 
duce large masses of tuberculous tissue, which undergo cheesy degenera- 
tion, and may involve the brain tissue. 
In almost all cases of tuberculous meningitis there is tuberculous 
inflammation in other parts of the body. THE NERVOUS SYSTEM 
919 
Miliary tubercles in the choroid of the eye are present in a considerable 
proportion of cases. 
The cortex of the brain may be hyperaemic, and punctate haemor- 
rhages may be present in the cortex and in the pia mater. 
Syphilitic Meningitis.-In this form of inflammation, which is usually 
circumscribed, there is a development of gummy tumors of variable size, 
frequently associated with simple inflammation of the membrane, either 
with the formation of serum, fibrin, and pus, or with the development 
Fig. 641.-A Miliary Tubercle of the Ependyma of the Lateral Ventricle. 
This shows an early stage of tubercle formation on the ependyma without marked caseation. 
of new connective tissue and consequent thickening of the membrane. 
The gummata may form in the pia mater covering the convexity, or at 
the base of the brain. They may grow outward, involving the dura 
mater; or inward, encroaching upon or involving the brain tissue. 
Although usually circumscribed, syphilitic inflammation may occur as 
a diffuse thickening of the membrane. The syphilitic nodules, includ- 
ing the gummata and new-formed connective tissue, are often very 
small, but may be as large as a hen's egg. 
TUMORS. 
Haematoma.-In chronic pachymeningitis of long standing the new 
connective tissue may form large, flat cysts between the dura mater and 
the pia mater, which may compress the surface of the brain. The blood 
originally contained in these cysts may be absorbed and replaced by 
serum, the attachments to the dura mater may disappear, and the whole 
appearance becomes that of an independent cyst between the dura mater 920 
THE NERVOUS SYSTEM 
and the pia mater. Fibroma, lipoma, myxoma, chondroma, and osteoma 
are of rare occurrence. 
Endotheliomata.-These tumors are of not infrequent occurrence, and 
may grow from the pia of the cerebrum or cerebellum or from the choroid 
plexus. They may be single or multiple. They may be small or so 
large as seriously to compress the brain. 
Some of them are composed of a connective-tissue stroma which 
encloses regular spaces filled with large, flat, nucleated cells. These may 
resemble carcinoma. Some of them are composed of a connective-tissue 
Fig. 642.-Endothelioma of the Cerebellum Originating in the Pia Mater 
Showing general appearance of the tumor (see Fig. 643). 
stroma which forms cavities lined with cylindrical epithelium. In such 
tumors the stroma may grow so as to form papillae covered with cylin- 
drical epithelium; or in addition there may be mucous degeneration of 
the stroma. In some of them there is a connective-tissue stroma which 
contains large numbers of blood-vessels. Around these blood-vessels are 
arranged regular masses of polyhedral cells (Figs. 642 and 643). 
In some endotheliomata the stroma is scanty. The cells are numer- 
ous, large, flat, and arranged in little globular masses or nests (Fig. 219). 
If in these little nests there is a deposition of the salts of lime, forming 
concretions like the so-called " brain sand," the tumor is called a " psam- 
moma." Some of the tumors seem to be formed of very thin, nucleated 
membranes arranged concentrically like the layers of an onion. 
Some of the tumors are composed of balls or nests of large, flat cells, 
with which are found crystals of cholesterin-"cholesteatoma."1 
1 For a critical review of these and other pial tumors, with bibliography, see Bostroem, Centrbl. f. 
allg. Path. u. path. Anat., Bd. viii., p. 1, 1897. THE NERVOUS SYSTEM 
921 
Sarcoma.-Tumors belonging to the ordinary types of round- and 
fusiform-celled sarcoma, and of myxo-sarcoma, are occasionally found 
in the pia mater. 
Cysts.-Small cysts are often found in the choroid plexus. Rarely 
such cysts reach a larger size, even as large as a pigeon's egg. 
Cysts of the pia mater containing serum, with walls and septa of con- 
nective tissue, and compressing the brain have been described. 
Fig. 643.-Endothelioma of the Pia Mater of the Cerebellum. 
From specimen shown in Fig. 642 more highly magnified. A, Section of pia mater dipping into 
a sulcus; B, tumor cells growing at each side of the pia; C, surface of cerebellar convolutions. 
Variously shaped pigment cells not infrequently occur in the pia mater 
either scattered or sometimes in considerable masses; they seem to have 
little pathological significance. Not infrequently thin plates of newly 
formed bone are found in the pia mater, associated with a thickening of 
the membrane. 
PARASITES. 
Cysticercus has been observed in the pia mater. 
The Dura Mater Spinalis. 
The dura mater spinalis, unlike that of the brain, does not serve as periosteum 
to the bones forming the cavity, so that the lesions of the two membranes differ 
somewhat. 922 
THE NERVOUS SYSTEM 
haemorrhage. 
Haemorrhage may occur, as the result of injury, between the dura 
mater and periosteum, or it may occur in tetanus, as a result of circula- 
tory changes induced by muscular spasm, or in the asphyxia of newborn 
children. Small haemorrhages on the surfaces of the membrane may 
occur as the result of inflammation. 
Serous fluid may accumulate outside of the dura mater as a result of 
post-mortem changes, or in connection with circulatory or inflammatory 
changes in the membranes. 
INFLAMMATION. (Pachymeningitis.) 
Acute external pachymeningitis is usually secondary to disease or 
injury of the spinal column, and may result in collections of pus between 
the dura mater and periosteum, usually most abundant posteriorly. 
Haemorrhagic pachymeningitis occurs in the dura mater spinalis, with the 
formation of products similar to those observed in the brain, in the 
chronic insane, and in drunkards. Simple chronic pachymeningitis 
interna, with the formation of new connective tissue containing brain 
sand, is not infrequent. The new tissue may form minute projections 
from the surface, or, when more abundant, may take the form of psam- 
momata. Tuberculous inflammation of the dura mater spinalis may 
occur in connection with tuberculous meningitis, or be secondary to 
tuberculous inflammation of the vertebra?. 
TUMORS. 
Fibromata, lipomata, chondromata, myxomata, endotheliomata, and 
adenosarcomata occur in the dura mater spinalis as primary tumors. 
Carcinomata and sarcomata may be found as secondary tumors. Small 
plates of newly formed bone are of rare occurrence. 
PARASITES. 
Echinococcus developing outside of the spinal canal may perforate the 
dura mater; or the cysts may lie between the dura mater and the pia 
mater. 
The Pia Mater Spinalis. 
It is difficult in most cases in the pia mater, as well as in the dura mater spinalis 
and in the spinal cord, to judge with certainty, from the appearances after death of 
the blood contents of the vessels, of these parts during life. The same is true of abnor- 
mal quantities of serum found after death. The veins of the pia mater, especially in 
the posterior region, may be greatly distended with blood after death, without pre- 
existing disease; and the intermeningeal space may contain much fluid under the same 
condition. 
HaEMORRHAGE. 
Haemorrhages may occur from injury, in connection with severe con- 
vulsions, or in general diseases such as the haemorrhagic diathesis, scurvy, THE NERVOUS SYSTEM 
923 
smallpox, etc. The haemorrhages under these conditions, except from 
injury, are not usually extensive. But in some cases of injury or cere- 
bral apoplexy, from the bursting of aneurisms of the basilar or vertebral 
arteries, or in cases in which we cannot find a cause, a very large quantity 
of blood may collect between the dura and pia mater, and in the meshes 
of or beneath the latter. 
INFLAMMATION. (Meningitis.) 
Acute exudative spinal meningitis occurs under essentially the same 
conditions and with essentially the same post-mortem appearances as 
acute cerebral meningitis, though it is less frequent. The exudate is 
apt to be most abundant in the posterior portions. It may be asso- 
ciated with a similar inflammation of the pia mater cerebralis, and the 
inner surface of the dura mater may be involved. The disease may be 
circumscribed, but usually affects the entire length of the membrane. 
Chronic spinal meningitis is not infrequent, manifesting itself in the 
formation of larger or smaller patches of new connective tissue or in 
Fig. 644.-Plates of Bone in the Pia Mater Spinalis. 
thickenings of the pia mater. The pia and dura mater may thus be 
firmly united in places by adhesions, or the pia mater may become closely 
adherent to the substance of the cord. 
Not very infrequently large numbers of pigment cells are found in 
the pia mater spinalis, sometimes giving it a distinct gray or blackish 
color. 
Tuberculous inflammation is usually associated with a similar condi- 
tion of the pia mater cerebralis, in which case the lesion is most marked in 
the upper portions of the cord; but it may extend over the entire mem- 
brane. The conditions under which it occurs and the character of the 
lesions are similar in both. 
TUMORS. 
Fibromata, myxomata, sarcomata, and endotheliomata have been 
found. 
Small plates of cartilage and bone (Fig. 644) are sometimes found in 
the pia mater. 
PARASITES. 
Cysticercus sometimes occurs in the meshes of the pia mater. 924 
THE NERVOUS SYSTEM 
THE VENTRICLES OF THE BRAIN. THE EPENDYMA AND 
CHOROID PLEXUS. 
As the lymph-spaces of the pia mater and the ventricles of the brain 
are in communication, it might be supposed that they would share alike 
in the accumulation of fluids. This, however, is not the case. The 
membranes of the brain may be highly oedematous while the ventricles 
contain about the normal quantity of fluid; or, on the other hand, the 
ventricles may be widely dilated and the pia mater unusually dry. Many 
of these varying conditions may be understood by remembering that the 
skull and spinal canal form a closed cavity, and that accumulations of 
fluid in one part must be at the expense of some material occupying 
other parts, either blood, serum, or brain tissue. It is not always easy 
to see, however, exactly how the compensation occurs. 
There may be an unusual amount of fluid in the ventricles of the 
brain as a result of post-mortem change; in connection with senile or 
other atrophy of the brain, or in the general vascular changes which lead 
to oedema of the brain; in connection with inflammation of the meninges 
or of the ependyma; or under conditions which we do not understand, 
as in some cases of congenital and acquired hydrocephalus. Accumula- 
tions of fluid in the ventricles are often called internal hydrocephalus to 
distinguish them from accumulations in the meninges-external hydro- 
cephalus. 
GENERAL CONSIDERATIONS. 
INFLAMMATION. (Ependymitis.) 
Acute Ependymitis.-In this condition, which may occur by itself, but 
is usually associated with inflammation of other parts of the brain, the 
ependyma is congested, the vessels are more prominent than usual and 
are often tortuous. The ependyma and the adjacent brain tissue may be 
thickened and infiltrated with pus cells, and the surface of the ependyma 
covered with fibrin and pus in variable quantity (Fig. 645). The cavi- 
ties of the ventricles may contain purulent serum. Small haemorrhages 
may also be present in the tissue of the ependyma. This, as well as 
other forms of inflammation, is more common in the lateral ventricles 
than in the others, but not infrequently involves the fourth ventricle. 
The choroid plexus may participate in the inflammatory changes of the 
ependyma. Tuberculous inflammation of the ependyma is, as above 
mentioned, a not infrequent accompaniment of tuberculous meningitis. 
Chronic Ependymitis.-This lesion, which is much more common than 
simple acute inflammation of the ependyma, occurs under a variety of 
conditions, and its nature and causation are in general very obscure. 
The ependyma is thicker, whiter, and more opaque than normal, so that 
the vessels may be nearly or quite invisible. The thickenings may 
occur in patches or diffusely, and the surface of the ependyma may be 
smooth, or roughened and granular. On microscopical examination the 
surface of the ependyma may be covered with the usual epithelium, but 
the new connective tissue -which forms beneath it often raises it up in THE NERVOUS SYSTEM 
925 
places, causing the roughness of the surface. The new tissue is usually 
rather loose in texture and may contain many small spheroidal cells; 
but it may be dense in texture and contain few cells. The brain tissue 
beneath the thickened ependyma may be softened or infiltrated with cells. 
The sides of the ventricles may be grown together in places by the adhe- 
sion of the thickened and roughened ependyma. The ventricles usually 
contain more serum than normal, and sometimes this accumulation is 
so great as to cause an enormous dilatation of them. While these are 
in general the prominent lesions in chronic inflammation of the epen- 
Fig. 645.-Acute Ependymitis. 
Showing replacement of the epithelium of the ventricle by inflammatory exudate: collections 
of pus cells near the epithelium and about the adjacent small blood-vessels. 
dyma, the comparative development of the several lesions varies greatly 
in different cases. 
The accumulation of fluid and the dilatation of the ventricles being 
the most marked feature in all this class of lesions, they are often called 
chronic hydrocephalus, but in many cases we have no evidence that the 
change in the ependyma is an important or even an actual primary 
factor. 
Hydrocephalus.1-We may, for convenience of study, consider three 
classes of cases of hydrocephalus: first, congenital hydrocephalus in 
young children; second, secondary hydrocephalus in children and adults; 
third, primary hydrocephalus in adults. 
1. Congenital Hydrocephalus.-The lesion may be in an advanced 
stage at the time of birth, or it may be scarcely evident or but moder- 
ately developed. It may progress rapidly and cause the early death 
of the child, or it may develop gradually or come to a standstill. In 
the more marked forms of the disease the ventricles are widely dilated 
t Consult Margulis, Arch. f. Psychiat., 1912, L, 31. 926 
THE NERVOUS SYSTEM 
(Fig. 646) and filled with serum, which is usually transparent. Not only 
the lateral ventricles, but also the third and fifth, may be involved; the 
fourth is less apt to participate in the lesion, although it is sometimes 
dilated, as well as the central canal of the cord. 
The distention, especially of the lateral ventricles, may be so great 
that the brain tissue over the vertex is crowded up into a thin layer 
beneath the dura mater, or it may be entirely destroyed. When the dila- 
tation of the ventricles is considerable, the convolutions are flattened 
and may be almost entirely obliterated. The skull bones may be thin 
and bulging over the forehead and vertex; the fontanelles and sutures 
Fig. 646.-Congenital Hydrocephalus in Child. About half natural size. 
a, a, Dilated lateral ventricles; b, cornua, unequally dilated; c, third ventricle; d, middle commissure. 
widely open. The ependyma in these cases is usually thick and rough, 
but it may be softened, and the blood-vessels may be dilated. The basal 
portions of the brain may be flattened, but are usually much less affected 
than the upper portions. The brain tissue is usually soft and anaemic. 
2. Secondary Hydrocephalus.-This may occur in children and 
adults, and may be a result of epidemic cerebro-spinal meningitis, or of 
acute meningitis, or of chronic meningitis. It sometimes occurs in 
chronic alcoholic poisoning and in general paralysis of the insane. The 
amount of dilatation of the ventricles varies greatly in these cases, but 
it is never so great as in congenital hydrocephalus, and is not accompa- 
nied by the changes in the shape of the skull which form so prominent a 
feature in the latter disease, since the bones are firmer and the sutures 
united. In this form of chronic hydrocephalus the changes in the epen- 
dyma above described are usually more or less well marked, and they 
may be associated with the production of fibrin and pus. 
3. Primary Hydrocephalus in Adults.-The conditions leading 
to this form of lesion are not understood. It is apt to occur in persons 
over thirty years of age. Sometimes one, sometimes both lateral ven- 
tricles are dilated. The dilatation is usually moderate, sometimes very 
slight and never as great as in congenital hydrocephalus. The ven- THE NERVOUS SYSTEM 
927 
tricles usually contain transparent serum, and the ependyma is thickened 
and roughened. In some cases it is the only lesion found to account for 
the death of the patient. 
TUMORS. 
New formations of connective tissue in the ependyma, although usually 
diffuse, may be circumscribed, and form small, projecting connective- 
tissue nodules, which may be classed among the fibromata. Small fibro- 
mata are sometimes detached from the walls of the ventricles and lie free 
in the cavity. Small lipomata, angiomata, and also sarcomata and glio- 
mata occur rarely. Chondromata and angiomata may occur in the choroid 
plexus, the latter sometimes being as large as a hen's egg. The choroid 
plexus is not infrequently the seat of transparent cysts, usually of small 
size; they may contain a clear fluid, or colloid material, or droplets of 
fat, or calcareous particles. A small dermoid cyst containing hairs has 
been described. The cysts have no special pathological significance. 
Primary carcinomata sometimes involve the ventricles. 
The calcareous bodies called brain sand1 (see Fig. 634) occur fre- 
quently in the choroid plexus, and corpora amylacea may occur here and 
beneath the ependyma. 
PARASITES. 
Cysticercus and echinococcus cysts are sometimes attached to the walls 
of the ventricles or may be free in their cavities. 
The Brain and Spinal Cord. 
Malformations of the Brain. 
Cyclopia.-This malformation consists in an arrest of development affecting the 
cerebrum, which, instead of separating into two hemispheres, remains single, with one 
ventricle, the rudiments of the eyes usually uniting to form one eye (Fig. 177). This 
single eye is in the middle of the face, near the place of the root of the nose, in a single 
orbit. Over this is an irregular body representing the nose. The rest of the face is 
well formed. The eyeball may be wanting entirely, or there may be two eyes joined 
together, or, more seldom, two separate eyes. The orbit is surrounded by rudiments 
of four eyelids. The frontal bone is single, the nasal bones are undeveloped; the 
ethmoid, vomer, and turbinate bones are absent. The optic nerve is double, single, or 
absent. There may be hydrocephalus. Such children are incapable of prolonged 
existence. 
Anencephalia.-This malformation may be of various degrees. The brain may 
be entirely absent, the base of the cranium being covered with a thick membrane, into 
which the nerves pass. The membranes may form a sort of cyst containing blood and 
serum or portions of brain. Of the cranial bones, only those which form the base of 
the skull are present (acrania). The scalp is usually partly or entirely absent over 
the opening in the skull; the eyes are prominent, and the forehead slopes sharply 
backward. This malformation may occur in otherwise well-developed children. 
Hydrocephalus.-This lesion has been already considered above. It is proba- 
ble that in some cases hydrocephalus internus is due to a primary partial anencephalia, 
1 The little, hard masses called brain sand consist of aggregations of small particles of carbonate 
and phosphate of lime with a small amount of phosphate of ammonia and magnesium. With these 
there is more or less organic matter. 928 
THE NERVOUS SYSTEM 
and that the accumulation of fluid is of secondary occurrence. In rare cases, only 
part of one lateral ventricle is hydrocephalic, giving to the head a protuberance on 
one side. The viability of the foetus depends upon the degree of the hydrocephalus. 
Hydrocephalus externus is an accumulation of serum beneath the pia mater, or, accord- 
ing to some authors, between the pia and dura mater. It causes dilatation of the 
cranium and compression of the brain. It is of very rare occurrence, and may also be 
secondary to partial anencephalia. 
Cephalocele, or Brain Hernia.-When abnormal openings exist in the skull 
from malformation, the contents of the cerebral cavity are apt to protrude in the 
form of larger or smaller sacs. This may occur in cases of well-marked anencephalia 
or in cases in which the brain is well developed. The protruding sac formed of the 
meninges may or may not be covered with skin. If the contents of the sac are simply 
fluid, the lesion is called hydromeningocele; if composed of brain substance, encephalo- 
cele (Fig. 181); if the sac contain both fluid and brain substance, it is called hydren- 
cephalocele. The sacs may be very small or as large as a child's head. They may 
protrude from the top of the skull in acrania. They most frequently protrude 
through openings in the occipital bone, often hanging down in large sacs upon the 
neck; also at the root of the nose, along the line of the sutures, at the base of the skull, 
and elsewhere. 
Microcephalia.-This is an abnormally small size of the brain, with a correspond- 
ingly small cranium. The diminution in size affects principally the cerebral hemi- 
spheres, though the other parts of the brain are also small. Thus the cerebellum may 
be of extremely small size. The cord may be smaller than normal, in which case the 
diminution in size is apt to show a direct dependence upon the cerebral lesions, the 
direct and the crossed pyramidal tracts being most affected. There may also be 
present imperfect development of the posterior columns and of the direct cerebellar 
tracts. The convolutions are few and simple, the cavities often dilated with serum; 
on the membranes there may be traces of inflammation.. The cranium is small, the 
face large, the rest of the body small. This malformation is in some cases caused by 
inflammation or dropsy of the brain during foetal life. It is endemic in some countries, 
but single cases may occur anywhere. The foetus is viable. Absence or incomplete 
development of portions of the brain may occur, not only in idiots, but in persons 
whose minds are perfect.1 
Malformations of the Spinal Cord. 
The malformations of the spinal cord may be conveniently classed as follows (Van 
Gieson2): 
I. Congenital Deformities Associated with Monstrosities, and Incompati- 
ble with Extra-uterine Life. 
These may be divided into: 
1. Amyelia, or absence of the spinal cord. This is almost invariably associated 
with absence of the brain. 
2. Atelomyelia, or partial development of the spinal cord. This is often seen in the 
anencephalous or acephalic monsters, where, corresponding to the incompletely devel- 
oped brain, there may be various degrees of defective development of the cord. 
3. Diastematomyelia, a condition in which a portion or the whole of the cord is 
split into two lateral halves. Each half of the cord is developed in its own membranes 
and gives rise to its own nerve roots. There may be union at one or more points to 
form a single cord. 
4. Diplomyelia, or a formation of two spinal cords-a duplication of the spinal 
cord. This happens in the various kinds of double monsters. 
1 For a general consideration of malformations of the central nervous system consult Thoma, 
"Text-book of Pathological Anatomy," vol. i., p. 206 et seq., also Ernst in Schwalbe's Morphologic d. 
Missbildungen des Menschen u. Tiere, 1909. 
2 Van Gieson, "Artefacts of the Nervous System," New York Medical Journal, vol. Ivi., pp. 337, 
365, 421, 1892. THE NEilVOUS SYSTEM 
929 
II. Minor Congenital Malformations not Inconsistent with the Mainte- 
nance of Life. 
1. Hydrorrhachis interna is a defective closure or arrangement of the divisions of 
the primary foetal central canal often resulting in the dilatation of the central canal 
by fluid (Hydromyelid) (Fig. 647). This dilatation may be moderate, or so extreme 
that but little of the substance of the cord is left as a thin shell around the central 
cavity. When they have not been destroyed by atrophy epithelial cells may be found 
lining the cavity. 
This condition may be accidentally found after death. Its presence may also be 
indicated by its association with spina bifida.1 
2. H eterotopia, or misplacement of the substances of the cord. 
(a) There may be misplaced portions of the gray matter. 
(6) Portions of the white matter may be arranged in an unusual manner. 
3. Anomalies of the Spinal Nerve Roots. 
4. Asymmetries of the Spinal Cord. 
Fig. 647.--Hydkomyblia. 
In the section from which this drawing was made, the epithelial cells surrounding the dilated 
central canal were well preserved. 
III. Malformations of the Spinal Cord Acquired during Extra-uterine 
Life or Secondary to Defective Development in Other Parts of the Body. 
1. Distortions following other cord lesions-. 
2. Asymmetry of the cord due to arrested development after birth or to secondary 
atrophy of portions of the cord in association with defective development or absence 
of some other part of the body. 
3. Asymmetry of the cord with congenital defects of the extremities or muscles, 
such as intra-uterine or other amputations, clubfoot, etc. 
4. Variations in the volume of the cord as a whole. 
False Heterotopia.-Congenital displacement of the gray or white matter of the 
spinal cord-heterotopia-has been frequently described. Van Gieson2 has shown, 
however, that in a large proportion of cases the so-called heterotopia is an artefact 
(Fig. 648) and has been caused by bruises or careless handling of the cord during its 
removal from the body or in the process of examination or hardening. 
Spina Bifida.-In the majority of cases hydrorrhachis is accompanied by a more 
or less complete lack of closure of the spinal canal posteriorly, so that the collections 
of fluid within may pouch outward through the opening in the form of a sac. The sac 
may be covered by skin, or this may be absent, either from the beginning or as a result 
1 Under this subdivision the condition known as hydrorrhachis externa may be conveniently alluded 
to, which consists in an abnormal congenital accumulation of fluid between the meninges of the cord, 
causing more or less diminution in the volume of the latter. 
2 Van Gieson, New York Medical Journal, vol. Ivi., pp. 337, 365, 421, 1892. 930 
THE NERVOUS SYSTEM 
of thinning and rupture. The walls of the sac may consist of the dura mater and the 
pia mater, or, in cases of hydrorrhachis externa, of the dura mater alone. When both 
are present they are usually more or less fused together. Inside of the membranes of 
the sac there may be a shell of distended nerve tissue of the cord; or the spinal cord 
may be split posteriorly and the sides crowded sideways; or there may be a rudimen- 
tary fragment of the cord suspended in the sac or attached to the walls; or the cord 
may be but little changed and remain inside the spinal canal. The openings in the 
spinal canal may be due to the complete or partial absence of the vertebral arches, or 
more rarely the sac may protrude through 
openings between the completely formed 
arches. Spina bifida most frequently occurs 
in the lumbar and sacral regions, but it may 
occur in the dorsal or cervical regions, or the 
canal may be open over its entire length. 
Very rarely it is open on the anterior sur- 
face. The protruding sac may be very small 
or as large as a child's head. The fluid in the 
sac is usually clear, but may be turbid from 
flocculi of degenerated nerve tissue. 
INJURIES OF THE BRAIN. 
Fig. 648.-False Heterotopia. Scction 
from Cervical Region of Spinal Cord. 
The brain may be directly wounded 
by a foreign body, or indirectly by 
fragments of bone driven into it, or it 
may be lacerated by severe contusion 
without fracture or solution of con- 
tinuity of the skull. Very severe injuries of the brain are often caused 
in parts of the organ remote from the seat of violence. Thus blows on 
the skull frequently cause laceration of the brain on the opposite side. 
This is called injury by contrecoup. It is very difficult to estimate the 
degree of injury which must cause death, since some persons die from 
slight, and others recover from very severe, wounds of the brain. In 
incised wounds of the brain more or less haemorrhage occurs at the seat 
of lesion, and the brain tissue in the vicinity soon undergoes degenera- 
tive changes. These may be comparatively slight or extensive. In- 
flammatory reaction may occur in the vicinity, and the adjacent brain 
tissue, as well as the haemorrhagic and degenerated area, may become 
infiltrated with pus cells. After a time the injured and degenerated 
area may become surrounded by new-formed connective tissue, and 
the decomposed extravasated blood and detritus of brain tissue, more or 
less fatty, may be absorbed. In this way the part heals, leaving a some- 
what pigmented cicatrix. The healing is in most cases very slow and 
may occupy months or even years. The pia mater may participate to a 
marked degree in the inflammatory healing process. Abscesses may 
form near the seat of injury. 
After wounds which involve the removal of portions of the cranial 
bones, it is not uncommon after a few days to see a bleeding fungous 
mass projecting through the opening. This mass, sometimes wrongly 
called hernia cerebri, consists of degenerated brain tissue, blood, and 
granulation tissue, with more or less pus. The brain tissue below it is 
degenerated, soft, broken down, and purulent, and there is often abscess 
Showing artificial displacement of the 
structures by an experimental bruise ("false 
heterotopia") after the removal of the cord 
from the body. (Van Gieson.) THE NERVOUS SYSTEM 
931 
in the adjacent brain tissue. Such wounds may finally heal by the absorp- 
tion of the broken-down brain tissue and blood, and its replacement by 
granulation tissue. 
Lacerations of the brain tissue without fracture may appear shortly 
after the injury as simple more or less circumscribed areas of capillary 
haemorrhage; the brain tissue about these may degenerate, pus may 
form, and abscesses be developed; or the degenerated and lacerated tis- 
sue may be gradually replaced by granulation tissue which finally forms 
a cicatrix. • The process of degeneration and softening and of healing 
in such lacerations of brain tissue may occur very slowly indeed, even 
occupying years, and not infrequently the degenerative changes are very 
extensive and progressive. In many cases, of course, the injury is so 
extensive, or involves such important parts of the organ, that very little 
or no inflammatory or degenerative change takes place before death. 
INJURIES OF THE CORD. 
The spinal cord may be compressed or lacerated by penetrating 
wounds, by fracture or dislocation of the vertebrae, or by concussion 
without injury to the vertebrae. The spinal cord is found simply disin- 
tegrated, or there may be much haemorrhage and the disintegrated nerve 
tissue be mixed with blood. If life continue, the nerve elements may 
degenerate; Gluge's corpuscles and free fat droplets may form; blood 
pigments may be formed; and when inflammation supervenes more or 
less pus may be intermingled with the degenerated material. There may 
be marked changes in the minute structure of the cord, without any 
change being evident to the naked eye. 
INJURIES OF THE NERVES. 
The secondary effects of injuries to nerves are described in the sec- 
tion on degenerations following injury. After amputation of a limb, 
there often occur swellings of the peripheral ends of the divided nerve 
trunks. These bulbous ends are called false or amputation neuromata. 
They are made up almost entirely of fibrous tissue, although nerve fibres 
have been found in them. 
HYPERTROPHY AND ATROPHY OF THE BRAIN. 
True Hypertrophy of the brain is rare, and probably always congeni- 
tal. An increase in the size of the brain from the proliferation of the 
neuroglia sometimes occurs in children either before or after birth, less 
frequently in youths, and very seldom in adults. The white substance of 
the hemispheres is increased in amount. If it takes place before the ossi- 
fication of the cranium, the bones are separated at the sutures and fon- 
tanelles; if after this, the inner table of the skull may be eroded and 
thinned. When the cranium is opened the dura mater appears tense and 
anaemic, the convolutions of the brain are flattened, the brain substance 932 
THE NERVOUS SYSTEM 
is firm and anaemic, the ventricles are small, the ganglia and cerebellum 
are either of normal size or compressed. 
The disease is usually very chronic, and destroys life with symptoms 
of compression of the brain. There may, however, be acute exacerbations. 
Atrophy.-This may occur as a senile change, or, in chronic alcohol, 
opium, or lead poisoning, in chronic insanity, and in chronic meningitis, 
or from local interference with the circulation. In children who are 
much reduced by chronic diseases atrophy of the brain may accompany 
atrophy of the rest of the body. 
The atrophy affects principally the cerebral hemispheres, and may be 
uniform or more marked in some parts than in others, involving the 
Fig. 649.-Atrophy of a Circumscribed Portion of Brain Convolutions in a Child. 
From a lesion of the corresponding blood-vessels. 
whole of a hemisphere or of a lobe or only single convolutions or groups 
of these (Fig. 649). The convolutions are small, the sulci broad, the 
ventricles usually dilated, the brain tissue is firm, the gray matter discol- 
ored, the white substance grayish in color; the blood-vessels may be 
dilated. The basal ganglia may be small. Serum accumulates in the 
pia mater and in the ventricles; the pia mater, and often the skull, 
become thickened; the brain tissue may be oedematous or contain small 
haemorrhages. The nerve elements of the brain tissue are those most 
involved in the atrophy, the diminished areas being usually harder and 
firmer than normal. THE NERVOUS SYSTEM 
933 
PIGMENTATION OF THE BRAIN. 
This may occur in any portion of the brain or its meninges from the 
decomposition of extravasated blood. In persons affected by malaria 
the gray matter of the brain has sometimes a dark or even blackish 
appearance. This color is due to the presence of black pigment granules 
within the capillary blood-vessels. The obstruction to the vessels by 
masses of these pigment granules may cause capillary apoplexies. The 
pigment may also be found in the walls and in the lumina of the vessels 
of the pia mater. 
Pigment patches of congenital origin are not infrequently seen in the 
pia mater. They may be due to the presence of branching pigmented 
cells. 
CIRCULATORY AND VASCULAR CHANGES IN THE BRAIN AND SPINAL CORD. 
Anatomical Considerations. 
In studying the circulatory changes in the brain and cord certain peculiarities in 
that circulation should be borne in mind. The vessels which nourish the brain arise 
from a remarkable anastomosis of large arterial trunks at its base, known as the circle 
of Willis (see diagram Fig. 650). From this " circle" pass 
off to each hemisphere three main branches-the anterior, 
the middle, and the posterior cerebral. These arteries 
ramify in the pia, where they anastomose freely. From 
this anastomosis small branches are given off which 
penetrate the brain substance, the shorter breaking up 
into capillaries in the gray matter, the longer passing to 
the underlying white matter. After entering the cortex 
there is no further anastomosis, the capillaries of a corti- 
cal artery passing directly over into a venous system of 
capillaries without communicating with capillaries of 
other arteries. They are thus "terminal arteries." In 
addition to these arteries, which supply the hemispheres, 
branches from the circle of Willis are distributed to the 
basal ganglia. These arteries are much larger than those 
which pass from the pia into the cortex, and beyond the 
circle of Willis do not form anastomoses with one another. 
Thus it is that occlusions of the arteries supplying the 
basal ganglia are much more serious, aside from the im- 
portance of the parts involved, than of those passing to 
the cortex. 
Three main arteries furnish blood to the cord: the 
anterior spinal, lying along the opening of the anterior 
median fissure, and two posterior spinal, lying near the 
entrances of the posterior roots. Branches of these 
arteries anastomose in the pia, and from this pial network 
branches pass directly into the substance of the cord. 
The largest, a branch of the anterior spinal, passes into 
the pia of the anterior fissure, and, penetrating the cord, 
is distributed to the gray matter of the anterior horn, 
and to the median gray matter as far back as Clarke's column. Smaller arteries from 
the posterior spinal supply the posterior regions of the cord. These arteries, like 
those in the brain, are terminal in the sense that, while anastomosing freely in the 
pia, after penetrating the substance of the cord there are no further anastomoses. 
Fig. 650.-Diagram of the 
Circle of Willis and Asso- 
ciated Vessels. 
a. Anterior cerebral; b, an- 
terior communicating; c, in- 
ternal carotids; d, middle cere- 
bral; e, posterior communicat- 
ing; f, posterior cerebral; g, 
basilar; h, vertebral. 934 
THE NERVOUS SYSTEM 
Hyperaemia and Anaemia. 
The appearance of the brain tissue after death does not always 
furnish reliable indications of its blood contents during life, though 
it is perhaps more to be depended on than the appearance of the meninges. 
Some of the more common conditions determining hyperaemia which 
are mentioned above as influencing the meninges apply also to the sub- 
stance of the brain. 
Active hyperaemia may occur in various inflammatory conditions of 
the brain. Hyperaemia of the brain is quite common in deaths from 
insolation and after conditions accompanied by acute delirium. Passive 
hyperaemia may occur in conditions similar to those which determine 
congestions in other organs of the body, such as chronic diseases of the 
heart or lungs. It may be induced by anything which prevents venous 
return, such as intracranial tumors which compress the sinuses, or by 
thrombosis. 
In sections of hyperaemic brains the small blood-points from the cut 
ends of small vessels are more numerous and conspicuous than under 
normal conditions, and the brain tissue, particularly the gray matter, 
may have a diffuse red color. If excessive, the convolutions may be 
somewhat flattened, the brain tissue and pia mater may be oedematous, 
and the ventricles contain fluid. The congestion of the vessels may be 
general or localized. 
The most constant lesion of what is known as caisson disease, a con- 
dition resulting from exposure to sudden changes in atmospheric pressure, 
is a congestion of the brain, cord, and meninges. Areas of softening in 
the brain and cord are not infrequent and there may be effusion into the 
meninges. 
Anaemia of the brain may be either local or general. It may depend 
upon a general anaemia or upon general disturbances of the circulation, 
such as mitral stenosis or regurgitation; or upon local interference with 
the arterial blood supply, such as complete or partial obstruction of the 
arteries from thrombi, emboli, inflammatory changes, spasmodic con- 
tractions, etc., or from tumors, exudations, and blood extravasations 
pressing upon the vessels from without. In oedema of the meninges, and 
in the presence of internal hydrocephalus, the brain tissue is apt to be 
anaemic. The brain tissue in anaemia looks whiter than usual, the con- 
trast between the gray and the white matter is less marked, and the 
small blood-points usually seen on section from divided vessels may be 
very inconspicuous or almost entirely absent. 
(Edema. 
(Edema of the brain tissue may accompany either general or localized 
hypersemia, or it may accompany ansemia, and it seems in most cases, 
though not always, to be dependent upon conditions which induce these 
alterations in the blood contents of the brain. It is, perhaps, most com- 
mon in conditions which determine a passive hyperaemia. In some cases THE NERVOUS SYSTEM 
935 
of marked impoverishment of the blood a so-called hydremic edema of 
the brain is found. 
In oedema the brain tissue appears unusually wet and shiny. The 
same underlying condition is apt to determine an exudation into the 
membranes and ventricles. There is usually considerable distention of 
the perivascular lymph-spaces. 
Marked oedema of the brain may exist without brain symptoms. On 
the other hand, persons may die comatose with no other gross lesion than 
oedema, either with or without oedema of the pia mater. This is seen 
w'ith especial frequency in acute and chronic alcohol poisoning, but may 
occur under other conditions. A careful microscopical examination of 
the brain under these conditions will frequently reveal structural lesions 
of more serious import than the oedema. 
Under the designation of " serous apoplexy, " oedema of the brain was 
formerly considered of importance, in the absence of other lesions, as a 
cause of death. But increased knowledge has led to the general belief 
that simple cerebral oedema as an independent condition has not the sig- 
nificance formerly ascribed to it, and it should be accepted, if ever, with 
great reserve as a cause of death. 
Hemorrhage. 
Haemorrhages in the substance of the brain may be very small and 
punctate, and are then usually called capillary haemorrhages; or they may 
result in the collection in the brain tissue of masses of blood of consid- 
erable size, which are called apoplectic joci or clots. These forms of 
haemorrhages may be associated, or a number of capillary haemorrhages 
may join to form an extensive clot. 
Capillary hemorrhages may appear, on section of the brain, like the 
severed ends of hyperaemic blood-vessels, or the tissue about them may 
be more or less tinged with blood. Microscopically, the perivascular 
spaces are distended with blood, which may have escaped into them. 
This is associated with more or less broken-down brain tissue. The 
haemorrhages may be single, but are frequently multiple, so that the brain 
tissue is besprinkled with blood-points. Degeneration of the extrava- 
sated blood may give rise in later stages to reddish or brown or yellowish 
circumscribed discoloration of the brain tissue, due to granules and crys- 
tals of blood pigment intermingled with broken-down brain tissue, with 
more or less fatty degeneration of its elements. Capillary haemorrhages 
may be due to fatty degeneration of the vessels leading to rupture; or 
the extravasation may be due to diapedesis, or it may depend upon con- 
ditions which we do not understand. They frequently occur in the 
vicinity of apoplectic clots and tumors, they may be due to thrombosis 
of the veins or of the sinuses of the dura mater; they not infrequently 
occur in acute encephalitis, in congestive hyperaemia, in acute mania, 
and in delirium tremens; and they may be associated with general 
diseases, such as scurvy, purpura haemorrhagica, typhus fever, pyaemia, 
ulcerative endocarditis, etc.; they may be associated with embolic 
softening. 936 
THE NERVOUS SYSTEM 
Apoplectic foci may result from the coalescence of numerous capillary 
haemorrhages; from injury; or from rupture of diseased arteries, either 
with or without changes in the blood pressure. Haemorrhages from 
injury to the skull may occur as well without as with fracture, and may 
be situated over the vertex or at the base of the brain. They vary in 
extent and location, depending upon the character and point of the 
injury and the size of the vessels involved. The so-called spontaneous 
haemorrhages, other than those of capillary origin, which give rise to 
masses of blood and broken-down brain tissue, may vary in size from that 
of a pea to those occupying a large part of a hemisphere. They are due, 
in a very considerable proportion of cases, to the rupture of small arterial 
aneurisms, but may arise from weakening of the walls of the arteries, 
from arteritis, atheroma, or fatty degeneration. These latter forms of 
lesions doubtless give rise in most cases to the formation of the aneurisms 
whose rupture is in so many cases the immediate cause of the haemorrhage. 
Aneurisms of the cerebral arteries may be as large as a pea or hazel- 
nut, but those most frequently met with and causing apoplexy are usually 
small-called miliary aneurisms-and may be microscopic in size, 
varying from this up to that of a large pin's head or larger. They may 
be sacculate or fusiform, and frequently exist in considerable num- 
bers. They may occur in any of the small arteries of the brain, but are 
said to be most frequent on the branches of the middle cerebral artery, 
It is asserted that the bursting of miliary aneurisms is the nearly, if not 
quite, exclusive cause of the formation of spontaneous apoplectic clots, 
but this we do not believe to be true. 
As to the immediate cause of rupture, either of aneurisms or other- 
wise diseased blood-vessels in the brain, we are in many cases entirely 
ignorant. In some cases it seems to be due to an increased arterial ten- 
sion in such diseases of the heart as induce this change, as in the cardiac 
hypertrophy which may accompany some forms of chronic diffuse 
nephritis; or it may result from unusual exertion or mental excitement. 
Haemorrhages most frequently occur in the corpora striata and optic 
thalami (Fig. 651), and in the brain tissue in their vicinity, and here they 
are most common in the parts supplied by the branches of the middle 
cerebral artery. The possibility of haemorrhage in the floor of the fourth 
ventricle should be borne in mind in investigating cases of sudden death 
from obscure causes. 
Haemorrhages frequently seriously affect other portions of the brain 
than those immediately supplied by the ruptured vessels. Thus haemor- 
rhages in the cortical substance or beneath the pia mater may force their 
way deep into the brain substance; or, in haemorrhage in the brain sub- 
stance, the blood may burst into the ventricles or work its way into the 
intermeningeal space, and, either at the seat of its occurrence or in the 
situations into which it is forced, may give rise to serious compression 
of the brain. Portions of the brain containing large extravasations may 
be enlarged, the tissue anaemic from pressure, the convolutions flattened, 
and the surface dry. As the blood is poured out, the brain tissue is usu- 
ally torn and lacerated, so that the apoplectic clot usually consists of THE NERVOUS SYSTEM 
937 
detritus of brain tissue intermingled with blood. If, however, the blood 
is poured out from a single vessel, the lacerated brain tissue may be 
pressed aside, and the greater portion of the red mass may consist of 
pure blood clot. 
The appearances presented by haemorrhages in the brain vary greatly, 
depending upon the time which has elapsed since their occurrence. If 
life continue, the oedema which usually soon occurs in the vicinity of the 
Fig. 651.-Large Haemorrhage in the Brain. "Cerebral Apoplexy." 
The haemorrhage involves the right basal ganglia and adjoining brain tissue. The blood is in 
both lateral ventricles. The right side of the brain (the upper side in the figure) is pressed out with 
flattening of the convolutions. 
haemorrhage disappears and the clot becomes drier and firmer; gradually 
the blood undergoes the usual series of changes seen in extravasation; 
the hemoglobin decomposes, forming granules and crystals of blood 
pigment; the blood cells and fibrin undergo degeneration and absorption; 
the detritus of brain tissue undergoes fatty degeneration. As these 
alterations occur the color changes to reddish brown, orange, or yellow, 
and the adjacent brain tissue may be discolored by imbibition. 
Inflammatory reaction may occur in the vicinity, leading either to the 938 
THE NERVOUS SYSTEM 
formation of a more or less pigmented cicatrix, or to a cyst with yellow- 
ish fluid contents and a fibrous, more or less pigmented wall. The proc- 
ess of degeneration and absorption of the blood and broken-down brain 
tissue, and their replacement by a cyst or by a cicatrix, is a slow one, 
and the cysts and cicatrices may resemble those formed at the seat of 
embolic softening. Not infrequently we find in the brain of a person 
dead from recent apoplexy the remains of old clots presenting some one 
of the above-described stages of absorption. The apoplectic cysts and 
cicatrices persist for a long time after their formation. 
Secondary degenerations (see p. 953) following haemorrhages depend 
entirely upon the cells destroyed or the fibre tracts interrupted. Most 
common are degenerations of the pyramidal tracts from haemorrhages 
Fig. 652.-Section of the Spinal. Cord Showing Hemorrhage into the Gray Matter 
and Extending Lengthwise of the Cord. (An early phase of haematomyelopore.) 
This lesion is sometimes called "hsematomyelia." 
into the sensory-motor region of the cortex, or from haemorrhages into 
the internal capsule (lenticulo-striate artery). Haemorrhages involving 
the optic centres or the optic fibres lead to degeneration in the optic 
tracts. Haemorrhages into other portions of the brain, by destroying 
commissural cells or interrupting their fibres, lead to degeneration of 
intracranial fibre tracts. 
I Haemorrhage in the spinal cord is much less frequent than in the brain, 
but may occur either as capillary apoplexy or as larger apoplectic clots. 
Capillary haemorrhages, similar in appearance to those of the brain, may 
occur as the result of injury, or near areas of softening or tumors, or may 
accompany severe convulsions, as in tetanus. Apoplectic clots, which 
are comparatively rare in the spinal cord, are usually small, commonly 
not more than one centimetre in diameter, and are similar in their appear- 
ance, and in the changes subsequent to their formation, to those in the 
brain. They are usually the result of injury; but may occur spontane- 
ously. These so-called "spontaneous haemorrhages" are undoubtedly THE NERVOUS SYSTEM 
939 
in most cases the result of inflammation. They may occur in any acute 
disease of the cord, and are an especially frequent complication of acute 
myelitis. Haemorrhage into the cord, occurring in the course of an 
acute infectious disease, is probably, as a rule, due to an unrecognized 
myelitis or acute degeneration. Haemorrhages in the course of a chronic 
myelitis are not common, and are probably due to a softening dependent 
on interference with nutrition. Haemorrhages into the cord have been 
reported in syphilitic myelitis, in syringomyelia, and in tumors of the cord. 
Gliomata especially are often very vascular, and their thin-walled vessels 
are subject to rupture. Sometimes, however, haemorrhagic foci are 
found in the spinal cord without traumatism or evidence of inflammatory 
change. 
Larger haemorrhages naturally follow the lines of least resistance, and 
their long diameter corresponds to that of the cord. To such columnar 
The section shows at one point a cyst-like cavity in the spinal cord, originating in a haemorrhage 
in the posterior root (see Fig. 652) and extending nearly the entire length of the cord. The cavity 
is lined by tissue detritus and neuroglia. 
Fig. 653.-H^matomyelopore. 
haemorrhages, usually traumatic in origin, the name hoematomyelia has 
been applied (Fig. 652). The term is being now more properly used to 
cover the general subject of haemorrhage into the spinal cord. 
The smaller capillary haemorrhages may be entirely absorbed. They 
may, on the other hand, form microscopic sclerotic areas. The larger 
haemorrhages determine a considerable destruction of tissue. They may 
be absorbed and replaced by fibrous tissue, or the central area may break 
down into a fluid or semi-fluid mass of blood and tissue, with a more or 
less definite fibrous wall (Fig. 653). To these columnar cavities or canals 
the term hoematomyelopore has been applied by Van Gieson.1 To a 
1 Van Gieson, " Haematomyelopore-a New Spinal-Cord Disease," New York Polyclinic, 1897, 
vol. x., p. 87. 940 
THE NERVOUS SYSTEM 
similar condition in which proliferation of the neuroglia is the most 
marked feature, the name of "false or secondary syringomyelia" has 
been given. 
Thrombosis and Embolism. 
Thrombi may form in the arteries as a result of any degenerative or 
inflammatory process in their walls leading to a roughening or death of 
the intima, or from pressure from without, or they may occur in vessels 
in whose walls we can detect no primary lesion. The most common 
causes are atheroma and simple endarteritis. Thrombi may also form 
around an embolus which does not entirely occlude the vessel. 
Emboli of the cerebral arteries most commonly arise from acute or 
chronic endocarditis or cardiac thrombi; they may arise from aneurisms 
or atheroma of the aorta, from the carotid or vertebral arteries, or from 
the pulmonary veins. The materials constituting emboli vary greatly, 
depending on their mode of origin (see p. 28). The effects on the brain 
tissue of emboli and thrombi of the arteries are essentially the same 
in their main features. In some cases, however, in which large emboli, 
usually from endocarditis, suddenly block up a large vessel, the individual 
may die almost instantly without other apparent lesion than the stoppage 
of the vessel. 
In general, the first effect of the occlusion of an artery is to deprive 
the region to which it is distributed of blood. In arteries whose branches 
anastomose, the affected area is soon supplied with blood by the estab- 
lishment of a collateral circulation. In terminal arteries, on the other 
hand, the blocking of the vessel is followed, as a rule, by degenerative 
changes and softening in the brain tissue. The appearances which these 
degenerated areas present vary greatly, depending upon the stage of the 
degeneration and the amount of blood which may be extravasated. 
Dense infiltrations of the brain tissue with blood, as in haemorrhagic 
infarctions from emboli in other parts of the body, do not usually occur, 
although considerable blood may be extravasated. Areas of softening 
in which there is little extravasation of blood are usually white or yellow 
in color, white or yellow sojtening. When much blood is present the proc- 
ess is frequently called red softening. Yellow softening is probably often 
only a secondary stage of the red, resulting from absorption of most of the 
pigment. The term "white softening" is often used interchangeably 
with "yellow." It is also applied to that condition into which the latter 
passes after more complete liquefaction, and after fatty changes have 
taken place. Young proliferating neuroglia tissue often give a glisten- 
ing white appearance to the lesion. 
The tissue in the affected area gradually softens and may become dif- 
fluent. Microscopically, the softened tissue is seen to consist of more or 
less fluid with broken-down brain tissue, fragments of nerve fibres, drop- 
lets of myelin, nerve cells, shreds of neuroglia tissue and blood-vessels, 
and red and white blood cells. The evidence of degeneration is seen 
n the presence of fat granules and droplets, larger and smaller cells THE NERVOUS SYSTEM 
941 
densely crowded with droplets of fat (so-called Gluge's corpuscles or com- 
pound granular corpuscles'). Various kinds of cells and cell fragments, 
more or less granular and fatty, and also corpora amylacea, blood pig- 
Fig. 654.-Degenerated Cells, Cholesterin Crystals, and Corpora Amylacea from 
Brain Tissue in Embolic Softening. 
a, Fatty ganglion cells; b, corpora amylacea; c, cell containing very large number of fat droplets 
(compound granular or Gluge's corpuscles); d, cholesterin crystals. 
ment, fat crystals, and cholesterin crystals, may be found (Fig. 654). 
The walls of the blood-vessels may also be in a condition of fatty degen- 
The walls of the vessels, particularly the endothelial cells, contain fat granules and fat droplets. 
Fig. 655.-Blood-vessels From an Area of Embolic Softening of Brain. 
eration (Fig. 655). The color of the softened mass will of course depend 
upon the relative amounts of these elements. 942 
THE NERVOUS SYSTEM 
The tissue may remain for a long time in the soft condition, or it 
may be absorbed and replaced by a connective-tissue cicatrix which 
may be more or less pigmented; or a wall of connective tissue may 
form about it, converting it into a well-defined cyst, with or without 
pigmented walls; or the mass may dry and form a dense, structureless 
nodule. Acute inflammatory changes may occur about the dead tissue. 
In cases of infectious emboli numerous abscesses may be formed in addi- 
tion to their mechanical action. 
Thrombi are most frequent in the internal carotids, less frequent in the 
middle cerebral, basilar, and vertebrals. They may occur, but still less 
frequently, in other cerebral arteries. Emboli are most common in the 
middle cerebral artery, next in the internal carotid, and then in the basi- 
lar. The relative frequency with which embolism occurs in the middle 
cerebral artery is attributable to the directness with which the blood 
passes into this artery from the heart. The great significance attaching 
to embolism of the middle cerebral artery is evident when wre remember 
that its branches within the brain are terminal arteries, and are dis- 
tributed to such important structures as the lenticular and caudate 
nuclei, the internal capsule, and the optic thalamus. 
Thrombosis and embolism also occur in the vessels of the spinal cord, 
though less frequently than in those of the brain. As in the brain, when 
they involve terminal arteries, they determine areas of softening and 
consequent secondary degenerations. 
Lesions of the Vessel Walls in the Brain and Cord. 
The mural changes in the vessels are not peculiar to the nervous sys- 
tem: the most frequent is that known as atheroma or arterio-sclerosis. 
It is especially common in the system of arterial trunks which make up 
the circle of Willis. Fatty degeneration is often found in the vessel 
walls coincident with the increase in the connective-tissue elements. 
Calcification may occur and may be so extensive that the whole or a 
greater part of the circle of Willis is converted into a series of hard 
tubes usually somewhat larger than normal. More commonly the cal- 
careous areas are irregular in their distribution, giving to the vessels a 
nodular appearance. Fatty degeneration may also occur, though more 
rarely, as an independent lesion. It affects particularly the muscular 
coat. Hyaline degeneration may also occur either as an independent 
lesion, which is quite frequent in the brains of idiots, or as the initial 
lesion of a sclerosis. 
DEGENERATION AND INFLAMMATION IN THE BRAIN, SPINAL CORD, AND 
NERVES. 
Review of Normal Morphology. 
While the scope of this work does not warrant a detailed description of the mor- 
phology of the nervous system,1 our appreciation of the pathological changes to which 
it is subject is so dependent upon an accurate knowledge of its morphology, that, 
before proceeding further, a brief resume of some of the more fundamental points in its 
structure and architecture cannot wisely be omitted. 
'For this the reader is referred to such works as "The Nervous System," by Barker, and the 
"Anatomie du Systfeme Nerveux de i'Homme," by Van Gehuchten. THE NERVOUS SYSTEM 
943 
The studies of Golgi and of his successors in the use of his technique have led to the 
so-called neurone conception of nervous-system structure. According to this view, 
the neurone represents the structural unit of the nervous system. The neurone is the 
nerve cell with all its prolongations, and the nervous system in toto is but an orderly 
association of an immense number of these neurone units. Although these neurones 
differ from one another as to details of structure they still present an essential 
similarity. 
The neurone is first distinguishable as a small round cell in the epiblastic lining of 
the embryonic neural canal. Such a cell is entirely devoid of processes. It soon, 
however, becomes pyriform, and from the tip of the pear grows out a process, which is 
the axis-cylinder process or axone. Later other processes appear as outgrowths of the 
cell body. These are the protoplasmic processes or dendrites. Each adult neurone 
then consists of a cell body, and passing off from this cell body two kinds of processes 
(Figs. 656 and 657). 
The Cell Body.-Our knowledge of the internal structure of the nerve cell has been 
greatly increased in the last few years by the application of a special technique devised 
by Nissl.1 Subjected to this technique nerve cells present two very different types of 
reaction. Certain cells, such, for example, as the cells of the granule layers of the 
cerebellum and of the olfactory lobe, stain only as to their nuclei, the cell bodies them- 
selves remaining entirely unstained. To such cells Nissl has given the name of caryo- 
chromes. It is obvious that the method of Nissl gives no insight into the structure of 
these cells. The majority of nerve cells, however, react both as to their nuclei and 
as to their cell bodies to the Nissl stain. These cells Nissl designates as somatochromes. 
Such a cell presents the following appearance (Plate XIII., 1).. There is a nucleus 
identical in structure with nuclei found in other cells. It is bounded by a nuclear 
membrane and traversed by a network which takes a comparatively light blue stain. 
Within the nucleus is a nucleolus staining an intense blue. In the cell body two 
distinct elements appear: a clear ground substance, unstained; and scattered through 
it deep staining masses, known as chromophilic bodies. These chromophilic bodies 
are granular, and differ in size, shape, and arrangement. These differences have 
served as a basis of classification. Presenting variations in different types of cells, 
their appearance in a given type remains constant. Most investigators, while differing 
in details, agree in ascribing to the unstainable substance a definite structure. This 
structure is usually described as composed of a fibrillar or reticular network lying in 
a more or less homogenous ground substance. With the use of the ordinary technique 
of Nissl, all of the cell body, excepting the chromophilic bodies, remains unstained and 
apparently structureless. Our ideas as to the physiology of these different elements 
of the nerve cell rest largely upon a theoretical basis. It has been shown that the 
nerve cell represents the genetic centre of the neurone. From the behavior of the 
processes, when cut off from the nerve cell, it is evident that the cell body represents 
the nutritive or trophic centre of the neurone. It seems probable that from the stand- 
point of neurone activity, the cell body represents the functional centre of the neurone, 
while the processes act as organs of reception or distribution. Certain facts, such as 
the entire absence of the chromatic substance in many nerve cells, in the axones of all 
nerve cells, and its diminution during functional activity and in fatigue, together with 
its behavior under certain pathological conditions, lend weight to the view that the 
stainable substance of Nissl represents a food element of the cell. The achromatic 
element, on the other hand, is continuous with the fibrillae of the axone, and is con- 
sidered by most investigators as representing the essential nervous mechanism of the 
cell. The relation of the Nissl picture to the conditions existing in the protoplasm of 
the living cell still remains an unsolved problem. The importance of the Nissl method 
from the standpoint of pathology lies in the fact that when subjected to a given 
technique, a given type of nerve cell presents always the same appearance, and that 
this appearance furnishes a norm of comparison with cells showing pathological 
changes which have been subjected to the same technique. 
Pigment.-In addition to the elements al*eady described, more or less pigment in 
the shape of fine brownish yellow granules is often present in nerve cells. It is not 
1 See Nissl's method of staining, p. 982. 944 
THE NERVOUS SYSTEM 
found in cells of the new-born. It increases with age, and in old age often fills up a 
large part of the cell body. Its significance is not known. 
The protoplasmic processes or dendrites are-at least the larger trunks-of the 
same structure as the cell body (Plate XIII., 1). That these larger trunks have 
functions similar to those of the cell body seems probable from the fact that the axone 
not infrequently takes origin from a large dendritic 
trunk instead of directly from the body of the cell. 
The chromatic substance is present in the den- 
drites, as elongated rods with triangular masses at 
the points of bifurcation. The achromatic ele- 
ments are apparently of the same character as in 
the body of the cell. The protoplasmic processes 
divide dichotomously, becoming rapidly smaller, 
and end at a comparatively short distance from 
the cell body.1 Stained by the method of Golgi, 
the dendrites are seen to be covered with minute 
projections or "gemmules," often ending in a 
small bulb. These processes are cellulipetal in 
character, carrying impulses always toward the 
cell. 
The axis-cylinder process or axone-so called 
from its often becoming the axis cylinder of a 
nerve fibre-is usually single. It generally arises 
directly from the body of the cell, but may arise, 
as already mentioned, from one of the larger pro- 
toplasmic trunks. It is differentiated from the 
dendrites in Nissl preparations by always taking 
origin from an area in the cell body free from 
chromatic substance, and by being itself entirely 
achromatic (Plate XIII., 1); in Golgi specimens, it 
is recognized by its straight course, uniform 
diameter, and smooth outline (Fig. 656). It sends 
off few branches, and these at right angles (collat- 
erals). This axone may extend a great distance 
from the cell body; for example, the axones of 
certain motor cells of the spinal cord extend to the 
muscles of the hands or feet. Both the axone 
proper and its collaterals end in terminal arboriza- 
tions. Their conductivity is cellulifugal-that is, 
they always carry impulses from the cell. In cer- 
tain cells the axis-cylinder processes branch rapidly 
and end in the gray matter in the vicinity of their 
cells of origin (Fig. 657). An axone may pass from 
its cell of origin to its termination uncovered by 
any sheath. Such axones are found in certain 
portions of the gray matter. An axone may be 
enveloped only by a thin membrane, the sheath of 
Schwann, as, e.g., the fibres of Remak found mainly 
in the sympathetic system. An axone may be sur- 
rounded by a myelin sheath alone, as in the white 
matter of the brain and cord, or by both a myelin 
sheath and a sheath of Schwann, as in the fibres of the peripheral nerves, with the 
exception of the olfactory and optic. 
According to the strict neurone conception of nervous-system structure, each neu- 
rone is considered a complete morphological and, to a lesser degree, physiological 
entity. It has no anatomical connection with any other neurone. Association 
between neurones takes place by contact or contiguity, and never by continuity of 
Fig. 656.-Neurone (Nerve Cell 
or Ganglion Cell and Processes) 
from Human Cerebral Cortex. 
Showing main or apical dendrite 
passing upward and numerous smaller 
dendrites coming off from the main 
dendrite and from the body of the cell. 
A single axone (axis-cylinder process) 
passes downward from the base of the 
cell, giving off two collaterals. 
1 Exception, peripheral arm of spinal ganglion cell. Explanation of Plate XIII.1 
1. Normal GangLion Cell. Large motor cell from anterior horn of human spinal cord, showing 
the nucleus in its normal central position with its nucleolus. In the body of the cell are seen the 
chromophilic bodies of various shapes and sizes. Three main protoplasmic trunks or dendrites 
pass off from the upper portion of the cell. In these the chromophilic bodies are rod-shaped. The 
largest process branches at a short distance from the cell. To the left is seen the axone or axis- 
cylinder process free from chromatic substance, as is also that portion of the cell from which it 
takes origin (axone hill). 
2. Ganglion Cell from the Anterior Horn of the Human Spinal Cord of a Case of Alcoholic 
Neuritis. Showing eccentricity of the nucleus and a large central area of the cell body free 
from chromatic substance (central chromatolysis), with an arrangement of the remaining chromo- 
philic bodies around the periphery. (The similarity between the appearance of this cell and the 
one shown in Fig. 6 should be noted.) 
3. Ganglion Cell from the Anterior Horn of the Spinal Cord of a Rabbit Inoculated with 
Rabic Virus and Killed Shortly After the Onset of Symptoms. Shows an early stage of 
chromato lysis; the chromophilic bodies being pale, ragged, and vacuolated. 
4 Ganglion Cell from the Anterior Horn of the Spinal Cord of a Rabbit which Died on the 
Ninth Day After Inoculation with Rabic Virus. Shows extreme chromatolysis, only a 
few fine granules of chromatic substance remaining at the periphery. The cell is swollen, the 
nucleus has disappeared, and the cell body and processes are stained more deeply with the erythrosin 
than is the case in normal cells. 
5. Normal Ganglion Cell from a Human Spinal Ganglion of the Posterior Root. Showing 
central position of the nucleus and the concentric arrangement of the chromophilic bodies. 
6. Ganglion Cell from the Posterior Root Ganglion of a Rabbit Three Weeks After Section 
of the Sciatic Nerve. The cell shows extreme eccentricity of the nucleus with central chro- 
matolysis and a peripheral arrangement of the remaining chromophilic bodies-axonal degeneration. 
(There also remains in the central portion of the cell some chromatic substance in the shape o 
fine granules forming an irregular reticulum. The similarity between this picture and the one 
shown in Fig. 2 is apparent.) 
7. Portion of a Posterior Root Ganglion from a Case of Tabes Dorsalis. Showing degeneration 
in the ganglion cells with increase in the interstitial connective tissue. 
8. Two Pyramidal Cells from the Normal Human Cerebral Cortex. While the pyramida 
cells in the human cortex vary considerably in the amount of chromatic substance which they 
contain, these are of an average type. 
9. Two Pyramidal Cells of the Human Cerebral Cortex from a Case of Eclampsia. These 
cells show marked chromatolysis. 
1 In the staining of the specimens from which these drawings were made, Held's modification of 
Nissl's method was used. This consists essentially in a preliminary staining of the sections with a 
one-per-cent, aqueous solution of erythrosin. Pathology-Delafield & Prudden. 
Plate XIII. 
FIG. 1. 
FiG 5. 
FIG. 2. 
FIG. 6. 
FIG 3. 
FIG. 7. 
FIG. 4. 
FIG. 8. 
FIG. 9. 
Lesions of Ganglion Cells.-(Stained by Nissl's Method.) 
Drawn by F. R. Bailey. THE NERVOUS SYSTEM 
945 
their protoplasm. The passage of an impulse is always from the terminal arboriza- 
tions of axones or collaterals to the dendrites or cell body of the other neurone. 
The validity of the neurone theory has been recently called in question by such 
prominent neurologists as Held, Apathy, Bethe, and Nissl,1 on the ground that in 
many cases axones pass directly into the proto- 
plasm of another neurone and that the neurofibrils 
are sometimes continuous throughout a series of 
neurones. Nissl in a critical review upon the 
present status of the neurone theory announces his 
belief that the entire neurone concept has been 
proved fallacious and must be abandoned. 
Admitting that the discovery of anastomoses 
between neurones and of the continuity of the 
neurofibrils must be accepted as invalidating some 
of our ideas as to the separateness of the neurone 
units, it can still hardly be considered as over- 
throwing the entire neurone theory. Embryo- 
logically, morphologically, and physiologically the 
neurone shows a marked degree of individuality, 
and the fact that neurones sometimes, usually, or 
even always, anastomose no more warrants the 
giving up of the neurone as essentially a unit than 
did the discovery of the fact that the protoplasm of 
epithelial cells was continuous through intercellular 
"bridges" necessitate the giving up of the epi- 
thelial cell as the structural unit of epithelium. 
The cell bodies of neurones are grouped mainly in the gray matter of the brain and 
cord, in the ganglia of cranial, spinal, and sympathetic nerves, and in the peripheral 
end organs of certain of the nerves of special sense. Protoplasmic processes ramify 
mainly within the gray matter.2 While some terminate in the gray matter in the 
immediate vicinity of their cells of origin, it is the axones that make up the bulk of 
the white matter of the brain, cord, and peripheral nerves. 
Neuroglia.-In addition to the extensions inward of the pia mater and the con- 
nective tissue of the blood-vessels, there is found in both gray and white matter a 
tissue, probably supportive in function, and peculiar 
to the nervous system-the neuroglia. Like the 
neurone, it originates in the epiblastic cells lining 
the embryonic neural canal. These cells, at^first 
morphologically identical, soon differentiate into 
neuroblasts or future neurones, and spongiobasts, 
or future neuroglia cells. In the adult two main 
types of neuroglia cells are found, spider cells 
(Fig. 658), with spine-like, straight, unbranching 
processes, and mossy cells (Fig. 659) with thick, 
rough, branching arms. The former are found 
chiefly in the white matter, the latter in the gray 
matter in connection with blood-vessels. As in the 
case of the nerve cell, the processes of these cells do 
not anastomose, but interlace, forming a dense 
feltwork. By a special stain, Weigert demon- 
strates neuroglia cell nuclei and separate fibrils. 
It seems probable that this method fails to show the body of the cell, while staining 
its nuclei and the fibrils which pass through it. 
It would thus appear that the architecture of the central nervous system, consid- 
ered as an organ, is analogous to that of other organs. It has in the neurone its paren- 
chyma, and this parenchyma is supported and bound together by a framework of 
Fig. 657.-Neurone (Nerve-Cell 
orGanglion-CellProcesses). From 
the Granular Layer of the Cere- 
bellar Cortex of a Guinea-Pig. 
The short axone passes off to the 
left and terminates near its cell of 
origin. 
Fig. 658.-Neuroglia Cell-Spider 
Type-Human Cerebrum. 
1 For a critical view of the opinions of these writers consult the last edition of Van Gehuchten's 
"Anatomie du Systbme Nerveux." 
2 Exception, peripheral arm of spinal ganglion cell. 946 
THE NERVOUS SYSTEM 
connective tissue. The essential difference lies in the fact that in the neurone is the 
highest morphological differentiation which protoplasm has attained, representing 
chemically the most complex molecules known. In the axone, sometimes a metre or 
more in length, of a cell of microscopic dimensions, there is a distribution of cell 
protoplasm, such as occurs in no other tissue or organ. The neuroglia also, while 
without question a tissue supportive in func- 
tion, is embryologically and morphologically 
different from other forms of connective tissue. 
DEGENERATION. 
Neurone Degeneration. 
Degenerative changes may affect the 
entire neurone or any of its parts. Such 
changes may result from direct injury 
to some part of the neurone, to diminu- 
tion or modification of its nutritive sup- 
ply, to various toxic conditions, etc. 
I. Changes in the Neurone from In- 
jury to One of Its Parts.-((i)~Changes in the Axone Resulting from 
Separation from Its Cell Body.-That changes, presumably of a 
degenerative character, occur in the peripheral end of a nerve when its 
connection with the central nervous system is broken has long been 
known. This degeneration takes place as well in the central as in the 
peripheral nervous system, and is complete, involving every portion 
of the axone distal to the point of section. The changes are not 
progressive from the point of lesion, but occur at nearly the same time 
in all parts of the distal stump. These changes consist in a breaking 
up of the medullary sheath into segments (Fig. 660), which in turn dis- 
integrate, forming variously shaped masses of myelin, among which 
may be seen the axis cylinder, the whole being enclosed by the neu- 
rilemma. The method of Marchi (see p. 981), 
which differentiates between fat and myelin, 
shows that coincident with the breaking up of 
the myelin there is an appearance of fat drop- 
lets. These fat droplets increase in number 
pari passu with the decrease in myelin, but 
also ultimately disappear. During the progress 
of these changes in the medullary sheath, the 
axis cylinder at first segments and then under- 
goes dissolution. The neurilemma, on the 
other hand, appears to take no part in the 
degenerative process. On the contrary, it 
and its nuclei remain intact to take part later in regenerative changes, 
should these occur. If there is no reunion of the severed ends of the 
axone, the peripheral portion completely disappears, its place being 
taken by connective tissue. 
(b) Changes in Dendrites Resulting from Their Separation 
from Their Cell Bodies.-If we consider, as does Van Gehuchten,1 that 
Fig. 659.-Neuroglia Cell-Mossy 
Type-Human Cerebrum. 
Fig. 660.-Neurone Degenera- 
tion After Injury. 
Teased nerve fibres from distal 
portion of sciatic nerve of rabbit 
three weeks after division of the 
nerve. Osmic-acid stain. The 
large and small black masses 
represent disintegrated myelin 
and fat droplets. 
1 Van Gehuchten, "Anatomie du Systtme Nerveux de 1'Homme," p. 213. THE NERVOUS SYSTEM 
947 
the peripheral arm of the spinal ganglion cell is a protoplasmic process, 
making a physiological rather than a morphological differentiation, we 
find that the same law holds good for dendrites as for axones when 
separated from their cell bodies. Thus in the divided peripheral nerve 
those fibres which are the processes of the spinal ganglion cells undergo 
the same degenerative changes as do the fibres which are processes 
of cells of the anterior horn. Most dendritic processes are, however, 
so short and terminate in the gray matter so near the cells from which 
they originate that experimental separation of the process from its 
cell body is impracticable. In view of the fate of the axone, however, 
and the relation of the dendrites to the cell body, there can be 
little doubt that as complete degeneration follows the severance of a 
protoplasmic process from its cell of origin as follows in the case of 
the axone. 
(c) Changes in the Proximal Stump and in the Cell Body Re- 
sulting from Lesion to the Axone.-The fundamental principle 
of the law of Waller was the complete degeneration of the distal portion 
of the divided nerve, while the proximal stump remained intact. Our 
present conceptions, however, of the interdependence of the different 
parts of the neurone, and of the axone as the outlet for neurone energy, 
would lead us to expect certain changes of an atrophic nature in the 
proximal stump and in the cell body, as a result of separation from its 
axone and consequent inability to functionate. That such changes take 
place recent improvements in cytological technique have enabled us 
to determine. The method of Marchi shows that degenerative changes 
occur, not only in the distal, but in the proximal end of the divided 
nerve. These changes take place more slowly than in the distal portion, 
but are apparently identical in character. 
In the body of the cell the method of Nissl demonstrates marked 
changes after section of the axone. These changes may be observed 
within twenty-four hours after the injury. They consist in a diminu- 
tion in the chromatic elements of the cell, chromatolysis. This is most 
marked in the central portion (central chromatolysis), a distinct ring 
of chromophilic bodies around the periphery often remaining. The 
nucleus usually migrates toward the periphery and may even bulge 
from the cell. In the case of the hypoglossal nerve in the rabbit, these 
changes reach their maximum in from two to three weeks. The future 
of some of these cells is complete degeneration. Others apparently un- 
dergo regeneration. The intensity of the reaction of the nerve cell to 
injury to its axone depends upon the severity of the injury. Thus cut- 
ting the nerve is followed by more prompt and marked changes in the 
nerve cell than simple compression, while pulling out the nerve roots is 
followed by a still more intense reaction. Again, there is a difference in 
the resisting-powers of different types of cells. Thus the motor cells of 
the anterior horn are peculiarly resistant to injury to their axones, as 
are also the spinal ganglion cells to injury to their central processes. 
Again, between cells of the same type there are marked variations in re- 948 
THE NERVOUS SYSTEM 
sisting-powers. Thus the motor cells of the anterior horn are much more 
resistant than the cells of the motor cranial nuclei.1 
(d) Changes in the Cell Body Resulting from Lesions to Its 
Dendrites.-In the study of the effect upon the cell body of a lesion 
depriving it of one or all of its dendritic processes, we meet with the 
same experimental obstacles already mentioned in connection with 
changes in the dendrites. It is, again, only in the peripheral arm of the 
spinal ganglion cell that we have a cellulipetal process of any considerable 
length. Section of this process results in changes in the spinal gan- 
glion cell quite similar in character to the so-called 11 axonal " degenera- 
tion (Plate XIII., 6). If we consider that a cell's dendrites probably 
furnish its most important avenue for the reception of impulses, it follows 
that a neurone may be thrown as completely out of circuit, as it were, 
by injury to its dendrites as by injury to its axone. The experiments 
of Warrington2 are interesting in this connection. He attempted to 
bring about the same functional effect as would result from section of a 
cell's dendrites, by inhibiting afferent impulses. Cutting the posterior 
roots, he noted changes in the cells of the anterior horn. The inference 
was that these changes were induced by an inhibition of the customary 
normal stimulation by means of the afferent impulses reaching the cells 
through their dendritic processes. 
IL Changes in the Neurone from Interference With Its Nutrition.- 
Changes apparently of a degenerative character have been described in 
neurones as a result of interference with nutrition. Thus Brieger and 
Ehrlich3 found that by temporarily applying a ligature to the abdominal 
aorta, they induced an acute necrosis of the cells of the lumbar cord. 
Later experiments of a similar nature followed by the Marchi staining 
showed that the degenerative process affected not only the cell bodies, 
but the entire neurone. Similar degenerative changes have been induced 
by experimentally produced multiple emboli, cells in the vicinity of the 
occluded vessels being in marked contrast to cells from regions whose 
vessels remained patent. Ewing4 describes definite degenerative changes 
in nerve cells as a result of anaemia consecutive to pressure from cere- 
bral haemorrhage and to thrombosis of the basilar artery. Less marked 
changes have been observed in cases of general malnutrition and in se- 
vere anaemias. 
III. Effects of Toxins upon Neurones.-Changes of a degenerative 
character occur in neurones as a result of the action of toxins. These 
toxins may be introduced into the body from without, for example, such 
poisons as alcohol, arsenic, lead, strychnin, etc.; they may be elaborated 
within the body as the result of faulty metabolism, for example, in urae- 
mia, eclampsia, etc., or as a result of the action of bacteria, as in tetanus, 
rabies, (Plate XIII., 3, 4, and 8), diphtheria, etc., or of the Plasmodium 
1 For review and bibliography of changes in the nerve cell and in the proximal stump after section 
of a peripheral nerve consult Barker, "The Nervous System," p. 229 et seq. 
2 Warrington, W. B., "On the Structural Alterations in Nerve Cells," Jour, of Physiol., London, 
vol. xxiii., p. 112, 1898. 
3 Brieger und Ehrlich, "Ueber die Ausschaltung des Lendenmarkgrau," Zeitschr. f. klin. Med., 
Berlin, Bd. vii., Suppl., 1883-84. 
4 Ewing, J., "Studies on Ganglion Cells," Arch, of Neur. and Psychopath., vol. i., 1898. THE NERVOUS SYSTEM 
949 
malariae. The effects of these poisons upon the neurone vary with dif- 
ferent poisons and in different types of neurones. The effects of the 
same poison upon a given type of neurone also vary according to its 
rapidity of action, whether rapidly fatal or extending over a considerable 
period of time. Again, given the same poison and the same time of 
action, not all neurones even of the same type show an equal suscepti- 
bility. There seem to be marked individual differences among neu- 
rones of the same type as regards their resisting powers. 
These changes in the neurone from the action of toxins may affect one 
or all of its structural elements, and vary from the slightest appreciable 
loss of staining qualities of the chromophilic bodies to complete destruc- 
tion of the neurone. In the chromophilic bodies the essential change 
seems to be a decrease in the amount of chromatic substance, chromatoly- 
sis. This may be evidenced merely by a decreased staining intensity, 
the chromatic masses appearing abnormally pale; the bodies may have a 
ragged or frayed-out appearance at their edges; they may be shrunken, 
or, retaining their normal shape and size, become vacuolated (Plate 
XIII., 3); they may completely disintegrate, giving to the cell a diffuse 
granular appearance; they may disappear, leaving the cell entirely devoid 
of chromatic substance. The chromatic masses in the dendrites seem in 
many cases to be more resistant or less exposed than are those in the body 
of the cell, often remaining unchanged at a time when the latter show an 
advanced degree of chromatolysis. During these changes in the chro- 
matic element the cyto-reticulum may remain apparently normal or it 
may more or less completely disintegrate. This disintegration usually 
marks the more advanced degenerative changes (Plate XIII., 4). 
In the truly achromatic element of the cell or cytoplasm, our present 
methods of staining fail to demonstrate lesions. Diffuse staining of this 
basement substance is a common phenomenon of chromatolysis, but 
seems more properly referable to a diffusion of the fine granules resulting 
from disintegration of the chromatic masses than to any changes in the 
cytoplasm itself. Disappearance of the formed elements of the cell often 
leaves clear holes or vacuoles in the cell body or gives the appearance of 
cracks or fissures. The nucleus may remain normal; it may swell and 
its contour become abnormally distinct; it often takes a diffuse stain; 
later it shrinks, becomes crenated, its reticulum and limiting membrane 
break up and its outline is lost. During these nuclear changes the nu- 
cleolus may also disintegrate. It is often extremely resistant, remaining 
apparently unchanged after most of the other parts of the cell have be- 
come unrecognizable. Concurrent with these changes in internal struc- 
ture are changes in the shape and size of the cell. Its contour becomes 
irregular, and its edges present an eroded appearance; the cell body 
shrinks away from its cell space, breaks up, and ultimately disappears. 
The dendrites undergo alterations similar to those in the body of the 
cell. They shrink, become separated from the cell body, and finally 
disintegrate. 
That part of the neurone which shows most marked evidences of its 
effect is not necessarily the part upon which the poison is most directly 950 
THE NERVOUS SYSTEM 
acting. Thus a toxin affecting directly the cell body may cause the 
earliest and most pronounced changes far out in its dendritic or axonal 
processes, i.e., in those parts of the neurone farthest removed from the 
trophic centre. 
To the action of a specific poison certain neurones seem less resistant 
than others. Thus, to the action of lead those neurones governing the 
extensor muscles of the wrist seem especially susceptible. The cells of 
the motor nucleus of the trigeminus seem to be less resistant than other 
motor cells to the poison of tetanus. Again, the frequency with which 
tabes dorsalis is associated with a syphilitic history seems to indicate a 
special susceptibility to the syphilitic poison on the part of the peripheral 
sensory neurone. 
Comparing the changes in the nerve cell in toxaemias (Plate XIII., 3 and 4) with 
those induced by lesions to its axone-axonal degeneration (Plate XIII., 6)-we note 
that while in the latter the chromatolysis is central in character, beginning in the 
region of the axone hill and nucleus, in the former the changes begin at the periphery, 
the portion of the cell in most direct relation to the surrounding lymph. In axonal 
degeneration the nucleus is usually eccentric. In toxaemia it usually remains central, 
at least until the process of degeneration is far advanced'. While this distinction holds 
good in general and while the phenomena of central chromatolysis and eccentricity 
of the nucleus regularly follow injury to the axone, we are not yet warranted in stating 
that such changes never occur except after some injury, or that the presence of such 
changes in the cell can be explained only on the basis of injury to its axis-cylinder 
process. 
IV. Effects of Fatigue upon Neurones.-Studies upon the effect of fa- 
tigue upon the neurone have been made in animals after prolonged mus- 
cular activity and after electrical stimulation. While the results are not 
in complete accord, there seems to be little doubt that definite morpho- 
logical changes occur in the neurone as a result of fatigue. These changes 
consist in a decrease in the size of the cell body, a decrease in the size of 
the nucleus, often with distortion, and a marked decrease in the amount 
of chromatic substance with more or less diffuse staining of both cell 
body and nucleus. 
It seems not at all improbable that the clinical pictures presented by certain psy- 
choses and neuroses are the expression of the effects upon the neurones of prolonged 
fatigue. Certain local expressions of neurone exhaustion, as, for example, writer's 
cramp, may possibly also be placed in the same category. 
As to the significance of those changes in the nerve cell, which are marked by dim- 
inution in the chromatic substance alone, and to which the term " chromatolysis" has 
been given, there is a considerable difference of opinion. Marinesco1 considers them 
of the nature of degeneration. Van Gehuchten2 is inclined to look upon the phenome- 
non as conservative in character, a means by which the neurone assumes a condition 
most advantageous for self-defence. It has been shown that even an extreme degree 
of chromatolysis is not incompatible with function. Marinesco insists that so long as 
the changes are confined to the chromatic substance recovery is possible, no matter 
how extensive the alterations, while changes in the achromatic elements are always 
permanent in character. It seems quite probable that a comparatively easy method 
1 Marinesco, G. See Van Gehuchten's " Anatomie du Systeme Nerveux," p. 339. 
2 Van Gehuchten, loc. cit., p. 339. THE NERVOUS SYSTEM 
951 
of investigation has led to an overestimation of the significance of changes in the 
chromatic substance of the neurone, and to a neglect of probably more important but 
less easily studied changes in the achromatic element. 
Regeneration. 
Regeneration of nerve tissue in the sense of an actual reproduction 
of neurones probably never occurs in the adult human nervous system.1 
As has been noted, extreme chromatolysis may be succeeded by complete 
recovery. In the case of axonal chromatolysis, the degenerative process 
usually reaches its maximum in about three weeks. Regeneration of 
chromophilic bodies then begins. This reconstructive process is slow, 
the cells often requiring months to return to a normal condition. At 
some stage of the process there is usually an overprodution of chro- 
matic substance, and the cells appear darker than normal. 
Primary union between the ends of divided nerve fibres does not 
occur. Complete degeneration of the distal portion always precedes the 
regenerative process. In this reconstruction the nuclei of the neurilemma 
seem to play an important part. They increase in number, and there is 
also an increase in the protoplasm which surrounds them. With union 
of the divided ends, the axones of the central stump may grow out again, 
if the ganglion cells be intact, and ultimately resume function. The 
myelin first reappears as droplets which coalesce and finally form a 
complete sheath. This reconstructive process in the nerve fibre is ex- 
tremely slow, often requiring many months for its completion. 
Replacement Neuroglia Hyperplasia.-Under various condi- 
tions in which there is destruction of the parenchyma, as, e.y., in ascend- 
ing and in descending degeneration of the spinal cord, there occurs a 
compensatory increase in the interstitial elements. This new tissue is at 
first cellular, most of the cells being of the spider variety. Later there 
is an increase in the neuroglia fibres, and the tissue often becomes dense 
and hard. What part the mossy cells or other less common types of 
neuroglia cells take in the proliferative process is as yet unknown. 
With the increase in fibres there are often shrinkage and the formation of 
dense fibrous tissue. This replacement hyperplasia in neuroglia seems 
quite similar in nature to replacement connective-tissue hyperplasia in 
other organs, and is often wrongly considered inflammatory. 
Degenerations Affecting Systems of Neurones. 
General Considerations Concerning Neurone Systems. 
Before considering the subject of systemic degeneration we may refer briefly to 
the situation in the nervous system of certain of the more important groups of neu- 
rones and the paths which their axones take. 
That the cell bodies of neurones are grouped in the gray matter of the brain, cord, 
and ganglia, and in the end organs of certain nerves of special sense, has already been 
mentioned. This grouping of neurones serves definite physiological ends. Their cell 
bodies form centres or nuclei, while their axones are collected into bundles or fibre 
1For review and literature on "Regeneration" see Barker, "The Nervous System," p. 245 et seq. 952 
THE NERVOUS SYSTEM 
tracts. Thus, in the region of the fissure of Rolando are grouped the centres of those 
neurones which have to do with voluntary motion, and what is known as cerebral 
localization means the grouping of cell bodies of neurones for specific function. After 
the known localizations are eliminated, there still remains unaccounted for the greater 
part of the cerebral cortex, and our present belief is that these neurones are neurones 
of association by which the various centres are brought into physiological relationship. 
Some understanding of this neurone grouping, and especially of the arrangement of 
their neuraxones as fibre tracts of the cord, is essential to an appreciation of those 
degenerations which affect definite systems of neurones. 
Peripheral Motor Neurones.-These neurones have their cell bodies in the 
gray matter of the anterior horn and in the motor nuclei of the cranial nerves. Their 
neuraxones pass out as the motor fibres of the cranial and of the spinal nerves. The 
entire neurone lies upon the same side of the body; that is, the peripheral motor neu- 
rone is "direct." 
The Upper or Cortico-spinal Motor Neurones have their cell bodies situated 
mainly in the cerebral cortex near the fissure of Rolando. Their neuraxones converg- 
ing, pass through the internal bapsule, pons, and medulla, sending off fibres to the 
motor nuclei of the cranial nerves. In the medulla the tract comes to the surface as 
the anterior pyramids. At the junction of medulla and cord occurs the pyramidal 
decussation in which most of the fibres of the tract cross to the opposite lateral region 
of the cord, to be known as the crossed pyramidal tract, while a minority remain on the 
same side, to pass down the cord as the direct pyramidal tract. As the tracts descend, 
fibres Continuously leave them to terminate, those of the crossed tract in the gray 
matter of the same side, those of the direct tract, after passing through the anterior 
commissure, in the gray matter of the opposite side. The cortico-spinal motor tract 
is a crossed tract.1 These tracts present variations in size and length. They are 
often asymmetrical. The crossed tract extends to the lower sacral cord. The direct 
tract usually ends about the mid-dorsal region, though it has been follow'ed as low 
as the second lumbar segment. 
The Sensory (Afferent) Tract, like the motor, consists of two segments, an 
upper and a lower. 
The lower or peripheral sensory neurone tract has its cell bodies in the ganglia of the 
spinal and of the cranial nerves. Their peripheral arms, which Van Gehuchten con- 
siders protoplasmic processes, are axis cylinders of cranial or of spinal nerves. Their 
central processes or axones pass into the cord as the fibres of the posterior roots and 
enter the posterior columns. Here they divide into ascending and descending arms. 
The descending arm is short, and with its collateral branches soon terminates in the 
gray matter of the same side of the cord. The ascending arm may also be short, and 
with its collaterals terminates as does the descending. It may pass a considerable 
distance up the cord and then end in the gray matter. It may, as one of the long 
fibres of the posterior columns, continue upward to the medulla, where it terminates 
in one of the posterior column nuclei. These long fibres pass inward as they pass 
upward, so that the lower the origin of the fibre the more mesial is its position in the 
upper part of the cord. The entire neurone lies upon the same side of the cord. The 
lower sensory, like the lower motor neurone, is direct. 
Upper Sensory Neurones.-The arrangement of these neurones is extremely com- 
plex, and only those whose axones enter into the formation of distinct tracts of the 
cord will be here mentioned. Of the above-described central arms of the peripheral 
sensory neurones, some of the shorter enter the gray matter of the cord and with their 
collaterals terminate around motor cells (reflexes). Others terminate around cells 
whose axones cross to the opposite side of the cord and pass upward as the antero- 
lateral ascending tract, or tract of Gowers. Other fibres terminate around cells of the 
column of Clarke, the axones of which pass upward as the direct cerebellar tract. 
In addition to these main fibre tracts, there are in all regions of the cord fibres 
which are commissural in character. These fibres are the axones of cells situated in 
the gray matter of the cord, and after passing a short distance up or down and sending 
1 Certain recent observations tend to show that there may be a small number of "direct" fibres 
in the so-called crossed pyramidal tract. THE NERVOUS SYSTEM 
953 
collaterals into the gray matter, themselves re-enter the gray matter and terminate 
there. These short fibres make up the so-called ground bundles or fundamental col- 
umns of the cord. They attain their greatest development in those regions of the 
cord where the reflex centres are most extensive, i.e., in the lumbar and cervical 
enlargements. 
Secondary Degenerations. 
Secondary degenerations are dependent upon the fact already noted, 
that, the cell body being the trophic centre of the neurone, the axone 
when separated from its cell body dies. 
Descending Degeneration.-Any cortical lesion, such as embolic 
softening and apoplectic clots, which destroys the nerve cells, or any 
lesion of the brain or cord which interrupts the axone tracts of the cortico- 
Fig. 661.-Secondary Descending Degeneration. 
From haemorrhage into the internal capsule, almost complete degeneration of the direct pyramidal 
tract on the same side as the lesion and of the crossed pyramidal tract on the opposite side. There 
were a few degenerated fibres in the crossed tract on the same side as the lesion. 
spinal system of neurones, determines a complete degeneration of the 
affected axones (Fig. 661). The course of these axones has been de- 
scribed. Thus a lesion of the brain affecting motor neurones is fol- 
lowed by a degeneration in the motor tract of the same side down to the 
pyramidal decussation, and below that point, in the direct motor tract 
on the same side and in the crossed tract on the opposite side, the num- 
ber of degenerated fibres being proportionate to the number of cells de- 
stroyed or axones interrupted. In a number of cases of descending de- 
generation due to cerebral lesions, degenerated fibres were found in the 
crossed pyramidal tract on the same side as the lesion. This degenera- 
tion was not present in all cases, and in no case was it as marked as the 
degeneration in the opposite lateral tract. The explanation is that 
in some cords a small number of fibres instead of decussating pass down 
into the cord in the lateral tract of the same side. 954 
THE NERVOUS SYSTEM 
In descending degeneration due to a lesion below the pyramidal de- 
cussation a somewhat different picture is presented. In a complete trans- 
verse lesion there is degeneration of both crossed and of both direct py- 
ramidal tracts. If the lesion is unilateral the degenerations are upon the 
same side as the lesion. The areas of degeneration are also larger and 
less sharply defined than in cerebral lesions. Then in addition to the 
degeneration of the pyramidal tracts there is a degeneration of a con- 
siderable number of fibres in a crescent-shaped area lying near the periph- 
ery of the antero-lateral region and extending from the crossed to the 
direct tract. Degeneration of these fibres has been described by Marchi1 
Fig. 662.-Secondary Ascending Degeneration. 
Following complete crushing of the cord about two segments below the level at which the section 
was taken. Degeneration is almost complete in the columns of Goll, of Gowers, and the direct cere- 
bellar tracts. A few normal fibres are seen in the columns of Burdach. These are the ascending 
axones of spinal ganglion cells between the point of injury and the level of the section, and are seen 
to occupy that part of the posterior columns adjacent to the posterior horns. 
after removal of the cerebellum. He considers them descending cere- 
bellar fibres. The so-called comma-shaped degeneration in the posterior 
columns is sometimes present. Schultze2 regards these fibres, which 
are.situated about the middle of the posterior columns, as descending 
axones of spinal ganglion cells. Tooth3 thinks that they are more prob- 
ably descending branches of commissural neurones. In the fundamental 
columns the degeneration extends but a short distance below the seat of 
injury, and of course affects only those axones which descend. 
Ascending Degeneration.-Any lesion which destroys the spinal 
ganglion cells or which interrupts their axones determines a secondary 
ascending degeneration in the posterior columns (Fig. 652). Any lesion 
1 Marchi, "Origine e decoroso dei peduncoli cerebellari." Rev. Sper. de Fren. e Med. e leg., Bd. 
xvii., p. 367. 
2 Schultze, "On Comma-shaped Degeneration of the Posterior Columns," Arch. f. Psych., 1883. 
3 Tooth, "Goulstonian Lectures on Secondary Degeneration of the Spinal Cord," London, 1889. 955 
THE NERVOUS SYSTEM 
of the cord which interrupts the tract of Gowers or the direct cerebellar 
tract is followed by degeneration of the fibres of these tracts above the 
lesion (Fig. 662). Immediately above the lesion there is complete de- 
generation of the tracts. As we pass upward new undegenerated fibres 
from the spinal ganglia above the lesion enter the column of Burdach, 
so that there appears in the posterior columns a constantly increasing 
number of normal fibres. Also in the column of Gowers undegenerated 
fibres appear as one passes upward from the lesion. Some of these fibres 
probably have their origin in the gray matter of the cord, and the num- 
ber of normal fibres is in proportion to the number of these cells be- 
tween the lesion and the point at which the section is taken. Descending 
fibres in these columns have already been mentioned. They, of course, 
do not degenerate. If the lesion be above Clarke's columns the degen- 
eration in the cerebellar tracts remains complete; if not, the number of 
normal fibres is in proportion to the number of Clarke's column cells 
between the lesion and the point of section. The ascending fibres of the 
fundamental columns also degenerate, but are so short that they cannot 
usually be traced beyond the area of direct action of the traumatism. 
Primary Degenerations. 
Degeneration of the Peripheral Motor Neurones. 
Progressive spinal muscular atrophy is the clinical designation of a 
disease, the underlying lesion of which is a progressive atrophy or de- 
generation of the lower motor neurones. There is a degeneration of 
the large motor cells of the anterior horns and of their processes. This 
degeneration goes on to complete destruction of some neurones. With 
the loss of nerve tissue proper there is a compensatory growth of neu- 
roglia. In a well-advanced case, section of the cord shows a marked 
diminution in the number of anterior horn cells and an atrophic condition 
of the horn itself and of the anterior roots. The lesion usually begins in 
the cervical region. More rarely it starts in the lumbar cord. The de- 
generation may extend to the motor cranial nerve nuclei, giving the 
picture of a progressive bulbar paralysis. The medullary nuclei most 
commonly involved are the hypoglossal and the spinal accessory. Less 
often the degeneration affects the cells of origin of the fifth and seventh. 
Degeneration of the peripheral nerves has been described. The muscu- 
lar lesions correspond to the lesions in the cord, the muscles of the hand 
and arm being usually first affected. For the degenerative changes in 
the muscles see page 869. This lesion is sometimes described as a 
chronic anteropoliomyelitis. Both its clinical history and its pathology, 
however, indicate the degeneration as the initial lesion and the neuroglia 
increase as secondary-a replacement hyperplasia. 
Degeneration of the Cortico-spinal Motor Neurones. 
Spastic Paraplegia-Spastic Spinal Paralysis.-This may be described 
as a primary lesion of the upper or cortico-spinal motor neurones. It 956 
THE NERVOUS SYSTEM 
is probable that the lesion affects the entire neurone. As a distinct 
pathological entity the condition is extremely rare. Whether it origin- 
ates in a degeneration of the cell bodies of these neurones in the cor- 
tex is not known. The clinical picture of spastic paraplegia, due to 
compression, to a transverse myelitis, or to a multiple sclerosis, is not 
uncommon. Marie1 considers spastic paraplegia as a disease appearing 
in childhood, and due to a faulty development of the cortico-spinal motor 
neurones, rather than to their degeneration. 
Degeneration of Both Peripheral and Cortico-spinal Motor 
Neurones. 
Amyotrophic Lateral Sclerosis.-This is a primary progressive degener- 
ation involving both cortico-spinal and spino-peripheral motor neurones. 
The appearance of the transverse section of the cord is a combination of 
that in spastic paraplegia and that in progressive muscular atrophy. 
There is a degeneration of the cells of the anterior horn with atrophy of 
Degeneration of the crossed pyramidal and of the direct pyramidal tracts. In this case there was 
but little atrophy of the anterior horns. Very few cells, however, were present in the anterior horns 
and there was an increase in the connective tissue of the horns. 
Fig. 663.-Amyotrophic Lateral Sclerosis. 
the horn itself, and a degeneration of the fibres of the direct and of the 
crossed pyramidal tracts (Fig. 663). The lesion in the horns is usually 
most pronounced in the cervical region. The extent of involvement of 
the motor tracts of the cord is extremely variable. The degeneration, 
which is the initial lesion, is accompanied by a replacement connective- 
tissue hyperplasia, and the picture presented on section of the cord is 
that of a sclerosis of the motor tracts and of the anterior horns. Quite 
frequently the sclerosis is not wholly confined to the motor tracts, but 
extends into the neighboring anterior and lateral tracts, especially in 
1 Marie, "Lectures on Diseases of the Spinal Cord," London, N. S. Soc., 1895. THE NERVOUS SYSTEM 
957 
the cervical region. The degeneration in these tracts has been traced 
through the medulla, pons, and crus to the cortex, where changes have 
been observed in the large pyramidal cells. In the gray matter of the 
medulla are also found changes analogous to those in the anterior horns, 
consisting in degeneration of the cells of the motor cranial-nerve nuclei 
(hypoglossal, spinal accessory, pneumogastric, glosso-pharyngeal, and 
facial). The atrophy of the muscles innervated by these nerves gives 
the clinical picture of glosso-labio-laryngeal paralysis or progressive 
bulbar paralysis. The medullary lesion may occur without any corre- 
sponding lesion of the cord, thus giving rise to a bulbar paralysis with- 
out any spinal symptoms. The seat of the initial lesion, whether in the 
cell bodies in the cortex or in their axones, is as yet undetermined. 
The fact that disturbances of nutrition acting primarily upon the cell 
body are frequently most evidenced by changes in parts of the neurone 
farthest from the trophic center has already been mentioned. The mus- 
cle changes are those of a progressive muscular atrophy. 
Degeneration of the Peripheral Sensory Neurones. {Tabes Dor- 
salis-Posterior Spinal Sclerosis-Locomotor Ataxia.) 
The essential lesion of tabes is a primary progressive degeneration of 
the peripheral sensory neurone system. As its older title indicates, the 
clinical picture of locomotor ataxia had been attributed to a primary 
sclerosis of the posterior columns. This was not because in these col- 
umns was the only lesion, but because, owing to the close packing to- 
gether here of the sensory axones, this lesion was the most conspicuous. 
The distribution of the lesion is coextensive with the peripheral sensory 
neurone system (p. 952). Any part of the system may be affected or 
the lesion may involve practically the whole system. Again, the entire 
neurone may be affected, or only part of the neurone, or one part more 
than other parts. In general it may be said that it is the central process 
of the neurone, which enters the cord in the posterior nerve roots, that 
shows the earliest and most extensive changes. 
It is convenient to classify the lesions of tabes according to the anat- 
omy of the peripheral sensory neurone system, as follows: 
1. The Peripheral Processes.-(a) The sensory nerve endings. Changes 
of a degenerative character have been described in the sensory nerve 
endings of the skin, joints, and muscle. Especially well marked are 
lesions of the (sensory) muscle spindles which are almost constantly 
present. 
(5) The peripheral nerves. Degenerations of the peripheral nerves 
are common. Like similar conditions due to toxic agents, they are usu- 
ally referred to as a neuritis. The changes in both axones and medullary 
sheaths are, however, degenerative in character and similar to those of 
a Wallerian degeneration. The lesion is confined wholly to the sensory 
fibres, the motor fibres remaining intact. It is usually most pronounced 
in the smaller peripheral branches of the nerves. Degeneration of the 
optic nerve-so-called optic neuritis-occurs in from ten to twenty per 958 
THE NERVOUS SYSTEM 
cent, of cases. Degeneration of the auditory nerve and of the sensory 
fibres of the pneumogastric, glosso-pharyngeal, and trigeminus is of 
less frequent occurrence. 
2. The Cell Bodies.-Marked degenerative changes in the cells of the 
spinal and analogous cranial ganglia have been described. In a number 
of cases they have been found early in the disease. There is a reduction 
both in number and in size of the ganglion cells, with a replacement 
connective-tissue hyperplasia. Chromatolysis with nuclear eccentricity 
as demonstrated by the method of Nissl has also been observed. Similar 
changes have been noted in the nerve cells of the retina.1 
3. The Central Processes.-(a) The sensory nerve roots, consisting as 
they do of the central processes of the spinal ganglion cells, show more 
or less complete degeneration. It is, in fact, in this part of the neurone 
that the earliest and most conspicuous changes are usually found. The 
extent and location of the degeneration vary. In the more common 
type of the disease-lumbar tabes-the earliest lesions appear in the 
posterior roots of the lumbar nerves. Only a few of the roots are at first 
affected, and only some of the fibres in these roots. With the progress 
of the disease more fibres are involved and the degeneration extends 
downward to the sacral roots and upward to those of the dorsal and cer- 
vical nerves. In specimens stained by Weigert's method the con- 
trast between the darkly stained anterior root fibres and the almost 
unstained posterior root fibres is often marked. 
(6) The spinal cord. On removing the cord in a case of advanced 
tabes, certain changes are usually apparent to the naked eye. The pia 
mater between the two posterior horns is apt to be thickened, of a dull 
appearance, and adherent to the cord. This, in contrast to the normal 
condition of the rest of the pia, gives the effect of a narrow band ex- 
tending the length of the cord. The posterior columns may be depressed, 
of a grayish color, and firmer than the rest of the cord. On section the 
contrast between the posterior columns and the rest of the white matter 
of the cord is often very distinct. In cords removed from cases dying 
during the earlier stages of the disease there are often no macroscopic 
lesions. 
The microscopic appearances vary, depending on the stage, extent, 
and location of the lesion (Fig. 664). 
In a case which comes to autopsy early in the disease the appearance 
of the lesion differs from that in a case of advanced tabes. As already 
noted, the most marked changes are in the posterior columns. In the 
more common type of the disease in which the degeneration begins in 
the lumbar region, sections of the cord at this level show certain quite 
well-defined areas of degeneration. The zone of Lissauer early shows 
marked degenerative changes. This zone extends across the entering 
fibres of the posterior root which divide the zone into two parts. The de- 
generation of the outer part has been wrongly described by some writers 
as a lateral-column degeneration. It will be remembered that these 
1 In Plate XIII., 7, is seen a portion of a spinal ganglion from a case of advanced tabes. In addition 
to a degeneration of the cells present, there was a marked reduction in the number of cells in the ganglion. THE NERVOUS SYSTEM 
959 
fibres are short fibres which have entered the cord in the nearest posterior 
root. Degeneration usually appears early in that part of the column of 
Burdach which borders the posterior horn. The column of Goll varies 
as to the extent of involvement. In many cases it is only slightly af- 
fected, in others the degeneration is marked. As the fibres of this column 
come mainly from the last lumbar and first two sacral segments, it 
is seen that its condition depends entirely upon the integrity of these 
roots. The fibres of the posterior columns have two sources: (1) enter- 
ing fibres of the posterior roots; (2) fibres from cells in the gray matter 
Fig. 664.-Tabes Dorsalis. 
Cervical region, showing an early stage of the lesion. 
of the cord. The latter are situated mainly in a narrow strip behind the 
posterior commissure and in the median oval area of Flechsig. These 
fibres are unaffected in tabes. 
The degenerations seen in sections of the dorsal and cervical cord 
in lumbar tabes are dependent upon an ascending degeneration of the 
fibres affected below. The columns of Goll are thus usually affected, 
while the columns of Burdach are often only slightly involved. If at 
any level of the cord degenerated root fibres enter the cord, there results 
a degeneration in the zone of Lissauer and in the band of fibres lying 
along the posterior horn at that level. 
Rarely the tabetic process begins in the cervical region. In these 
cases section of the cervical cord shows not only normal endogenous 
fibres, but a normal condition of the column of Goll and of such part of 
the column of Burdach as originated below the level of the lesion. Some- 
times the dorsal roots are affected with the cervical. In cervical tabes 
the cord below the affected region is normal, while above is the lesion of 
an ascending degeneration. The lesion may in any case be asymmetrical, 
one root of a segment being affected while the other remains normal. 
Marie describes a variety of tabes in which the lesions begin in the 
cranial nerves. 960 
THE NERVOUS SYSTEM 
In cases of advanced tabes (Fig. 665) there are often almost no nor- 
mal nerve fibres in the posterior columns; the columns of Goll, of Bur- 
dach, and of Lissauer presenting little but dense fibrous tissue. The 
Fig. 665.-Tabes Dorsalis. 
Cervical region, showing an advanced stage of the lesion. 
posterior fissure may be completely obliterated. There usually remain, 
however, even in advanced tabes, undegenerated fibres bordering the pos- 
terior commissure and the adjacent parts of the posterior horns. The 
A portion of sclerosed area in the posterior columns of the spinal cord, a, New-formed connective 
tissue; b, blood-vessels; c, nerve fibres; d, atrophied nerve fibres. 
Fig. 666.-Posterior Spinal Sclerosis. (Tabes Dorsalis.) 
median area of Flechsig also remains intact. As already noted, these 
fibres are endogenous. 
The microscopical appearance of the degenerated areas varies with the 
stage of the process (Fig. 666). The new connective tissue may be at THE NERVOUS SYSTEM 
961 
first quite cellular; later the fibrillar- elements predominate and the 
tissue becomes dense and firm. Of the nerve roots some have disap- 
peared, others show degeneration of their medullary sheaths and axis 
cylinders. Some few normal fibres are usually present even in advanced 
sclerosis. The blood-vessels often have thickened walls. There may be 
corpora amylacea and fat globules, the latter either free or collected in 
cells. 
The lesion of tabes is not, however, confined to the posterior columns. 
The fibers of these columns are constantly sending collaterals and termi- 
nals into the gray matter. Most of these pass into the posterior horns, 
an especially well-marked group entering Clarke's cell column. The 
posterior horns are therefore usually smaller than normal, with a marked 
reduction in the number of fibres entering them from the posterior col- 
umns, while the columns of Clarke show a diminution in the number of 
delicate fibrils which normally surround the ganglion cells. 
Changes have also been described in the spinal root of the fifth cranial 
nerve and in the fasciculus solitarius which consists of afferent fibres of 
the vagus and glosso-pharyngeal nerves. These fibres are analogous to 
those of the posterior columns, and the changes in them are similar. 
Degenerations of a secondary character may occur in those systems 
of neurones which are more or less dependent upon the peripheral sen- 
sory neurone system for their impulses. Thus the cells of Clarke's col- 
umn may be affected, with resulting degeneration of their axones which 
make up the direct cerebellar tract. This degeneration extends through 
the restiform body to the termination of the tract in the cerebellum. 
The cells of the gray matter whose axones form Gowers' tract may be 
degenerated with consequent degeneration of the fibres of this tract. 
In the medulla the cells of the nucleus gracilis and nucleus cuneatus 
may be affected, thus determining an ascending degeneration along the 
tracts followed by their axones. Similar in character is the degeneration 
of the cells of the anterior horns noted by Condoleon. These changes in 
the anterior-horn cells have been accepted by some investigators as ex- 
planatory of the various trophic disturbances which so frequently occur 
during the course of tabes. Similar changes have been found in the 
nuclei of two of the motor cranial nerves, the oculomotor and the hypo- 
glossal. Others ascribe the trophic disturbances to a peripheral neuritis. 
Marie1 describes a case interesting in this connection, in which there was 
marked hemiatrophy of the tongue with distinct changes in both main 
and accessory nuclei of the hypoglossal nerve on the same side, the oppo- 
site nuclei being normal. Oppenheimer describes a similar case of tabes 
with laryngeal crises in which there were pronounced degenerative 
changes in the pneumogastric nucleus and in the ascending root of the 
glosso-pharyngeal. Changes have been described in the cells of the cere- 
bral cortex. They are similar to those found in dementia paralytica, 
but less marked. 
Although various hypotheses have been advanced in explanation of the tabetic 
lesion, and especially in reference to the fairly constant selection of certain groups of 
1 Marie, loc. cit., p. 956. 962 
THE NERVOUS SYSTEM 
neurones, doubt still exists as to the origin and essential nature of the process. Earlier 
writers look upon the lesion as a primary sclerosis of the posterior columns, probably 
of vascular origin. Flechsig1 and Trepinski2 describe the posterior columns as made 
up of several distinct systems of fibres, each system distinguishable from the others 
by its period of ripening or myelinization. They assert that the tabetic process 
affects these different systems successively. As the systems overlap one another, 
this would explain the admixture at certain stages of tabes of normal and abnormal 
fibres. Present knowledge favors the view that tabes is a primary degeneration of 
the peripheral sensory system of neurones, the degeneration affecting the entire neu- 
rone, and that the picture presented by the tabes cord varies with the particular 
neurones affected. The cell bodies of these neurones are in the spinal ganglia and their 
cranial analogues. Thorough examinations of spinal ganglion cells have as yet been 
made in too few cases to warrant any general conclusions. Degeneration of spinal 
ganglion cells in tabes has been reported even in cases dying early in the disease. Such 
Fig. 667.-Combined System Disease. 
Showing degeneration and sclerosis in the columns of Goll, the direct and the crossed pyramidal tracts, 
and the direct cerebellar tract. 
degenerations are best shown by the method of Nissl, the general application ol which 
is comparatively recent. Certain it is that a degeneration which affects both peripheral 
and central processes of the neurone, and yet is most pronounced in those parts of the 
neurone farthest removed from its nutritive centre, is most easily explained on the 
basis of some agent affecting the general metabolism of the neurone. A majority 
of the cases of tabes give a syphilitic history, and in a very large percentage, though not 
all of the cases, a Wassermann or luetin reaction can be obtained. The disease is, 
therefore, considered at present to be of a parasyphilitic nature. 
Combined System Degeneration-Ataxic Paraplegia.-This is 
a disease of uncertain etiology, in which there are degenerative changes 
in both motor and sensory neurone systems (Fig. 667). The tracts usu- 
ally involved are those of Burdach and of Goll, the direct cerebellar 
tracts, and the crossed pyramidal tracts. Less commonly the degenera- 
tion extends to the tracts of Gowers and to the direct pyramidal tracts. 
It seems probable that the lesion in the cord is not always the expression 
of the same pathological process, and that in many cases it is not the 
result of a true systemic degeneration. In perhaps the minority of cases 
1 Flechsig, ''Die Leitungsbahnen im Gehim und Riickenmark," Leipsic, 1878. "1st die Tabes 
Dorsalis eine System-Erkrankung ?" Neur. Cent., Bd. ix. 
2 Trepinski, "Die embryonalen Fasersysteme in den Hinterstrangen und ihre Degeneration bei 
der Tabes Dorsalis," Arch. f. Psych, und Nerv., Bd. xxx., 1897. THE NERVOUS SYSTEM 
963 
the lesion corresponds to the tract systems of the cord and probably 
represents a combined sensory-motor degeneration. Such are those rare 
cases in which the degeneration affects all of the above-mentioned tracts. 
According to Dejerine, the appearance of a combined system disease may be 
induced by the chronic meningitis, which exists over the posterior columns in tabes, 
extending forward over the direct cerebellar tract, the productive inflammation finally 
spreading to this tract and to the crossed pyramidal. In these cases that part of the 
latter tract which lies deepest, i.e., close to the gray matter, usually remains unin- 
volved. Marie lays particular stress upon the arterial systems of the cord as the 
prime factor in many cases, calling attention to the fact that the lesion, as it is most 
commonly found, coincides almost exactly with the distribution of the posterior 
spinal arteries. By others the lesion is ascribed to a multiple sclerosis, the restriction 
of the degeneration to definite tracts being only apparent. It is possible that in some 
cases the pathological picture of a combined sclerosis may be due to secondary 
degeneration following myelitis. 
A subacute type of combined system degeneration has been described by Russell.1 
The degeneration involved the same tracts affected in the more chronic type, and was 
often very extensive at some levels of the cords studied, there being only a thin layer 
of normal fibres covering the gray matter. 
Under the name of diffuse degeneration of the spinal cord, Putnam and Taylor2 
describe a somewhat similar condition, leaving open the question as to the systemic 
nature of the process. 
Friedreich's Ataxia. {Hereditary Ataxia). 
This disease, while often referred to as hereditary ataxia, has more of 
a family than of a distinctly hereditary character. Its pathology is 
marked by a decrease in the size of the spinal cord, the diameter of which 
is often not more than three-quarters that of the normal cord. Degen- 
eration of the columns of Goll is usually quite complete. Less marked 
degeneration is found in the columns of Burdach, in the direct cerebellar 
and in the crossed pyramidal tracts. The marginal tract of Lissauer may 
or may not be affected. In the posterior horns and in the columns of 
Clarke the condition resembles that in tabes. There may be atrophy of 
the cerebellum. 
Marie notes in addition, atrophy and disappearance of the cells of Clarke's column. 
Blocq and Marinesco3 describe degeneration of the posterior root fibres similar to that 
found in tabes. Friedreich4 and Riitimeyer5 find atrophy of the anterior horn cells 
The determining cause of the disease and the nature of the morbid process are as yet 
undetermined. It seems probable that the condition of the cord may be more prop- 
erly considered an abnormality of development rather than a degeneration. 
Cerebellar Ataxia. 
Atrophy of the cerebellum was noted as sometimes occurring in Fried- 
reich's ataxia. In that disease, however, the cord lesion was most 
1 Russell, Batten, and Collier, Brain, vol. xxiii., p. 39, 1900. 
2 Putnam and Taylor, Journal of Nerv. and Ment. Disease, vol. xxviii., pp. 1 and 74, 1901. 
3 Blocq, P., and Marinesco, G., "Sur FAnatomie Pathologique de la Maladie de Friedreich" 
Compte rend. Soc. de Biol., 1890. 
4 Friedreich, N., Virchow's Archiv, Bd. Ixxxvi., 1881. 
5 Rutimeyer, L., Virchow's Archiv, Bd. ex., 1887. 964 
THE NERVOUS SYSTEM 
marked. In cerebellar ataxia the lesion of the cord is slight or absent, 
the chief lesion being an atrophy of the cerebellum. This atrophy is 
accompanied by little or no sclerosis, the organ being simply smaller 
than normal. 
INFLAMMATION. 
Inflammation of the Brain. (Encephalitis j 
Acute Encephalitis.-Inflammatory processes in the nervous system, 
whether of an exudative or of a productive type, are frequently consecu- 
tive to or coincident with the more severe forms of degeneration or other 
lesions, thus making differentiation of the processes often extremely dif- 
ficult. It has been already mentioned that the brain tissue about haemor- 
rhages and areas of embolic and thrombotic softening may undergo in- 
flammatory changes leading to the formation of new connective tissue. 
There is a class of cases in which localized areas of the brain undergo 
softening, with more or less extravasation of red and white blood cells 
and hyperaemia, so that the softened material consists, as seen under the 
microscope, of detritus of brain tissue in a condition of fatty degenera- 
tion, often with more or less pus cells and pigment. When such areas are 
red in color from intermingled blood cells or pigment, the condition is 
called red inflammatory sojtening. When fatty degeneration prevails, and 
the red blood cells or their derivatives are not abundant, the softened 
area looks yellow or yellowish-white, and this is often called yellow in- 
flammatory sojtening. The origin of these processes is very obscure and 
their inflammatory nature not well defined. 
Abscess of the Brain.-Small multiple abscesses of the brain may 
occur in pysemia. Large abscesses of the brain are usually single; they 
may attain a large size. They are most frequent in the cerebral and 
cerebellar hemisphere, rare in the basal ganglia, the pons, and the 
medulla oblongata. 
There may be an irregular cavity containing thin pus and softened 
brain tissue. The walls of the cavity are ragged and infiltrated with 
pus, and outside of the walls is a zone of oedematous and softened brain 
tissue. If the abscess be near the pia mater, meningitis may follow; if 
it be near the lateral ventricles, it may rupture into them; if it be near 
the sinuses of the dura mater, it may induce thrombosis, An abscess 
may in time become enclosed in a capsule of connective tissue. 
Abscess of the brain is most frequently secondary to chronic suppu- 
rative otitis (42.5 per cent., Gowers), much less frequently to acute otitis. 
With the otitis there may also be caries of the temporal bone, suppura- 
tion of the mastoid cells, and inflammation of the dura mater. The 
abscess is usually situated deep in the brain, commonly in the temporo- 
sphenoidal, the frontal, the occipital or the parietal lobes, or in the 
cerebellum; rarely it is continuous with the inflamed dura mater and 
bone. Abscess may follow chronic lesions in the orbit or caries of vari- 
ous parts of the cranial bones. THE NERVOUS SYSTEM 
965 
Abscess of the brain frequently follows traumatism, blows, or falls 
on the head. Such injuries may not damage the skull, or may produce 
fractures or necrosis. There is often a considerable interval between 
the time when the injury is inflicted and the development of the symp- 
toms. 
When the cranial bones are uninjured the abscess is usually deep in 
the brain; when there is necrosis of the bones the abscess may be super- 
ficial; when the bones are fractured the abscess may be either superficial 
or deep. The abscess develops rarely in the opposite side of the brain. 
In acute exudative meningitis from various excitants there may be an 
infiltration of the brain with leucocytes; this may be especially marked 
in the perivascular tissue and around the ganglion cells. 
An Acute Disseminated Encephalitis,1 haematogenous in character, may 
develop during the progress of an infectious disease. It is most com- 
mon in infective endocarditis, in pyaemia, and in epidemic cerebro-spinal 
meningitis. It may be associated with acute anteropoliomyelitis, ap- 
parently due to the same obscure etiological factor. The lesion consists 
of disseminated foci of inflammation, or minute multiple abscesses. 
Some of these are microscopic in size, others may be seen with the naked 
eye. The smallest show simply small-round-cell infiltration of the walls 
of one or more small vessels and of the surrounding tissue. The larger 
spots, which undoubtedly take origin in the same way, are seen to be 
softer than the rest of the tissue, and resemble red or yellow softening, 
according to the amount of red-blood-cell extravasation. Congestion is 
usually marked. There may be distinct haemorrhages. Degenerative 
changes with disintegration of the exudate usually set in and determine 
destructive changes in the neighboring neurone and neuroglia elements. 
At the periphery of one of these abscesses the neuroglia, instead of being 
in a degenerating condition, usually shows proliferation. The more 
minute inflammatory foci may undergo complete resolution with absorp- 
tion of the exudate. In the larger abscesses there may be absorption of 
the exudate and of the products of degeneration, and a replacement neu- 
roglia hyperplasia, ultimately resulting in a sclerotic patch. 
Suppurative encephalitis may occur as a result of traumatism or from 
extension of suppurative meningitis. 
A form of encephalitis which has been designated acute non-suppu- 
rative haemorrhagic encephalitis, has been described by Strumpell, Leich- 
tenstein, Oppenheim, Putnam,2 and others. The lesion consists in the 
occurrence of multiple haemorrhagic, inflammatory foci, which are non- 
suppurative, and which are accompanied by leucocytic infiltration. These 
foci may occur in any part of the brain, but are most numerous in the 
white matter of the brain and basal ganglia. Some of these haemorrhages 
may be quite large. 
1 Under the head of "Acute Parenchymatous Encephalitis" has been described a lesion of the 
ganglion cells without vascular or interstitial changes. These lesions are the result of toxaemias of 
either endogenous or exogenous nature. They are more properly classed as parenchymatous degenera- 
tion. 
2 Putnam, Jour, of Nerv. and Ment. Dis., vol. xxiv., 1897, bibliography. 966 
THE NERVOUS SYSTEM 
Acute Inflammation of the Spinal Cord. (Acute Myelitis.') 
Inflammation in the spinal cord is quite analogous to inflammation 
in the brain. 
Acute Disseminated Myelitis1 runs a rapid course and proves fatal in a 
short time. The inflammation may involve nearly the whole length of 
the cord, but is usually more intense in some places than in others. The 
cord is swollen and congested, it is infiltrated with pus cells, the connec- 
tive tissue is swollen, and there is degeneration of the nerve elements 
proper. 
More frequently an acute myelitis is localized. It involves but 
a small portion of the length of the cord, while laterally it may com- 
pletely cross it, and is hence spoken of as a transverse myelitis. When 
the cord is removed and laid upon the table, if the lesion is marked, a 
flattening of the cord at its seat may 
be observed; or on passing the finger 
gently along the organ, the affected 
segment will be found softer than the 
rest of the cord, sometimes almost 
diffluent. On making a section through 
the affected portion the nerve tissue 
may appear white or red or yellowish 
or grayish.2 
Microscopical examination shows 
different appearances, depending upon 
the stage of the degenerative or in- 
flammatory process. There may be 
much blood, or, if the lesion has existed for some time, blood pig- 
ments; also fragments of more or less degenerated nerve fibres and 
ganglion cells (Fig. 668), myelin droplets, free fat granules, larger and 
smaller cells filled with fat granules (Gluge's corpuscles), pus cells, 
granular matter, neuroglia cells, and sometimes corpora amylacea. The 
various proportions of these elements give rise to the different gross 
appearances which the diseased part presents. In earlier stages of the 
lesion the blood-vessels may be dilated, the nerve fibres and cells swollen; 
or the walls of the blood-vessels may be thickened or fatty, or surrounded 
by a sheath of leucocytes and cells derived from the connective-tissue 
cells of the adventitia. 
The lesion is apt to commence in the gray matter or at its edge, and 
then extend first laterally and afterward upwmrd and downward. 
In a certain number of cases the degenerated material may be 
Fig. 668.-Degenerated Tissue from 
Acute Myelitis. 
1 Acute parenchymatous myelitis, like its analogue in the brain, is a lesion of the ganglion cells, 
and is more properly classed as a degeneration. Embolic and thrombotic softenings are more rare 
in the cord than in the brain, and are necessarily much more restricted in extent. When of an inflam- 
matory character they resemble the similar brain lesion and are red or yellow according to the amount 
of extravasation. 
2 It should be remembered that the mechanical injury to the cord in removal, such as crushing or 
bruising, may reduce the injured portion to a pulpy consistence and thus produce appearances some- 
what similar to those of some forms of inflammatory softening. See reference to Van Gieson, on "Arte- 
facts of the Nervous System," p. 928. THE NERVOUS SYSTEM 
967 
absorbed and a cicatrix or cyst formed. After the least extensive forms 
of the lesion there may be a restoration of the functions of the cord. 
Secondary degeneration, both ascending and descending, may occur 
in this form of myelitis, varying in extent according to the size of the 
primary lesion. The terms central myelitis, peripheral myelitis, and uni- 
lateral myelitis, are sometimes used to designate localizations of the lesion. 
Poliomyelitis Anterior-Myelitis of the Anterior Horn.-This name is 
applied to a group of cases which are characterized by clinical symptoms 
indicating changes in the anterior horns. The disease is most common 
in children, under the name of infantile spinal paralysis, but occurs also 
Fig. 669.-Poliomyelitis Anterior. 
A, Normal ganglion cells surrounded by nerve fibres; B, degenerated ganglion cells; C, granular masses 
at place of ganglion cells; D, small cavity containing fluid. 
in adults. It usually begins with symptoms of an acute infectious dis- 
ease, the paralysis supervening after a few days. It varies in acuteness, 
severity, and duration. In many cases there is complete recovery, and 
then we must suppose that the changes in the nervous tissue were not 
destructive in character. In other cases the symptoms are more perma- 
nent, indicating a destructive lesion. 
At first a considerable group of muscles, usually of the arms or legs, 
is affected. Resolution taking place, there may be complete disappear- 
ance of the paralysis. More commonly there is return of function in 
most of the muscles, while some few remain permanently paralyzed and 
become atrophied. The lesion is most frequent in the lumbar and cer- 
vical enlargements, but may occur anywhere, and is often found in 
scattered patches. Earlier autopsies were in cases of long standing, 
and the changes found consisted in degeneration (Fig. 669), shrinkage, 
pigmentation, and atrophy of the ganglion cells of the anterior horns, an 
increase in the connective tissue of the cornua and of the adjacent white 
matter, often -with destruction of considerable portions of the horns, 
atrophy of the anterior roots, and distortion of the cord. 968 
THE NERVOUS SYSTEM 
Instead of this shrinkage and atrophy of the horns there is sometimes 
found, especially if the case come to autopsy not too long after the onset, 
a gelatinous condition of the horns, the place of the horns being occupied 
by young neuroglia tissue with many branching cells and fine delicate 
fibrils resembling glioma (Fig. 670). This gliomatous tissue may break 
Fig. 670.-Acute Anterior Poliomyelitis. 
Death seven weeks after onset. Showing gliomatous tissue in both horns, with cavity formation in 
one of them. 
down, forming a cavity surrounded by young neuroglia tissue. More 
recently autopsies made early in the course of the disease show that the 
changes described above represent only later stages of what originated 
as an acute inflammatory process. Examination of the cords from 
Fig. 671A.-Perivascular Infiltration in Cord in Case of Acute Anterior Poliomyelitis. 
Preparation of Dr. Simon Flexner. 
such early cases shows congestion, oedema, the presence of mono- 
nuclear cells in the perivascular and nerve-cell spaces, and proliferation 
of the neuroglia. Degeneration of the nerve cells occurs, probably 
secondary to the inflammatory lesion. The inflammation is similar 
to that of an ordinary acute myelitis, but is usually confined largely to 
the area of distribution of the anterior spinal artery. The brain, the THE NERVOUS SYSTEM 
969 
posterior root fibres, and the spinal ganglia may be involved in the 
exudative process. It is an acute infectious communicable disease, 
whose infective agent has probably been isolated and concerning which 
much knowledge has recently been gained through experimental studies. 
(See page 299).1 
Fig. 671B.-Ganglion Cell Lesions in Acute Anterior Poliomyelitis. Preparation of Dr. 
Simon Flexner. 
Acute Ascending Paralysis-Landry's Paralysis.-This is a rare disease 
characterized clinically by a rapidly ascending paralysis, beginning in the 
lower extremities and progressing upward to involve the body, arms, 
and head. Recently a number of cases have been reported in which the 
lesion was an acute myelitis with or 
without an accompanying polyneuritis, 
and congestion, haemorrhages, and cir- 
cumvascular in Hitration (Fig. 673), 
the ganglion cells being in various stages 
of degeneration.2 A great variety of 
parasites have been isolated from the 
lesions, including streptococcus, an- 
thrax and tubercle bacilli, and an 
organism of the Friedlander type.1 
Fig. 672.-Organism Isolated from 
Acute Poliomyelitis by Noguchi. Possi- 
bly the Inciting Agent of the Disease. 
Fig. 673.-Landry's Paralysis. 
Showing acute inflammatory process 
about blood-vessels, with leucocytes in the 
walls. 
1 For resume of recent studies on acute poliomyelitis see Strauss and Flexner, Pediatrics, 1910, 
Aug. See also numerous notes by Flexner and Lewis in the Jour. Amer. Med. Assn., 1909, liii, and 
1910, liv and Iv. For cultivation of organism see Flexner and Noguchi, Jour. Exper. Med., 1913, 
xviii, 461. For a study of the possibility of the transfer of the virus by the stable fly (Stomoxys cal- 
citrans) see Rosenau, Jour. Amer. Med. Assn., 1912, lix, 1314. 
2 For further details see Bailey and Ewing, N. Y. Med. Jour., 1896, July; Cramer, Centralbl. f. 
Path., 1892, iii, 6. 970 
THE NERVOUS SYSTEM 
Inflammation of the Nerves. (Neuritis.) 
In the nerves, as in the brain and cord, degenerative changes commonly accompany 
inflammation, and a distinction is often difficult. The difficulty in sharp differentia- 
tion lies in the fact that degenerative changes in nerves, when intense or long continued, 
often lead to inflammations, and that inflammatory conditions in nerves often deter- 
mine secondary degenerative changes in the nerve fibres. 
Acute Exudative Neuritis.-Acute inflammation of the nerves may 
occur as the result of injury, or it may be secondary to an inflammatory 
process in their vicinity, although, owing to the dense lamellar sheaths 
and the special blood supply, the nerve trunks may escape participation 
even in very severe inflammatory processes in surrounding tissues. The 
inflamed nerve may be red and swollen and infiltrated with serum and 
pus cells. The process may undergo resolution or terminate in destruc- 
tion of the nerve, or it may become chronic and result in the formation 
of new connective tissue. Degeneration and regeneration of the nerve 
fibres, similar to those described as following division of nerve trunks, 
may occur in acute neuritis. 
"Multiple Neuritis" (Degeneration).-While for convenience of refer- 
ence described under its usual title, this lesion is probably always a degen- 
eration, and would be properly classified under the head of neurone 
degenerations of toxic origin. It is caused by the action of certain min- 
eral poisons, for example, alcohol and lead. It occurs as a complication 
of, or succedaneum to, certain infectious diseases, for example, diph- 
theria, septicaemia, measles, smallpox, etc. It is sometimes apparently 
idiopathic. Changes of a degenerative nature are found in the peripheral 
nerves, and are more marked near the peripheral than near the cord. 
Fig. 674.-Degeneration of Nerve Fibres in Multiple Neuritis. 
From a case of alcohol poisoning. Specimen stained with osmic acid. The broken-down medullary 
sheath and fat droplets are stained deep black. 
Thus the most common nerves affected are the anterior tibial and the 
radial. The most marked changes are in the nerves themselves, there 
being little or no change in the connective tissue. More rarely, espe- 
cially in very acute cases, there are reddening and swelling with some 
inflammatory reaction in the interstitial tissue. The fibre lesion shows 
best in specimens treated with osmic acid and teased in glycerin (Fig. 
674). Here the myelin sheath is seen to be broken up, and instead of a 
continuous envelope of black stained myelin, the myelin is represented 
by larger or smaller black droplets scattered along a broken or degener- 
ated axis cylinder. There may be some increase in the connective tissue. 
The sheath of Schwann is usually intact. It is of interest to note that in 
a number of cases (as yet too few to warrant general conclusions) changes 
have been found in the cells of the anterior horn analogous to those THE NERVOUS SYSTEM 
971 
found after injury to motor nerves. The muscles supplied by the 
affected nerves show various stages of atrophy. The cord and meninges 
usually remain normal. In some cases a spinal meningitis and more or 
less myelitis have been described. 
Chronic Inflammation of the Brain, Cord, and Nerves. 
While this term should be applied only to a primary increase in the 
neuroglia elements at the expense of the parenchymatous, thus making 
the degeneration of the nerve tissue proper entirely secondary, it is 
often difficult to eliminate the possibility of a primary degeneration of 
the nerve cells. Histologically the lesion consists in a proliferation of the 
neuroglia elements. The neuroglia cells increase in number, some of the 
new-formed cells having many processes, others few. In the early cellu- 
lar stage of its formation the proliferative area is soft and gelatinous, 
and tends to increase the size of the part. With further progress of the 
sclerosis, there is a disproportionate development of fibres attached to 
the cells, and finally of fibres independent of cells. With the increase 
of fibres the affected area becomes firmer, making a sort of dense felt- 
work of interlacing fibrils. In this meshwork are found nerve fibres in 
various stages of degeneration. 
Chronic Interstitial Encephalitis-Sclerosis.-This lesion of the brain 
tissue may occur diffusely occupying an entire lobe or more or less of the 
whole brain, or in circumscribed small areas. It consists essentially in 
an increase of the connective-tissue elements, the neuroglia, and an 
atrophy of the nerve elements, particularly the ganglion cells and the 
medullary sheaths of the nerves. With these changes are usually asso- 
ciated the formation of Gluge's corpuscles, corpora amylacea, granular 
and fatty degeneration of the nerve elements, and thickening and pro- 
liferation of cells of the walls of the blood-vessels. The areas of sclerosis 
may be very dense and hard, or gelatinous in consistence. 
The diffuse form of sclerosis is most frequently seen in general pare- 
sis of the insane, and not infrequently in the brains of drunkards. 
A peculiar feature of disseminated sclerosis is that the patches, 
whether in the brain or cord, do not induce the expected secondary 
degeneration. It is, in fact, uncommon to find secondary degeneration 
resulting from even a large patch of sclerosis. This is believed to be due 
to the fact that in nearly all of the patches the axis cylinders persist even 
after complete destruction of the medullary sheaths. 
The circumscribed form of sclerosis, multiple sclerosis (sclerose en 
plaque), is much more common than the diffuse form, and may occur 
in the brain alone, or more commonly is associated with a similar lesion 
in the spinal cord. The areas of sclerosis vary in size from that of a 
pea to that of an almond. They may be few or numerous, they may 
be white, grayish, or grayish red in color, and are usually but not always 
sharply outlined by the unaltered brain tissue. Although in many 
cases the increase in the connective-tissue elements seems to be the 
primary lesion, and the degeneration of the nerve elements secondary 972 
THE NERVOUS SYSTEM 
to this, it is quite possible that in some cases the increase in connective 
tissue may be secondary to a degeneration of the nerve elements from 
loss of nutrition or from other causes. 
There is reason for the belief that multiple sclerosis may sometimes 
be the result of disseminated local necrotic lesions of acute infectious 
diseases-scarlatina, for example, occurring at an early period of life. 
Encephalitis in the New-born. 
This condition, first described by Virchow, is said to consist in the formation of 
circumscribed collections of cells of various sizes containing many fat granules (granu- 
lar corpuscles) and forming yellowish masses, from 1 millimetre to 6 millimetres in 
diameter, in the brain tissue. A more diffuse occurrence of granular corpuscles is 
also described, but this is said by some observers to be physiological. The nature of 
this lesion is but little understood, and is still the subject of controversy. 
LESIONS OF THE BRAIN IN GENERAL PARESIS OF THE INSANE. 
The changes in this disease are in the main those of chronic diffuse 
encephalitis, but appearances vary greatly and depend to some extent 
upon whether the brain is examined in early or late stages of the disease. 
According to Meyer, in the early stages of the disease the convolutions, 
particularly of the anterior cerebral lobes, are swollen, the gray matter 
is congested and softened in places. The brain tissue is more or less 
infiltrated with leucocytes. Fatty degeneration of the walls of the 
capillaries, and punctate haemorrhages, are also common. 
In later stages of the disease a great variety of changes may be 
observed: haemorrhagic pachymeningitis, thickening of the dura mater, 
and close adhesions to the skull; thickening and opacities of the pia 
mater, adhesions of the latter to the dura mater and to the brain tissue. 
The brain tissue is apt to be atrophied, is often very soft, and the ventri- 
cles are dilated and filled with fluid. The pia mater may be oedematous, 
the ependyma thickened and roughened. The neuroglia is increased in 
amount; the ganglion celjs are shrunken and sometimes pigmented; and 
the nerve fibers may be atrophied. The blood vessels show fatty or 
hyaline degeneration, and along their walls there may be an accumulation 
of fatty and granular cells. Secondary degenerations in the spinal cord 
are not infrequently observed.1 
In 1913 Noguchi2 recorded the finding of Treponema pallidum in 
twelve out of seventy specimens of paretic brains, thus confirming a prev- 
alent conjecture regarding the syphilitic nature of such cases. These 
organisms have also been recently demonstrated in the blood. 
Chronic Interstitial Myelitis.-Under this heading are embraced a 
variety of lesions which probably differ from one another somewhat 
in the nature of the changes involved, but more in the seat of the disease. 
We shall consider without special classification the most important 
forms. 
1 It is unwise to make positive statements regarding many brain lesions revealed by microsco- 
pical study, because technical procedures in the examination even of normal brains are still unsatis- 
factory and incomplete. Brain tissue is so delicate and so liable to post-mortem changes, and the ef- 
fects of preservative agents are so liable to variations, that great caution is necessary in arriving at 
conclusions regarding the minute lesions affecting the nerve tissue. 
2 See references to Noguchi and Moore and to Mott, footnote p. 275. THE NERVOUS SYSTEM 
973 
Chronic Transverse Myelitis.-In certain cases of pressure on the 
spinal cord from a tumor or from displacement of the bones of the verte- 
bral column, etc., the cord, instead of becoming softened or undergoing 
acute inflammatory changes, becomes the seat of a localized formation 
of new connective tissue with consecutive atrophy of more or less of the 
nerve elements in the gray and white matter. The cord becomes in this 
way harder, and sometimes shrunken at the seat of lesion, and gray in 
color. This change may be followed by ascending and descending 
degeneration. 
Chronic Disseminated Myelitis-Multiple Sclerosis.-This lesion, 
similar in its nature to multiple sclerosis of the brain, often occurs with it. 
It consists in the formation, in more or less numerous scattered, circum- 
scribed areas, of new connective tissue, apparently derived from the 
neuroglia. The formation of new connective tissue is preceded or accom- 
panied by degeneration and atrophy of the nerve fibres and ganglion 
cells. The new connective tissue consists of the characteristic branching 
neuroglia cells, surrounded by a more or less dense network of fine 
fibrilke, many, if not most, of which seem to be branches of the neuroglia 
cells. Corpora amylacea and sometimes fat droplets, either free or con- 
tained in cells, may be present in the sclerosed areas. 
The areas of sclerosis may involve both gray and white matter, and 
may be very small or large (Fig. 675). If very small or in early stages 
Fig. 675.-Multiple Sclerosis in the Spinal Cord. 
Showing irregular areas in which there are atrophy of the nerve fibres and their replacement by connec- 
tive tissue. 
of formation, they may not be recognizable by the naked eye, but when 
visible they are grayish, translucent, and firmer than the surrounding 
tissue, and may or may not present a depressed surface; they sometimes 
project above the general level. The cause of this as of all other forms 
of so-called idiopathic interstitial myelitis is very obscure. As noted in 
multiple sclerosis in the brain, secondary degenerations are rare, and 
probably for the reason there given. 
Chronic Interstitial Neuritis.-This is essentially a chronic interstitial 
inflammation resulting in an increase of the connective tissue in the nerve 974 
THE NERVOUS SYSTEM 
sheaths and intrafascicular bands. As a result of this the nerve fibres 
undergo atrophy from pressure; the medullary sheaths and finally the 
axis cylinders being in many of the fibres partially or completely destroyed. 
Tic Douloureux.-Changes in the peripheral branches of the fifth 
cranial nerve removed from obstinate cases of trifacial neuralgia have 
been reported in a considerable number of cases. These changes consist 
in degeneration of the axis cylinders and of their medullary sheaths. In 
a smaller number of instances changes have been reported in Gasserian 
ganglia removed from such cases. The changes in the ganglia consist in 
atrophy and disappearance of the nerve cells with increase in the con- 
nective-tissue elements. A peculiar shrunken condition of the cell in 
w'hich the cell retracts to one side of its cell space is a fairly characteristic 
feature. 
TUBERCULOUS LESIONS IN THE NERVOUS SYSTEM. 
Tuberculous inflammation whether of the brain or cord is usually sec- 
ondary to tuberculous inflammation in other organs, and is most frequent 
as an extension of tuberculosis of the meninges. In the brain substance 
Fig. 676.-Solitary Tubercle of Cerebellum. 
a, a, Miliary tubercles with giant cells; b, b, miliary tubercles without giant cells; c, diffuse tubercle 
tissue; d, central cheesy mass; e, nerve tissue of the cerebellum. 
it usually manifests itself in the formation of circumscribed masses of 
new tissue from 0.5 to 1 centimetre in diameter, or larger. These may 
be single or multiple, are most common in young persons, and very fre- 
quently occur in the cerebellum (Fig. 676). They are apt to occur in THE NERVOUS SYSTEM 
975 
connection with tuberculous inflammation of other organs. They are 
frequently solitary tubercles, each consisting of a dense central cheesy 
mass, around which is a grayish zone containing tubercle granula, 
numerous small spheroidal cells, with occasionally larger polyhedral cells 
and giant cells. They do not, as a rule, seem to be formed by an aggre- 
gation of miliary tubercles, although these may be present at the periph- 
ery. They sometimes suppurate and break down, and then they simu- 
late simple abscesses. Tubercle bacilli have been found in these solitary 
tubercles. 
Conglomerate and scattered miliary tubercles of the ordinary form 
sometimes occur in the brain, usually in connection with tuberculous 
inflammation of the meninges or ependyma. 
In the spinal cord solitary nodules may determine extensive second- 
ary degenerations. Multiple tuberculous foci may occur in the cord. 
They are rare and usually secondary to tuberculosis of the spinal meninges. 
Tuberculous inflammation of nerves is rare except at their origins, 
where it is due to an extension from tuberculous meninges. When a 
nerve traverses tuberculous tissues, it may be involved in the inflamma- 
tory process. 
SYPHILITIC LESIONS OF THE NERVOUS SYSTEM. 
Syphilitic lesions of the nervous system may occur in either the inher- 
ited or the acquired form of the disease. In the former they usually 
show themselves early in life, though cases have been reported after 
puberty. Gasne in an examination of twenty-six foetuses of syphilitic 
parents found well-marked syphilitic lesions in four. More commonly 
it is a tertiary manifestation of the acquired disease occurring from ten 
to twenty years after the initial lesion. Less commonly cerebral symp- 
toms make their appearance within a few months after the chancre. The 
lesion sometimes appears in the brain as the so-called gummy tumors. 
These are most frequently found near the periphery of the brain, are 
usually connected with the meninges, and may be sharply circumscribed. 
The central portion of the tumor is apt to be in a condition of cheesy 
degeneration, while at the periphery is fibrous tissue or a dense infil- 
tration of small spheroidal cells. 
Syphilitic inflammation of the brain very frequently occurs in a dif- 
fuse form, characterized by the formation of a gelatinous, grayish tissue, 
consisting of a more or less homogeneous or granular basement substance, 
with numerous small round cells. The neighboring nerve elements are 
apt to be atrophied. A most common syphilitic lesion is a specific arte- 
ritis with or without the formation of small gummatous tumors in the 
walls of the vessels. 
Syphilitic inflammation in the cord is usually secondary to a similar 
process in the spinal meninges. The size and shape of the gummata are 
modified by the restriction of the vertebral canal. The tumors are 
mainly significant from the more or less extensive secondary degenerations 
which thev induce. 976 
THE NERVOUS SYSTEM 
The relation of syphilis to multiple cerebral and spinal sclerosis is 
still uncertain. Its relation to tabes and to dementia paralytica has been 
noted under their respective titles. It is probable that most or all of 
those rare cases of tabes occurring in children are the results of inherited 
syphilis. 
Syphilitic inflammation of the peripheral nerves is, like tuberculous 
inflammation of nerves, usually dependent upon an extension of the 
process either from the meninges or from some tissue through which the 
nerves pass. 
ACTINOMYCOSIS. 
Actinomycosis of the brain has been described. It is a rare form of 
brain infection, and is usually secondary to actinomycosis of the neck or 
face. The condition is apt to lead to suppuration and abscess formation. 
A case has been reported by Bollinger in which the disease was appa- 
rently primary in the brain. 
LEPROUS INFLAMMATION. 
This occurs in the peripheral nerves and consists in the formation 
within the nerves of masses of new-formed tissue somewhat resembling 
granulation tissue. In the cells of this tissue multitudes of characteristic 
bacilli are uniformly found (see Leprosy). It constitutes the variety of 
leprosy known as lepra anaesthetica. 
TUMORS. 
Tumors occurring in the nervous system may be of the types found 
in the other organs or of types peculiar to nervous tissue. They may be 
primary, or secondary to similar growths in other parts of the body. 
Tumors of the Brain. 
Myxoma, fibroma, lipoma, and osteoma are rare forms of brain tumor. 
Neuroglioma Ganglionare.-This is a form of tumor probably due to 
disturbances in the development of the brain. It is peculiar to nervous 
tissue and occurs in the form of circumscribed tumors or of diffuse 
enlargements of portions of the brain. The pia mater over these tumors 
is unchanged and the convolutions retain their shape. The tumors 
are formed of neuroglia, in which are contained little groups of ganglion 
cells (Ziegler). 
Glioma.-This is the most common tumor of the brain, and like the 
preceding is found only in the nervous system. It occurs with especial 
frequency in children and young adults. Such tumors occur in all 
parts of the brain, but are found most frequently in the cerebrum. 
There may be a single tumor, or there may be several such tumors in 
different parts of the brain; some of them attain a large size. ^Bramwell THE NERVOUS SYSTEM 
977 
reports a case in which considerably more than one-half of a hemisphere 
was involved. 3?These tumors may be sharply circumscribed, or merge 
imperceptibly into the brain substance; sometimes the tumor is arranged 
so as to form the wall of a cyst which contains clear serum. They may 
be white and hard; gray, soft, and gelatinous; infiltrated with small 
haemorrhages or partly degenerated and softened. The centre of a gli- 
oma may break down and become soft and necrotic or even fluid. In 
this way a cyst is formed having a wall of gliomatous tissue. The 
brain tissue around these tumors may be inflamed or necrotic. These 
tumors arise from the neuroglia. The relative quantity of cells and fibrils 
varies in different tumors. They are composed of neuroglia cells and 
their delicate interlacing processes^for minute structure see "Glioma"). 
If the tissue is of a loose formation with wide meshes between the fibres it 
presents a myxomatous appearance, and has been described as myxo- 
glioma. When the cellular elements are very numerous the tumor is 
often referred to as a glio-sarcoma. In some cases the vascularity is such 
a marked feature that the name of telangiectatic glioma is applied to it. 
(According to Ziegler, a simple preponderance of cells, so long as they 
are of the neuroglia type, does not warrant classing the tumor as a sar- 
coma, and he insists that the latter term should be reserved for those 
gliomata in which an active proliferation of the connective tissue of the 
walls of the blood-vessels occurs.) Osler reports three out of five cases 
of gliomata as made up of large cells in contradistinction to the small- 
cell variety. 
< Sarcoma occurs in any part of the brain. It may be single or mul- 
tiple. The tumors are composed of round or fusiform cells with more or 
less basement substance, u 
Endothelioma is found in the substance of the brain. The tumors are 
of the types described as occurring in the pia mater. 
Angioma.-Small collections of dilated vessels are found in the sub- 
stance of the brain. They seem to be congenital like the naevi of the 
skin. 
Carcinoma occurs in the brain. It is usually, if not always, second- 
ary to carcinoma in some other organ. 
Tumors of the Cord. 
In the pia mater of the cord are sometimes found small fibromata, 
osteomata, and lipomata. Multiple fibromata occasionally occur in the 
cord in connection with multiple fibromata of the peripheral nerves. 
Endotheliomata of the types described as existing in the pia mater of 
the brain are much more rarely found in the pia mater of the cord. 
A fatty sarcoma1 of the pia mater, which infiltrated the cord, formed 
a tumor as large as a filbert, and had for twelve years caused gradually 
increasing paraplegia, has been described. 
Two curious cases2 of diffuse sarcoma and one of endothelioma of the 
1 Turner, Trans. London Path. Soc., vol. xxxix., p. 25, 1888. 
2 Coupland and Pasteur, Trans. London Path. Soc., vol. xxxviii., p. 26, 1887; Arch, fur Psych., 1885. 978 
THE NERVOUS SYSTEM 
pia mater of the whole length of the cord are recorded. They occurred 
in girls of four-and-a-half, sixteen, and twenty-two years of age. In each 
case the pia mater of the whole length of the cord was diffusely thickened 
and studded with nodules. In two of the cases the grow'th was com- 
posed of round cells, in the third case of large endothelial cells arranged 
in alveoli. In two of the cases the clinical symptoms lasted only for 
about three weeks, in the third case for five months. The acuteness 
of the symptoms was such as to indicate the existence of spinal meningitis. 
In the spinal cord itself gliomata, fibromata, sarcomata, glio-sarco- 
mata, and angio-sarcomata occur, but are rare. 
When gliomata or glio-sarcomata do occur in the spinal cord, the new 
growth is apt to extend for some distance lengthwise in the cord and to 
Fig. 677.-Syringomyelia. 
An irregular cavity in the gray matter of the spinal cord, lined by a thick layer of gliomatous tissue. 
be attended with the formation of a cavity; this condition is usually 
described under the name of syringomyelia. 
Cysts may occur as a result of softening or from unknown causes. 
Sometimes very long, narrow canals are found in the spinal cord, even 
reaching nearly its whole length. Some of these are evidently the 
dilated central canal, as they are lined with epithelium. Others, 
however, doubtless originate in hemorrhages (see Hematomyel- 
opore, p. 939). 
Syringomyelia.-This lesion of the spinal cord consists in the formation 
of gliomatous or glio-sarcomatous tissue in the vicinity of the central 
canal, and its subsequent partial disintegration with the formation of one 
or more cavities within the substance of the cord (Fig. 677). These cav- 
ities, which are filled with fluid, vary greatly in size, shape, and extent, 
and, while usually situated in the central region of the cord, may involve 
the anterior and posterior cornua and invade the posterior columns. 
There may be two communicating cavities, and these may, but usually do 
not, open into the central canal. The longitudinal extent of these cav- 
ities varies greatly. The lower cervical and upper dorsal regions are most 
frequently involved. The cavity is usually lined with tissue somewhat 
denser than that which makes up the bulk of the tumor. The gliomatous THE NERVOUS SYSTEM 
979 
or glio-sarcomatous tissue which forms the basis of the lesion in syringo- 
myelia probably originates from the layer of neuroglia which surrounds 
or extends away from the central canal. 
Syringomyelia is frequently mistaken for hydromyelia, which is a 
congenital malformation, in which the longitudinal cavity in the cord 
is at some period lined with epithelial cells. Syringomyelia has also 
been confused with hsematomyelopore. 
There seems, furthermore, to be a class of lesions of the cord, usually 
classed as syringomyelia, in which cavities of various forms coexist with 
a tumor in the vicinity of the central canal. But these cavities do not 
appear to be formed by a breaking down of the tumor tissue, but in some 
other way as yet little understood. 
Tumors of Nerves. 
The tumors of the nerves may be divided into those consisting largely 
of or containing new'-formed nerve tissue, true neuromata, and the 
so-called false neuromata, which are for the most part fibromata or myxo- 
mata originating in the connective tissue of the nerve (see Neuroma). 
Myxo-sarcomata are less common, and primary sarcomata rare. The 
nerves may be secondarily involved in sarcomata, or in carcinomata 
through which they pass, though not infrequently nerves pass through 
these tumors without being in the least involved in their peculiar struc- 
ture. Paltauf has described as endotheliomata rare tumors of the glan- 
dula carotica. 
Cysticercus and more rarely echinococcus occur in the brain. 
PARASITES. 
Larger or smaller holes may be found in the brain tissue from dilata- 
tion of the perivascular lymph-spaces, or well-formed cysts may exist 
as a result of haemorrhage, inflammatory softening, hydatids, etc. 
HOLES AND CYSTS IN THE BRAIN. 
PoRENCEPHALUS 
is a term which has had a wide range of application to various defects of 
the brain substance. By some writers the term has been used to cover 
almost any congenital absence of brain tissue. By others, brain defects 
not congenital are included. Its most common application is to certain 
quite well defined congenital conditions in which there is an absence of a 
considerable portion of one or both hemispheres. These holes may lie 
deep in the substance of the brain. More commonly they come to the 
surface making conical depressions in the cortex, which the dura mater 
bridges over, but into which the pia extends. There may or may not be 
communication with the ventricles. This condition may coexist with 
various mental aberrations, hydrocephalus, etc. Similar defects may 
occur in the cerebellum. 980 
THE NERVOUS SYSTEM 
Pineal Gland. 
This little body, about the size of a cherry stone, is composed of con- 
nective tissue enclosing cavities which are filled with reticulated tissue 
and round cells. The cavities often contain brain sand. 
A small number of tumors belonging to the class of teratoma have 
been described as originating in the pineal gland.1 
Weigert describes a tumor, about 3.5 centimetres in diameter, com- 
posed of epidermis, hair follicles, hair, sebaceous glands, cartilage, fat, 
smooth muscle, and cylindrical epithelium. 
Falkson describes a chondro-cysto-sarcoma, 5.8 centimetres in 
diameter, which apparently originated in the pineal gland. 
Turner describes a tumor of the pineal gland, projecting into the 
third ventricle and the left lateral ventricle, of the size of a kidney. The 
tumor was composed of fusiform cells, of nerve-ganglion cells, of tubules 
and acini lined with cylindrical epithelium, and of more irregular spaces 
filled with large polygonal cells. 
Coats describes a tumor, three inches in diameter, growing into the 
third ventricle, the aqueduct of Sylvius, and the fourth ventricle. It 
was composed of fusiform cells, of tubules lined with cylindrical epi- 
thelium, of irregular masses of epithelium, of cartilage, and of smooth 
muscle. 
Hypertrophy with cystic degeneration may occur. 
Haemorrhage into the substance of the gland has been described. 
Hypophysis Cerebri. (The Pituitary Body.) 
This organ consists of three lobes: an anterior, of epithelial cells and 
blood vessels; an intermediary, of epithelial cells and neuroglia; and a 
posterior, of neuroglia cells and fibers. The cells of the anterior lobe 
are basophile or chief cells, and eosinophile or cromophilic cells. 
Tumors.-Weigert2 describes a tumor, as large as a hen's egg, which 
resembled in its structure the normal anterior lobe of the pituitary body, 
and which he regards as a hypertrophy of that body. Weigert also 
describes a gummy tumor of the pituitary body as large as a hazelnut. 
Weichselbaum describes an adenoma of the pituitary body as large as a 
pigeon's egg, closely resembling the structure of the normal anterior lobe 
of this body; a small lipoma; and a pituitary body with colloid cysts, 
lined with ciliated epithelium.3 
Methods of Preparation of Nerve Tissue for Microscopical Study. 
The general methods of hardening will be found in Part III. For minute study 
there is no one method of staining and mounting upon which we can rely exclusively 
for the study of all lesions. A preliminary examination of areas of inflammatory 
1 For study, with bibl., of tumors of the pineal gland see Bailey and Jelliffe, Arch. Int. Med., 
1911, viii., 851. See also resume of Dana and W. N. Berkeley, Med. Record., 1913, Ixxxiii., 835. 
2 Weigert, Virch. Arch., Bd. Ixv., p. 219, 1875. 
3 For an extended study of tumors of the hypophysis see monograph of Erdheim, Sitzungsber. d. 
kais, Akad. d. Wiss. in Wein, Math.-naturw. KL, Bd. cxiii. Abth., 3, 1904; also Cushing, Pituitary Body 
and Its Disorders, 1912. THE NERVOUS SYSTEM 
981 
softening, or of the disintegrated tissue in apoplectic clots, or of the new-formed tissue 
in chronic haemorrhagic pachymeningitis interna, may be made by teasing portions 
of the affected tissues in 0.5-per-cent. salt solution. Or the tissues in these lesions, 
or in any others in which fatty degeneration is suspected, may be placed for twenty- 
four hours in 1-per-cent. aqueous solution of osmic acid, and then washed and teased 
in glycerin. In this way the myelin and the fat will be stained brown or black. 
Secondary and other degenerations of medullated nerves may be studied by soaking 
the nerves for twenty-four hours in 1-per-cent. solution of osmic acid, and then staining 
with picrocarmine and teasing and mounting in glycerin. 
To demonstrate the presence of miliary aneurisms in or about apoplectic clots, it 
is usually necessary to macerate the brain tissue in water until the nerve elements dis- 
integrate, and they may then be washed away under a stream of water, leaving the 
blood-vessels with their aneurisms exposed. 
Marchi's Method.-For studying early stages of degeneration in medullated nerve 
fibres this method is invaluable. It depends upon the fact that while myelin and fat 
both stain black when the fresh nerve fibres are placed directly into osmic acid, a pre- 
liminary soaking in a solution of potassium bichromate so affects the tissue that the 
myelin sheaths of normal fibres no longer impregnate with osmium, the fat droplets 
alone staining. 
Tissues are first hardened from one to three weeks in Muller's fluid, or simply in a 
2- or 3-per-cent. aqueous solution of potassium bichromate. They are then trans- 
ferred to a mixture of 1-per-cent. aqueous solution of osmic acid one part, Muller's 
fluid two parts, where they remain from three days to a week. 
By following the lines of fat droplets, degenerative changes in nerve fibres may be 
traced either in the peripheral nerves or in the central nervous system. 
Eosin-Haematoxylin Staining.-Suppurative inflammation of the central nervous 
system and its membranes, or the connective-tissue changes in general, may be studied 
in sections from the tissues hardened in Muller's fluid and alcohol, stained double with 
haematoxylin and eosin (see p. 1035), and mounted in Canada balsam. 
Weigert's Method.-A very useful method of staining sections of nerve tissue, espe- 
cially of the brain and cord, is that known as Weigert's haematoxylin method. The 
tissue is first well hardened in Muller's fluid. 
Blocks of the hardened tissue are embedded in celloidin and sections made in the 
usual way. The sections are first soaked for twenty-four hours in a saturated aqueous 
solution of neutral cupric acetate diluted with an equal bulk of water, or, if the mate- 
rial has been kept some time and takes the haematoxylin stain with difficulty, a better 
result is often obtained by soaking the sections for from twelve to twenty-four hours 
in a 3- to 5-per-cent. aqueous solution of bichromate of copper before staining. They 
are now thoroughly washed twice in water, then in alcohol, and then are transferred 
to the haematoxylin solution, made as follows: 
Haematoxylin crystals. 1 gm. 
Alcohol, 97 per cent 10 c.c. 
Water 90 c.c. 
Saturated aqueous solution lithium carbonate 1 c.c. 
In this solution the sections remain for two hours. (If the finer fibres of the cere- 
bral cortex are to be brought out, the sections must remain for twenty-four hours in 
the haematoxylin solution.) The sections are now thoroughly washed in two or three 
waters and transferred to the bleaching solution, composed as follows: 
Potassium ferricyanide 2.5 gm. 
Sodium biborate 2 gm. 
Water 200 c.c. 
In this fluid the sections discharge a brownish color, and they remain in it until the 
gray matter has a distinct yellow color and the white matter is bluish black. The 
time required to produce this effect varies considerably, and is usually from half an 
hour to an hour. The sections are now washed, dehydrated with alcohol, cleared up 
in oil of cloves or oil of origanum, and mounted in balsam. The sections may be 982 
THE NERVOUS SYSTEM 
stained in alum carmine before dehydration, to bring out the nuclei. In sections 
stained by this method the gray matter, connective-tissue elements, and ganglion 
cells have a yellow or yellowish brown color, the axis cylinders are uncolored or have 
a slight yellowish tint, while the medullary sheaths are bluish black or black. 
Nissl's Staining Method.-There are several variations of this method, but the 
following gives good results in most cases: 
The essential feature of the so-called Nissl's method is the application of the anilin 
dyes to the staining of certain structural elements in the nucleus and cytoplasm, which 
are distinguished from the other structures of the cell by a differentiating decoloriza- 
tion with alcohol. 
Methylene blue is the most generally useful of the anilin dyes for this purpose. 
The specimens should have been carefully hardened in sublimate solution or in 
alcohol or in formalin. 
Very thin sections are stained in 1-per-cent. solution of methylene blue. The 
staining may be effected on a slide on which the sections are floating in the blue solu- 
tion by gently heating over a lamp until the fluid steams. 
The sections are now transferred to a mixture of absolute alcohol 90 parts, with 
anilin oil 10 parts, in which the differentiation is effected by the use of successive fresh 
portions of fluid until slight but distinct differentiation in color is seen between the 
gray and white matter of the nerve tissue. The exact degree of decolorization which 
gives the best pictures will be learned by practice of the method. In most cases the 
use of alcohol alone without anilin oil is preferable to the mixture, and in any case 
the sections should always be washed in strong, pure alcohol before passing on to the 
xylol. The sections are now freed from the bulk of the alcohol upon the slide, cleared 
in xylol, and mounted in dammar varnish, in which the color is apt to be preserved 
better than in balsam. By this procedure the chromophilic bodies in the cytoplasm of 
ganglion cells are sharply differentiated, and thus abnormal conditions may be detected 
in them (see Plate XIII.). 
A contrast stain with erythrosin (Held1) is useful in demonstrating cell structures 
which are not visible with the simple Nissl staining. This may be secured as follows: 
The sections are first warmed from one to two minutes in the following solution: 
erythrosin, gm. 1; acetone, gtt. ij.; aqua dest., 150 c.c. They are then washed thor- 
oughly in water and transferred to a solution consisting of equal parts of Nissl's methyl- 
ene-blue solution and a 5-per-cent. aqueous solution of acetone. In this they are 
warmed until the odor of acetone ceases to be given off. The sections are decolorized 
in a 0.1-per-cent. solution of alum until they appear red in color, and are then 
dehydrated in alcohol and cleared and mounted in the usual way. 
1 Held, Arch. f. Anat, und Phys., Anat. Abt., 1895, p. 396, 1897, p. 204. PART III. 
THE METHOD OF MAKING POST-MORTEM EXAMINATIONS: 
AND THE METHODS OF PRESERVING AND 
EXAMINING PATHOLOGICAL TISSUES CHAPTER I. 
THE METHOD OF MAKING POST-MORTEM 
EXAMINATIONS. 
General Considerations. 
The object in making a post-mortem examination may be to deter- 
mine whether a person has died from violence or poisoning; to account 
for a sudden death; or to study the lesions of disease. In any case the 
examination should include all the important parts of the body, not 
merely a suspected organ, and the results should be recorded at the time 
the examination is made. 
Great care is necessary in endeavoring to ascertain the cause of death 
w'hen the clinical history is imperfect or unknown. Mechanical injuries 
which destroy life by abolishing the function of one of the important 
viscera, are relatively infrequent. Most of the lesions found after death 
are rather the marks of disease than the cause of death. We do not 
know, for example, how great a degree of meningitis, or of pneumonia, 
or of endocarditis, or of cirrhosis, or of nephritis necessarily leads to 
death. On the contrary, one patient may recover with an extent of 
lesion which is sufficient to destroy the life of another. So with acci- 
dents; there is often no evident reason why fractures of the skull or of 
the pelvis should destroy life, yet they usually do. In some of the infec- 
tious diseases, such as typhoid fever, the visible lesions cannot always 
be called the cause of death. Sudden deaths of persons apparently in 
good health are often particularly obscure. In many of them we have 
to acknowledge that wre can find no sufficient cause for the death. This 
is of course due to our imperfect knowledge, but it is much better in 
such cases to avow ignorance than to attribute the death to some trifling 
lesion. The brain and the heart are the organs which are especially capa- 
ble of giving symptoms during life, without corresponding lesions after 
death. Very well-marked cardiac or cerebral symptoms may continue 
for days or months, and apparently destroy life, and yet after death 
we find no corresponding anatomical changes.1 But it should be remem- 
bered that recent advances in our knowledge of the cell, which an 
improved technique in hardening and preparation has greatly fostered, 
have already shown that under various abnormal conditions the cells, 
especially of the nervous system, may undergo morphological changes of 
great significance, without perceptible alteration in the gross appearance 
of the affected part, changes which even the microscopical examinations 
of the past have failed to disclose. So that while there often appears to 
be a wide discrepancy between symptoms and lesions, with the increase 
1 See Sudden Death, p. 446. 
985 986 
MAKING POST-MORTEM EXAMINATIONS 
of knowledge the scope of this discrepancy is steadily narrowing. It is 
the novice in post-mortem examinations who is particularly apt to mis- 
take for lesions ordinary post-mortem alterations or the effects of 
embalming processes. 
The cause of death is not always to be found in the organ primarily 
affected or which shows the most pronounced lesions. Thus chronic dif- 
fuse nephritis may exist for years with more or less marked symptoms of 
disease. But death may finally be due to a weakened heart which was 
secondarily involved, or occur in uraemic convulsions, the brain showing 
no lesions at all. It is desirable, therefore, and in the majority of cases 
possible, to differentiate between obvious lesions and. the cause of death. 
External Inspection. 
Before commencing the examination of the internal viscera an inspec- 
tion should be made of the external surface of the body. The minute- 
ness of this inspection will depend upon the character of the case. In 
the case of an unknown person, or of one suspected to have died from 
unnatural causes, it is necessary to search for and record not only all 
contusions, wounds, etc., their size, situation, and condition, but also 
deformities from disease and any physical peculiarities of hair, eyes, 
teeth, moles, etc., by which the person may be identified. In such cases 
it is well, if possible, to photograph, weigh, and measure the body. In 
cases of doubtful identity it is sometimes wise to make a wax or plaster 
cast of the outside of the teeth and jaws. In ordinary examinations we 
note the general nutritive condition of the body, and look for evidences 
of external injury, for skin diseases, ulcers, oedema, gouty deposits, 
abscesses, enlarged lymph-nodes, etc. The external organs of generation 
should be searched for syphilitic lesions. 
It is well to weigh the body, since the significance of the weight of 
the individual organs is often closely dependent upon the relationship 
of their weight to that of the entire body. 
Cadaveric Lividity.-It is usual to find certain changes in the exter- 
nal appearances of the body, which are due to the cessation of life and 
the commencement of decomposition. We speak now of bodies which 
have not been buried, but which have been kept in the ordinary way, 
lying on the back, and loosely covered with a shroud or dressed with the 
ordinary clothing. 
After life becomes extinct, and before the blood coagulates, it changes 
its position chiefly in two ways: first, it is driven by their contraction 
out of the arteries into the veins; second, it settles in the veins and 
capillaries of the more dependent parts of the body, inducing usually 
within a few hours after death a mottling of the surface with irregular 
livid patches. These patches may coalesce, forming a uniform dusky 
red color over the back of the trunk, head, and extremities, and some- 
times over the ears, face, and neck. The same effect is observed on the 
anterior aspect of the body if it has lain on the face. At points of pres- 
sure, from folds in the clothing, or from the weight of the body on the 
table, the red color is absent or less marked. These changes occur MAKING POST-MORTEM EXAMINATIONS 
987 
before putrefaction sets in. This cadaveric lividity or hypostasis should 
not be mistaken for ante-mortem ecchymosis, from which it may usually 
be readily distinguished by its position and extent, by the fact that the 
surface of the skin is not elevated, and by the fact that on incision no 
blood is found free in the interstices of the tissues. Not infrequently 
the subcutaneous tissue in the vicinity of these post-mortem hypostases 
becomes infiltrated with reddish serum. Very soon after death, particu- 
larly in warm weather, the tissues immediately around the subcutaneous 
veins of the neck and thorax, and in other situations, may become 
stained of a bluish red color from the decomposition and escape from 
the vessel of the coloring matter of the blood. If the epidermis has 
been detached at any point, the skin beneath soon becomes dry and 
brown. 
Putrefactive Changes.-Usually in from one to three days, depending 
upon circumstances, a greenish discoloration of the skin appears, at first 
upon the middle of the abdomen, over which it gradually spreads, assum- 
ing a deeper hue and often changing to a greenish purple or brown. 
Greenish patches may now appear on different parts of the body, earliest 
upon those overlying the internal cavities; this discoloration is probably 
produced by the action on the haemoglobin of gases developed by decom- 
position. The eyeballs now become flaccid, and if the eyelids are not 
closed the conjunctiva and cornea become brown and dry. The pressure 
of gases developed by decomposition in the internal cavities not infre- 
quently forces a greater or less quantity of frothy, reddish fluid or mucus 
from the mouth and nostrils, distends the abdomen, and, if excessive, 
may lead to changes of position of the blood in the vessels, and even a 
moderate amount of displacement of the internal organs.1 
After a varying period, sometimes within five or six days, the entire 
surface of the body may be discolored, green or brown. Then the epi- 
dermis may become loosened by the accumulation of gases and fluids 
beneath and the tissues become flaccid. The abdomen may be greatly 
distended and the features distorted from swelling. The rapidity with 
which these changes occur depends upon various conditions. Thus an 
elevated temperature and the presencce of air and moisture hasten the 
advent and progress of putrefaction. 
The bodies of infants usually decompose more rapidly than those of 
adults, fat bodies more quickly than lean ones. The infectious diseases, 
intemperance, and the puerperal condition promote rapid decomposition, 
as does also death from suffocating gases. Poisoning by arsenic, alcohol, 
antimony, sulphuric acid, strychnin, and chloroform may retard the 
progress of decomposition. Burial in dry soil and submersion in water 
also retard the progress of decay.2 
1 In cases with the early and marked formation of gas in the tissues and organs, especially in the 
liver, the possibility of infection with Bacillus aerogenes capsulatus should be borne in mind. See 
p. 289. 
2 For a study of bacteria in the blood of the cadaver see Ottolenghi, Vierteljahresschrift. f. gerichtl. 
Medicin, Bd. iv., SuppL; see also Babes, "Les maladies infectieuses en medecine legale," Annales 
d'Hygiene Publique, t. xli., p. 193, 1899. 
Concerning the conversion of the body into adipocere see Ewing, Peterson and Haines' "Text- 
book of Legal Medicine," vol. i., p. 138; see also Ascarelli, Vierteljahresschrift f. gerichtl. Med. xxxii., 
p. 219, 1906; and Muller, Post-mortem Decomposition, etc., Zurich, 1913. 988 
MAKING POST-MORTEM EXAMINATIONS 
Cooling of the Body.-After death the chemical changes upon which 
the maintenance of the temperature depends rapidly diminish, and the 
body gradually cools to the temperature of the surrounding medium. 
This usually occurs in from about fifteen to twenty hours, but the time 
required depends upon a variety of conditions. Immediately after death 
there is, in nearly all cases, a slight elevation of internal temperature, 
owing to the fact that the metabolic changes in the tissues still continue 
for a time, while the blood ceases to be cooled by passing through the 
lungs and peripheral capillaries. After death from certain diseases- 
yellow fever, cholera, rheumatic fever, and tetanus-a considerable ele- 
vation of internal temperature has been repeatedly observed. The time 
occupied by the cooling of the body may be prolonged after sudden death 
from accidents, acute diseases, apoplexy, and asphyxia. A number of 
cases are recorded in which the body retained its heat for several days, 
without known cause. 
After death from wasting chronic disease, and in some cases after 
severe hsemorrhages, the cooling of the body is very rapid, the internal 
temperature being reduced to that of the surrounding air within four or 
five hours. Fat bodies cool less quickly than lean ones, the bodies of 
well-nourished adults less quickly than those of children or old persons. 
The temperature of the surrounding medium, and the degree of protection 
of the body from currents of air, of course, modify the progress of cool- 
ing; and the internal organs naturally retain their heat longer than the 
surface of the body. The rate at which cooling occurs is most rapid, as 
a rule, during the hours immediately following death, notwithstanding 
the post-mortem rise which may ensue. 
It will thus be seen that, if required to pronounce upon the time 
which has elapsed since death in a given case, we can do so only approxi- 
mately. It is necessary to take into account all of the above-mentioned 
conditions which modify the rate of cooling of the body, and then we 
may be able to state only the probabilities of the case. It is furthermore 
unsafe in any case to infer the cause of death from the rate of cooling of 
the body. 
Rigor Mortis.-Death is usually succeeded immediately by a period of 
complete muscular relaxation. The jaws drops and the limbs become 
flaccid. The muscles may retain for two or three hours, however, the 
capacity of contracting, on the application of appropriate stimuli. On 
the average, within six hours the muscles become firm and rigid. This 
post-mortem rigidity is called rigor mortis. On the occurrence of the 
rigor mortis the muscles becomes fixed in whatever position they may 
have had at the time of its occurrence. It usually begins in the muscles 
of the eyelids, extends to those of the back of the neck and lower jaw, 
then to the face and neck, and thence passing downward affects the mus- 
cles of the thorax and lower extremities. It usually disappears in the 
same order. Although commencing on the average six hours after death, 
it may set in at once or be delayed for twenty-four hours or more. It 
may pass off very rapidly, in rare cases in from one to three hours; or 
it may persist for two or three weeks or longer. It may be said in gen- MAKING POST-MORTEM EXAMINATIONS 
989 
eral that the average time of its disappearance is within twenty-four or 
forty-eight hours after its occurrence, depending on temperature, its 
intensity, the mode of death, the period of its advent, etc. Caspar 
states that in foetuses before term he has never observed rigidity, and 
that in young children it is feeble and of short duration. Its occurrence 
and phenomena may be in some cases of the highest medico-legal impor- 
tance; but its careful observation does not, with our present knowledge 
of its significance, appear essentially to further the aims of the practical 
pathologist.1 
Contusions.-It is often important to determine whether violence has 
been inflicted upon a body before death. In regard to this point, we 
must remember, first, that blows and falls of sufficient violence to fracture 
bones and rupture the viscera may leave no marks on the skin, even 
though the person has survived for several days; and, second, that there 
are post-mortem appearances which simulate ante-mortem bruises. A 
severe contusion during life may present, at first, no mark or only a 
general redness. After a short time the injured part becomes swollen 
and of a red color; this color may be succeeded by a dark blue, and this 
in turn fade into a greenish yellow or yellow; these later appearances 
are due to an escape of blood from the vessels and to a subsequent decom- 
position of haemoglobin. If therefore we cut into such an ecchymosis 
after death, we find extravasated blood or the coloring matter of the 
blood, in the form of pigment granules, free in the tissues. Post-mortem 
discolorations, on the other hand, although their external appearance 
may resemble that of ante-mortem ecchymosis, are not formed by an 
extravasation of blood, but by a circumscribed congestion of the vessels 
or by an escape of blood-stained serum. If w'e cut into such discolor- 
ations, therefore, we find no blood outside the vessels. Care should 
be taken not to mistake the lesions of haemorrhagic infection for trau- 
matic ecchymoses. 
Blows on the skin of a body which has been dead for not more than 
about two hours may produce true ecchymoses with extravasation of 
blood, such as can be distinguished with great difficulty or not at all 
from those formed during life. If putrefactive changes be present, the 
difficulty of distinguishing between ante-mortem and post-mortem bruises 
is greatly enhanced. 
Hanging and strangulation are attended with the formation of marks 
on the neck which are described in works on forensic medicine. These 
marks must not be confounded with the natural creases of the skin of 
the neck. Many adults during life have creases of the skin of the neck, 
one or more in number, running downward from the ear under the chin 
or encircling the neck. After death these creases may be much more 
evident than during life, and may be rendered more decided by the posi- 
tion of the head and the freezing of the body. They usually persist 
until the skin putrefies. 
1 For further details concerning rigor mortis, putrefactive changes, particularly the later stages, 
and the phenomena of cooling of the body, see Tidy, "Legal Medicine," vol. i., or other works on medical 
jurisprudence. 990 
MAKING POST-MORTEM EXAMINATIONS 
Wounds.-We should notice the situation, extent, and direction of a 
wound, the condition of its edges and the surrounding tissues. If it be 
a deep, penetrating wound, its course and extent should be ascertained by 
careful dissection rather than by the use of a probe. 
If the edges of a wound be inflamed and suppurating, or commencing 
to cicatrize, it must have been inflicted some time before death. In a 
wound inflicted a short time before death, the edges are usually everted; 
there may be more or less extravasation of blood into the surrounding 
tissues, and the vessels contain coagula; but sometimes none of these 
changes are observed. The chief characteristics of a wound inflicted 
after death are absence of a Considerable amount of bleeding, non- 
retraction of the edges, and the absence of extravasation of blood into the 
tissues. But a wound inflicted within two hours after death may 
resemble very closely one received during life. In general, unless a 
wound is old enough for its edges to present inflammatory changes, 
we must be very careful in asserting its ante-mortem or post-mortem 
character. 
Fractures.-It may be important to determine whether a bone was 
fractured before or after death. This point cannot always be decided. 
Fractures inflicted during life are, as a rule, attended with more extrava- 
sation of blood and evidences of reaction in the surrounding tissues; but 
fractures produced within a few hours after death may resemble these 
very closely. Usually a greater degree of force is necessary to fracture 
bones in the dead than in the living body. 
Scars and Tattoo Marks.-The presence and character of cicatrices 
should be noticed. Scars produced by any considerable loss of substance 
may become very much smaller and less conspicuous, but never entirely 
disappear. Slight and superficial wounds, however, leave marks which 
may not be permanent. The discoloration produced by tattooing may, 
although it rarely does, disappear during life. 
Internal Examination.1 
After completing the external inspection of the body, we commence 
the internal examination. In order that this examination may be made 
both thoroughly and rapidly, we should follow a regular method. The 
method should be such as will enable us to examine the relations of parts 
to one another, without seriously disturbing them, and to remove and 
inspect the organs in such an order and manner as will not interfere with 
the examination of parts which are to follow. In certain cases it may 
be necessary to depart from the regular method;2 but, as a rule, the 
following plan will be found most advantageous. 
It is important to remember the difference between the distribution 
of the blood in the body during life and after death. During life the 
1 For sizes and weights of various organs, and other data, see Vierordt's "Anatom. Physiol, und 
Physikalische Daten u. Tabellen," 3d ed., 1906. For a study of the weights of the viscera in infancy 
and childhood see Bovaird and Nicoll, Arch, of Pediatrics, vol. xxiii., p. 641, 1906. 
2 Sometimes the thoracic or abdominal viscera or both together may wisely be taken out in mass. 
See for advantages of this method Heller, Vierteljahrssch. f. gerichtl. Med., Bd. xxvii., p. 110. MAKING POST-MORTEM EXAMINATIONS 
991 
blood is in constant motion and is distributed in a regular way in the 
heart, capillaries, arteries, and veins. Inflammations and obstructions 
to the circulation may disturb this natural distribution and produce con- 
gestion of particular parts of the body. After death the blood ceases to 
circulate; it leaves the left cavities of the heart, the arteries and capil- 
laries, and collects in the veins and the right cavities of the heart. Ac- 
cording to the character of the disease which causes death, coagulation 
of the blood takes place more or less extensively and at an earlier or 
later period. The local congestions which existed during life often dis- 
appear after death. On the other hand, local congestions are found after 
death which did not exist during life. Thus, after death the scalp often 
contains a large amount of venous blood. The veins of the pia mater 
and the sinuses of the dura mater may be filled with blood. The mucous 
membrane of the larynx and trachea may appear to be deeply congested. 
The lungs are congested if the patient has been comatose for some hours 
before death. All the tissues of the back and the membranes of the 
spinal cord are often gorged with venous blood. The right auricle and 
ventricle of the heart may contain fluid or clotted blood in considerable 
quantity. 
THE HEAD. 
The scalp is divided by an incision across the vertex, from ear to ear. 
The flaps are dissected forward and backward, taking up the temporal 
muscles with the skin and leaving the pericranium attached to the bone. 
The internal surface of the scalp and the pericranium are to be searched 
for ecchymoses and inflammatory lesions. 
A circular incision is now made through the cranium with a saw. 
The incision should, in front, pass through a point about three and one- 
half inches above the bridge of the nose; behind, through the occipital 
protuberance. Care should be taken not to cut through the dura mater 
with the saw. When the roof of the cranium is thus entirely loosened, 
a stout hook is introduced under the upper edge of the calvarium, and 
this is wrenched off with a jerk. 
Sometimes the dura mater is so firmly adherent to the calvarium that 
the latter cannot be torn from it without injury to the brain. In this 
case, and also if the dura mater should have been accidentally cut 
through by the saw in making the circular incision, the dura mater may 
be cut through at the level of the cranial incision, and the brain removed 
with the calvarium and separated afterward. Or, which is better, in 
addition to the circular incision, a longitudinal incision is made, from 
front to back, about three-quarters of an inch to one side of the median 
line of the skull, and a segment of bone removed. The knife blade may 
now be inserted from the open side, and the dura cut away from the 
skull-cap along the line of the longitudinal sinus, where the adhesions are 
apt to be most firm. 
We should notice whether or not the calvarium is symmetrical. The 
cranial bones increase in size by a growth of bone at the edges of the 992 
MAKING POST-MORTEM EXAMINATIONS 
sutures. If any suture becomes completely ossified and closed prema- 
turely, the bones will be unequally developed. The thickness and density 
of the cranial bones vary considerably within the limits of health. There 
are often deep depressions on the inner surface of the skull along the 
sagittal suture, caused by the pressure of the Pacchionian bodies , and of 
no pathological significance. We should observe the blood content of 
the bone, determine the existence or absence of fractures, inflammatory 
lesions, exostoses, etc. 
The dura mater is now exposed. It is more or less adherent to the 
calvarium; a moderate amount of adherence, especially in old persons, 
does not denote disease. Very extensive and firm adhesions are usually 
produced by inflammation. Near the median line the Pacchionian bodies 
often project through the dura mater and may produce indentations in 
the internal surface of the calvarium. We must look for clots and for 
tumors and for inflammatory lesions on the external surface of the dura 
mater. The longitudinal sinus should be laid open and its contents 
examined. A circular incision is then made through the dura mater in a 
line corresponding to the cranial incision; the falx is divided between 
the anterior lobes of the brain, and the entire membrane drawn back. 
We should observe the existence of abnormal adhesions of the dura mater 
to the pia mater, bearing in mind that a moderate amount of adhesion 
along the longitudinal fissure is normal. The internal surface of the 
dura mater is to be examined for the products of inflammation and for 
tumors. 
The pia mater covering the convex surface of the brain is now 
exposed. The degree of congestion, and the existence of serum, pus, or 
blood, beneath, within, or upon it, are now to be ascertained before the 
brain is removed. The pia mater in old persons frequently loses its 
transparency and becomes thick and white; this change is most marked 
along the longitudinal fissure and large vessels. Marked and general 
thickening of the pia mater is the result of chronic inflammation. Along 
the longitudinal fissure, and sometimes at a considerable distance from it, 
we usually find small, elevated, whitish nodules, which are the Pacchio- 
nian bodies and are normal in the adult. 
The amount of serum beneath the pia mater varies. A considerable 
amount, especially in cachectic persons, may exist without brain disease. 
Clear serum, raising the pia mater and separating the convolutions of the 
brain, may be simply dropsical or due to chronic meningitis. Turbid 
and purulent serum, beneath and in the pia mater, is due to acute or 
chronic meningitis. The degree of flatness of the surface of the convo- 
lutions should be observed before removing the brain; for, when marked, 
it affords an important indication of pressure, from haemorrhage, inflam- 
matory products, internal fluid effusions, and tumors. The pia mater 
should be carefully examined for miliary tubercles. 
The Brain.-After examining the convex surface of the brain, the 
anterior lobes of the cerebrum are to be pulled gently backward, the 
nerves, vessels, and tentorium severed, and the medulla cut squarely 
across, as low' down as possible. The brain is now removed from the MAKING POST-MORTEM EXAMINATIONS 
993 
cranium by passing the fingers of one hand down, beneath, and behind 
the lobes of the cerebellum, and drawing the brain out, supporting the 
convexity with the other hand. 
The adult brain in the male weighs on the average about 1,400 grams; 
that of the female, about 155 grams less. The average proportional 
weight of the brain to that of the body is about one-forty-fifth, although 
in this, as in the absolute weight, there is considerable variation.1 
The exact situation of any lesion which is apparent externally should 
be described by its relation to the lobes, fissures, convolutions, and sulci 
(Fig. 678). . 
The brain is first laid upon its convex surface, and the anterior, mid- 
dle, and posterior cerebral arteries, as well as the basilar and the carotids, 
Fig. 678.-Side View of the Human Brain, Showing its Fissures and Convolutions. 
are to be examined for emboli, thrombi, atheroma, and aneurisms. 
Evidences of extravasations of blood, tumors, and inflammatory lesions 
are now to be looked for. The brain is next turned over on to its base. 
An incision is made through the pia mater, over the convex surface of 
the cerebrum. The membrane is stripped up, and its adherence to the 
brain and its thickness are noted. 
The more common method of opening the brain is as follows: The 
halves of the cerebrum are to be separated until the superior surface of 
the corpus callosum is exposed (Fig. 679). A longitudinal incision is 
made through the junction of the corpus callosum and the cerebrum, and 
downward into the ventricle. The incision should be made carefully, so 
as not to cut through the ventricle into the ganglia below. The incision 
1 For a study of the weight of the brain at various ages see Handmann, Arch. f. Anat. u. Phys., 
Anat. Abth., Jahrg. 1906, p. 1 994 
MAKING POST-MORTEM EXAMINATIONS 
thus made through the roof of the ventricle is prolonged backward and 
forward in the direction of the cornua, so as to expose the entire ventri- 
cle. A longitudinal incision is then made outward and backward into 
the hemisphere, from the outer edge of the lateral ventricle nearly to 
the pia mater. A second incision is then made through this cut surface 
outward, and this is repeated until the hemisphere is divided into a 
number of long, prism-shaped pieces, held together by the pia mater 
Fig. 679.-Method of Opening the Brain, Showing the Direction of First Incision. 
and a small portion of the cortex. The brain is now turned around so 
as to bring the other hemisphere under the hand, and the operation is 
repeated on the other side. 
The size, shape, and contents of the ventricles should be noticed, and 
the thickness and appearance of the ependyma. 
The fornix and the central portion of the corpus callosum are cut 
across by passing the point of the knife through the foramen of Munro 
and cutting upward. They are then drawn backward, one of the pos- 
terior cornua of the fornix being severed and laid to one side. The MAKING POST-MORTEM EXAMINATIONS 
995 
velum interpositium and the choroid plexus are now dissected up, the 
blood contents and the general appearance noted, and the third ventricle 
examined. Not infrequently small cysts of the choroid are found, which 
seem to have little or no pathological significance. 
The fourth ventricle is now opened by a longitudinal incision through 
the vermiform process. Each hemisphere of the cerebellum is divided 
first into two parts, by an incision through the upper and inner convex 
border, and then each segment is further divided by incisions in the same 
direction. 
Thin transverse sections are now made through the cerebral ganglia, 
commencing in front (Fig. 680). The ganglia are supported, and the sec- 
Fig. 680.-Method of Opening the Brain, Showing the Unfolded Segments of the Cere- 
brum and Lines of Transverse Incision of the Basal Ganglia and Directions of the Incisions 
of the Cerebellum. 
tions caused to fall apart as they are cut, by carrying the fingers of one 
hand under the brain, and gently lifting the ganglia at points just 
beneath where the sections are made. It is important to observe the 
exact position of any lesion which may be discovered in the cerebral 
ganglia, their relations to the external and internal capsule and to the 
caudate and lenticular nuclei. 
Finally, the segments of the cerebrum and cerebellum are folded up 
together into their original positions, the whole is turned over on to the 
vertex, and thin sections are made through the medulla. Small clots in 
the medulla should not be overlooked. 
In case of the discovery of apoplectic clots, areas of softening, etc., 
either in the hemispheres or in the basal ganglia, after their location and 996 
MAKING POST MORTEM EXAMINATIONS 
extent are determined, they should be carefully searched for lesions of 
the blood-vessels, minute aneurisms, areas of degeneration, and rup- 
tures. For this purpose it may be necessary to allow a stream of water 
to run over the affected portion, so as to wash out the brain substance 
Fig. 681.-Schematic Picture of Brain, Showing the Method of Dissection from the Base 
(Meynert's method). 
E and F, Temporal lobes turned backward and outward; AB, AC, BD, line of incision to remove basal 
piece. 
and expose the vessels. In some cases the blood-vessels are best exposed 
by macerating the brain tissue at the seat of the lesion for some hours 
in water, and then washing out the brain substance under the faucet. 
While the above mode of dissecting the brain gives a very complete 
view of the seat and extent of lesions in 
general, when a more exact localization of 
lesions with a microscopic examination is to 
be made, the following-called Meynert's 
method-is a better method of opening the 
brain: 
After completing the external examina- 
tion, as detailed above, the brain is laid on 
its vertex, the cerebellar end toward the oper- 
ator. The cerebellum is raised by the fingers 
of the left hand, and the pia cut through along 
the sides of the corpora quadrigemina, around 
the crura and along the inner margins of the 
temporal lobes, to the middle cerebral artery 
on both sides (Fig. 681). Then, raising the 
temporal lobes, in turn, by their apices, the pia is cut through along the 
course of the middle cerebral artery into the Sylvian fissure, and along 
the course of its posterior branch to its end. Now, drawing the temporal 
lobes one after the other upward and outward, their junction with the 
Fig. 682.-The Brain Axis 
Separated from the Brain 
Mantle, as Seen from Above. MAKING POST-MORTEM EXAMINATIONS 
997 
base is cut, the knife being held horizontally so as not to injure the 
basal ganglia until the descending horn is opened. The point of the 
knife being in the descending horn, the incision through the brain sub- 
stance then passes outward and backward well into the posterior horn, 
thus partially severing the lateral surface of the brain, the junction of 
the occipital and temporal lobes. The temporal lobes are then turned 
outward and backward (Fig. 681). 
The operculum is now pulled well outward, completely exposing the 
island of Reil, and a slightly curved transverse incision is made, deep 
enough to pass into the anterior horns of the ventricles, connecting the 
anterior sulci of the island of Reil (Fig. 681, A, B). 
Fig. 683.-The Brain Mantle, as Seen from Below 
A, Internal capsule; B, operculum; C, posterior border of corpus callosum; D, descending horn; E, 
cornu ammonis. 
Now raising the cerebellum and inserting the point of the knife into 
the ventricle, with short incisions from within outward, cut through the 
internal capsule on either side from back to front (Fig. 681, CA and DB), 
care being taken not to injure the basal ganglia. Then cut across the 
crura of the fornix and the septum lucidum, leaving the fornix lying on 
the corpus callosum. 
The square basal piece (Fig. 682) thus freed-the brain axis-includes 
the island of Reil, the basal ganglia, the crura, pons, medulla, and 
cerebellum. The remaining portion-the brain mantle-includes the 
convolutions, corpus callosum, and fornix (Fig. 683). 
The basal piece may be further examined by a series of transverse 
incisions, from one-half to three-quarters of an inch apart, and it may be 998 
MAKING POST-MORTEM EXAMINATIONS 
hardened either with or without the cerebellum. The convolutions may 
be cut into small pieces by longitudinal and transverse incisions, made 
from within and not reaching quite to the pia mater, which will then serve 
to hold the pieces together in their proper relations to one another.1 
The Base of the Cranium.-We now return to the skull. The re- 
maining sinuses of the dura mater should be opened, and this membrane 
then entirely stripped from the bone. The bones at the base of the skull 
are to be examined for fractures, inflammatory lesions, and tumors. In 
cases of acute purulent meningitis, the temporal and frontal bones should 
be carefully examined, as the inflammatory process is sometimes trans- 
mitted from the internal ear, or mastoid cells, or frontal sinuses. 
The eyes may be removed by breaking the roof of the orbit with a 
hammer, removing the fragments of bone, and dissecting away bone and 
muscles, so as to expose the optic nerve and posterior segment of the 
eye. That portion of the globe which is not covered by conjunctiva can 
now be cut away with scissors and removed with the optic nerve, or, 
when permissible, the whole eye may be cut out. 
The examination of the internal ear may be made by removing its 
entire bony encasement with the saw and chisel, or by the exposure of 
special parts by hammer and chisel, and by suitable opening of the re- 
moved parts with a fine saw. 
Hardening and Preservation of the Tissues for Microscopical Examination. 
For the study of tumors and inflammatory lesions of the bones of the skull and 
ossifications of the dura mater and pia mater, the affected portions should be cut into 
small pieces, fixed in 5-per-cent. formalin or in Orth's fluid (see p. 1029), and decalci- 
fied. The dura mater should be stretched on a flat piece of wood or cork with pins, be- 
fore hardening.2 
The pia mater is so delicate that if it be separated from the brain when quite fresh 
its tissues are apt to be injured. The portions of the pia mater which are to be pre- 
served should therefore be removed by cutting off slices of the brain substance about 
half an inch thick, with the membrane still attached, and placing the whole in Orth's 
fluid. After twenty-four hours, the pia mater will have become sufficiently hard to 
permit of its being stripped off without injury, and it is then spread loosely on a flat 
cork with pins, the free surface outward, and the cork floated, specimen side down, in 
80-per-cent. alcohol, changing to strong alcohol after twenty-four hours. 
When sections are required showing the pia in its relationship to the underlying 
brain tissue, small blocks of the brain and pia together should be cut out and hardened 
in Orth's fluid or in formalin (10 : 100) solution (see p. 1029). 
When the ependyma is to be studied apart from the associated nerve tissue, it may 
be sliced off with a sufficient quantity of underlying brain substance to prevent its 
folding, and hardened in Orth's fluid. The brain, for general purposes, may be hard- 
ened in Orth's fluid, or in 5-per-cent. formalin. The pieces of brain tissue should not 
be more than 1 centimetre thick; it is better if they are thinner than this. They should 
be suspended in gauze or rest upon a layer of absorbent cotton on the bottom of the 
jar, the pieces, if these are numerous, being held apart by a little cotton. Thus the 
preservative fluid, which should be abundant, is in contact with the surfaces of the 
pieces of tissue. Ordinarily, with a change of fluid on the second day, the fixation by 
formalin or Orth's fluid is complete in a week, when the fixatives are thoroughly 
1 For further details of this method of opening the brain, and a consideration of its advantages, see 
Van Gieson, "Laboratory Notes," etc., New York Medical Journal, July 20th, 1889. 
2 For details of the methods of hardening, decalcifying, staining, etc., see p. 1029. MAKING POST-MORTEM EXAMINATIONS 
999 
washed out and replaced by 50-per-cent. alcohol, which, in turn, is replaced after 
forty-eight hours by 80-per-cent. or by 95-per-cent. alcohol. 
When degeneration in nerves is to be studied, the specimens of nerve tissue may, 
by Marchi's method, be hardened for a week in Muller's fluid, and then transferred to 
the following solution: 
Miiller's fluid 2 parts. 
Osmic acid, 1 per cent 1 part. 
After a week the specimens are washed and transferred to 95-per-cent. alcohol. 
In such specimens the fat droplets in the degenerate areas are black, while the myelin 
is yellowish in color. 
Certain lesions, particularly the softenings of the brain, are best studied by teasing, 
when fresh, in 0.5 per-cent, solution of sodium chlorid, or in frozen sections of the 
fresh tissue. The blood-vessels may be stretched on cork with pins and hardened 
with Orth's fluid or formalin. The eye and portion of the optic nerve, if removed, 
should be fixed by Orth's fluid and the hardening completed by alcohol. 
For many methods of fixation and study which are useful for special purposes, we 
refer to special works on technique. 
THE SPINAL CORD. 
The examination of the spinal cord is usually most conveniently made 
after the removal of the brain. 
The body should be placed face downward, with a block under the 
thorax and the head hanging over the edge of the table. An incision is 
made through the skin and muscles along the entire length of the spine, 
and the soft parts are dissected away on each side so as to expose the 
laminae of the vertebral column. The laminae are then divided, close 
within the articular processes, with the saw. 
The saw should be so directed in severing the laminae that the inci- 
sion shall touch the outer border of the spinal canal, as otherwise the 
laminae and spinous processes are not easily separated. Great care 
should be taken on the one hand not to injure the cord with the saw, 
and on the other completely to loosen the portions of bone to be removed. 
These, which are the spinous processes and laminae, are now torn away 
together, with a stout hook, exposing the cord. 
By means of a long, curved chisel, made for this purpose, the bodies 
of the vertebrae may be removed from the front after the thoracic and 
abdominal viscera are taken out, and the cord thus exposed and re- 
moved. But in this anterior method of removing the cord, as well as by 
the use of chisel and mallet, bone-shears, etc., in the ordinary method, 
there is great liability of injuring the delicate tissues of the cord and 
producing, as Van Gieson has shown,1 mechanical alterations which are 
likely to be mistaken for malformations or the results of disease. 
When the body has lain on the back, the membranes of the cord may 
be found considerably congested, without indicating the pre-existence of 
disease. If the body has lain for some time, especially in warm weather, 
serous fluid may have accumulated within the membranes, as a result of 
post-mortem change. 
1 Van Gieson, "A Study of the Artefacts of the Nervous System," New York Medical Journal, vol. 
vi„ pp. 337, 365, 421, 1892. 1000 
MAKING POST-MORTEM EXAMINATIONS 
The roots of the nerves are now to be cut across, as far away as pos- 
sible from the cord, and the cord removed in its membranes, care being 
taken not to press it in any way. It is the safest plan not to grasp the 
cord itself, but with a forceps to seize the dura mater and thus lift it up 
at once as it is freed from its attachments. It is now laid on the table, 
Fig. 684.-Outlines of Sections of the Spinal Cord at Different Levels. 
Copies of these outlines may be used for memoranda of the situation of lesions of the spinal cord. 
I, Second cervical; II, fifth cervical; III, eighth cervical; IV, first dorsal; V, eighth dorsal; VI, third 
lumbar; VII, fourth sacral. 
and the dura mater laid open with scissors on the anterior and posterior 
surfaces over its entire length, and searched for tumors, inflammatory 
lesions, etc. The finger should be passed gently along the cord as it lies 
on the table, so as to detect any marked softening or sclerosis. The 
weight of the spinal cord is from 30 to 38 grams. It should now be held 
lightly over the fingers, and smooth transverse incisions made, with a MAKING POST-MORTEM EXAMINATIONS 
1001 
very sharp knife or razor, about half an inch apart through its entire sub- 
stance between the segments, leaving these attached to the pia mater. 
The segments of the spinal cord are those parts from which the spi- 
nal nerves arise, and it is convenient for the location and description of 
lesions to number the segments in correspondence with the nerves which 
arise from them, and to indicate on outline diagrams of the cord (Fig. 684) 
the exact seat of small lesions. 
The cut surfaces should be carefully examined for abnormal blood 
contents, hsemorrhages, inflammatory lesions, softening, scleroses, and 
pigmentations. Important lesions of the cord may be invisible to the 
naked eye, and hence, if disease be suspected, the organs should be pre- 
served for microscopical examination. The spinal ganglia may now be 
removed and preserved for further examination. After removal of the 
cord, fractures and displacements of the vertebrae are easily recognized. 
Preservation of the Spinal Cord and Its Membranes, and of Peripheral 
Nerves.-After the removal of the spinal dura, the entire cord with its nerve roots- 
the segments into which it has been cut for gross examination being left in place- 
should be laid on a wad of absorbent cotton in a large jar of Orth's fluid or formalin, 
the segments being slightly separated from each other by a little absorbent cotton. 
Van Gieson recommends the careful rolling of the segmented cord into a loose spiral 
and laying this coil on a wad of absorbent cotton in the fixative. In this way the cut 
ends of the segments are held apart, accessible to the fluid, and harden with little 
distortion. 
The hardening and preservation of the cord may be done by the same methods as 
suggested above for the brain. If the dura mater of the cord alone is to be preserved, 
it should be treated in the manner suggested for the dura mater cerebralis. The pia 
mater spinalis is best studied in sections through the entire cord, the membranes being 
left in situ. 
Peripheral nerves may be hardened in Orth's fluid or in formalin. 
For the hardening of the peripheral nerves, osmic acid is very useful, especially 
when changes in the myelin are to be sought after. As osmic acid does not readily 
penetrate the lamellar sheath so as to come in contact with the nerve fibres, in trunks 
of any considerable size, the following procedure, as suggested by Van Gieson, will be 
found useful: A piece about one-half inch long is cut from the nerve to be examined; one 
end of this segment is held with a forceps, while with another forceps the individual 
nerve fibres, or small clusters of these, are pulled out of the lamellar sheath and put at 
once in a 1-per-cent. aqueous solution of osmic acid, in which they remain twenty- 
four hours, and are then washed and transferred to glycerin, to which 25-per-cent. 
alcohol is added. In this mixture they may be preserved. Marchi's method is useful 
for the study of degeneration in peripheral nerves. 
THE THORAX AND ABDOMEN. 
The body is replaced on its back, and a single straight incision is 
made from the top of the sternum to the pubes, passing to the left of the 
umbilicus. For this purpose a large knife should be used, held firmly 
in the whole hand, and the movement should be mainly from the shoul- 
der. The first incision should divide everything down to the sternum 
and peritoneum. A short incision should then be made through the 
peritoneum, just below the ensiform cartilage. Into this opening two 
fingers of the left hand are introduced and separated from one another, 
and, the parietes being raised and the sides of the opening being held 1002 
MAKING POST-MORTEM EXAMINATIONS 
apart by the fingers, the peritoneum is divided to the pubes, care being 
taken to hold the knife horizontally so as not to cut the intestines. The 
skin and muscles are then dissected off from the thorax on both sides as 
far back as the false ribs. 
This dissection should be made by long sweeps of the knife, which 
should be made to cut with the full blade and not with the point only; 
and if the skin and muscles be pulled strongly away from the chest with 
the left hand, it may be done very rapidly and with a few strokes of the 
knife. We notice here the amount of subcutaneous fat and the condi- 
tion of the muscles. In order better to expose the abdominal cavity, the 
rectus should be divided transversely beneath the skin just above the 
pubes, and the abdominal flaps may then be turned freely outward. 
General Inspection of the Abdominal Cavity.-We first notice the posi- 
tion and general condition of the viscera. It is best at this stage of the 
examination to note the condition of the vermiform appendix, and to 
look over the peritoneal cavity for serum, inflammatory lesions, evi- 
dences of perforation, and for the existence of invagination, incarcera- 
tion, and herniae of the intestines. A small quantity of reddish serum 
is frequently found in the abdominal cavity, particularly in warm 
weather, as the result of commencing decomposition. 
It should be remarked here that various striking changes in the 
character and appearance of the internal organs are produced by putre- 
faction-changes which are often mistakenly regarded as evidences of 
disease, and much experience is required, in judging correctly of their 
significance. These changes are, in general, softening and discoloration, 
both of which may occur as the result of disease. It may be said in 
general that the post-mortem reddening, or hypostases, are most marked 
in the more dependent parts of the organs. Post-mortem softening usu- 
ally affects entire organs, not being limited to a part, as is often the case 
in disease. Gray or grayish-brown post-mortem discolorations are apt 
to appear in those organs or parts of organs which lie in contact with the 
intestinal canal. Parts of internal organs, such as the liver, which have 
been the seat of localized congestion during life, may after death assume 
a dark greenish color. 
The omentum is usually spread over the surface of the small intes- 
tines, but it may be rolled up and displaced in a variety of ways, or may 
be adherent at some point to the small intestines or to the abdominal 
wall. 
The surface of the small intestines should be smooth and shining. 
They may be greatly distended with gas, and thus so completely cover 
the other abdominal viscera that it becomes necessary to let out some of 
the gas by a small puncture. The transverse colon passes across the 
abdomen through the upper part of the umbilical region. It may be 
lower than the umbilicus, or higher up against the liver and diaphragm; 
it may be distended with gas or contracted. 
The liver is situated in the right hypochondriac and epigastric re- 
gions, filling the concavity of the diaphragm. Its upper border reaches, 
in the linea mammillaris, to the fifth intercostal space; in the linea axil- MAKING POST-MORTEM EXAMINATIONS 
1003 
laris, to the seventh intercostal space; close to the vertebral column, to 
the tenth intercostal space. At the median line the upper border of the 
liver corresponds to the lower border of the heart. The left lobe extends 
about three inches to the left of the median line. The lower border of 
the right lobe usually reaches to the free border of the ribs, while the 
left lobe is visible for about an inch below the ensiform cartilage. In 
women the liver is usually lower than in men. 
The position of the liver is affected by changes in the thoracic cav- 
ity, forcing it downward; by changes in the abdominal cavity, forcing 
it upward; by constriction of the waist in tight lacing, forcing it either 
upward or downward; by changes in the size of the organ itself. The 
liver may not only be displaced downward, but dislocated so that its 
convex surface faces the abdominal wall and its posterior edge is turned 
upward against the diaphragm. 
The stomach is situated in the left hypochondriac and epigastric re- 
gions, extending also into the right hypochondrium; it lies in part 
against the anterior wall of the abdomen, in part beneath the liver and 
diaphragm, and above the transverse colon. Its anterior surface, which 
is directed upward and forward, is in contact above with the diaphragm 
and the under surface of the liver, and lower down with the abdominal 
wall opposite to the epigastric region. Its posterior surface is turned 
downward and backward, and rests on the transverse mesocolon, the 
pancreas, and the great vessels. To its lesser curvature or upper border 
are attached the gastro-phrenic ligament and the gastro-hepatic omen- 
tum. To the greater curvature or lower border is attached the gastro- 
colic omentum. Its cardiac orifice communicates with the oesophagus, 
its pyloric end with the duodenum. 
When the stomach is distended the greater curvature is elevated and 
carried forward, the anterior surface is turned upward and the posterior 
surface downward. When distended with food or gas the organ is prom- 
inent; when empty it may hardly be visible below the ribs; when the 
intestines are dilated it may be entirely covered by them. 
Before opening the thorax the hand should be passed up against the 
under surface of the diaphragm on either side, to determine its height. 
According to Quain, the vault of the diaphragm rises, in the dead body, 
on the right side to the level of the junction of the fifth rib and sternum, 
on the left side as high as the sixth rib. Both the relative and the 
absolute height of the diaphragm vary under a variety of pathological 
conditions. 
If the existence of air or gas in the pleural cavities be suspected, the 
abdominal cavity should be filled with water and the diaphragm punc- 
tured below the level of the fluid. If air be present, it will escape in 
bubbles through the water. 
The Thorax. 
We now leave the abdominal viscera and proceed to the examination 
of the thorax. With a costotome or a strong knife the costal cartilages 1004 
MAKING POST-MORTEM EXAMINATIONS 
are divided close to the ribs, the clavicles are disarticulated from the 
sternum, and the latter is removed, care being taken not to wound the 
large veins. We first examine the position of the heart and lungs. 
The Heart.-The upper border of the heart is on a level with the 
third costal cartilage; the lower border extends from 1.3 centimetres be- 
low the lower end of the sternum to the fifth left intercostal space. The 
left boundary of the heart is situated to the left of the junction of the 
fifth rib with its costal cartilage, and behind or to the left of a vertical 
line drawn downward from the left nipple. The right boundary extends 
2.5 centimetres to the right of the right edge of the sternum. The por- 
tion of the heart uncovered by the lungs is of an irregular quadrangular 
shape. Its lateral diameter is from 8.3 centimetres to 11.1 centimetres; 
its upper boundary varies from the level of the second costal cartilage 
to that of the fifth, but it is usually behind the third or fourth cartilage 
or fourth space. 
The area of the heart which is found uncovered will, however, vary 
much, according to the degree to which the lungs collapse after opening 
the chest. Any disease which diminishes the size of the lungs, or pleu- 
ritic adhesions which retract or bind them down, may increase the area 
of exposed heart. On the other hand, emphysema, pneumonia, or any 
disease which increases the size of, or retains the air in, the lungs, may 
diminish the area of exposed heart. The exposed area varies also with 
the size of the heart itself. 
The pericardium is now opened by a slightly oblique incision on its 
anterior surface. The existence of serous, fibrinous, or purulent exu- 
date, and of adhesions, is to be noted. A small quantity of clear serum 
exists normally in the pericardial sac, and this serum may be blood- 
stained from beginning decomposition. White thickenings of the peri- 
cardium on the surfaces of the heart are often seen; they do not indicate 
important disease. 
Now that the pericardial sac is open, the position of the heart can be 
clearly seen. It lies obliquely in the chest, its long axis at an angle of 
about sixty degrees with that of the thorax. The portion of the heart 
which is first seen is the anterior surface of the right ventricle; upward 
and to the right of this is the right auricle, which lies about two-thirds 
on the right of the sternum and about one-third behind it. Its upper 
border usually corresponds to the plane of the middle of the anterior 
end of the second intercostal space on the right side. Its size varies 
with the amount of blood which it contains. The left auricle lies behind 
the root of the pulmonary artery, so that only its appendix is visible. 
The middle of the auricle corresponds to the third costal cartilage. Of 
the left ventricle only a narrow rim is seen, on the left side of the right 
ventricle. The pulmonary valve is usually entirely or in part on the 
left side of the sternum, behind the second space or third costal 
cartilage. 
The aortic valve is usually at the level of the third cartilage or the 
third space, and behind the left two-thirds or half of the sternum. The 
mitral valve is oblique, the upper end of the left. It is on the level of MAKING POST-MORTEM EXAMINATIONS 
1005 
the third to the fourth cartilage, near the middle of the sternum. The 
tricuspid is oblique, its upper end to the left; the upper end is at the 
level of the third cartilage, the third space, or the fourth cartilage. 
The valve is opposite the middle of the sternum. 
The hand should now be passed over the arch of the aorta, to ascer- 
tain whether or not an aneurism is present. The heart is then grasped 
at the apex, raised out of the pericardium, tilted upward, and removed 
unopened by cutting through the great vessels at its base. It is advisable 
in many cases to remove with the heart the arch of the aorta and as much 
as is practicable of the associated great vessels. In some instances, 
for example when thrombosis of the pulmonary artery is suspected, it is 
well to remove the heart and lungs together.1 
One may gain some knowledge of the sufficiency of the aortic and pul- 
monary valves if the heart is held horizontally by both auricles, so as 
not to pull the valves open, and water is poured into the aortic and pul- 
monary arteries. One observes how well the valves support the column 
of liquid. To ascertain the sufficiency of the mitral and tricuspid valves, 
the auricles are first laid open so as to expose the upper surfaces of the 
valves. A large pipe is passed through the aorta or pulmonary artery 
beyond their valves, and a small stream of water allowed to flow into the 
ventricles. The auriculo-ventricular valves will be swollen upward, and 
one may observe their degree of sufficiency. The tricuspid valve is 
normally somewhat insufficient. These water tests, however carefully 
applied, are not very reliable, since under the most favorable conditions 
the natural bearings of the valves are not perfectly preserved. 
To ascertain the size of the different valvular openings, we introduce 
the fingers, held flat with their sides in contact, into each of the orifices, 
and then measure the width of the fingers at the point where they fill the 
orifice. In this way we find that, under normal conditions in the adult, 
the aortic measures about 2.5 centimetres, the mitral valve about 4.5 
centimetres, the pulmonary about 3.1 centimetres, the tricuspid about 
5 centimetres. 
In order to examine the interior of the heart, one first makes an incision 
through the anterior wall of the left ventricle close by and parallel to 
the septum, and reaching to the apex of the ventricle (Fig. 685). Through 
this opening the blade of the enterotome is passed up into the aorta, the 
pulmonary artery being drawn aside with the fingers, and the ventricle 
and aorta are laid open (Fig. 685). With a little care the incision may be 
made to pass through one of the points of junction of the aortic valves. 
The auricles and ventricles may be empty, or may contain fluid blood 
or the so-called heart clots. These heart clots are of two kinds-those 
which are formed some time before death, and those which are formed 
during the last hours of life and after death. The clots which are formed 
some time before death are usually associated with organic disease of the 
heart, especially with dilatation of the ventricles. They are firm, dry, 
1 The opening of the heart in situ is recommended by many, but we are of the opinion that if care 
be exercised in the removal of the organ from the body and a sufficient portion of the great vessels 
at the base be included there is little risk of premature disturbance of thrombi, etc., on the valves, while 
the examination of the interior may be much more thoroughly, conveniently, and safely done. 1006 
MAKING POST-MORTEM EXAMINATIONS 
and of whitish color; they may be infiltrated with the salts of lime. 
They are free in the cavities of the heart, or entangled in the trabeculae, 
or firmly adherent to the endocardium. They are usually composed of 
coagulated fibrin, blood platelets, leucocytes, and red blood cells, and are 
often lamellated. The clots which are formed during the last hours of 
Fig. 685.-Heart Showing Lines for Incision in Opening. 
life and after death are red, yellow, or white. They may be soft or suc- 
culent or quite firm. They may be free in the heart cavities, or be 
adherent to the trabeculae, or extend into the large vessels. They are 
usually most constant and of largest size in the right auricle and ven- 
tricle. Such clots may be formed within two hours after death. Clots 
of this character are common. If, then, the blood coagulates in the heart MAKING POST-MORTEM EXAMINATIONS 
1007 
within twenty-four hours before death, this coagulum may not be dis- 
tinguishable from the ordinary post-mortem clots. If it is supposed, 
therefore, that a person dies from heart clot developed a few hours before 
death, the proof of this must be derived largely from the clinical symp- 
toms, and not from the autopsy. 
The condition of the aortic valves and of the endocardium, and the 
thickness and appearance of the walls of the left ventricle, papillary 
muscles, chordae tendineae, etc., are now noticed. 
Fig. 686.-Heart Opened, Exposing the Aortic Valves. 
The right ventricle is now opened by an incision through its anterior 
wall, close to the septum (Fig. 685), and examined in the same way. 
The endocardium of the upper part of the left ventricle is sometimes 
thick and white, without the existence of valvular lesions or clinical 
history of disease. The endocardium and valves are often stained red, 
particularly in warm weather, by imbibition of coloring matter of the 
blood, set free by decomposition. This discoloration is especially 
marked in cases of infection with Bacillus aerogenes capsulatus. 
To complete the examination of the cavities the enterotome is passed 1008 
MAKING POST-MORTEM EXAMINATIONS 
into each auricle, carried down into the corresponding ventricle, and an 
incision made along the outer border of both auricle and ventricle to the 
apex of the latter. In this way the auriculo-ventricular valves are com- 
pletely exposed. The coronary arteries should be opened through all 
their main trunks, with fine probe-pointed scissors, and carefully ex- 
amined for marks of inflammation, emboli, thrombi, etc. 
In cases of Stokes-Adams' disease look for lesions involving the auric- 
ulo-ventricular bundle of His.1 For this purpose the heart should be 
opened according to the subjoined diagram, as suggested by Oppen- 
heimer2 (Fig. 687). 
Fig. 687.-Special Incision for Opening Heart, in Order to avoid Injury to Conducting 
System. 
After removing the blood, the heart should be finally weighed. The 
normal average weight of the heart in adults is, according to an estimate 
of H. D. Arnold,3 in males about 290 grams; in females about 260 grams. 
The weight of the heart relative to that of the body is in males about 
1 : 158 to 178; in females, about 1 : 149 to 176. According to Buhl, the 
average thickness of the wall of the left ventricle at about the middle of 
the cavity is from 1.6 centimetres to 1.7 centimetres; of the right ven- 
tricle, from 0.4 to 0.6 centimetre. 
The size of the heart, speaking generally, corresponds to the size and 
1 See Erlanger, Jour. Exp. Med., vol. viii., p. 8, 1906. 
2 Oppenheimer, Jour. Amer. Med. Assn., 1912, lix, 937. 
* Arnold, "Observations on the Weight of the Normal Heart in Adults, in Two Hundred and 
Sixteen Cases." Reports of the Boston City Hospital, tenth series, 1899, p. 83. MAKING POST-MORTEM EXAMINATIONS 
1009 
the development of the individual. In judging of an increase or de- 
crease in its size we must consider the weight of the organ and the thick- 
ness of its walls. If the person die while the heart is contracted, the 
walls of the ventricles will appear thicker, their cavities smaller than 
usual.1 If he die of some exhausting disease like typhoid fever, or if 
decomposition have commenced, the heart walls will usually be flabby 
and the cavities will appear larger than usual. 
Preservation of Specimens.-Parenchymatous and fatty degeneration of the 
heart may be studied microscopically by teasing the fresh muscle in 0.85-per-cent. 
salt solution, or by examining in the same solution fresh sections made with the 
freezing microtome, or by hardening small pieces of the muscle in 1-per-cent osmic 
acid and teasing in equal parts of glycerin and water. 
When lesions of the conducting system are to be studied the whole heart should 
be fixed for forty-eight hours in warm Orth's fluid or four-per-cent, formaldehyde. 
When the presence of bacteria is suspected cultures should be made and the tissues 
should be preserved in strong alcohol. 
The pleural cavities are next examined. The hand is passed into 
each, and the existence of serous or fibrinous exudation or of old adhe- 
sions ascertained. The method of detecting the presence of air has been 
given above. After the commencement of putrefaction reddish serum 
may accumulate in the pleural cavities. This should not be mistaken 
for the result of disease. 
The Lungs.-Each lung is lifted up in turn, the vessels, etc., at its base 
are divided, and the organ is removed. If the pleura is very adherent it 
is better to strip off the costal pleura with the lung. After inspecting 
the external surface of the lung, observing its size, shape, color, and con- 
sistence, and the condition of the bronchial lymph-nodes, the bronchi 
are opened with scissors having long, narrow, blunt-pointed blades, one 
blade a little longer than the other. The lung is held in the left hand 
with its base upward, the large bronchi which run on the inner side of 
the lower lobe being first opened, afterward those of the upper lobe. 
Each bronchus should be followed to its smaller ramifications. 
We should observe the contents of the bronchi and the appearance of 
their walls. In the larger and medium-size bronchi the cartilages in 
their walls do not form complete rings, but appear shining through the 
mucous membrane like irregular white patches. This appearance should 
not be mistaken for a pathological change. In bodies which have been 
dead for some time, especially in cold weather, the bronchial mucous 
membrane may be red and swollen as a post-mortem change. The 
contents of the stomach are sometimes forced, after death, into the 
pharynx, and thence find their way into the trachea and bronchi, giving 
them a peculiar reddish and even gangrenous appearance. Bronchitis 
does not always leave lesions which can be seen after death. The large 
vessels should now be examined for thrombi, emboli, or other lesions. 
After the examination of the bronchi the lung is turned over, the 
vessels, etc., at its root, are grasped with the left hand, and a long, deep in- 
1 For method of determining hypertrophy of the heart see ref. to Muller, p. 554. 1010 
MAKING POST-MORTEM EXAMINATIONS 
cision is made from apex to base. We observe the appearance and tex- 
ture of the lungs, whether the air vesicles are dilated (emphysematous) or 
filled with serum, blood, or inflammatory exudation. Fluid can be 
pressed out of the air vesicles without breaking down the lung tissue. 
Solid inflammatory exudation, on the other hand, renders the lung more 
resistant and easily broken down. Attention should be paid to the ooz- 
ing of purulent or other fluid from the smaller bronchi when the lung 
is squeezed near the cut surface. It is the rule to find the lower lobes 
more congested than the upper. 
Preservation of the Lungs and Bronchi.-If the lungs have been cut, small 
pieces from the affected portions of lung tissue or bronchi should be hardened in Orth's 
fluid, care being taken not to squeeze or handle them unnecessarily. It is better, 
when the microscopical examination is more important than the macroscopical, not to 
open the lungs at once, but to fill the air spaces with preservative fluid by means of a 
funnel attached to a short rubber tube and cannula, which is tied into the main bron- 
chus. In this way not only are the minute structures better preserved, but the air 
vesicles are filled out and hardened in an approximately natural condition. Care 
should be taken not to have too great a pressure from the inflowing fluid, since then 
exudations might be displaced or the lung distorted or ruptured. While the lung is 
being filled it should be immersed in a vessel of the same preservative fluid, in which, 
after closing the cannula or ligating the bronchus, it lies for twenty-four hours. It is 
then cut into small pieces and the hardening completed For the display of certain 
gross lesions, such as tuberculous and other cavities of the lungs and bronchi, tumors, 
etc., the lungs filled in this way are opened by an incision along the posterior surface 
from apex to base and hung in jars. For this purpose 5-per-cent. formaldehyde solu- 
tion may be used for both fixation and preservation in the jars. A variety of harden- 
ing agents may be used: Orth's fluid or formalin solution (10 : 100) is on the whole the 
best. If, however, the lung is commencing to decay, strong alcohol will stop the proc- 
ess most quickly and give as good results as are possible under the circumstances 
Alcohol should be used when the lungs are to be examined for bacteria. 
It is often desirable, and particularly in cases in which the topography of lesions is 
to be studied, as in acute miliary tuberculosis, acute and chronic phthisis, infarctions, 
etc., to inject the blood-vessels with colored gelatin. The lung should, after the injec- 
tion, be hardened in alcohol. 
The Pharynx, Larynx, (Esophagus, and Thyroid Gland.-For the re- 
moval of these parts the incision through the skin should be carried 
upward as far as practicable-when permissible, to a point 1 inch be- 
low the chin, the head being allowed to hang backward over the edge of 
the table. 
The soft parts are dissected from the larynx, taking care not to cut 
the thyroid body, and an incision is made through the floor of the 
mouth, following the internal surface of the inferior maxilla. Through 
this incision the fingers are introduced into the mouth, the tongue is 
drawn down, the posterior wall of the pharynx is divided above the tonsils, 
and the tongue, pharynx, and larynx are drawn out together. These 
organs are then pulled downward, and with the aid of the knife the trachea 
and oesophagus are removed entire, the oesophagus being cut just above 
the stomach. If the contents of the stomach are to be preserved, as in 
cases of suspected poisoning, a ligature is put around the oesophagus just 
below the point at which it is to be cut off. MAKING POST-MORTEM EXAMINATIONS 
1011 
With the enterotome the pharynx and oesophagus are now slit open 
upon their posterior surfaces. The mucous membrane thus exposed is 
examined for evidences of caustic poisons, of inflammation, tumors, 
strictures, varices, etc. The enterotome is next introduced into the 
larynx, and this organ and the trachea are laid open along the poste- 
rior wall. Here we look for oedema of the aryteno-epiglottidean folds 
(oedema of the glottis), for evidences of catarrhal, croupous, ulcerative, 
and syphilitic inflammation, and for tumors and lesions of the laryngeal 
cartilages. CEdema and redness of the larynx may result from post-mor- 
tem changes, especially in bodies which have been kept for several days 
in cold weather. A well-marked oedema glottidis during life may leave 
no trace after death. Putrefactive changes usually commence early in 
the larynx and trachea. 
The thyroid gland is dissected off and examined. Its weight varies 
considerably, being, according to Krause, somewhat over 30 grams. 
Preservation of the Pharynx, Larynx, Trachea, Etc.-These structures are 
freed from superfluous tissue and suspended entire by a thread in a large quantity of 
Orth's fluid or Flemming's osmic-acid mixture, after which the hardening is completed 
in the usual way. The oesophagus should be stretched loosely on sheet cork with pins, 
and hardened in either of the above fluids. The thyroid may be cut into small pieces 
and similarly hardened. 
The Abdomen. 
Returning now to the abdominal cavity, we first dissect off the omen- 
tum. Tubercles of the peritoneum may be best seen in the omentum. 
The colon is then raised and dissected free, to the caecum on one side and 
to the rectum on the other. The colon and small intestines are then 
drawn first to the right and then to the left side, so as to expose in turn 
the right and left kidneys. As each kidney is brought into view an in- 
cision is made through the peritoneum over the track of the ureter. The 
ureter is followed through its entire length and its condition ascertained. 
Sometimes one, more rarely all, of the abdominal viscera are un- 
usually movable, owing to a relaxation of their ligamentous or other sup- 
ports. This condition-enteroptosis-is common in the liver, more fre- 
quent in the spleen, and especially so in the kidneys. It has been 
occasionally described in the stomach and intestines. 
The Kidneys.-These organs are now removed, the peritoneum and 
fat being separated from them with the hand, and the vessels being di- 
vided with the knife. The adrenals, at the upper end of each kidney, 
are removed at the same time. The kidneys may be softened by putre- 
faction, or the surface may have a greenish gray color, caused by the 
post-mortem action of putrefactive gases on the haemoglobin. 
An incision is made through the capsule along the convex border of 
the kidney, and the membrane stripped off. We notice the degree of 
adherence of the capsule to the kidney, and also the surface of the latter, 
whether smooth or roughened, pale, congested, or mottled; an incision 
is made along the convex surface down to the pelvis, so that the organ 1012 
MAKING POST-MORTEM EXAMINATIONS 
is divided into halves. We observe the relative thickness of the cortical 
and pyramidal portions, as well as the size of the entire organ. To as- 
certain the latter point, it is well to weigh each kidney; the normal 
weight is from 130 to 150 grams. The left kidney is, according to Orth, 
from five to seven grams heavier than the right. At from twenty to 
thirty-five years of age, according to Thoma, the weight of the heart is to 
the weight of both kidneys as 1 : 1.1. The weight of the kidneys of adults 
is given by Vierordt in general as about 0.48 per cent, of that of the entire 
body. 
It is necessary to remember that in a kidney which is much atrophied 
there may be an increase of fat in the pelvis, which gives the organ 
nearly its normal size and weight, while the kidney tissue proper may 
have in great measure disappeared. 
We now inspect the kidney tissue more closely, especally the cortical 
portion. The pyramids consist largely of tubes running in nearly 
straight lines from the apex to the base of each pyramid. These straight 
tubes pass from the pyramids into the cortex in bundles, called medul- 
lary rays, many of them retaining their straight course until they nearly 
reach the surface of the kidney. These straight tubules send off branches 
on all sides of the rays, which become convoluted, form Henle's loops, 
and finally terminate in the glomeruli or Malpighian bodies. In this 
way the cortex of the kidney, as seen in section, is divided into alternate 
bands of straight tubes, and convoluted tubes, with glomeruli; both sets 
of bands being perpendicular to the surface of the kidney, and called re- 
spectively medullary rays and labyrinths. About the convoluted tubules 
and glomeruli is a rich venous plexus; and since after death the blood 
usually remains in this plexus and in the glomeruli, the bands containing 
the convoluted tubules, i.e., the labyrinths, usually appear red, while the 
medullary rays are grayish white. In a normal kidney, therefore, the 
cortex should be regularly striped in narrow alternating red and whitish 
bands. 
The average thickness of the cortex of the kidney is from four to six 
millimetres. 
If there be extensive congestion, the entire cortex is red. If the epi- 
thelium of the tubules degenerates and fills them up, or if there are con- 
siderable changes in the interstitial tissue, the regular bands are lost and 
the cortex is irregularly mottled. If the tubular epithelium becomes 
filled with fat globules, this is indicated by an opaque yellow color of the 
affected parts; in many cases, therefore, the existence of a kidney lesion 
can be recognized with the naked eye. 
If waxy degeneration be present to a marked extent, it may be mani- 
fest by a peculiar translucent appearance of the affected parts, but in 
most cases it is necessary to apply reagents to demonstrate it satisfac- 
torily. The cut surface of the kidney is washed with water, to free it 
from blood, and repeatedly brushed with an aqueous solution of iodin 
(iodin 1 part, potassium iodid 3 parts, water 100 parts). The glo- 
meruli and the blood-vessels are most frequently affected, and, if so, they 
may appear as mahogany-colored dots and lines on a yellow ground. MAKING POST-MORTEM EXAMINATIONS 
1013 
But this reaction is not constant, and, for accurate detection of amy- 
loid substance, recourse should be had to other reagents applied to sec- 
tions of the hardened tissues (see p. 50). 
The pelvis of the kidney should be examined for inflammatory lesions 
and calculi. Sometimes a whitish fluid is seen in the pelvis and can be 
squeezed from the papillae; this is produced by a post-mortem desqua- 
mation of the epithelium, but is likely to be mistaken for pus. 
Preservation oe the Kidney.-If the kidney be not opened, the blood-vessels 
may be injected through the renal artery, slowly and under a low pressure, with Orth's 
fluid or Flemming's osmic-acid mixture. After the vessels are filled with either of the 
above fluids, they are tied, and the entire organ is placed in a large quantity of the 
injecting fluid for twenty-four hours. The kidney is then cut into small pieces, and 
the hardening is completed in the usual way. 
In most cases, however, the kidneys will have been opened for inspection at the 
autopsy. Then small pieces are removed from the various regions and hardened in 
the above fluids. 
Kidneys which are to be examined for the presence of bacteria should be cut into 
small pieces and placed at once in strong alcohol, which should be changed once or 
twice, and in which they are permanently preserved. 
The Adrenals-Suprarenal Capsules.-These are, in the foetus, of an 
ovoidal, in the adult, of a triangular shape. They are situated at the 
upper and inner border of the kidney, to which they are loosely attached 
by connective tissue. On the anterior surface is an irregular fissure, 
called the hilus, from which the veins emerge. The size of the adrenals 
varies considerably, but in the adult the average vertical diameter is from 
3.2 cm. to 4.5 cm., the transverse diameter about 3.2 cm., and they are 
from 4.2 mm. to 6.4 mm. in thickness. They weigh in the adult from 4 
to 8 grams. They are relatively larger in children than in adults. They 
are composed of a cortical and a medullary portion, the cortex forming a 
yellowish shell around the dark red or brown medulla. They are en- 
closed in a connective-tissue capsule, from which fibrous processes extend 
inward, dividing the gland into a series of irregular chambers. Those in 
the cortex are mostly elongated, giving this portion a striated appear- 
ance, while those in the medulla are polyhedral. It is in these spaces 
that the parenchyma cells lie. The adrenals readily decompose; the 
inner layer of the cortex may soften and break down, so that the outer 
zone forms a sort of cyst filled with reddish brown broken-down sub- 
stance. Hypertrophy, tuberculosis, and cheesy degeneration, fatty de- 
generation, and tumors are to be looked for. 
Preservation.-The adrenals should be hardened in Orth's fluid or in strong 
alcohol. 
The Spleen.-This organ has, when removed from the body, the gen- 
eral shape of a flattened ellipsoid, most curved on its external and pos- 
terior surface. It is situated in an oblique position on the left side of 
the stomach, and between its cardiac end and the diaphragm. The 
vessels are given off from its inner surface, which is crossed by a more 
or less well-marked vertical ridge. The point of emergence of the vessels 1014 
MAKING POST-MORTEM EXAMINATIONS 
is called the hilus. Its long diameter extends from the seventh inter- 
costal space to the eleventh rib. Its upper portion is separated from the 
ribs by the lungs; its lower portion, by the diaphragm. 
It is, according to Vierordt, on the average, from 12 to 13 cm. long; 
from 7 to 8 cm. broad, and about 3 cm. thick. Its average weight is 
about 171 grams. The dimensions of the spleen as given by Krause are 
somewhat greater than the above. But its measurement and weight 
vary considerably within the limits of health. It is in these respects 
the most variable organ in the body. In old age the average weight 
gradually diminishes. 
The spleen is enclosed in a fibrous capsule covered with peritoneum. 
The parenchyma is formed of blood-vessels and fibrillar connective tissue, 
and of a soft, dark red pulp in which are embedded whitish spheroidal 
or elongated bodies, the glomeruli, or Malpighian bodies. In the normal 
human spleen the glomeruli are usually hardly perceptible to the naked 
eye, but sometimes they are very plain. Sometimes the fibrous stroma 
is very apparent, sometimes not. 
The size, consistence, and color of the organ vary a good deal within 
normal limits; it may soften in decomposition. Thickenings of the capsule 
and abnormal adhesions are very common, and often occur without any 
clinical history indicating disease. We should look for changes in size, 
color, and hardness; for pigmentation, hyperplasia of the connective 
tissue, amyloid degeneration, tubercles, and infarctions. 
Not infrequently one or more spheroidal or flattened so-called acces- 
sory spleens are found in the vicinity of the spleen; they vary in size 
from that of a pea to that of a walnut. 
Preservation.-In certain diseases of the pulp, anaemia, leucocythaeinia, etc., the 
tissue should be teased, when fresh, in 0.85-per-cent. salt solution, or examined by 
the staining methods described under the Lesions of the Blood. For general purposes 
small pieces of the organ are hardened in Orth's fluid, Flemming's osmic-acid mixture, 
or in alcohol. 
The Intestines.-The rectum is divided, the intestine is seized with the 
left hand, and, being kept stretched, is separated from its attachments 
by repeated incisions through the mesentery close to the gut, until the 
duodenum is reached, where the intestine is again cut off. The operation 
is more cleanly if, before dividing the gut, ligatures are placed around 
it at either end. The entire length of the gut is now laid open with the 
enterotome along the mesenteric attachment; the mucous membrane 
is cleaned with a stream of water and then examined. 
In cases of suspected poisoning, a ligature should be placed around 
the rectal end of the gut and two around the duodenal end, and it should 
then be cut off below the former and between the latter ligatures. The 
gut is now opened and the contents are emptied into a clean glass jar for 
delivery to the chemist, care being taken that they be not allowed to 
touch anything but the inner surface of the jar. After washing the in- 
testine in pure, fresh water and examining it, it should be placed entire 
in another clean jar and the jar sealed. MAKING POST-MORTEM EXAMINATIONS 
1015 
Cadaveric lividities are very common in the intestines, and are 
usually most marked in the dependent portions. They are apt to occur 
in patches, but may be diffuse and very extensive. If the wall of the 
gut be stretched, they are often seen to be discontinuous, owing to the 
pressure of the blood from the parts which are squeezed by folds. Small 
patches of arborescent or diffuse red staining are often seen, formed by 
the imbibition from the vessels of decomposing haemoglobin. In the 
more advanced stages of decomposition the mucosa may be softened and 
loosened. A dark purple or brownish discoloration of the entire intes- 
tinal wall is frequently seen, either diffuse or in patches. Much experi- 
ence and careful observation are requisite in forming a correct judgment 
regarding the significance of changes of color in the intestines. Caution 
is necessary in distinguishing normal digestive hyperaemia from ab- 
normal congestion. A very considerable congestion may exist without 
disease. 
The lesions ordinarily to be looked for are catarrhal, croupous, and 
ulcerative inflammations, perforations, haemorrhages, strictures, tumors, 
amyloid degeneration, swelling and ulceration of the solitary follicles 
and Peyer's patches, and pigmentation. For the detection of amyloid 
degeneration of the mucosa this structure should be carefully washed 
and brushed with a solution of iodin. 
Preservation.-For the general purposes of microscopic study, portions of the 
gut should be gently stretched on cork (the mucosa side free) and hardened in Orth's 
fluid or in Flemming's osmic-acid mixture. 
For obvious reasons the mucous membrane should be handled as little as possible, 
for, in the majority of cases, decomposition and softening have already set in at the 
time of the autopsy, and, under the most favorable conditions, the epithelium is very 
easily rubbed off. 
In cases in which the most perfect preservation of the topographical features, as 
well as the minute structure of the intestinal mucosa, is desired, even at the expense of 
an inspection of the fresh tissue, another mode of procedure is to be recommended. 
Selected segments of the gut are, after removal from the body, allowed to remain 
unopened on the table while ligatures are tied around the ends. The isolated seg- 
ments, or the whole gut, may now be moderately filled-not distended-with one of 
the above fluids by means of a syringe with a needle cannula; or one end of the seg- 
ment may be tied and the fixative introduced through a funnel at the other, which 
end is then ligated. The segments to be preserved should now be placed unopened in 
the fixative solution. After twenty-four hours they may be opened with scissors or a 
sharp knife, cut into suitable pieces, and kept permanently in 80-per-cent. alcohol. 
The Stomach and Duodenum.-We now introduce the enterotome into 
the duodenum at its transverse portion, and open it on the convex border. 
When the pylorus is reached the incision is carried obliquely over to 
the greater curvature of the stomach, along which it is extended as far as 
the oesophageal opening, and the organ examined in situ; or, if a more 
careful examination of the stomach is called for, after ascertaining 
whether or not the bile duct is pervious (see below), the duodenum and 
stomach may be removed together, and the stomach opened and exam- 
ined on the table. Alterations in size and form, the presence of tumors, 
ulcers, etc., may now be sought for. 1016 
MAKING POST-MORTEM EXAMINATIONS 
If poisoning be suspected, a ligature should have been placed, earlier 
in the examination (see above), around the lower end of the oesophagus 
and the duodenum. The stomach and duodenum are now removed to- 
gether unopened. They are to be opened in a carefully cleansed glass 
jar, and after an inspection of the mucous membrane and the contents 
with the naked eye and a hand lens, stomach, duodenum, and contents 
are to be sealed in the jar for the chemist. 
We now look for the orifice of the bile-duct, which will be found 
about the middle of the descending portion of the duodenum on its con- 
cave border. Pressure on the gall-bladder or on the common duct will 
usually cause the bile to flow into the intestine if the ducts are pervious. 
But a sufficient degree of stoppage may exist in the ducts to give rise to 
marked symptoms of disease, without preventing the flow of bile under 
these conditions, even with a moderate pressure. A long director is now 
passed into the gall-duct, which is laid completely open; ulcerations, 
cicatrices, gall-stones, inflammatory lesions, and tumors are looked for. 
In stricture of the gall-duct the mucous membrane above will often be 
found bile-stained, while below it is colorless. At this point, should 
there be any special reason for doing so, the portal vein, which lies close 
behind the ductus choledochus, should be opened and examined for peri- 
phlebitis, phlebitis, and thrombosis. The mucous membranes of the 
duodenum and stomach are now examined. Acute inflammation from 
caustic poisons, chronic catarrhal inflammations, haemorrhages, ulcers, 
erosions, swelling of the solitary follicles (lymph-nodules), and tumors 
are lesions most frequently seen. We sometimes find a diffuse congestion 
of the stomach, similar to that produced by irritant poisons, as a result 
of doses of croton oil given just before death. 
Preservation.-The same methods should be used as for the intestines (see 
above). Tumors should be cut into small pieces and hardened in Orth's fluid or 
5-per-cent. formaldehyde. 
The Liver.-To remove the liver, the diaphragm is first divided on 
one side of the suspensory ligament as far back as the spine; the suspen- 
sory ligament is then divided; then the right and left lobes being in turn 
raised, the lateral ligaments are severed. Then, the left lobe being seized, 
the organ is dragged obliquely downward into the abdominal cavity, the 
remaining attachments being dissected away. The liver is first laid on 
its superior surface and the gall-bladder and its contents are examined. 
The character of the gall is to be determined, and gall-stones, inflam- 
matory lesions, and tumors are to be sought for. To determine the 
actual size of the organ, it should be both measured and weighed. Its 
size varies greatly in different healthy individuals, but in general it may 
be said that it measures from 25 to 30 cm. transversely, from 15.3 to 18 
cm. antero-posteriorly, and from 9 to 12 cm. at its thickest part; its or- 
dinary weight is between 1,550 and 1,860 grams. In children its weight 
relative to that of the body is greater than in adults. The liver is 
increased in size and weight during digestion and by congestion from 
any cause. MAKING POST-MORTEM EXAMINATIONS 
1017 
The convex surface of the right lobe of the liver not infrequently 
shows several grooves running from front to back, approximately par- 
allel with the suspensory ligament of the liver. These grooves, which 
may be found in persons of all ages, are believed by some to be usually 
congenital, by others to be the result of pressure of the diaphragm and 
the abdominal muscles on a relaxed atrophic liver. They seem in any 
event to be of no practical importance. On the other hand, a transverse 
groove running at right angles to the axis of the body is a not infrequent 
result of tight lacing, and is usually associated with local connective- 
tissue thickening of the capsule and underlying tissue of the liver. In 
this way the liver may become much distorted and the gall-bladder com- 
promised. 
The capsule of the liver is now examined; the organ is then laid on its 
lower surface and several deep incisions are made from above downward. 
The color and consistence of the liver tissue should be noticed, also the 
distinctness with which the lobular outlines can be seen; whether or not 
the centres of the lobules are congested or their peripheries lighter in 
color than usual; the presence of tumors, tubercles, abscesses, ecchinococ- 
cus, new connective tissue, and pigmentation. Suspected amyloid de- 
generation should be tested for by iodin solution. 
We often find the surface of the liver of a greenish or very dark 
brown color; less frequently the same color extends into the substance of 
the organ. This discoloration, which is entirely post mortem, is, like 
the similar discoloration of other internal organs, produced by the action 
of the gases of putrefaction on the coloring matter of the blood. 
Preservation.-For the study of parenchymatous degeneration, sections of the 
fresh frozen tissue or small teased fragments should be examined in 0.85-per-cent. salt 
solution. For general purposes small pieces should be hardened in Orth's fluid or in 
formalin solution (10: 100) or in alcohol. Tumors should be treated in the same way. 
The Pancreas.-This organ, of a light yellowish red color, is elon- 
gated, irregularly prismatic in shape, and flattened antero-posteriorly; 
the right end, called the head, is broader than the rest and lies in the 
concavity of the duodenum. The remainder of the organ, the body and 
tail, are usually tapering and lie transversely in the abdominal cavity, 
the tail reaching to the spleen. Its size and weight vary considerably; 
its usual length is from 15.3 to 23 cm.; its breadth about 3.8 to 4.5 cm.; 
its thickness about 1.3 to 3.8 cm.; its weight is usually from 70 to 108 
grams. The organ may be rounded instead of flattened; the head and 
tail may be disproportionately large; the tail may be unusually long or 
may be divided or curved. The superior mesenteric artery and vein, 
which pass behind the gland, are usually partly embedded in it, but are 
sometimes completely enclosed. 
A longitudinal incision should be made through the whole gland, 
and its substance and duct should be searched for calculi, tumors, mal- 
formations, and evidences of acute and chronic inflammation, fat necro- 
sis, and amyloid degeneration of the blood-vessels. The pancreas is 
frequently of a dark red color from post-mortem staining. 1018 
MAKING POST-MORTEM EXAMINATIONS 
Preservation.-Portions of this organ should be hardened in strong alcohol, 
Orth's fluid, or in Flemming's osmic-acid mixture. 
The examination of the thoracic duct, which lies to the right and 
posterior to the aorta, may now be made. Among the most important 
of its lesions is tuberculosis, since it has been shown that from a tuber- 
culous lesion here the generalization of bacilli not infrequently oc- 
curs. Inflammatory lesions, carcinoma, partial or total occlusion from 
pressure may be found. 
The solar plexus, which surrounds the origin of the coeliac axis and 
the superior mesenteric artery and lies between the adrenals, may now 
besought. Lesions of the semilunar and other ganglia are to be noted- 
atrophy, pigmentation, and degenerations. 
The condition of the haemolymph nodes in the prevertebral fat should 
be ascertained (see p. 497). 
The Aorta.-The size of the lumen of this vessel should be determined. 
The average circumference of the ascending aorta in the adult may be 
taken in general as about 69 millimetres.1 Either in situ or after re- 
moval the aorta should be opened by an incision extending its whole 
length and continued into its larger branches. 
The Genito-urinary Organs. 
The Male Organs.-If the urine is to be examined it may be drawn off 
with a catheter; or a vertical incision may be made into the bladder just 
above the symphysis pubis, and some of the urine dipped out. The cut 
end of the rectum should now be grasped with the left hand and raised 
up, and this and the bladder, prostate gland, etc., dissected away from 
the pelvis, the knife being carried close to the bone. The bladder is 
now drawn backward and the loose tissue close under the symphysis 
pubis cut. The body of the penis is then shoved backward within the 
skin and dissected away from behind, beneath the symphysis, and finally 
cut off just behind the glans penis. The penis and bladder are now 
drawn backward and upward, and the pelvic organs removed together. 
Or, the penis may be removed by sawing away the bones above the pubic 
arch, and then dissecting away the penis, whose root is thus exposed. 
The pelvic organs are then laid on the table, the bladder uppermost; 
a long director is passed into the urethra, which is opened on its upper 
surface through its entire length, and the bladder widely opened. In 
the urethra the presence of strictures, diverticula, ulcers, inflammatory 
lesions, is to be noticed; in the bladder inflammatory lesions, hypertro- 
phies, congestion and ecchymosis of the mucous membrane, hyperplasia 
and ulcers of the lymph-nodules, and tumors. The organs are now 
turned over; the rectum is opened and examined for varicose veins, haem- 
orrhages, ulcers, strictures, and tumors. The prostate gland is then cut 
into and the presence of calculi, inflammatory lesions, hypertrophies, 
and tumors sought for. Lastly, the vesiculce seminales are examined, in 
1 See Vierordt's Tables; also v. Rito6k, Zeits. f. klin. Med., Bd. Ixi., p. 36, 1907. MAKING POST-MORTEM EXAMINATIONS 
1019 
which, though rarely, we may find evidences of tuberculous inflamma- 
tion and dilatation. 
The testicles may be removed, when necessary, without cutting the 
scrotum, by enlarging the inguinal canals from within and crowding the 
glands through them and cutting them off. The average weight of the 
adult testicle with its epididymis is, according to Krause, from 15 to 
24.5 grams. Inflammatory lesions, tuberculosis, abscesses, and tumors 
are the most frequent lesions. 
Preservation.-The urethral canal and bladder may be pinned open and hard- 
ened in Orth's fluid or in Flemming's osmic-acid mixture. The prostate, vesiculse 
seminales, testicles, and tumors may be hardened in the same fluids. 
The Female Organs.-The position and general condition of the pelvic 
organs should first be determined by inspection. Abnormal adhesions 
of the ovaries, broad ligaments, Fallopian tubes, and uterus; malposi- 
tions of the uterus; subserous tumors of the uterus, and ovarian tumors, 
are frequently observed. Hiemorrhage into the posterior cul-de-sac is 
sometimes found. The urine should be collected, if necessary, as above 
directed; the organs should be dissected away laterally, as in the male, 
care being taken not to injure the ovaries and Fallopian tubes. The 
bladder is then drawn strongly backward and upward, and dissected 
away from the symphysis and the pubic arch, and, the point of the knife 
being carried forward and downward, the vagina is cut off in its lower 
third, the rectum severed just above the anus, the remaining attachments 
cut, and the pelvic organs are taken out together. If it be necessary to 
remove the external generative organs, after freeing the lateral surfaces 
of the internal organs and the bladder, the legs are widely separated and 
the vulva and anus circumscribed by a deep incision. The tissues close 
beneath the pubic arch are now dissected away from below, and the 
vulva is thrust back beneath the symphysis; it is now seized above the 
bone, and together with the anus dissected away and removed with the 
other organs. 
The bladder is first opened and examined. The vulva may now be 
examined for hypertrophies, inflammatory lesions, ulcers, cicatrices, 
cysts, and tumors. The vagina is opened along the anterior surface; its 
more common lesions are inflammations, fistuke, ulcers, tumors, and 
rarely cysts. 
The Uterus.-Before opening this organ its size and shape should be 
determined. The adult virgin uterus is a pear-shaped body, flattened 
antero-posteriorly; the upper portion, or body, is directed upward and 
forward, while the lower portion, the cervix, is directed downward and 
backward. It is covered anteriorly by peritoneum to a point a little 
below the level of the os internum; posteriorly, to a point a little below 
the level of its junction with the vagina. The peritoneal investment 
separates from the organ at the sides to form the broad ligaments. The 
uterus is held in position by the broad and round ligaments and by its 
attachments to the bladder and rectum and vagina. The upper end, 
the fundus, does not extend above the level of the brim of the pelvis. 1020 
MAKING POST-MORTEM EXAMINATIONS 
Its average length is about 7.6 cm.; its breadth about 5.1 cm.; its thick- 
ness about 2.5 cm.; its average weight is about 31 to 46 grams. During 
menstruation the uterus is slightly enlarged, the mucous membrane 
of the body becomes thicker, softer, and its vessels are engorged with 
blood; while its inner surface is more or less thickly covered with blood 
and cell detritus. A description of the complicated changes in the 
uterus which pregnancy entails may be found in the works on obstetrics. 
After pregnancy the uterus does not return to its original size, but 
remains somewhat larger; the os is w'ider and frequently fissured. 
We not infrequently find in the mucous membrane of the lower part 
of the cervix small, transparent, spheroidal structures, called ovula 
Nabothi; these are small retention cysts caused by the closure of the 
orifices of the mucous glands. The more common lesions observed in 
the uterus are malpositions, malformations, lacerations, ulcerations of 
the cervix, acute and chronic inflammation of the mucous membrane or 
muscularis, or both, thrombosis and inflammation of the veins, and 
tumors. 
In the infant the uterus is small, the body flattened, the cervix dis- 
proportionately large. During childhood the organ increases in size, 
but the body remains small in proportion to the cervix. At puberty, the 
shape changes, and the body becomes larger. 
The ovaries are flattened, ovoidal bodies, situated one on each side, 
and lying nearly horizontally at the back of the broad ligament of the 
uterus. Their size is variable, and they are usually largest in the virgin 
state. They measure about 3.8 cm. in length, 1.9 cm. in breadth, and 
nearly 1.3 cm. in thickness. Their average weight is from 3.9 to 6.5 
grams. The sides of the ovary and its posterior border are free; it is 
attached along the anterior border; to its end is attached the ovarian 
ligament, to its outer extremity one of the fimbriae of the Fallopian tube. 
The ovary is covered on its free surface by cylindrical epithelium, and 
its surface is less glistening than the general peritoneum. The surface 
of the ovary is smooth in the young, but becomes rougher and depressed 
in spots as the process of ovulation goes on. In adult females we 
usually find corpora lutea in their various stages. We should seek for 
evidences of acute and chronic inflammation, for tumors and cysts. 
The Fallopian tubes, lying in the upper margin of the broad liga- 
ments, are from 7.6 to 10 cm. in length. The length often differs con- 
siderably on the two sides. They commence at the upper angles of the 
uterus as small perforated cords, which become larger farther outward, 
and bend backward and downward toward the ovary. They terminate 
in an expanded fimbriated extremity about 2.5 cm. beyond the ovary. 
They are covered by peritoneum, and the mucous membrane lining 
them, continuous with that of the uterus, is thrown into longitudinal 
folds. Malpositions by adhesions, closure, inflammations, and cysts 
are the more common lesions. The possibility of tubal pregnancy should 
be borne in mind. 
Preservation.-All of these organs and their tumors may be hardened in Orth's 
fluid or in Flemming's osmic-acid mixture. The vagina should be stretched flat on MAKING POST-MORTEM EXAMINATIONS 
1021 
cork, and the cavity of the uterus laid wide open. Great care should be taken not to 
touch either the internal surface of the uterus or the external surfaces of the ovaries, 
since in both the epithelium is very easily rubbed off. 
It is better, after opening them by a transverse incision, to suspend the ovaries by 
a thread in a jar of the preservative fluid than to let them lie on the bottom, since the 
epithelium is thus less likely to be rubbed off. Larger cysts of the ovary for exhibition 
purposes should be distended with preservative fluid. 
The Closure of the Body after the Post-mortem Examination. 
At the end of the autopsy the body should be restored as nearly as 
possible to its natural external appearance. 
Fluids should be removed, vacant spaces filled with absorbent mate- 
rial, such as cotton, jute, or sawdust, and the incisions closed by sutures. 
Bacterial Examination of Post-mortem Specimens. 
It is often important to make a thorough post-mortem examination 
by cultures as well as morphologically of the blood and of all the viscera. 
This is important not only in those cases which during life gave clinical 
evidence of general infection, but also in many forms of disease whose 
nature is still wholly obscure. 
In the interpretation of the result of all such examinations, however, 
it should be borne in mind that after death a new distribution of germs 
may occur, and that from the gastro-intestinal canal and from other sur- 
faces or cavities of the body micro-organisms may, as decomposition 
progresses, penetrate the tissues and the viscera. 
A careful consideration of the general conditions under which the 
body has been kept and its state of decomposition is of special importance 
in the interpretation of the significance of the Bacillus coli communis, 
which is always present in such enormous numbers in the intestinal canal, 
and which is not only apt to effect wide distribution in the body after 
death, but as a result of careless manipulation is likely to be accidentally 
brought in contact with other viscera after the opening of the gut. The 
preparation of cover-slips for staining and the making of cultures is, as 
a rule, best done at the autopsy table. 
It is well as each organ is exposed-commencing with the heart-to 
sear the surface of the organ to be examined with a broad-bladed knife 
heated over a flame, and then, making an incision through the seared 
surface with a sterilized scalpel, to press a sterilized cotton swab into 
the opening and absorb the juices which exude, or to pick out a small 
fragment of the solid tissue from the depths of the opening, or to secure 
some of the blood or fluid on a sterilized platinum loop; and then with 
the material thus procured make the required cultures and afterward 
the cover-slip smears for staining. 
If it be necessary to transport the material to the laboratory before 
making cultures, it is well to reserve the unopened organs, or large por- 
tions of these in the case of the solid viscera, and to wrap each separately 
in a cloth saturated with sublimate solution, or to put each in a separate 
sterile receptacle for transportation. 1022 
MAKING POST-MORTEM EXAMINATIONS 
It is well to remember that in the last hours of life the safeguards 
of the body against the entrance and growth of micro-organisms may 
be ineffective, so that the determination of the significance of bacteria 
in the tissues a short time after death requires care and experience.1 
Autopsies in Medico-legal Cases. 
While every autopsy should be made as carefully and completely 
as circumstances permit, it should be always borne in mind that in 
examinations which may have medico-legal bearings it is of the highest 
importance to examine thoroughly both macroscopically and micro- 
scopically every part of the body from which light may be derived as to 
the1 cause of death, for in medico-legal cases it is not infrequently as 
important to be able by a complete examination to declare the absence 
of lesions which could cause death, as to determine the presence of those 
upon which the opinion as to the actual cause of death in a particular 
case rests. Bearing this in mind, the technic of autopsy-making is 
essentially the same whatever the ends which the facts elicited may be 
destined to serve. 
Autopsies in Cases of Suspected Poisoning. 
In cases of suspected poisoning which may possibly have a medico- 
legal bearing, the examination should be made with extreme care and 
thoroughness. The inspection of the body and the examination of all 
the viscera should be thorough and detailed. Every appearance should 
be noted at the time, and nothing left to the memory. It is well to have 
an assistant record the observations as they are made. The disposition 
of the parts and organs in jars should be also noted at the same time. 
It is important to remember that many poisons destroy life without 
producing appreciable lesions, and also that many cases of sudden death 
occur, not due to poisons, and without any discoverable cause. 
In bodies which are exhumed for examination, the tissues may be so 
changed by decomposition that it is impossible to say whether lesions 
have or have not existed. In such cases the careful and separate preser- 
vation of the viscera and other parts for chemical examination, is often 
all that can be done. 
It is always best, in cases of suspected poisoning, to preserve for the 
chemist not only the stomach and intestines, but the entire liver and 
brain; or, if only portions of these can be saved, these portions should 
be carefully weighed, as well as the entire organs, and the relative 
amount of tissue reserved carefully noted at the time. It is even well, 
particularly in cases in which the administration of the readily diffusible 
poisons, such as arsenic, strychnia, etc., is suspected, to preserve the 
whole of all the internal organs, together with a large piece of muscle 
and bone; since with large quantities of tissue the results of the chemical 
1 For details of bacterial flora of the human bodjr see references pp. 150 and 319. MAKING POST-MORTEM EXAMINATIONS 
1023 
analysis depend less upon calculations, and are hence more compre- 
hensible to the average jury. In all such cases jars should, if possible, 
be procured which have never been used before, and these should be 
carefully washed and rinsed with distilled water. They should have 
glass stoppers and be sealed at once and carefully labelled before leaving 
the hands of the operator. If they can be delivered to the chemist with- 
out much delay, no preservative fluid should be added. If they are to 
be kept for a considerable time, pending the action of a coroner's jury 
or for some other reason, a small quantity of pure strong alcohol may 
be poured over them. In this the operator should be particular to 
preserve a quantity, at least half a pint, of the specimen of alcohol used, 
in a clean, sealed, and labelled bottle, so that this may be tested by the 
chemist and be proven to be free from the poison. It is better in all 
cases, however, to avoid, if possible, the use of alcohol. In all autop- 
sies which may have medico-legal importance full notes should be taken 
by an assistant as the operation proceeds, carefully read over immediately 
afterward and dated, and kept by the operator for future reference. 
The labelling and disposition of the jars should be recorded in the notes. 
The specimens should not for a moment be out of the sight of the oper- 
ator until they are placed under lock and key and seal, or are delivered 
to some authorized person, so that there may be no question of their 
identity should the case come into court. 
Examination of the Bodies of New-born Children.1 
In examining the bodies of new-born children, we may have to determine, besides 
the ordinary lesions of disease, the age of the child, whether it was born alive, how long 
it has been dead, what was the cause of death. 
Size, Age, and Characters of the New-born Child.-The fresh corpse of a new- 
born child at term no longer resembles that of the immature foetus. The skin is firm 
and pale, like that of an adult. The lanugo has disappeared except on the shoulders. 
In the majority of cases the hair on the head is 1.5 to 2 cm. long. The great fonta- 
nelle is, in the average, 2 to 3 cm. long. As determined by an analysis of 661 cases, 
the average length is 50 cm., the weight 3,256 grams. The nails are hard and reach 
to the tips of the fingers, but not to those of the toes. The cartilages of the ears and 
nose are hard. The labia are more nearly closed. An ossification centre in the lower 
epiphysis of the femur should be sought for, as its presence is one of the most reliable 
signs of the maturity of the foetus. If it is absent, the foetus is, as a rule, not more 
than thirty-seven weeks old; but in rare cases it may be absent at term. A centre of 
ossification 1 mm. in diameter indicates an age of thirty-seven to thirty-eight weeks, 
if the child was born dead or died soon after birth. Rarely it is no larger than this 
at term. A diameter, at birth, of 1.5 to 9 mm. indicates an age of 40 weeks. A 
diameter of more than 9 mm. indicates, as a rule, that the child has lived some time 
after its birth; a less diameter than 7 mm., however, does not prove the contrary. 
Twenty-four hours after the birth of the child the skin is firmer and paler. The 
umbilical cord is somewhat shrivelled, although still soft and bluish in color. From 
the second to the third day the skin has a yellowish tinge and the cuticle sometimes 
appears cracked. The umbilical cord is brown and dry. From the third to the fourth 
1 The human embryo, according to the estimate of His, measures in length approximately at 4 
weeks from 7-8 mm.; at 5 weeks 13 mm.; at the end of the second month 25-28 mm. Schroder estimates 
the approximate length of the foetus at later lunar months as follows: 3d, 70-90 mm.; 4th, 100-170 mm.; 
5th, 180-270 mm.; 6th, 280-340 mm.; 7th, 350-380 mm.; 8th, 425 mm.: 9th, 467 mm.; 10th, 490-500 
mm. Consult for further data McMurrich, "The Development of the Human Body," 1903, p. 108, bibl. 1024 
MAKING POST-MORTEM EXAMINATIONS 
day the skin is yellower, and the cuticle is apt to separate from the skin. The umbili- 
cal cord is of a brownish red color, flattened, semi-transparent, and twisted. The 
skin around its insertion is red and congested. 
General Inspection.-The head should be examined for the marks of injuries. 
Very commonly some portion of the scalp will be found swollen and infiltrated with 
blood and serum. This may be the caput succedaneum formed during delivery. The 
mouth and nose should be examined for the presence of foreign bodies which might 
have caused suffocation. 
The neck should be examined for marks of strangulation. The umbilical cord may 
be twisted around the child's neck and strangle it. The mark left by the cord is usu- 
ally continuous, broad, not excoriated, sometimes accompanied by ecchymoses in the 
skin. 
The surface of the body should be examined for the presence of vernix caseosa, 
blood, marks of injury, and the existence of putrefaction. It should be remembered 
that putrefaction is apt to commence earlier in the bodies of young children than in 
those of adults. 
The umbilical cord may be cut or torn. It usually separates by the fifth day, some- 
times not until the tenth. If the umbilicus is cicatrized and healed, the child has 
probably lived for three weeks. A zone of redness around the insertion of the -cord 
may exist previous to birth. Redness and swelling (which may disappear after death) 
with suppuration can be found only in a child which has lived for several days. The 
drying and mummification of the cord may take place as well in dead as in living 
children. It is possible for a child to die by haemorrhage from a cut or torn cord, either 
before or after it has breathed. The umbilical vessels should be examined, as they 
may be the seat of umbilical infection. 
The extremities may exhibit fracture of the bones. These may occur during intra- 
uterine life, from injuries to the woman or from unknown causes; or may be produced 
by violence in delivery, or by injuries after birth. 
Internal Examination.-The Head.-The fontanelles and sutures should first be 
examined as to their size and for penetrating wounds. An incision should then be 
made through the scalp across the vertex, and the flaps turned backward and forward 
as in the adult. With a small knife the edges of the bones should be separated from 
the membranous sutures and the dura mater, beginning low down in the frontal and 
going back into the lambdoidal suture on either side. The bones are then drawn out- 
ward and cut through around the skull with strong scissors. The brain is removed 
and examined as in the adult.1 
Effusions of blood-cephalhaematoma-may be formed, soon after birth, between 
the pericranium and bone, or, more rarely, between the dura and bone. Clots are 
also found between the dura mater and skull; between the dura and pia mater; more 
rarely in the substance of the brain, as the result of protracted or instrumental 
deliveries, or of injuries after birth. 
The cranial bones may be malformed, or exhibit the lesions of rickets or caries, or 
be indented, fissured, or fractured. These latter lesions may be produced during 
intra-uterine life by injuries to the mother, by unknown agencies, by difficult deliveries, 
or by direct violence after birth. 
In cases of chronic internal hydrocephalus in young children, in which the ventri- 
cles are much dilated and the brain substance is thinned over the vertex, the brain is 
very apt to be torn in removal, and the amount of dilatation thus becomes difficult of 
determination. It is, therefore, better in such cases to place a pail of water beneath 
the head, or even immerse the latter in it, and remove the brain in the water. In this 
way it floats after removal, supported on all sides. It may now be opened in the 
water and the extent of the lesion determined at once, and parts saved for microscopi- 
cal examination. 
If it be desired to preserve the brain for demonstration of the lesion or for a 
museum specimen, it should be transferred unopened to a large jar containing 5-per- 
cent. formalin. A portion of the ventricular fluid should now be removed with a 
syringe provided with a small cannula, and replaced by formalin. This may be done 
1 Or an incision through the bones with a fine saw may be made as in the adult. MAKING POST-MORTEM EXAMINATIONS 
1025 
by puncturing the ventricles from below. The fluid in the jar, as well as in the 
ventricles, should be changed in forty-eight hours. The brain may then be cut trans- 
versely across, when the degree of dilatation of the ventricles, etc., will be revealed. 
The weight of the brain, according to Bischoff, is 380 grams. 
It is normally much softer and pinker than in the adult, the pia more delicate; both 
may be much congested or anaemic without known cause. The ventricles contain 
very little serum. Malformations, apoplexies, hydrocephalus, simple and tuberculous 
inflammatory lesions, are to be looked for. 
The Spinal Cord.-Extravasations of blood between the membranes of the cord 
may occur from the same causes as those in the brain. Spina bifida is the most fre- 
quent malformation. 
The Thorax and Abdomen.-These are opened as in the adult. The peritoneal 
cavity contains a very little clear serum. A red fluid may be produced by decompo- 
sition. The peritoneum is often the seat of intra-uterine inflammation. 
The Diaphragm.--In still-born infants its convexity reaches to the fourth or fifth 
rib. After respiration it reaches a point between the fourth and seventh ribs. Its 
position is, however, so variable that it is of little diagnostic importance. 
The Thorax.-The thymus gland, at this period very large, occupies the upper por- 
tion of the anterior mediastinum, covering the trachea and large vessels. Its average 
weight is about 15.5 grams. It is usually about 5 cm. long, 3.8 cm. wide at its lower 
part, and about .63 to .85 cm. in thickness. It may be hypertrophied and compress 
the large vessels, or be inflamed and suppurating. 
The heart lies more nearly in the median line than in the adult. It weighs from 
20 to 24 grams. The ventricular walls are of nearly equal thickness. The pericar- 
dium contains very little serum. A considerable quantity of red fluid may accumu- 
late here as a result of decomposition. There may be small extravasations of blood 
beneath the pericardium in still-born children and in those born alive. Pericarditis 
with effusion of serum and fibrin, and endocarditis with consequent changes in the 
valves, may exist before birth. Malformations and malpositions of the heart and 
large vessels are not infrequent. Small soft reddish nodules may be present on the 
edges of the valves which are remnants of the foetal mucous tissue, but may be mis- 
taken for the marks of endocarditis. The time of closure of the foramen ovale and 
the ductus arteriosus varies very widely in different cases. 
The pleural cavities contain very little serum, but decomposition may lead to the 
accumulation of a considerable quantity of red fluid. Small extravasations of blood 
in the subpleural tissue may be found in children who have died before birth and after 
protracted labors. Inflammation, with exudation of serum, fibrin, and pus, may 
exist before birth. 
The lungs in a still-born child are small, do not cover the heart, are situated in the 
upper and posterior portions of the thorax, are of a dark red color and of firm, liver- 
like consistence, and do not crepitate. In a child born alive, and which has respired 
freely, the lungs fill the thoracic cavity, but do not cover the heart as much as in the 
adult; they are of a light red or pink color, and crepitate on pressure. If respiration 
has been incompletely performed, we find various intermediate conditions between 
the foetal and inflated states. 
If any doubt exists as to respiration having taken place, it is customary to employ 
the hydrostatic test. This is done by placing the lungs, first together, then separately, 
and afterward cut into small pieces, in water. It is commonly said that if they sink 
the child has not breathed; if they float it has. This test is not, however, a certain 
one.1 
The lesions of inflammation, and vesicular and subpleural emphysema, may be 
found in the lungs of new-born children. 
The pharynx should be opened and examined for foreign bodies. 
The larynx and trachea should be examined for the lesions of inflammation and for 
injuries to the cartilages. 
The thyroid gland weighs about 12 grams. It may be so enlarged as to interfere 
with respiration. 
1 See works on medical jurisprudence. 1026 
MAKING POST-MORTEM EXAMINATIONS 
The Abdomen.-1The kidneys are lobulated and proportionately larger than in the 
adult. Thoma estimates the average weight of both organs together as 23.6 grams. 
There may be ecchymoses on their surface; inflammation; deposits of uric acid and 
urates in the tubules of the pyramids; cystic dilatation of the tubules, sometimes 
reaching an enormous size. There may be absence or retarded development of one 
kidney. Malformations and malpositions of the kidneys are of frequent occurrence. 
The adrenals are large. They may be dilated into large cysts filled with blood. 
The spleen is large and firm. Its average weight is about 11 grams. It may be 
abnormally enlarged, and its surface is sometimes covered with fresh inflammatory 
exudations. 
The Intestines.-In the small intestines, inflammation and swelling and pigmenta- 
tion of the solitary and agminated follicles (lymph-nodules) are sometimes found. 
The large intestine usually contains meconium, but this may be evacuated before or 
during birth. The sigmoid flexure is not as marked as in the adult. 
The formation of gas in the stomach and intestines does not usually take place 
until respiration is established. If decomposition has commenced, however, gas may 
be formed as a part of the process. 
The liver is of a dark red color, is large, and contains much blood. Its size dimin- 
ishes after respiration is established. Its average weight is 118 grams. The size is so 
variable, before and after respiration, that it gives little information as to the age of 
the child. Large extravasations of blood are sometimes found beneath the capsule of 
the liver without known cause. A variety of pathological conditions, fatty and waxy 
degeneration, gummy tumors, etc., may be found. 
The bladder may be full or empty, both in still-born children and in those which 
have breathed. Dilatation and hypertrophy may exist during intra-uterine life. 
Generative Organs.-The external generative organs in both males and females are 
more prominent than in adults. The ovaries are high up in the pelvis and large; the 
cervix uteri is long; the body small and lax, resting forward against the bladder. 
Phimosis in the males is the normal condition. Malpositions and retarted develop- 
ment of the testicles should be noticed. It should be observed whether the anus is 
perforate. 
The bones, in suspected cases, should be examined for the lesions of inflammation, 
rickets, and syphilis. 
Preservation.-The various foetal tissues may be preserved by the same methods 
are as employed for those of the adult; but as they are very delicate they should be 
handled with great care and the preservative fluids changed with sufficient frequency. CHAPTER II. 
GENERAL METHODS OF PRESERVING PATHOLOGICAL SPECI- 
MENS AND PREPARING THEM FOR STUDY. 
It is not our purpose in this section to give a complete account of 
the technical procedures required in the study of pathological specimens. 
We wish simply to furnish a few brief hints as to the most useful methods 
for ordinary purposes. Additional suggestions will be found in parts of 
the book dealing with special tissues and organs; but for the technical 
details of many complex methods which are invaluable for special pur- 
poses, one may consult Lee, 11 Microtomist's Vade-Mecum," 7th edition, 
1913; Mallory and Wright, "Pathological Technique," 5th edition, 1913; 
and Schmorl, " Die pathologisch-histologischen Untersuchungsmethoden," 
7th edition, 1914. The special technique of the blood will be found in 
Schridde und Naegeli, " Hifmatologische Technik," 1910; and Wood, 
"Chemical and Microscopical Diagnosis," 3d edition, 1912. 
The Study of Fresh Tissues. 
Although for the most part the conditions for the minute study of 
tissues are more favorable after these have been fixed and hardened by 
a suitable chemical agent, it is yet in many cases very important to 
examine them in the fresh state. 
In this condition many of the degenerative changes in cells are more 
clearly seen than after fixation, while the study of living cells in indif- 
ferent fluids with various stains may throw much light upon vital phe- 
nomena and the changes which supervene when life ceases and the cell 
falls under the sway of the simple physical and chemical forces. 
Fresh tissues may be teased apart, mounted and studied in 0.85 per 
cent, sodium chloride solution, but it is usually much more satisfactory to 
cut frozen sections of the tissue to be examined. 
The study of living cells is often facilitated by the addition to the 
physiological salt solution of small amounts of either neutral red, methy- 
lene blue, or thionin. These dyes stain the nuclei or other portions of the 
cell, and often give very satisfactory pictures.1 
In the method of Arnold2 the cells are protected from pressure of the 
cover-glass and the study facilitated by the use of thin sections of dried 
elder pith dipped in the fluid containing the living cells and tinged with 
the coloring agent. 
For the methods of studying the circulation on the curarized frog 
see page 111. 
1 Consult for theory of vital staining Ruzicha, Zeits. f. wiss. Mik., Bd. xxii., p. 91, 1905. For 
colorability of living cells see Coco, Cbl. f. allg. Path., Bd. xiii., p. 604, 1902. 
2 Arnold, Munch, med. Wochenschr., p. 585, 1906. 
1027 1028 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
Rapid Fixation and Frozen Sections. 
A rapid fixation and development of detail in structural elements in 
fluids may be secured by allowing a drop of formalin to run under the 
cover-glass and mingle with the salt solution, the flow being directed by 
a bit of filter paper put close to the edge of the cover-glass on the side 
opposite to that on which the fixative is added. The formalin may be 
washed out by saline and the latter replaced by a dilute aqueous solution 
of thionin to stain the nuclei. 
When an immediate diagnosis of a solid tissue is required, useful 
results may be obtained by a combination of the freezing method with 
the use of formalin as a fixative.1 Any form of freezing microtome and 
either ether, ethyl chloride, or liquid carbonic acid may be used. 
Many tissues can be frozen immediately after their removal from the 
body, cut, floated on to a slide with salt solution, and then stained with an 
aqueous solution of thionin blue. They can be mounted in the saline or 
preferably in Bruns'2 glucose medium, in which they keep for a few 
hours. When the tissues are gelatinous or contain considerable fat, they 
can be fixed in hot four-per-cent, formaldehyde (50° C.) or even boiled for 
a few minutes in the same solution. This will permit of an immediate 
examination. Such fixation is very imperfect, however, and portions of 
the tissue should always be reserved for regular fixation and sectioned 
after embedding. 
If an immediate examination is not of great importance Wright's 
method is the best to use. This is as follows: 
1. Fix pieces of tissue in four-per-cent, aqueous formaldehyde, for 
fifteen to twenty-four hours. 
2. Cut the tissue into slices not over 5 mm. thick, and after rinsing in 
water, freeze and section. 
3. Float the sections off the knife into water; select a suitable one; 
and spread it smoothly on a slide by passing the slide into the water 
under the section and drawing the latter gradually up on the glass. 
4. Drain off the water. 
5. Blot the section with smooth blotting paper. It will then adhere 
to the slide. If it contains much mucoid material cover the section with 
absolute alcohol for a few seconds before blotting it. 
6. Pour over the section a small quantity of absolute alcohol, allowing 
it to stay on for five seconds. 
7. Cover the slide with a thin solution of celloidin; drain off; allow the 
film to become firm by waving the slide in the air for a few seconds, and 
then place the slide in water. 
8. The section can be stained by any of the usual methods, as it is 
held permanently to the slide by the celloidin, unless the absolute alcohol 
is left on too long. 
1 Cullen, Johns Hopkins Hospital Bulletin, vol. vi., p. 67, 1895. 
2Bruns' glucose medium js made up as follows: Distilled water, 140 c.c.; glucose, 40 gms.; gly- 
cerin, 10 gms. About 5 c.c. of 40% formaldehyde should be added to prevent decomposition and 
fix the tissues. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1029 
Fragile sections had better be carried through ninety-seven-per-cent, 
alcohol and mounted in the new mounting medium of Gilson, known as 
Euparal, which can be obtained from Griibler, and mounts from ninety- 
seven-per-cent. alcohol. 
Fixation, Hardening and Preservation. 
Alcohol is the most commonly employed fixative and hardening 
agent for routine purposes. It is used in the strength of from 80 to 
95 per-cent, at first, the pieces of tissue to be hardened not being 
larger than 1 or 2 cubic centimetres. There should be in bulk many 
times as much alcohol as tissue to be hardened. A little absorbent 
cotton may be placed in the bottle to keep the blocks of tissue from 
sticking to the bottom. After twenty-four hours the alcohol should 
be renewed. On the third day the tissue is transferred to 97 per-cent, 
or to absolute alcohol for completion of the hardening, which will usually 
be within five or six days. 
While for many purposes other and more delicate methods of harden- 
ing tissues are to be recommended, alcohol is most useful for solid tissues 
in which bacteria are to be sought, for such specimens as are not quite 
fresh and in which the process of decay is to be immediately checked, 
and in general for tissues in which the determination of topographical 
features for diagnostic or other purposes is the chief end in view. 
Formalin, or formol, is the trade name for a 37-per-cent. aqueous 
solution of formaldehyde. In diluted solutions it is a valuable fixative 
for delicate tissues. It is most commonly used in a solution of 10 parts 
(of the commercial formalin) to 90 of water. The fresh tissues, in small 
pieces, are put in this solution for forty-eight hours, the fluid being 
renewed at the end of twenty-four hours. They are then transferred 
to 60-per-cent alcohol for twenty-four hours, and the hardening is 
completed with strong alcohol. 
Muller's fluid, which has been much used as a hardening agent, 
has the following composition: 
Potassium bichromate - 2 parts. 
Sodium sulphate 1 part. 
Water 100 parts. 
Muller's fluid is now most often used in combination with other 
fixatives. 
Thus Orth's fluid, which is Muller's fluid to 90 parts of which 10 parts 
of commercial formalin are added, is a most valuable agent for fixing and 
hardening delicate cells. The mixture should be made at the time of 
using because it soon changes. The pieces of tissue should be small, the 
fluid largely exceeding the tissue in bulk. The hardening is completed 
in three or four days, when the specimens should be thoroughly washed 
in water and preserved in 80-per-cent. alcohol. 
Osmic acid is of great value, especially in combination, for the 
hardening of small portions of delicate tissues, since it serves to fix the 1030 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
elements in a nearly normal condition and stains them brown or black. 
Osmic acid stains most forms of fat black and on this account is a valuable 
agent for the detection of this substance in the tissues. It is generally 
used in 1-per-cent. aqueous solution, the tissues, in very small pieces 
and when quite fresh, being placed in it and allowed to remain for twenty- 
four hours. They are now washed thoroughly in water and may be 
preserved in 80-per-cent. alcohol. 
Flemming's Osmic Acid Mixture.-For the purpose of fixing delicate 
tissue elements to show minute structural detail, such as mitotic figures, 
this mixture is of great value. It is made of 
1-per-cent. solution of chromic acid 15 parts. 
2-per-cent. solution of osmic acid 4 parts. 
Hydric acetate, glacial 1 part. 
This mixture does not keep well, and hence should be made up in small 
quantities. Small portions of tissue should soak in the mixture for 
twenty-four hours, then, after thorough washing in water, they are put 
for twenty-four hours in 70-per-cent. alcohol, and then in strong alcohol, 
in which they are kept. 
Corrosive Sublimate.-This is a most excellent fixative for delicate 
structures. A convenient form is Lang's Solution. Its formula is: 
Mercuric chlorid 5 gms. 
Sodium chlorid 6 gms. 
Hydric acetate, glacial 5 c.c. 
Water 100 c.c. 
The tissues should remain in sublimate solution, as a rule, not longer 
than from one to three hours. 
Specimens fixed in sublimate develop a mercurial precipitate, do not 
stain well, and become brittle unless the excess of sublimate is removed. 
This can be largely done by prolonged washing in running water. But 
it is much more easily and certainly accomplished by the chemical action 
of dilute iodin solution. The specimen is removed from the sublimate 
mixture and put at once into 70-per-cent. alcohol. To this is added 
from time to time a sufficient quantity of saturated alcoholic solution of 
iodin (or tincture of iodin) to give the alcohol a moderately deep iodin 
color. At first this color gradually disappears, and the iodin solution 
should be repeatedly added until the color persists. The specimens 
are now transferred to 70-per-cent. alcohol, and, after twenty-four-hours, 
to strong alcohol. 
Zenker's fluid is a good fixative and acts rapidly. It is a combina- 
tion of Muller's fluid and corrosive sublimate with acetic acid. Its 
formula is: 
Potassium bichromate 2.5 parts 
Sodium sulphate 1 part. 
Mercuric chloride 5 parts 
Hydric acetate, glacial 5 parts. 
Water 100 parts. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1031 
The acetic acid should be added at the time of using, since the com- 
plete mixture readily decomposes. Small pieces of tissue may be hard- 
ened in this solution in from four to twenty-four hours. They should 
be thoroughly washed in running water and preserved in 80-per-cent. 
alcohol. The use of iodin to remove the excess of sublimate, as described 
under Lang's solution, above, is desirable here also. 
Pathological specimens which occur, or are isolated, in the form of 
membranes, should be stretched with pins on a piece of wood or flat 
cork before being immersed in the preservative fluids. Minute struc- 
tures, such as occur in exudates from the mucous membranes and in 
cyst fluids, renal casts, etc., may be hardened in Flemming's osmic-acid 
mixture or in formalin followed by alcohol. Under these conditions 
renewals or changes of the fluids may be effected in tubes by the use of 
the centrifugal machine. The specimens may finally be preserved in 
80-per-cent. alcohol. 
Bones which are the seat of lesions, and calcified tissues, must be 
freed from lime salts before thin sections can be made. 
Tissues which are to be decalcified should be in small pieces and first 
well hardened in alcohol, formalin, or Orth's fluid. Zenker's fluid and 
sublimate are not satisfactory. 
The best method for the rapid decalcification of tissues is by means of 
a solution of nitric acid containing 5 parts by weight of the acid to 95 parts 
of water. The strong nitric acid of commerce has a specific gravity of 
1.414 and contains sixty-eight-per-cent, of acid; approximately 7.5 c.c. 
of acid, therefore, are to be used with 92.5 c.c. of water. The amount of 
fluid used should be large, and it should be frequently shaken, or, prefer- 
ably, kept turning with one of the small water motors used in chemical 
laboratories. The fragments of tissue should be tested repeatedly by 
pricking them with a fine steel needle. When no grating is felt along the 
needle it may be assumed that the lime has disappeared. The fragments 
are then transferred to a five-per-cent, solution of sodium sulphate for 
twelve to twenty-four hours, and then washed for forty-eight hours in 
running water. The tissue can then be cut on a freezing microtome, or 
embedded in celloidin or paraffin. 
Decalcifying. 
Embedding and Section Cutting. 
EMBEDDING. 
Some dense tissues, after being well hardened, are sufficiently solid to 
permit of thin sections being made from them without further prepara- 
tion, but in most cases very thin sections cannot be prepared without 
filling the interstices of the tissue with some embedding material, which 
gives it greater consistence and holds the tissue elements firmly in their 
natural relations to one another, while the section is being made. Cel- 
loidin and paraffin are the most generally useful materials for this purpose. 
Celloidin, a non-explosive, purified form of gun-cotton, is best 1032 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
obtained in the form of thin shavings, since in this form it is most easily 
dissolved. A 6-per-cent solution is made in equal parts of sulphuric 
ether and strong alcohol. The specimen in small pieces is soaked for 
twelve hours in this celloidin solution diluted with an equal amount of 
the mixture of alcohol and ether, then for twelve hours in the 6-per- 
cent. celloidin solution. If the specimen be small and require but little 
support, it may now be laid directly on the end of a small block of wood 
or cube of glass or vulcanite, and a few drops of celloidin poured around 
it. In most cases, however, it is better to make a small paper box, in 
which the specimen is placed in a proper position, and the celloidin 
poured in around it so as completely to enclose it. In either case a con- 
siderable quantity of celloidin should be poured around the specimen, 
since the celloidin shrinks considerably in hardening. The paper box 
may be made by winding a strip of thin paper around the end of the 
supporting block, allowing it to project for a sufficient distance beyond 
the end. The paper is held in place by a rubber band. We have thus 
a cylindrical box with a solid bottom projecting below it by which the 
whole can be held in the clamp of the microtome. 
After the specimen, either free on the end of the block or in its box, 
is surrounded by celloidin, it should be allowed to stand for a short time 
exposed to the air, so that the celloidin may harden on the outside by the 
evaporation of the ether. If the temperature be high, the too rapid 
evaporation of the ether will cause bubbles to appear in the mass. This 
should be avoided by covering the specimen with a bell-jar. After the 
celloidin mass has acquired sufficient hardness on the outside to keep its 
shape, the whole should be placed in 80-per-cent. alcohol, in which 
the celloidin will harden and acquire a sufficient consistence for cutting 
in a few hours. When this is accomplished the paper may be stripped 
off, and the specimen is ready for sectioning. 
After the sections have been cut they may be stained in the usual way 
(see below) and mounted in glycerin or balsam. If mounted in balsam, 
the oil of origanum cretici is used for clearing. 
The uncut portion of tissue may be preserved, embedded in celloidin, 
by keeping it in 80-per-cent. alcohol. It is better, in permanent pre- 
servation of uncut celloidin-embedded specimens in bulk, to cut them 
off from the wooden blocks, since alcohol extracts from these a dark 
resinous material which colors the specimen and interferes with the 
staining of sections. If glass or vulcanite blocks be used, the whole may 
be kept in alcohol. 
Stepanow has recently devised a more rapid procedure in celloidin 
embedding. The celloidin solution is made by the following formula, a 
few days being required for dissolving: 
Celloidin 15 gm. 
Oil of cloves 50 c.c. 
Ether 200 c.c. 
Absolute alcohol 10 c.c. 
The hardened specimen is transferred from strong alcohol to a small METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1033 
portion of the solution in a closed bottle. In from three to six hours a 
small piece of ordinary tissue is usually impregnated. It is then put in 
position on the mounting block and placed in pure chloroform. In this 
the proper consistency for section cutting is secured in from two to three 
hours, after which the whole is transferred to 80-per-cent. alcohol. If 
the specimen remaining after sections have been secured is to be kept, it 
should be removed from the block and placed in chloroform. 
For further details of this method see the original description.1 
Paraffin.-For some purposes, especially when extremely thin 
though not large sections are required, paraffin embedding is almost 
indispensable. The sections of tissues thus embedded may be cut 
exceedingly thin (2 to 3 n, or even 1 /z, with the Minot-Blake microtome), 
and when these are fixed to the slide and appropriately stained, the con- 
ditions for the study of cytological details are more favorable than by 
any other method. For the paraffin technique the specimen should be 
small, say one-half cubic centimetre as a maximum limit. The specimen, 
freed from the preservative fluid, is dehydrated by graded alcohols as 
follow's: 30-per-cent., 50-per-cent., 70-per-cent., 85-per-cent., and finally 
95-per-cent., remaining in each of these alcohols for two or several hours, 
and is then placed in absolute alcohol. Complete dehydration of the 
specimen is indispensable, for, if the slightest trace of water be left in 
the specimen, shrinkage or other artificial changes in the tissue are apt 
to occur, when the specimen is transferred to the clearing media prepara- 
tory to immersion in the melted paraffin. 
When the specimen is thoroughly dehydrated by absolute alcohol, it 
should be put into a mixture of carbon disulphide and alcohol, equal 
parts; then into pure carbon disulphide; then into carbon disulphide 
saturated with paraffin at room temperature; and, finally, into carbon 
disulphide saturated with paraffin at 37° C. If the block is thin, it 
must remain in each of these mixtures for from three to four hours. If 
it is large, the time must be proportionately longer. The specimen is 
then transferred to a dish of' melted paraffin, and, after one hour, to a 
second dish of melted paraffin for one hour. Paraffin with a melting 
point of 52° C. is usually employed. At the end of two hours the tissue 
is removed and embedded in fresh paraffin. 
A small paper box considerably larger than the specimen itself is 
filled with melted paraffin, and with a warm needle or forceps the speci- 
men is transferred to the paper box and set in its proper position in the 
bottom, so that the surface to be cut lies against the bottom of the box. 
In order to avoid the slow cooling of the paraffin around the specimen in 
successive layers, which prevents the formation of a homogeneous mass, 
the paper box with its contents is quickly cooled by being put into cold 
water, even iced water. When the paraffin block is hard, it is fastened 
with paraffin on to one of the various discs belonging to the paraffin 
microtome, trimmed so as to have a rectangular cutting surface, and 
sections are cut with a dry knife. In order to stain these sections, 
the paraffin must be removed from the interstices; this may be done with 
1 Stepanow, Zeitschr. f. wissenschaftl. Mikroscopie, Bd. xvii., p. 185, 1900. 1034 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
xylol. But when the supporting paraffin is removed from the sections 
they are liable to fall to pieces during the further staining and other 
manipulations. The only practical plan therefore with the great major- 
ity of paraffin sections is to affix them to a slide and carry them in this 
way through the various staining and mounting procedures. 
The best way of affixing delicate paraffin sections to a slide is by 
means of a thin film of albumen. Equal parts of white of egg and 
glycerin are thoroughly stirred together, filtered through paper, and a 
small amount of carbolic acid is added to prevent the growth of micro- 
organisms. A very small drop of this albumen mixture is placed on one 
end of the slide, and with the ball of the finger or a fold of cloth it is 
spread over the rest of the slide in as thin a film as possible. While this 
scarcely perceptible film of albumen fixative is still moist, the paraffin 
sections or the ribbons of serial sections, divided into proper lengths, are 
laid upon the film and gently tapped down flat with a small camel 's-hair 
brush or the finger-tip.1 
The slide with the attached paraffin sections is now heated over a 
flame, warmed just sufficiently to begin to melt the paraffin; this is a very 
delicate point in the operation. Just enough heat must be used to melt 
the paraffin and no more. If the slide be heated beyond this point, the 
sections may be shrunken or completely ruined. While the slide is still 
warm, it is plunged into a jar of xylol, oscillated to and fro a few seconds, 
then placed in a jar of absolute alcohol, then passed through a series of 
jars containing different strengths of alcohol-95-per-cent., 70-per-cent., 
50-per-cent., and 30-per-cent., remaining a few minutes in each, and 
finally into water. Now the sections upon the slide may be stained in 
whatever way desired, carried up through the graded alcohols to absolute 
alcohol, then cleared in xylol or other clearing media, and mounted in 
balsam. 
Tightly covered cylindrical jars-the Coplin jar is excellent-or wide- 
mouthed bottles are used for the better manipulation of paraffin sections, 
the whole slide being dropped into the receptacle for staining as well as 
for the dehydration and clearing. 
This may be done in an emergency by the free hand with a razor 
ground flat on the lower side, but better sections can be obtained by 
means of a microtome, and practically all section cutting for microscop- 
ical purposes is done by some form of this instrument. One of the 
most useful of these is Thoma's. The Schanze microtome is also well 
adapted for general work, as are some of the American instruments 
SECTION CUTTING. 
1 Not infrequently very thin paraffin sections curl or become corrugated as they leave the knife, 
so that it is difficult to place them flat upon the fixative film. Should this occur, a few drops of water 
may be spread out in a thin layer over the albumen film while it is still moist on the side, and the 
whole slide, with the layer of water upon its surface, is very gently heated over the flame-just suffi- 
cinetly to soften but not to melt the paraffin. If thejsections are then floated on the warm layer of 
water, they will uncurl and flatten out. The water is .then drained off, when the flattened sections will 
lie flat upon the fixative film and remain fastened there. All traces of the water are now allowed to 
evaporate in the air; or, the evaporation of the water may be hastened by exposure to a temperature 
four or five degrees below the melting-point of the paraffin. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1035 
made on the same plan. For cutting sections of tissues embedded in 
paraffin, and especially for serial sections, the Minot microtome of the 
improved form, as made by the International Instrument Company of 
Cambridge, Mass., is excellent. 
Methods of Staining. 
Sections of hardened tissues may be stained for microscopical study 
in a variety of ways, but for routine work the double staining with haema- 
toxylin and eosin is most generally useful, and is applicable to nearly 
all cases. 
Haematoxylin solution (Delafield's) is prepared as follows: To 100 
cubic centimetres of saturated solution of ammonia alum add 1 gram of 
haematoxylin crystals dissolved in 6 cubic centimetres of 95-per-cent. 
alcohol. This solution is exposed to the light for a week, the color 
meanwhile changing from a dirty red to a deep bluish-purple color.1 
Then 25 cubic centimetres each of glycerin and wood naphtha are added. 
This mixture is allowed to stand for a day or two and is then filtered, and 
the filtration is repeated at intervals until a sediment no longer forms. 
The solution is now ready for staining, the best results being obtained 
by diluting the fluid with from ten to twenty times its bulk of water. 
The sections are immersed in the fluid, and allowed to remain until they 
have acquired a distinct purple color which persists after rinsing in 
water. They are now placed for a moment in a dilute alcoholic solution 
of eosin, and then mounted in glycerin which has been colored lightly 
with an alcoholic solution of eosin. In this way the nuclei of the cells 
will be stained of a purple color, while the cell bodies, and to a certain 
extent the intercellular substance, will be colored a light rose red. 
If specimens are to be mounted in Canada balsam, they are stained 
with haematoxylin as before, and the eosin staining is done by tinging 
with a saturated alcoholic solution of eosin, the alcohol with which the 
final dehydration of the specimen is accomplished. A similar result 
may be obtained by tinging the oil of cloves or origanum with which the 
clearing of the sections is effected. 
Iron Haematoxylin (Heidenhain's).--Sections, preferably fixed to the 
slide, are soaked for three to six hours in a 2.5 per-cent, solution of ferric 
ammonium alum. They are then stained for twenty-four hours in a 
mixture of haematoxylin, 1 gram; absolute alcohol, 10 c.c.; water 90 c.c. 
After washing in tap water, the sections are differentiated in the alum 
solution, 2.5-per-cent. or weaker, depending upon the desired rate of 
decoloration. The preparations should be watched carefully under the 
microscope to determine when the desired depth of standing is reached. 
This method is especially valuable for the study of nuclear struc- 
tures, the color of these ranging from blue to black, depending upon the 
length of time of immersion in the stain and the grade of differentiation. 
Picro-acid Fuchsin (Van Gieson's Stain).-This double stain, first 
1 The time required for this "ripening" of the solution may be spared by the use of hicmatin in the 
place of haematoxylin. 1036 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
suggested by Van Gieson, especially for the nerve tissue, has wide appli- 
cations in both normal and pathological histology, and is most useful 
when following a deep haematoxylin stain. 
It colors the fibrillated connective-tissue fibres and the neuroglia in 
general a bright or garnet red, and also the axis cylinders and ganglion 
cells. Myelin, muscle fibres, and certain other cells are stained yellow, 
while the nuclei after the haematoxylin stain are brownish red in color. 
Van Gieson's stain is also of value, although its limitations in this par- 
ticular are not yet fully determined, as a coloring-agent for hyalin, 
amyloid, colloid, and mucin in the tissues. As a differential stain for 
fibrillated connective-tissue fibres it is of value in the study of various 
tumors and especially of the sarcomata. 
It is commonly prepared in two strengths, the stronger for use espe- 
cially in nerve-tissue staining, the weaker for general purposes. The 
formulae and method of using as suggested by Freeborn1 are as follows: 
Picro-acid Fuchsin. 
Stronger solution-- 
1-per-cent. aqueous solution acid fuchsin 15 c.c. 
Saturated aqueous solution picric acid and water, each 50 c.c. 
Weaker solution- 
1-per-cent. aqueous acid fuchsin 5 c.c. 
Saturated aqueous solution picric acid 100 c.c. 
The tissues may be hardened either in alcohol, or in Orth's fluid, or 
in formalin. 
Sections are first stained deeply with haematoxylin, washed in water, 
and put into the staining fluid, in which they remain for varying periods, 
depending upon the tissue and the strength of the stain, but in general 
from one to five minutes. The sections are now rapidly dehydrated by 
alcohol, cleared with oil of origanum, and mounted in balsam. 
Mallory's Anilin-blue Stain.-This stain is especially useful in 
bringing out in blue the fibrillae and reticulum of connective tissue, 
though various hyaline substances are similarly colored. The nuclei, 
protoplasm, elastic fibres, axis cylinders, neuroglia fibres, and fibrin are 
stained red; while red blood cells and myelin sheaths are yellow. 
The details of the method are as follows:2 
1. Fix in Zenker's fluid. 
2. Embed in celloidin or paraffin. 
3. Stain sections in a two-tenth-per-cent, aqueous solution of acid 
fuchsin for five minutes or longer. 
4. Transfer directly to the following solution for twenty minutes or 
longer: 
Anilin blue soluble in water (Griibler) . . 0.5 
Orange G. (Griibler) 2.0 
1-per-cent. aqueous solution of phosphomolybdic acid 100. 
5. Wash and dehydrate in several changes of 95-per-cent. alcohol. 
6. Clear in xylol or in oil of origanum. 
7. Xylol balsam. 
1 Freeborn, Proc. New York Path. Soc., 1893, p. 73. 
See\MaUory and Wright,"Pathological Technic," 5th edition, 1913, p. 322. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1037 
Methylene blue is a useful stain for many purposes. The tissues 
may be hardened in Zenker's or Orth's fluid. 
Giemsa's1 Stain for Blood and Tissues.-The stain is prepared as 
follows: 
Azur II-Eosin 3.0 gm. 
Azur II 0.8 gm. 
Glycerin c. p 250.0 c.c. 
Methyl alcohol c. p 250.0 c.c. 
The dyes are thoroughly dried over H2SO4, finely pulverized, and sifted through a 
fine-meshed silk sieve; then dissolved by shaking in the glycerin heated to 60° C. To 
this glycerin solution is added the methyl alcohol also heated to 60° 0., the whole 
thoroughly shaken and allowed to stand for twenty-four hours and then filtered. 
The stain is prepared for the market ready for use by Griibler. 
For Staining Blood.-1. Air-dried blood smears are fixed for two 
to three minutes in methyl alcohol and dried off with filter paper. 
2. The dye is diluted with water (1 drop of the dye to about 1 c.c. 
of distilled water). The water may to advantage be warmed to 30° 
to 40° C. 
3. Pour the freshly diluted dye over the smear and stain for ten to 
fifteen minutes. 
4. Wash off in water jet. 
5. Dry partially with blotting paper and then in the air. Mount in 
balsam. 
For Staining Tissues.-For staining tissues the following method 
of Schridcle2 may be useful. 
1. Five micra paraffin sections are stained for twenty minutes in a 
mixture of two drops of Giemsa's solution and 1 c.c. of water. 
2. Washed carefully in water. 
3. Dried off with blotting paper. 
4. Transferred immediately to anhydrous chemically pure neutral 
acetone. 
5. Transferred to xylol. Mounted in neutral dammar. 
Unna's Polychrome Methylene-blue Stain.-This is prepared 
for the market by Griibler. The formula for its use given by Mallory 
and Wright is as follows: 
1. Stain paraffin or celloidin sections hardened in alcohol in poly- 
chrome methylene-blue five to ten minutes or longer. 
2. Wash in acidulated water. 
3. Fix in 10-per-cent. solution of bichromate of potassium half a 
minute. 
4. Wash in water. 
5. Dry on slide with filter-paper. 
6. Decolorize in anilin plus 1-per-cent. hydrochloric acid (a few 
seconds only). 
7. Wash off with oil of bergamot. 
8. Balsam. 
1 Giemsa, Centbl. f. Bakt., Abth. I., Orig. Bd. xxxvii., p. 308, 1904. 
Schridde, Cent. f. allg. Path., Bd. xvi., p. 769, 1905. 1038 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
Thionin.-Thionin is especially useful as a stain for mucin. In the 
following-Hoyer's formula-the mucin is colored red, the remaining 
tissue blue. 
1. Harden in corrosive sublimate, followed by alcohol. 
2. Paraffin sections are passed through xylol or chloroform to free 
them from paraffin, then 95-per-cent. alcohol and, after washing in water, 
are then placed in a 5-per-cent. aqueous solution of corrosive sublimate 
for three to five minutes. 
3. Stain in a dilute solution of thionin for ten to fifteen minutes. 
4. Alcohol. 
5. Clear in the mixture of the oils of cloves and thyme. 
6. Turpentine oil or oil of cedar. 
7. Balsam. 
The sublimate should not be removed from the tissues by iodin, as is 
usual as a preliminary to staining. 
Thionin is useful for the staining of exudates, frozen sections, etc. It 
may be kept in a stock saturated aqueous solution to be variously diluted 
as used. 
Best's Method for Staining Glycogen.-The tissues are hardened in 
alcohol, ten-per-cent, trichloracetic acid, formalin, or sublimate. Wash- 
ing in water must be avoided, the preparations being transferred directly 
to alcohol. The material is then embedded in celloidin, and cut. Paraffin 
sections must be flooded with a thin celloidin solution after the paraffin 
has been removed, and should be flattened on warm alcohol instead of on 
warm water. 
The stain is made up as follows: 
Carmine, 2 gms. 
Potassium carbonate, 1 gm. 
Potassium chloride, 5 gms. 
Distilled water, 60 c.c. 
The mixture is boiled, and 20 c.c. of strong liquor ammoniae are added. 
It is then ready for use and keeps for some three weeks. The technique 
is as follows: 
1. Stain deeply with Delafield's haematoxylin. 
2. Wash in water. 
3. Stain in carmine solution, 2 parts; strong liquor ammoniac, 3 parts; 
methyl alcohol, 3 parts. 
4. Transfer to a mixture of methyl alcohol, 40 c.c.; absolute alcohol, 
80 c.c.; distilled water, 100 c.c. The sections are allowed to remain in 
this mixture for one to five minutes. 
5. Wash in eighty-per-cent, alcohol; transfer to absolute alcohol; and 
through xylol to balsam. 
The glycogen granules stain red; the nuclei are blue. The stain colors 
all of the glycogen and also certain secreting cells of the stomach, corpora 
amylacea of the nervous system, fibrin, and occasionally mucus and the 
granules of mast cells; it also colors calcified bone. METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
1039 
Methods of Preserving Specimens for Gross Demonstration and for 
Museums. 
When specimens of abnormal tissues or organs are to be preserved 
entire for exhibition in jars in a museum, the superfluous parts are first 
removed and the requisite dissections made. Then they are carefully 
placed in the position and form which it is wished to preserve, by stuff- 
ing with horsehair or absorbent cotton and by the use of thread. When 
thus carefully adjusted they are either suspended or laid on a wad 
of absorbent cotton in 60- to 80-per-cent. alcohol or in 5-per-cent. 
formalin solution. In this they usually become hard, and finally, after 
the removal of the temporary stuffing and braces, are transferred for 
permanent exhibition to fresh, clear, 80-per-cent. alcohol, or, in case 
of formalin hardening, to a fresh solution of the formalin, to which, if 
the jar is likely to be exposed to cold, a little glycerin is added to pre- 
vent freezing. This description applies especially to such specimens as 
have cavities to distend or display. 
The more simple specimens, such as the solid viscera, tumors, etc., 
may be washed and hardened in 60-per-cent. alcohol or in formalin 
solution.1 
In many cases an excellent hardening is obtained by injecting the 
preservative fluid through the blood-vessels. The lungs are well hard- 
ened by pouring the fluid through the trachea into the air spaces. 
Firm-walled cysts of various kinds are well preserved in a condition 
of distention by drawing off the natural contents through a fine cannula 
and refilling with, and immersing in, formalin solution. Delicate cysts, 
such as echinococcus cysts, small embryos in their membranes, cystic kid- 
neys, etc., may be preserved in a nearly natural condition in formalin.2 
Kaiserling's Method of Fixing Natural Colors in Museum Specimens.5 
1. Fixation for one to five days in: 
Formaldehyde 200 c.c. 
Water 1000 c.c. 
Nitrate of potassium 15 gm. 
Acetate of potassium 30 gm. 
Change the position of the specimen frequently. The time of fixation 
varies with the tissue or organ and size of the specimen. 
2. Drain and place in 80-per-cent. alcohol one to six hours, and 
then in 95-per-cent. alcohol for one to two hours, to restore the color, 
which is somewhat affected in the fixing solution. 
I For a method of preparing thick serial sections of brain for permanent preservation in formalin 
and gelatin see Mankowsky, Cbl. f. Path., Bd. xvii., 1906, p. 467. Also, for the method of preserving 
sections and whole structures for exhibition in gelatin see Watters, Medical Record, vol. Ixx., p. 985, 1906. 
2 For the technique of the clearing method by potassium hydroxid in the demonstration of ossifica- 
tion centres, distribution of blood-vessels, etc., see Hill, Johns Hopkins Hosp. Bull., vol. xvii., p. Ill, 
1906. 
3 See Mallory and Wright, "Pathological Technique," 1913, 5th Edition, p. 381. 1040 
METHODS OF PRESERVING PATHOLOGICAL SPECIMENS 
3. Preserve in: 
Acetate of potassium 200 gm. 
Glycerin 400 c.c. 
Water 2000 c.c. 
Since exposure to light reduces the color contrasts, the specimen 
should be prepared and kept in the dark. 
The Importance of Careful Fixation and Preservation. 
We would most urgently commend to the reader the importance of 
putting pathological specimens, which are to be hardened and subse- 
quently examined microscopically, at the earliest possible moment into 
the preservative fluids, which should always be abundant. Furthermore, 
when specimens are large it is very desirable to cut them open, so that 
the fluids may come into direct contact with the tissues. It should be 
borne in mind that immediately after death or the removal of parts from 
the body, especially in warm weather, changes commence in the tissues 
and progress very rapidly, so that in some cases a few hours' or even a 
few moments ' delay will not only render subsequent microscopical exam- 
inations difficult and unsatisfactory, but may lead to serious errors. 
Alcohol and 10-per-cent. formalin are the most generally useful agents. 
Carbolic acid and glycerin should not be used, even for the temporary preser- 
vation of fresh tissue. They not only do not harden and preserve the 
tissue elements, but they-especially glycerin-render them almost use- 
less for microscopic examination. 
The not uncommon practice of wrapping a specimen in a cloth soaked 
in alcohol or carbolic acid, and permitting it to remain in this for hours 
or days, is of no use whatever in preserving specimens of which micro- 
scopic examinations are to be made. Almost equally useless is the too 
common practice of placing a specimen in a bottle which it nearly fills, 
and pouring a little preservative fluid around it. Not only should the 
proper fluids be used, but these should be abundant, and the specimen 
so prepared and arranged that they may come into direct contact with it. INDEX. 
Abbott and Gilder sleeve, on acid-fast bac- 
teria, ref., 267 
Abderhalden, on ferments in diagnosis, 
ref., 191 
Abdomen, examination, post-mortem, of, 
1001, 1025 
Abdominal pregnancy, 842 
viscera, position of, 1002 
Abel, on suprarenal body, 434 
Abel and Davis, on skin pigment, ref., 55 
Abramow, on blood-vessel changes in 
syphilis, ref., 274; on peritonitis, ref., 
694 
Abrin poisoning, 153; ref., 203; 425 
Abscess, 89, 200 
metastatic, 204 
nature of, 199 
of bone, 885, 888 
brain, 964 
heart, 538 
kidney, 754 
liver, 722 
lung, 611 
mamma, 844 
muscle, 873 
prostate, 866 
spleen, 504 
testicle, 857 
repair of, 203 
retropharyngeal, 648 
splenic, 504 
tropical, of liver, 722 
Absorption, 23 
from peritoneum, 694 
Acardiacus acephalus, 328 
acormus, 328 
amorphus, 328 
anceps, 328 
Acarus scabiei, 131 
Achard and Phulpin, on terminal infec- 
tion, ref., 158 
Achondroplasia, 896 
Achorion Schonleinii, 148 
Achromatic figure in mitosis, 66 
Acid, arsenious, 420 
carbolic, 423 
carbonic, 425, 427 
hydrochloric, 418 
hydrocyanic, 422 
nitric, 418 
oleic, 44 
osmic, as hardening fluid, 1029 
oxalic, 418 
oxybutyric, 427 
sulphuric, 317 
tartaric, 419 
Aconite poisoning, 425 
Acrania, 324, 927 
Acromegalia, 438 
Actinomyces, 136 
bovis, 231 
in lung, 612 
Actinomycosis, 230 
of appendix, 691 
brain, 976 
intestine, 691 
Adamantinoma, 415 
Adami, on arterio-sclerosis, ref., 565, 566; 
on blood in septicaemia, ref., 205; on con- 
ditions of disease, ref., 14; on dissecting 
aneurism, ref., 568; on hypertrophy, 
ref., 62; on infection, ref., 151; on 
inflammation, 110; on inflammation 
and fibrosis, ref., 96; on mitosis, ref., 
67; on retroperitoneal lipoma, ref., 
697; on reversion, ref., 63 
Adaptation, 8 
of animals to alien substances, 195 
Addison's disease, 433 
internal secretions of adrenals in, 
434 
Adenitis, 483 
Adeno-carcinoma, 398 
of uterus, 814 
Adeno-cystoma of ovary, 830 
Adenoids, 581, 648, 649, 650 
1041 1042 
INDEX 
Adenoma, 395, 398 
fibre-, 365 
foetal, 398, 432 
of adrenals, 517 
Bartholin's glands, 795 
bladder, urinary, 788 
bronchi, 591 
gall-ducts, 743 
intestine, 690 
kidney, 776 
larynx, 585 
liver, 735 
lung, 635 
mamma, 849 
mouth, 645 
oesophagus, 653 
ovary, 830 
pancreas, 706 
pituitary body, 980 
prostate, 866 
stomach, 663 
testicle, 861 
thyroid, 513 
uterus, 814 
Adeno-sarcoma, 376 
Adler, on gumma of heart, ref., 542; on 
emigration of leucocytes, ref., 86; 
on reaction of blood, ref., 453; on 
tumors of lung, ref., 635; ref., 636 
Adler and Meltzer, on lymph-vessels, 576 
Adrenalin, degeneration of heart muscle 
after injections of, ref., 541 
Adrenals, 515 
accessory, 515 
atrophy of, 515 
degeneration of, 515 
examination, post-mortem, of, 1013, 
1026 
fat infiltration of, 515 
haemorrhage in, 516 
hypertrophy of, 62 
in Addison's disease, 434 
inflammation of, 516 
malformations of, 515 
myelin substances in, 515 
pigmentation of, 516 
preservation of, 1013 
size of, 1013 
syphilis of, 516 
thrombosis of, 516 
tuberculosis of, 434, 516 
tumors of, 517 
weight of, 1013 
Aerobes, facultative, 137 
obligate, 137 
Afanassieff, on granulation tissue, ref., 
152 
Age, relation of, to disease, 13 
relation of, to tumor growth, 344 
Agenesia, 321 
Agglutination, 179 
group, 180 
of streptococci, ref., 210 
test, 180 
technique of, 193 
Agglutinative substances, 179 
Agglutinins, 179 
in typhoid fever, 246 
Aggressins, 153 
Agnathia, 321 
Ague cake, 505 
Air emboli, 34 
in blood, 470 
blood, in caisson disease, 11 
pericardium, 518 
pleural cavities, 637 
micro-organisms in, 140, ref., 150 
supply, relation of, to disease, 9 
Akerland, on membranous colitis, ref., 
682 
Albert, on trichiniasis, ref., 130 
Albrecht, on albuminous degeneration, 
ref., 40; on myelogenous substances in 
cells, ref., 40; on origin of tumors, ref., 
353. 
Albumen film for fixing specimen to slide, 
1028, 1034 
Albuminous degeneration (see Degenera- 
tion, albuminous), 39 
Albuminuria, 749 
Alcock, on mosquitoes, ref., 316 
Alcohol as tissue fixative, 1029 
poisoning, 423 
Alcoholism, chronic, atrophy of brain in, 
932 
meningitis in, 917 
oedema of brain in, 913 
Aleuronat exudates, 195 
Alexander, on adrenals, ref., 515 
Alexines, 109, 161, 170, 172 
Allergins, 190 
Allergy, 190 
Aloes poisoning, 422 
Amboceptor, 177 
Amitosis, 65, 67 
Ammonia poisoning, 419 1043 
INDEX 
Amoeba dysenteriae, 115 
colitis, 676 
in liver abscess, 723 
Amyelia, 928 
Amyloid, 47 
degeneration (see Degeneration, 
amyloid), 48 
masses in larynx and trachea, 586 
technique of staining, 50 
tests for, 50, 1012 
tumors of larynx and trachea, 586 
of tongue, 646 
Anaemia, 16, 19, 454 
aplastic, 474 
chlorotic, 471 
bone marrow in, 897 
infantum pseudo-leukaemica, 479 
local, 19 
marrow changes in, 897 
of brain, 934 
kidney, 748 
lung, 593 
liver, 709 
spleen, 501 
pernicious, 473 
phagocytosis in, after transfu- 
sion, 185 
secondary, 472 
splenic, 479 
Von Jaksch, 479 
Anaerobes, facultative, 137 
obligate, 137 
Anaphylaxis, 190 
Anaplasia in tumors, 351 
Anasarca, 22 
Anastomosis of blood-vessels, 18 
Anders, on tuberculosis of heart, ref., 542 
Anderson, on B. tuberculosis in blood., 
ref., 264 
Anderson and Goldberger, on infective 
agent in Mexican typhus, 301 
Anderson and Rosenau, on anaphylaxis, 
ref., 190 
Anencephalia, 325, 927 
Aneurism, 567 
cirsoid, 569 
conditions leading to, 567 
cylindrical, 567 
dissecting, 568 
false, 568 
fusiform, 567 
miliary, 571 
multiple, 567 
Aneurism mycotic, 567 
of aorta, 570 
brain, 936, 981 
cerebral arteries, 936 
of coronary arteries, 570 
heart, 529 
heart valves, 530 
pulmonary arteries, 570 
splenic artery, 500 
sacculated, 567 
spurious, 568 
varicose, 569 
Aneurismal varix, 569 
Angina (see Pharyngitis), 648 
diphtheroid, 212 
membranous, 212 
Vincent's, 293 
Angio-lipoma, 382 
Angioma, 393 
cavernosum, 394 
haem-, 393 
lymph-, 393 
of bone, 902 
bladder, urinary, 788 
brain, 977 
choroid plexus, 927 
ependyma, 927 
intestine, 688 
kidney, 776 
larynx, 585 
lips, 645 
liver, 734 
mamma, 848 
mouth, 645 
muscle, 875 
oesophagus, 653 
ovary, 829 
penis, 855 
peritoneum, 697 
spleen, 510 
stomach, 663 
thymus, 511 
tongue, 646 
uterus, 813 
telangiectoides, 393 
Angio-sarcoma, 374 
Anguillula, 131 
Anhydrsemia, 454 
Anilin-blue stain, 1036 
dyes for bacteria, 143 
gentian-violet stain for bacteria, 143 
Animal, infectious diseases of, 319; 
also ref., 157 1044 
INDEX 
Animal parasites, 114 
species, relationships of, blood test 
in, 172 
venom, 424 
Ankylostoma duodenale, 128, 472 
Anopheles in malaria, 314 
Anspach, on teratoma of ovary, ref., 837 
Anterior horn, myelitis of, 967 
Anthracosis of lung, 616 
Anthrax, 228 
bacillus, 229 
of intestine, 691 
Antiamboceptor, 177 
Antibodies, 175 
Anticytolysins, 175 
Anticytotoxins, 175 
Antiformin in sputum examinations, 260 
Antigen, 175, 190 
Anti-immune substances, 177 
Anti-precipitin, 182 
Antithrombin, 453 
Antitoxin, 164 
Asiatic cholera, 250 
definition of, 167 
diphtheria, 164, 285 
unit of, ref., 164 
plague, 289 
streptococcus, 211 
tetanus, 165, 287 
unit, ref., 164 
Antivenins, 424 
Anus, atresia of, 667 
Aorta, aneurism of, 570 
double, 522 
examination, post-mortem, of, 1018 
hypoplasia of, 439, 556 
insufficiency of, 552 
malformations of, 522 
rupture of, 557 
stenosis and obliteration of, 552, 571 
tuberculosis of, 567 
Aphthae, 644 
Aplasia, 321 
Apoplectic foci in brain, 936 
Apoplexy, 21 
cerebral, 935 
of brain, 935 
placental, 823 
serous, of brain, 935 
spinal, 938 
Appendicitis, 684 
Appendix vermiformis, 684 
absence of, 667 
Appendix, actinomycosis of, 691 
bacteria in, 687 
concretions in, 686 
cysts of, 686 
dilatation of, 686 
diverticula of, 668 
foreign bodies in, 686 
gangrene of, 685 
in typhoid fever, 685 
inflammation of, 684 
inversion of, 688 
necrosis of, 685 
obliteration of lumen of, 686 
parasites in, 688 
strictures of, 686 
tuberculosis of, 686 
tumors of, 690 
Arachnoid (see Pia mater), 912 
Argyria, 56 
Arken, on syphilitic ulcers of intestine, 
ref., 674 
Arloing, on bactericidal action of mucus, 
ref., 150 
Arnaud, on Addison's disease, ref., 516 
Arnheim, on spirochetes, 119 
Arnold, on diapedesis, 21; on fibrin form- 
ation, ref., 86; on iron pigment in cells, 
ref., 616; on lymph-nodes, 481; on 
polyps of pharynx, ref., 650; on sar- 
coma of liver, 737; on weight of heart, 
ref., 1008 
Arnsperger, on dermoid cysts of ovary, 
ref., 836 
Arsenic poisoning, 420, 656 
Artefacts of nervous system, ref., 928, 
929, 999 
Arteries, aneurism of, 567, 570 
atheroma of, 562 
calcification of, 559 
cerebral, aneurisms of, 936 
embolism of, 31, 942 
thrombosis of, 942 
coronary, aneurism of, 570 
distribution of, ref., 537 
embolism of, 538 
endarteritis of, 537 
examination, post-mortem, of, 
1008 
fibrous nodules on, 521 
infarction of, 538 
lesions of, 537 
sclerosis of, 537 
thrombosis of, 537 INDEX 
1045 
Arteries, cysts, atheromatous, of, 561 
degeneration of, 557 
emboli in, 571 
hepatic, lesions of, 711 
inflammation of (see Arteritis), 559 
of brain and cord, 933 
pulmonary, aneurism of, 570 
embolism and thrombosis of, 596 
renal, embolism and thrombosis of, 
749 
rupture of, 557 
sclerosis of, 559 
syphilis of, 567 
terminal, embolism of, 29 
tuberculosis of, 566 
tumor emboli in, 571 
tumors of, 571 
wmunds of, 557 
Arterio-sclerosis, 559 
classification of, 565 
conditions leading to, 564 
relation to heart hypertrophy, 554 
kidney lesions, 769 
Arteritis, acute, 559 
chronic, 559 
embolic, 559 
end-, 559 
peri-, 559, 566 
syphilitic, 567 
thrombo-, 559 
tuberculous, 566 
Arthritis, 903 
chronic, 904 
deformans, 905 
exudative, 903 
gonococcal, 904 
gouty, 905 
pneumococcic, ref., 904 
rheumatic, 904 
sero-fibrinous, 904 
serous, 903 
suppurative, 904 
tuberculous, 906 
uratica, 905 
Arthropathy, hypertrophic pulmonary 
ref., 438 
Arthropoda, 131 
Ascarelli, on adipocere, ref., 987 
Ascaris in liver, 739 
pancreatic duct, 707 
lumbricoides, 127 
maritima, 127 
mystax, 127 
Asch, on excretion of bacteria by kidney, 
ref., 755 
Aschoff, on appendicitis, ref., 688; on 
compensatory hypertrophy, ref., 79; 
on conditions of disease, ref., 14; on 
cysts, ref., 361; on immunity, 196; 
on nature of contracted kidney, ref., 
767; on thrombosis, ref., 25; on tumors, 
416 
Aschoff nodules, ref., 538 
Ascites, 23, 692 
Ascospores, 146 
Ashton, Norris and Lavenson, on Stokes- 
Adams' disease, ref., 550 
Asiatic cholera, 247 
Askanasy, on dermoid cysts of ovary, ref., 
836; on pigment, ref., 53 
Aspergillus, ref., 147 
glaucus, 148 
Asphyxia, 9, 442 
Ataxia, cerebellar, 963 
Friedrich's, 963 
hereditary, 963 
locomotor, 957 
Ataxic paraplegia, 962 
Atelectasis of lung, 596 
Atelomyelia, 928 
Atheroma, 561 
Atlassoff, on experimental typhoid fever, 
ref., 235 
Atrophia musculorum lipomatosa, 871 
Atrophy, 36 
acute yellow, of liver, 716 
experimental, 718 
brown, 38, 56 
of heart, 38, 529 
degenerative, 37 
disuse, 38 
general from malnutrition, 38 
neurotic, 39 
of adrenals, 515 
blood-vessels, 556 
bone, 876 
brain, 932 
heart, 528 
liver, 714, 716 
lymph-nodes, 481 
muscle, 868, 871 
pancreas, 702 
prostate, 863 
spleen, 500 
stomach, 656 
testicle, 857 1046 
INDEX 
Atrophy, of uterus, 803 
pigment, 714 
pressure, 38 
progressive muscular, 869, 955 
senile, 38 
simple, 36 
Atresia ani, 667 
Attraxine, 352 
Auer and Lewis, on anaphylaxis, 191 
Auerbach, on B influenzae, 234 
Aufrecht, on portals of entry of B. tuber- 
culosis, ref., 264 
Auriculo-ventricular bundle of His, 550 
Auto-digestion of pancreas, 702 
Autohaemolysis, ref., 176 
Auto-intoxication, 153, 417, 426 
Addison's disease as an, 434 
burns as excitants of, 9 
cachexia strumipriva as an, 430 
dyscrasic, 427 
enterogenic, 426 
exophthalmic goitre as an, 432 
gout as an, 436 
retention, 427 
Autolysins, 176 
Autolysis, 60, 98, 106 
in absorption of infarcts, ref., 30 
lung exudates, 557 
Autosite, 332 
Autopsies, making of (see Post-mortem 
examination), 985 
medico-legal, 1022 
on cases of suspected poisoning, 1022 
new-born, 1023 
Avery and Lyall, on concurrent infection 
in tuberculosis, ref., 631 
Axis-cylinder process, nature of, 944 
Axone, degenerations in, 946 
nature of, 944 
Ayer, on cysts of intestine, ref., 690 
Azur II as a staining agent, 317, 1037 
Babes, on bacteria in blood of cadaver, 
ref., 987; on haemorrhagic infection, 
ref., 289.; on rhinoscleroma, ref., 282 
Babesia bovis, ref., 122 
Bacillus, 134 
acid-proof, 267 
aerogenes capsulatus, 34, 289 
in liver, 738 
anthracis, 228, 229 
immunization to, 230 
botulinus, 292 
Bacillus, choler® gallinarum, 289 
coli communis, 214, 246 
conjunctivitidis, 234 
diphtheriae, 282, 283 
action of, in animals, 285 
branching forms of, ref., 284 
carriers, 285 
characters of, 284 
communicability of, 285 
pseudo-, 285 
diplo-, 135 
Ducrey's, 228 
dysenteriae, 247, 677 
enteritidis, 291 
Friedlander, 216 
gas, 289 
glanders, 226 
grass, 267 
haemorrhagicus, 289 
septicus, 289 
velenosus, 289 
hay, 267 
Hoffmani, 285 
icteroides, ref., 302 
influenzae, 233 
Koch-Weeks, 234 
leprae, 269 
mallei, 226, 227 
toxic products of, 227 
mucosus capsulatus, 216 
cedematis maligni, 291 
of Shiga, 677 
whooping cough, 317 
paratyphosus, 247 
pestis, 288 
plague, 288 
proteus group of, 216 
proteus vulgaris, 217 
pseudodiphtheriae, 285 
pseudo-influenzae, 234 
pseudo-tetanicus, 287 
pseudo-tuberculosis, 227 
liquefaciens, 227 
pyocyaneus, 215 
in colitis, 678 
rhinoscleromatis, 282 
Shiga's, 247 
smegma, 267 
strepto-, 135 
suisepticus, 289 
tetani, 286 
toxins of, 286, 287 
tuberculosis, 251, 257 INDEX 
1047 
Bacillus, tuberculosis, action of, in body, 
262 
antiformin in examination of, 260 
bovine type, ref., 266 
branching forms of, ref., 257 
dead, action of, 260 
differentiation of, 267 
distribution of, 264 
in dried sputum and dust, 265 
methods of staining, 258 
numbers of, in lesions, 263 
portals of entry of, 264, 618 
sources of, 265 
toxic products of, 260 
varieties of, 260 
typhi murium, 289 
typhosus, 234, 235 
agglutination of, 246 
carriers, 245 
differentiation of, 246 
distribution of, in body, 244 
methods of staining, 246 
modes of infection with, 245 
viability of, 245 
Welchii, 289 
"X," ref., 302 
xerosis, 285 
Bacmeister, on myoma of heart, ref., 556 
Bacteria, 133 
absorption of, in peritoneum, 694 
acid-resisting, 267 
action of alexins on, 161 
cold and heat on, 137 
germicides on, 138 
in body, 152 
adaptation of, ref., 160 
aerobic, 137 
aerogenic, 139 
agglutination of, 179 
aggregations of, 135 
aggressins of, 153 
anaerobic, 137 
as disease excitants, 198 
attenuated cultures of, 162 
capsules of, 133 
chemotaxis in, 137 
chromogenic, 139 
classification of, 142 
Clostridium forms, 134 
commensals in, 141 
cultivation of, 145 
cultures of, 145 
destruction of, by phagocytes, 161 
Bacteria, destruction of, in body, 170 
disposal of in blood, 151 
distribution of, 140, 150 
elimination of, through secretions, 
151 
endotoxins of, 139 
enzymes of, 139 
etiological relationships of, 154 
examination of specimens, post- 
mortem, for, 1021 
fermentation and, 139 
filamentous, 135 
flagella of, 133 
forms of, 134 
functional characters of, 142 
gas-producing, 139 
growth of, conditions of, 137 
haemolysins of, ref., 153 
higher, 135 
in air, 140, 150 
appendix vermiformis, 687 
bladder, urinary, 786 
blood, ref., 470 
post-mortem, 987 
body, 150 
dust, 140 
fluids, stains for, 143 
heart, 539 
inflammation, 152 
intestine, 678, 681 
kidney, 755, 761 
lung, 601, 614 
lymph-nodes, 481 
mouth, 646, ref., 647 
of children, ref., 647 
nose, 580 
soil, 140 
spleen, 511 
stomach, ref., 659 
suppuration, 201 
tissues, stains for, 143 
tumors, 347 
vagina, 797 
water, 141 
infective nature of, proofs of, 153 
insects as carriers of, 151 
insusceptibility to, 160 
involution forms, 134 
life of, conditions of, 137 
messmates in, 141 
metabolism of, 138 
metachromatic granules in, 134 
monomorphism in, 136 1048 
INDEX 
Bacteria, motility of, 137 
multiplication of, 134, 137 
nutritional requirements of, 137 
opsonins of, 183 
parasitic, 141 
phagocytosis of, 183 
photogenic, 139 
pleomorphism, 136 
poisons of, 139, 152 
polymorphous, 135 
portals of entry of, 151 
products of, in body, 152 
protection of body against, 151 
ptomains of, 139 
pyogenic, 205 
relationships of, 141 
reproduction of, 134 
rod-like, 134 
role of, in nature, 140 
saprophytic, 141 
species of, 142 
spheroidal, 134 
spiral, 134 
spores in, 136 
staining of, 143 
sterilization of, 137 
study of, morphological, 143 
symbiosis of, 142 
thermophilic, 138 
toxins of, 139, 152 
ultramicroscopic, ref., 134 
variations in, 136 
varieties of, 142 
zymogenic, 139 
Bacteriaemia, 203 
Bacteriolysis, 170, 173 
Bacterio-opsonins, 184 
Bacterio-protein, 152 
Bacteriotropic substances, 184 
Baer, on typhoid ulcers, ref., 240 
Baginsky, on pseudo-membranous in- 
flammation, ref., 212 
Bail, on aggressins, 153; on disposal of 
bacteria in blood, ref., 151 
Bailey, C. H., on foreign bodies in heart, 
ref., 526 
Bailey, F. R., on lesions in hydrophobia, 
ref., 294 
Bailey and Ewing, on Landry's paralysis, 
969 
Bailey and Jelliffe, on tumors of pineal 
gland, ref., 980 
Bailey and Miller, on embryology, ref., 320 
Balanitis, 584 
Balantidium coli, 120 
Baldauf, on carcinoma of appendix vermi- 
formis, ref., 690 
Baldwin, E. R., on tuberculin, ref., 260 
Baldwin, F. A., on anaemic infarcts of 
liver, ref., 711 
Ballantyne, on antenatal pathology, ref., 
320; on congenital infection, ref., 151 
Bang, on lipoids, ref., 44 
Banti, on splenic anaemia, 479 
Banzhaf and Famulener, on anaphylaxis, 
ref., 191 
Bardeen, on visceral changes following 
burns, ref., 10 
Barger, on natural bases, ref., 139. 
Barker, on nervous system, ref., 942 
Barlow's disease, ref., 438 
Bartel and Bauer, on status lymphaticus, 
ref., 440 
Bartel and Spieler, on experimental 
tuberculosis, ref., 264 
Bartholin's glands, cysts of, 795 
Bartholow, on pellagra, ref., 318 
Basedow's disease, 432 
Bashford, on tumor transplantation, ref., 
79 
Bashford and Murray, on mitosis in 
tumors, ref., 351; on statistical investi- 
gation of cancer, ref., 353 
Bashford, Murray, and Cramer, on 
tumors, 355 
Basophile cells, 461 
Bass, on cultivation of malarial parasite, 
ref., 312 
Bassoe, on blastomycosis, ref., 146 
Bateson, on heredity, ref., 14 
Batten, on nerve lesions in diphtheria, 
ref., 283 
Bauer, on modification of Wassermann 
test, 279 
Baumgarten, on coronary arteries, ref., 
537; on portals of entry of B. tub- 
erculosis, ref., 264; on tissue formation 
by endothelium, ref., 73; on urogenital 
tuberculosis, ref., 770 
Bayer, on regeneration of lymph-nodes, 76 
Bayliss, on enzymes, ref., 139 
" Beaker cells," 46 
Beck, on B. influenzae, ref., 233; on rhab- 
domyoma, ref., 861 
Beebe and Ewing, on lympho-sarcoma of 
dogs, ref., 349, 369 INDEX 
1049 
Beer, on accessory adrenals, ref., 515; on 
atrophic glomerular cysts, ref., 767; 
on false diverticula of intestine, ref., 
668 
Behring, on portal of entry of B. tuber- 
culosis, ref., 264 
Beitzke, on cervical and bronchial lymph- 
nodes, ref., 592; on cervical and bron- 
chial lymph-nodes in tuberculous in- 
fection, ref., 650; on mode of infection 
in pulmonary tuberculosis, ref., 264 
Bence Jones' proteid, 902 
Benda, on origin of miliary tuberculosis, 
ref., 620 
" Bends," the, 11 
Bennecke, on angioma of intestine, ref., 688 
Beri-beri, 318 
Berkeley and Beebe, on parathyroids, 514 
Bernheim and Gruber, on mixed infec- 
tions, ref., 157 
Berry, on appendicitis, 688 
Bertarelli, on animal inoculations in 
syphilis, ref., 274 
Berthenson, on bibliography of tumors of 
heart, ref., 556 
Besredka, on anaphylaxis, 191 
Best's method of staining glycogen in 
tissue, 1038 
Bettmann, on bronchitis, ref., 589 
Bezant on and Labbe, on germicidal action 
of lymph-nodes, ref., 151 
Biedl, on internal secretions, ref., 427 
Biedl and Kraus, on elimination of 
bacteria, ref., 151; on bacteria in 
kidney, ref., 761 
Bierring and Egdahl, on splenectomy, 
ref., 479 
Biggs, on aortic aneurism, ref., 570 
Biland, on cysts of placenta, ref., 826 
Bile-ducts, lesions of (see Gall-ducts), 740 
Bilirubin, 55 
Billings, on infectious endocarditis, ref., 
547 
Billings and Capps, on myelogenous 
leukaemia, ref., 477 
Billings and Rosenow, on vaccines in 
Hodgkin's disease, 497 
Binder, on congenital liver cirrhosis, ref., 
730 
Biogen, 3 
Biophore, 3 
Birch-Hirschfeld, on intestine as portal 
of entry for bacteria, 694 
Birt and Lamb, on Micrococcus meli- 
tensis, ref., 288 
Bizzozero, on tissue regeneration, 64 
Black death, 288 
Black leg, 291 
Bladder, circulation in, study of, 111 
gall (see Gall-bladder), 740 
urinary, 781 
circulation in, 111 
cysts of, 788 
dilatation of, 782 
diverticula of, 782 
examination, post-mortem, of, 
1018, 1026 
extroversion of, 781 
foreign bodies in, 789 
haemorrhage of, 783 
hernia of, 782 
hyperaemia of, 783 
hyperplasia of epithelium of, 784 
hypertrophy of, 782 
inflammation of (see Cystitis), 
783 
malformations of, 781 
malpositions of, 782 
mucosa, repair of, ref., 71 
parasites of, 789 
perforation of, 783 
preservation of, 1013 
regeneration of mucous mem- 
brane in, 784 
rupture of, 782 
size of, 782, 1012 
study of inflammation in, 83 
tuberculosis of, 786 
tumors of, 786 
weight of, 1012, 1026 
wounds of, 782 
Blastomycetes, 133, 146 
Blastomycosis, generalized, 147 
Blastomycotic dermatitis, 146 
" Bleeders," 22 
Blennorrhoea, 199 
Block and Hall, on dermoid cyst of blad- 
der, ref., 788 
Blocq and Marinesco, on Friedrich's 
ataxia, ref., 963 
Blood, 452 
abnormal, leucocytes of, 461 
air in, 34, 470 
in caisson disease, 11 
alterations of, favoring thrombosis, 
25 1050 
INDEX 
Blood amount, determination of, 455 
anaemia, 454 
aplastic, 474 
infantum pseudo-leukaemica, 479 
pernicious, 473 
secondary, 472 
splenic, 479 
Von Jaksch, 479 
anhydraemia, 454 
B. tuberculosis in, in pulmonary 
tuberculosis, ref., 618 
bacteria in, ref., 470 
capillaries, lesions of, 575 
carbonic oxide, effects of, on, 425 
cells, red, 456 
agglutination of, test for, 194 
alterations in morphology of, 
457 
alterations in number of, 456 
altitude, effect of, on, ref., 458 
defective formation of, 456 
destruction of, 456 
diminution of, 456 
gigantoblasts, 459 
, lysis of, 171 
megalocytes, 458 
megaloblasts, 459 
microcytes, 457 
morphology of, 457 
normoblasts, 458 
nucleated, 458 
number of, 456 
opsonins of, 185 
phagocytosis of, 185 
poikilocytes, 457 
regeneration of, 77 
white, (see Leucocytes), 459 
changes in circulation of, 15 
chloroma, 478 
chlorosis, 471 
circulation of, 15, 83 
study of, in living animal, 
111 
clots, forms of, 452 
coagulability of, 452 
crises, 458, 474 
diseases of, 471 
erythrsemia, 455 
examination of, 316, 466 
extravasation of, 20 
fat in, 469 
fixed, examination of, in malaria, 
316 
Blood, foreign bodies in, 469 
forming organs, lesions of, 471 
fresh, examination of, in malaria, 
316 
frothing of, in caisson disease, 11 
gas in, 34 
haematogenesis, defective of, 457 
haemoglobin, free, in, 454, 456 
index, 474 
hydrsemia, 454 
in malaria, 310 
methods of examination 
of, 316 
septicaemia, ref., 235 
typhoid fever, 463 
laking of, 171 
leucocytes of, 459, 461 
leucocytosis, 462 
leukaemia, 475 
melanaemia, 470 
normal, leucocytes of, 459 
oligocythaemia, 454, 456 
parasites in, 470 
pigment, 53, 470 
test for, ref., 53 
plates, 465 
plethora, 455 
polycythaemia, 454 
precipitin test for, 181 
reaction of, 453 
regeneration of, 77 
relationships, 172 
staining of, 316, 468, 1037 
sugar in, 13 
transudation of, 22 
tubercle bacilli in, 264 
typhoid bacilli in, 244 
water of, 454 
Bloodgood, on adenoma of thyroid, ref., 
433; on cysts of bone, ref., 903 
Blood-vessels, anastomosis of, 18 
aneurism of, 570 
atrophy of, 556 
changes in walls of, 15 
embolism of, 28 
formation of, 75 
hypertrophy of, 557 
hypoplasia of, 556 
in frog, 113 
tumors, 338 
lesions of, in pulmonary tubercu- 
losis, 629 
relations of, to circulation, 15 INDEX 
1051 
Blood-vessels, sclerosis of, 559 
conditions leading to, 564 
thrombosis of, 24 
Blumenthal, on reaction of body in infec- 
tion, ref., 156 
Blumer, on bacteriology of lobular pneu- 
monia, ref., 613; on tuberculosis 
of arteries, ref., 567 
Blumer and Laird, on haemorrhagic septi- 
caemia, ref., 291 
Blumer and MacFarlane, on noma, ref., 
794 
Body, cooling of, as predisposing to in- 
fection, ref , 614 
cooling of, post-mortem, 988 
fluids, in inflammation, 108 
nature of living, 3 
safeguards of, against infection, 150 
Boils (see Furuncle) 199 
Bone, 876 
abscess of, 885, 888 
absorption of, 883 
achondroplasia, 896 
anaemia of, 897 
atrophy of, 876 
caries of, 891 
cells of, 876 
cysts of, 903 
decalcification of, 897, 1031 
enostoses, 899 
examination, post-mortem of, 1024, 
1026 
exostoses, 386, 899 
formation, new, of, 881 
in dura mater, 922 
muscle, 874 
pia mater, 921, 923 
fractures of, 877 
general considerations, 876 
haemorrhage of, 877 
healing of fractures of, 877 
hyperaemia of, 877 
hyperostosis, 900 
inflammation of (see Osteitis and 
Periostitis), 878 
lesions after typhoid fever, 243 
marrow in leukaemia and anaemia, 
897 
in malaria, 311 
pigmentation of, 877 
regeneration of, 76 
necrosis of, 889 
new-formed, 387 
Bone, osteomalacia, 896 
osteophytes of, 881, 899 
phosphorus necrosis of, 890 
rachitic, 891 
regeneration of, 76, 877 
rickets, 891 
sclerosis of, 885 
sequestrum in, 890 
softening of, 896 
syphilis of, 881, 888 
transplantation of, 78 
tuberculosis of, 882, 887 
tumors of, 899 
ulceration of, 891 
wounds of, 877 
Bordet, on immunity, 196 
Bordet and Gengou, on bacillus of whoop- 
ing-cough, 317; on fixation of com- 
plement, 189 
Borrmann, on carcinoma of stomach, ref., 
666; on metastasis in tumors, ref., 342 
Borst, on pathological organization, ref., 
110; on squamous epithelioma of 
stomach, ref., 666; on tumors, 416; on 
tumors of sacral region, ref., 359 
Bostroem, on cholesteatomata, ref., 379; 
on tumors of pia mater, ref., 920 
Bothriocephalus cordatus, 126 
cristatus, 126 
latus, 126, 472 
Bottomley, on operative treatment of 
tuberculous peritonitis, ref., 696 
Botulism, 291 
Bovaird, on human and bovine tubercu- 
losis, ref., 266; on primary spleno- 
megaly, ref., 508; on tuberculous 
bronchial lymph-nodes, ref., 487 
Bovaird and Nicoll, on weight of thymus, 
ref., 511; on weight of viscera in in- 
fancy, ref., 990 
Boveri, on mitosis, ref., 67 
Bradley, on cysts of thyroid, ref., 514 
Brain, 927 
abscess of, 964 
absence of, 927 
actinomycosis of, 976 
anaemia of, 934 
anencephalia, 325, 927 
aneurism, miliary, of, 936, 981 
apoplectic foci in, 936 
apoplexy of, 935 
serous, 935 
arteries of, 933 1052 
INDEX 
Brain, atrophy of, 932 
blood-vessels, lesions of, 942 
cephalocele, 928 
circulatory changes in, 933 
cyclopia, 325 
cysts of, 979 
degeneration of, 940, 942 
neurone, 946 
primary, 955 
secondary, 953 
dissection, methods of, 993, 996 
embolism of, 940 
encephalocele, 928 
examination, post-mortem, of, 992 
fixing and hardening methods, 999 
haemorrhage in, 935 
hernia of, 928 
holes in, 979 
hydrencephalocele, 928 
hydrocephalus, 927 
hydromeningocele, 928 
hyperaemia of, 934 
hypertrophy of, 931 
inflammation of (see Encephalitis), 
964 
injuries of, 930 
lesions of, in Asiatic cholera, 248 
general paresis, 972 
malaria, 311, 312 
malformations of, 324, 927 
mantle, demonstration of, 997 
method of opening, 993, 996 
Meynert's method of opening, 996 
microcephalia, 928 
morphology of, 942 
new-born, 1024 
weight of, 1025 
oedema of, 934 
parasites in, 979 
pigmentation of, 933 
porencephalus, 979 
preservation of, 998 
removal, post-mortem, of, 992 
in hydrocephalus, 1024 
sand, 376, 910, 912, 920, 927 
sclerosis of, 971 
softening of, 940, 964 
structure of, 942 
syphilis of, 975 
thrombosis of, 940 
tuberculosis of, 918, 974 
tumors of, 976 
vascular changes in, 933 
Brain, ventricles, nature and lesions of, 
924 
tumors of, 927 
vessel walls, lesions of, 942 
weight of, 993, 1025 
Branchial fistulae and cysts, 647 
Braunwarth, on cysts of kidney, ref., 774 
Breasts (see Mamma), 842 
Breus, on cysts of uterus, ref., 813 
Brewer, on infection of kidney after 
injury, ref., 152 
Brieger and Ehrlich, on degenerations in 
spinal cord, 948 
Bright's disease (see Nephritis), 753 
Brigidi and Piccoli, on persistent thymus 
and Hodgkin's disease, ref., 511 
Brill and Libman, on calcification of liver, 
ref., 722 
Brill, Mandlebaum, and Libman, on 
primary splenomegaly, ref., 508 
Brinckerhoff, on leprosy in the United 
States, ref., 270 
Brinckerhoff and Tyzzer, on experimental 
smallpox in monkeys, ref., 306 
Broman, on embryology, ref., 320 
Bronchi, 586 
calcification of, 592 
casts of, 589 
dilatation of, 589 
examination, post-mortem, of, 1009 
haemorrhage of, 586 
inflammation of (see Bronchitis), 586 
lung stones in, 592 
occlusion of, 591 
preservation of, 1010 
syphilis of, 589 
tuberculosis of, 589, 591 
tumors of, 591 
Bronchiectasia, 589 
Bronchiolitis, exudativa, 589 
acute catarrhal, 586 
capillary, 587 
chronic catarrhal, 588 
croupous, 588 
fibrinous, 589 
pseudo-membranous, 588 
purulent, 586 
syphilitic, 589 
tuberculous, 589 
Broncho-pneumonia, 608 
excitants of, 613 
persistent, 611 
tuberculous, 624 INDEX 
1053 
" Bronze skin," 54 
Brood capsules of tapeworm, 125 
Brooks, on acromegalia, ref., 439; on 
myocarditis, ref., 539; on syphilis of 
blood-vessels, ref., 567 
Brosch, on oesophageal diverticula, ref., 
652 on trauma andformation of 
malignant tumors, ref., 345 
Brouardel, on sudden death, ref., 448 
" Brown atrophy," 56 
Brown, on snake poisons, ref., 424 
Brown and Thiry, on diphtheritic septi- 
caemia, ref., 284 
Brumpt, on parasites, 132; on protozoa, 
ref. 115 
Brunn, on peritonitis, ref., 696 
Bruns and Kayser, on agglutinative reac- 
tions of colon-typhoid group, ref., 246 
Bruns' glucose medium, 1028 
Bubo, 485 
Buboes, 272 
Bubonic plague, 288 
Buchbinder, on entrance of bacteria 
through intestine, ref., 694 
Buday, on cystic adenoma of mamma, 
ref., 850 
Buerger, on S. mucous capsulatus, ref., 
221 
Bunting, on haemolysis, ref., 174 
Bunting and Yates, on Hodgkin's disease, 
497 
Burgess, on chloroma, ref., 479; on malig- 
nant rhabdomyoma, ref., 390 
Burnham, on actinomycosis of appendix, 
ref., 691 
Burns, death from, 10 
Burri, on staining Tr. pallidum, ref., 277 
Burrows, on cultivation of tissues, ref., 80 
Buscke, on yeasts and moulds, ef., 149 
Busse, on tumors of kidney, ref., 777 
Butler, on abnormalities of thoracic duct, 
ref., 576; on membranous enteritis, 
ref., 682 
Buttner, on peritonitis, ref., 694 
Buxton, on giant cells, ref., 103 
Buxton and Torrey, on absorption from 
peritoneum, ref., Ill; 694; on dis- 
posal of bacteria in blood, ref., 151; 
on removal of alien substances 
from peritoneal cavity, ref., 99 
Cachexia in tumors, 343 
strumipriva, 429 
Cadaveric lividity, 986 
Caecum, inflammation of, 682 
Caisson disease, 11 
congestion of brain in, 934 
Cajal method of staining Tr. pallidum in 
tissues, 276 
Calcareous infiltration, 50 
Calcification in tissues, 51 
of arteries, 559 
heart, 535 
kidney, 750, 753 
liver, 722 
muscle, 872 
penis, 855 
placenta, 823 
pleura, 639 
veins, 573 
Calcium carbonate in gall-stones, 744 
salts in blood, 452 
tissues, 51, 52 
demonstration of, 52 
Calculi, ref., 52, 789 
biliary, 743 
of appendix, 686 
bladder, urinary, 789 
composition of, 789, 790 
gall-bladder and -ducts, 743 
intestine, 690 
kidney, 774 
pancreatic ducts, 707 
prepuce, 855 
prostate, 866 
seminal vesicles, 863 
tonsil, ref., 649 
tonsillar, 52 
Calkins, on protozoa, ref., 115; on spiro- 
chetes, ref., 119; on vaccine bodies, 
306 
Callus in healing bone, 878 
Calmette and Guerin, on intestinal origin of 
pulmonary tuberculosis, ref., 264 
Campbell, on leptothrix, ref., 232 
Cancer (see Carcinoma), 395, 400 
bodies, 347 
" cages," 355 
cell, 402 
Canon, on bacteriology of blood, ref., 470 
Canon and Pielicke, on excitant of 
measles, 310 
Cantharides poisoning, 422 
Capps, on aneurism of coronary arteries, 
ref., 570 
Capsules, blood, of tapeworm, 125 1054 
INDEX 
Carbolic acid poisoning, 423 
Carbonic-oxide poisoning, 424 
Carbuncle, 200, 228 
Carcino-adenoma, 398 
Carcinoma, 395, 400 
and tuberculosis, ref., 267 
alveolar, 414 
characters of, 400 
colloid, ref., 412 
cylindrical-celled, 405, 410 
encephaloid, 412 
epitheliomatous type, 406 
fibro-/411 
gelatinous, 406, 412 
giant-celled, 410 
immunity to, 356 
medullary, 412 
melano-, 415 
mitosis in, 402 
molle, 412 
myxomatodes, 414 
neuro-, 410 
of adrenals, 517 
appendix vermiformis, 690 
arteries, 571 
bladder, urinary, 788 
bone, 903 
brain, 977 
bronchi, 591 
dura mater spinalis, 922 
gall-bladder and -ducts, 743 
Fallopian tubes, 841 
heart, 556 
intestine, 690 
kidney, 777 
larynx, 585 
lips, 645 
liver, 736 
lung, 635 
lymph-nodes, 498 
mamma, 850 
mamma, male, 867 
mouth, 645 
muscle, 875 
nerves, 979 
oesophagus, 653 
ovary, 830 
pancreas, 706 
penis, 855 
pericardium, 522 
peritoneum, 699 
pharynx, 651 
pleura, 642 
Carcinoma of prostate, 866 
salivary glands, 701 
seminal vesicles, 863 
spleen, 510 
stomach, 663 
statistics of, 664 
testicle, 861 
thyroid, 514 
tongue, 646 
urethra, 792 
uterus, 815 
vagina, 797 
veins, 575 
ventricles of brain, 927 
vulva, 795 
scirrhus, 411 
serum injections in, 356 
simplex, 406, 411 
squamous, 405 
stroma reaction in, 355 
telangiectoides, 412 
transplantation of, in mice, 356. 
Caries of bone, 891 
Carlisle, on relapsing fever, 292 
Carotid gland, 517 
Carrel, on cultivation of tissues, ref., 80; 
on tissue transplantation, 78 
Carroll, on mosquito in yellow fever, ref., 
302 
Carter, on excretion of pigment by 
kidney, ref., 755; on mosquito in yellow 
fever, ref., 302 
Cartilage in pia mater spinalis, 923 
loose, in joints, 907 
regeneration of, 76 
Caryochromes, 943 
Caseation, 59 
Castellani, on yaws, 293 
Castelli, on biliary angioma of liver, ref.r 
737 
Castle, on heredity, ref., 14 
Casts of kidney, 749 
Catarrh, dry, 588 
purulent, 199 
Catarrhal fever, epidemic, 233 
Cave, on pneumococcic arthritis, ref., 904 
Cecil, on adenoma of pancreas, ref., 704; 
on relation of pancreas to diabetes, 
ref., 435, 704 
Cecil and Bulkley, on parasites in ap- 
pendix, ref., 688 
Cecil and Soper, on meningococcus in en- 
docarditis, ref., 545 INDEX 
1055 
Cells, atrophy of, 36 
"beaker," 46 
blood, red, (see Blood cells), 456 
white, (see Leucocytes), 459 
changes in, 35 
chemistry of, as related to Ehrlich's 
hypothesis, 166 
degeneration of, 36, 39 
division, amitotic, 65, 67 
direct, 65, 67 
indirect, 65 
mitotic, 65 
modes of, 64 
giant, in epithelioma, 410 
inclusions in tumors, 347 
"mother," 586 
necrobiosis, 36 
necrosis of, 36 
prickle, 406 
regeneration of, 64, 68, 167 
impulse to, 79 
regressive changes in, 35 
relationship of, to organs, 5 
serous infiltration of, 45 
significance of, 4 
spider, in glioma, 387 
spinal, 406 
Celloidin as tissue embedding medium. 
1031 
Cephalhsematoma, 1024 
Cephalocele, 928 
Cerebellar ataxia, 963 
Cerebellum, atrophy of, 963 
Cerebrum, malformations of, 927 
Cerenville, Tavel, etc., on necrotic colitis, 
ref., 681 
Cervix uteri, hyperplasia of, 805 
Cestoda, 123 
Chalk-stones, 436 
Chalicosis of lung, 616 
Chancre, 271 
soft, 228 
Chancroid, 228 
Chantemesse and Powdyssotsky, on condi- 
tions of disease, ref., 14; on fever, ref., 
441 
Chapin, on air as vehicle of infection, 
ref., 150; on sources of infection, ref., 
151 
Chapman, on kidney lesions in scarlatina, 
ref., 307 
Charbon, 228 
Charcot-Leyden crystals, 589, 897 
Cheesman and Meltzer, on local predispo- 
sition in infection, ref., 152 
Cheesy degeneration, 59 
Cheloid, 364 
Chemotaxis, 85, 137 
negative, 85 
Chiari, on auto-digestion of pancreas, 
ref., 702; on atypical typhoid, ref., 243 
Chibret, on adamantinoma, ref., 416 
Chittenden and Albro, on skin pigment, 
ref., 55 
Chlamydozoa, 308 
Chloral hydrate poisoning, 424 
Chloroform, in experimental cirrhosis, 
730 
liver degeneration after use of, 716 
poisoning, 423, 716 
Chloroma, 376, 478 
Chlorosis, 471 
Cholsemia, 13 
Cholangitis, 740 
Cholecystitis, 740 
Cholelithiasis, 743 
Cholera, Asiatic, 247 
"carriers," 249 
communicability of, 249 
diagnosis of, 249 
immunity in, 170 
lesions of, 248 
preventive inoculation in, 250 
spirillum of, 247, 249 
chicken, bacillus of, 289 
spirillum, reproduction of, 135 
Cholesteatoma, 379 
of pia mater cerebralis, 920 
Cholesterin in gall-stones, 744 
Chondroma, 383 
of bone, 900 
bronchi, 591 
choroid plexus, 927 
clitoris, 795 
dura mater cerebralis, 911 
spinalis, 922 
heart, 556 
larynx, 585 
lips, 645 
liver, 737 
lung, 634 
lymph-nodes, 497 
mamma, 848 
mouth, 645 
muscle, 875 
ovary, 829 1056 
INDEX 
Chondroma of peritoneum, 697 
pia mater cerebralis, 920 
salivary glands, 700 
testicle, 860 
veins, 575 
uterus, 813 
osteoid, 900 
Chondro-sarcoma, 376 
Chorda dorsalis, 384 
Chordae tendinae, abnormal, 525 
Chordoma, 384 
Chorionepithelioma, 820 
hydatid moles, relation to, 826 
of pregnancy, 820 
testicle, 822, 863 
with teratoma, 822 
Chorionic villi, 820 
wandering cells, 821 
Choroid plexus, brain sand in, 927 
cysts of, 927 
lesions of (see Ependyma), 924 
tumors of, 927 
Christian, on myeloma, ref., 902; on pneu- 
monic exudates, ref., 605 
Christian and O'Hare, on experimental 
nephritis, ref., 769 
Chromatic figure in mitosis, 66 
Chromatolysis, 947, 949, 950, 958 
Chromophilic bodies, 943 
Chromosomes, 65 
Cicatricial tissue, 93 
Ciliata, 120 
Ciliophorata, 115 
Circle of Willis, 933 
Circulation, collateral, 18 
disturbances of, favoring throm- 
bosis, 25 
in living animal, study of, 34, 111 
of blood, 83 
Circulatory system, 518 
Cirrhosis hepatis anthrotica, 730 
of liver (see Liver, cirrhosis of), 725 
Citron, on immunity, ref., 165 
Cladothrix, 136 
Clairmont, on action of saliva on bacteria, 
ref., 150 
Clasmatocytes, 366 
Clegg, on cultures of B. leprae, ref., 
269 
Clitoris, anomalies of, 793 
Cloacae, 668 
Clostridium forms of bacteria, 134 
Clots, heart, 531 
Club-foot, 326 
Club-hand, 326 
Cloudy swelling (see Degeneration, albu- 
minous), 39 
Coagulation necrosis, 58, 59 
in tuberculosis, 254 
of blood, 452 
Coats, on tumor of pineal gland, 983 
Cobbett and Melsome, on granulation 
tissue in infection, ref., 152 
Cocci, 134 
Coccidia, 121 
oviforme, 121 
in liver, 740 
Coccus, diplo-, 135 
strepto-, 135 
Coco, on colorability of living cells, ref., 
1027 
Cohnheim's hypothesis of origin of 
tumors, 344, 351 
Colchicum poisoning, 422 
Cole, on pneumococcus, ref., 219; on 
pneumonia, ref., 220; on typhoid 
meningitis, ref., 243 
Coleman and Buxton, on typhoid bacilli 
in blood, 244 
Colitis, 675 
acute catarrhal, 675 
acute infectious, 675, 677 
amoebic, 676 
chronic, 682 
croupous, 680 
excitants of, 675, 677, 678, 681 
experimental, ref., 678 
membranous, 682 
mucous, 682 
necrotic, 681 
nodular, 680 
pseudo-membranous, 680 
Collateral circulation, 17 
Coilodium sacs, ref., 319 
Colloid degeneration, 45, 47 
technique of staining, 47 
Colocynth poisoning, 422 
Colon bacillus (see B. coli communis), 
214 
group, 214 
dilatation of, 671 
inflammation of (see Colitis), 675 
Complement, 177 
deviation of, 189 
fixation of, 189 
in whooping-cough, 317 INDEX 
1057 
Concretions in appendix vermiformis, 686 
in intestine, 690 
pancreas, 707 
Concurrent infection, 157 
Condyloma, 272 
pointed, of vulva, 794 
Cone, on chronic gastritis, 658 
on tuberculous oesophagitis, ref., 653 
Conforti, on tumors of omentum, ref., 698 
Congenital abnormalities, 320 
infection, ref., 151, 157 
Congestion (see Hypersemia), 16, 594 
chronic, 19 
hypostatic, 19, 594 
post-mortem, 986 
venous, 17 
Conium poisoning, 425 
Conjunctiva, trachoma, 308 
Conjunctivitis, gonorrhoeal, 222 
Connective tissue, regeneration of, 73 
tumors, 357 
Connell, on fat embolism, ref., 34 
Conradi and Bierast, on B. coli, ref., 214 
Constitutio lymphatica, 439 
Contagium, ref., 159 
Contrecoup, injury by, 930 
Contusions, post-mortem, 989 
Cooling of body, post-mortem, 988 
Coplin, on branchial cysts, ref., 647; on 
pulmonary oedema, ref., 595; on 
tumors of oesophagus, ref., 654 
Copper poisoning, 422 
Corner and Fairbanks, on sarcoma of 
stomach, ref., 663 
Cornet, on tuberculosis, 268 
Cornet and Meyer, on tuberculosis, 268 
Cornil and Carnot, on regeneration of 
mucous membranes, ref., 71 
Corning, on cysts of appendix, ref., 686; 
on diverticula of appendix, ref., 
668 
Corpora aliena articulorum, 907 
amylacea, 50 
in brain, 941 
ependyma, 927 
prostate, 866 
cavernosa, inflammation of, 854 
plates, fibrous, in, 854 
Corpuscles, Gluge's, 941, 966 
Corrosive sublimate as fixative, 1030 
for blood, 467 
poisoning, 421 
kidney in, 51, 750, 753 
Corynebacterium granulomatis maligni, 
497 
Councilman, on acute interstitial nephri- 
tis, ref., 759; on arterio-sclerosis, 565; 
on cerebro-spinal meningitis, ref., 224; 
on excitant of smallpox, 306; on 
gonorrhoeal myocarditis, ref., 538; on 
lung lobule, ref., 602; on sudden deaths 
due to heart, ref., 528 
Councilman and Lafleur, on amoeba dy- 
senterise, 115 
Councilman, Mallory, and Pearce, on 
bacteriology and pathology of diph- 
theria, ref., 283 
Councilman, Mallory, and Wright, on 
cerebro-spinal meningitits, ref., 225 
Coupland and Pasteur, on tumors of 
spinal cord, ref., 977 
Cour mont and Duffau, on spleen in in- 
fection, ref., 151; ref., 504 
Cowie, on differentiation of smegma and 
tubercle bacilli, ref., 267 
Cowper's glands, lesions of, 867 
Coyon, on bacteria of stomach, ref., 
659 
Craig, on entamoeba histolytica, ref., 116 
Cramer, on anterior poliomyelitis, ref., 
969; on sunstroke, 437 
Craniopagus, 330 
Craniorrhachischisis totalis, 324 
Cranioschisis, 324 
Craniotabes, 894 
Craw, on agglutination of typhoid bacilli, 
ref., 246 
Crenothrix, 136 
Cretinism, 430 
Croton oil poisoning, 422 
Croup, 583 
Crowder, on tuberculous lymphadenitis, 
ref., 488 
Cryptorchismus, 856 
Culex, in avian malaria, 314 
Cullen, on adenomatous myoma of uterus, 
ref., 813; on calcification of heart 
muscle, ref., 541; on carcinoma of 
uterus, 815; on cysts of Bartholin's 
glands, ref., 795; on cysts of vagina, 
ref., 797; on frozen sections, 1028; on 
hydrosalpinx, ref., 838; on myoma of 
round ligament, ref., 813; on peri- 
tonitis, ref., 694; on sarcomatous 
changes in myoma of uterus, ref., 813; 
on tuberculosis of uterus, ref., 806 1058 
INDEX 
Cunningham, on death from electric cur- 
rents, ref., 11; on lesions of thyroid, 
ref., 429 
Curare, use of, ref., 34 
Currie, Brinckerhoff, and Hollman, on 
cultures of B. leprae, ref., 269 
Curschmann, on B. typhosus in bladder, 
ref., 786 
Curschmann's spirals, 589 
Cushing, on gall-bladder infections, ref., 
742; on gonococcus peritonitis, ref., 
694; on pituitary body, ref., 439; on 
role of micro-organisms in gall-stones, 
ref., 745 
Cyclopia, 325, 927 
Cylindroma, 380 
Cystadenoma adamantinum, 415 
of mamma, 850 
ovary, 830 
glandular, 832 
papillary, 835 
Cysticercus cellulosae, 124 
in brain, 979 
heart, 556 
kidney, 781 
muscle, 875 
peritoneum, 699 
pia mater cerebralis, 921 
spinalis, 923 
in spleen, 511 
ventricles of brain, 927 
taeniae mediocanellatae, 124 
Cystitis, acute catarrhal, 783 
chronic, 784 
croupous, 785 
emphysematous, 786 
en plaque, 785 
excitants of, 786 
exudative, 783 
hyperplastic, 785 
necrotic, 784 
nodular, 785 
suppurative, 785 
tuberculous, 786 
with pyelo-nephritis, 771 
Cystocele, 795 
vaginal, 782 
Cysts, 359 
atheromatous, 561 
branchial, 645, 647 
ciliated, ref., 361 
congenital, 360 
daughter, 125 
Cysts, dermoid, 360 
of bladder, urinary, 788 
bone, 903 
choroid plexus, 927 
lungs, 635 
mouth, 645 
muscle, 875 
nose, 581 
ovary, 836 
penis, 855 
peritoneum, 699 
scrotum, 855 
skin, 360 
spleen, 510 
thymus, 511 
thyroid, 514 
echinococcus, 125 
follicular, of ovary, 836 
foreign body, 360 
grand-daughter, 125 
hydatid, 125 
of appendix vermiformis, 686 
bladder, urinary, 788 
bone, 903 
brain, 979 
choroid plexus, 927 
Fallopian tubes, 841 
intestine, 690 
kidney, 772 
liver, 737 
mamma, 852 
male, 867 
mesentery, 699 
oesophagus, 654 
omentum, 699 
ovary, 360, 830, 836, 837 
pancreas, 706 
parovarium, 837 
pericardium, 522 
pia mater cerebralis, 921 
placenta, 826 
pleura, 642 
prostate, 866 
spinal cord, 978 
spleen, 510 
stomach, 666 
tongue, 646 
urethra, 792 
uterus, 822 
vagina, 797 
vulva, 795 
preservation of, 1039 
retention, 360 INDEX 
1059 
Cysts, retention, of Cowper's glands, 867 
larynx, 585 
retroperitoneal, 699 
retro-ovarian, 841 
sebaceous, of penis, 855 
transudation, 360 
Cysto-sarcomata, 375 
Cytase, 179 
Cytolysins, anti-, 175 
Cytolysis, 60, 171, 174 
Ehrlich's hypothesis, application of, 
to, 176 
in liver, 715 
phagocytes in, 178 
Cytolytic substances, 171, 174 
Cytoryctes vaccinae, 305 
Cytotoxins, anti-, 175 
DaCosta, on blood, ref., 452 
Da Fano, on tissue transplantation, 79 
Dagonet, on tumors of dura mater, ref., 
911 
Dahms, on differentiation of smegma and 
tubercle bacilli, ref., 267 
Dana and Berkeley, on tumors of pineal 
gland, ref., 980 
Daughter cysts, echinococcus, 125 
Davenport, on chemotaxis, ref., 86; on 
heredity, ref., 14 
Davis, on adrenals, ref., 516; on bacte- 
riology of tonsils, ref., 649; on B. influ- 
enzae, ref., 234; on chronic strepto- 
coccus arthritis, ref., 904; on diabetic 
gangrene, ref., 435; on diverticula of 
duodenum, ref., 667; on Ducrey's bacil- 
lus, 228; on excitant of whooping-cough, 
ref., 317; on leptothrix, ref., 232; on 
meningococcus in blood, ref., 225; on 
tumors of adrenals, ref., 571 
Dayton, on haemolymph-nodes, ref., 498 
Dead tissues, disposal of, in body, 98, 
103 
Death, black, 288 
causes of, 9 
sudden, 446 
and persistent thymus, ref., 440, 
448 
in status lymphaticus, 439, 
448 
lesions leading to, 446 
violent, 442 
time of, as determined post-mortem, 
988 
de Beurmann and Gougerot, on sporotri- 
chosis, ref., 149 
Decalcification of tissues, 1031 
Deciduoma malignum, 820 
Decomposition, post-mortem, 987 
Degeneration, 39 
acute, 39 
albuminous, 39 
of heart, 533 
kidney, 751 
liver, 716 
muscle, 871 
pancreas, 703 
stomach, 656 
amyloid, 48 
of adrenals, 515 
arteries, 558 
heart, 535 
intestine, 671 
kidney, 753 
liver, 720 
lymph-nodes, 482 
muscle, 872 
pancreas, 703 
placenta, 823 
spleen, 500 
stomach, 656 
thyroid, 512 
uterus, 803 * 
tests for, 50, 1012 
ascending, of nervous system, 954 
axonal, 948 
cheesy, 59 
colloid, 45, 47 
of thyroid, 512 
combined system, 962 
descending, in nervous system, 953 
diffuse, of spinal cord, 963 
fatty, 40, 41 
of arteries, 557 
endocardium, 535 
kidney, 752 
heart muscle, 534 
joints, 903 
liver, 720 
muscle, 871 
pancreas, 703 
placenta, 823 
prostate, 863 
stomach, 656 
uterus, 803 
veins, 593 
glycogenic, 44 1060 
INDEX 
Degeneration, glycogenic, of kidney, 753 
liver, 721 
granular, 39 
hyaline, 48 
of arteries, 558 
heart, 535 
lymph-nodes, 482 
muscle, 871 
pancreas, 703 
prostate, 863 
thyroid, 512 
hydropic, 45 
in inflammation, 97 
lardaceous, 48 
lipoid, 43 
mucous, 45 
neurone, 946 
of dendrites, 946 
ganglion cells, ref., 965, 966 
neurone systems, 951 
nerves, 970 
nervous system, 946 
parenchymatous (see Degeneration, 
albuminous), 39 
of kidney, 751 
liver, 716 
primary, of nervous system, 953 
secondary, of nervous system, 953 
waxy, 48 
of muscle, 872 
Delafield, on colitis, 675 
Delafield's haematoxylin solution, 1035 
Delamare, on syphilitic nephritis, ref., 770 
Delamare and Lecene, on giant cells in 
carcinoma, ref., 410 
Dendrites, 943 
degeneration of, 947 
Dermacentor occidentalis as agent of in- 
fection in Rocky Mountain fever, 301 
Dermatitis, blastomycotic, 146 
Dermoid cysts (see Cysts, dermoid), 360 
Desmoid, 565 
Dewey, on tuberculosis of stomach, ref., 
659 
De Witt, on dysmenorrhcea, ref., 804; on 
islands of Langerhans, ref., 704; on 
myositis ossificans, ref., 874 
Diabetes, bronzed, 436 
mellitus, 435 
internal secretions in, 436 
phloridzin, ref., 436 
Diapedesis, 86 
haemorrhage by, 20 
Diaphragm, eventration of, 692 
examination, post-mortem, of, 1003 
malpositions of, 691 
vault of, 1003 
Diastematomyelia, 928 
Diaster phase of mitosis, 66 
Diathesis, haemorrhagic, 22 
Dicephalus, 331 
Dick, on fusiform bacilli, ref., 293 
Dieudonne, on plague bacillus, ref., 288 
Digestive system, 643 
Digitalis poisoning, 425 
Dioxydiamidoarsenobenzol, 119 
Diphtheria, 282 
antitoxin, 164, 285 
theory of, 165 
bacillus of, 282, 283, 284 
bacteriology of, 283 
carriers, 285 
communicability of, 285 
concurrent infections in, 284 
immunization, artificial, in, ref., 304 
lesions in, 282 
of larynx, 583 
of pharynx, 648 
pseudo-, 212 
septicaemia in, 284 
toxin, 164, 285 
Diplobacilli, 135 
Diplococci, 135 
Diplococcus intracellularis meningitidis, 
223 
characters of, 225 
pneumoniae, 217 
character of, 218 
in mouths of healthy persons, 
ref., 219 
occurrence of, 219 
sources of, 219 
staining reactions of, 220 
Diplomyelia, 928 
Diprosopus, 331 
Dipygi, 330 
Disease, adaptation to, 8 
characters of, 4 
conditions of, 8 
external, 9 
internal, 13 
contagious, ref., 159 
disposition to, 8 
excitants of, 5 
general, 429 
infectious, 156 INDEX 
1061 
Disease, infectious, bibliography of, 319 
classification of, 197 
communicable, 159 
communicability of, 158 
definition of, 160 
endemic, 159 
epidemic, 159 
general considerations, 197 
non-communicable, 159 
of animals, 319 
unknown origin, 318 
pandemic, 159 
occupational, 9 
"specific," 197 
Disposition to disease, 8 
Distoma haematobium, 123 
hepaticum, 123 
in liver, 739 
veins, 575 
lanceolatum, 123 
sinense, 123 
Diverticula, acute, of intestine, 668 
false, of intestine, 668 
Meckel's, 667 
of appendix, 668 
bladder, urinary, 782 
intestine, 667 
oesophagus, 652 
pharynx, 647 
Djewitsky, on tumors of heart valves, 
ref., 556 
Dmochowski and Janowski, on cysts in 
liver, ref., 736; on pyogenic powers of 
typhoid bacilus, ref., 244 
Dobrowolski, on lymph-nodules of larynx, 
etc., ref., 649 
Dochez, on D. pneumoniae in blood, ref., 
218; on pneumonia, 220 
Dochez and Gillespie, on lobar pneumonia, 
220 
Dock, on chloroma, ref., 376; ref., 479; 
on sarcoma of stomach, ref., 663; on 
trichomonas, ref., 119 
Dock and Warthin, on chloroma, ref., 
479 
Doerr and Russ, on anaphylaxis, 191 
Doflein, on protozoa, ref., 115 
Dohle bodies in scarlatina, 307 
Donath and Landsteiner, on paroxysmal, 
haemoglobinuria, ref., 456 
Dorset, on invisible microbes, ref., 319 
Doty, on quarantine in yellow fever, ref., 
302 
Dowd, on cervical tuberculous lymph- 
nodes, ref., 487; on cysts of mesentery, 
ref., 699; on cysts of omentum, ref., 699 
Draper and Hanford, on scarlatina, ref., 
307 
Dropsy, 22, 518 
Drowning, death from, 443 
Drysdale's corpuscles, 835 
Ducrey's bacillus, 228 
Duct, thoracic, lesions of, 576 
Duke, on purpura, ref., 439 
Dum-dum fever, 119 
Dunbar, on typhoid fever, ref., 244 
v. Dungern, on immunity, 196 
Dura mater cerebralis, 908 
bone in, 911 
haemorrhage of, 908 
inflammation of (see Pa- 
chymeningitis), 909 
structure of, 908 
syphilis of, 911 
thrombosis of, 908 
tuberculosis of, 911 
tumors of, 911 
examination, post-mortem, of, 
992 
methods of hardening, 998 
spinalis, 921 
bone in, 922 
haemorrhage of, 922 
inflammation of (see Pa- 
chymeningitis), 922 
parasites of, 922 
structure of, 921 
tuberculosis of, 922 
tumors of, 922 
Durham, on mosquito in yellow fever, 
ref., 302 
Dust infection in tuberculosis, 265 
Dutton and Todd, on tick fever in 
monkeys, 293 
Duval, on cultures of B. leprae, ref., 269; 
on parasites of scarlatina, ref., 307 
Duval and Wellman, on cultivation of 
B. leprae, ref., 268 
Dysentery (see Colitis), 675 
amoebic, ref., 116 
bacillus of, 247, 677 
Dysmenorrhcea, membranous, 804 
Dyspnoea, 9 
Ear, internal, examination, post-mortem, 
of, 998 1062 
INDEX 
Ear, middle, relation of, to meningitis, 
ref., 917 
Eber, on animal tuberculosis, ref., 260 
Ecchondroses, 384 
Ecchymoses, 21, 989 
Echinococcus, 125 
cysts, 125 
exogena, 126 
in brain, 979 
heart, 556 
kidney, 781 
liver, 738 
muscle, 875 
peritoneum, 699 
pleura, 642 
prostate, 866 
spleen, 511 
testicle, 863 
thyroid, 514 
uterus, 822 
veins, 575 
ventricles of brain, 927 
multilocularis, 126 
scolecipariens, 126 
Eckersdorff, on sarcoma of lung, ref., 
634 
Eclampsia, lesions of liver in, 716, 718 
Ectopia cordis, 323 
Ectopic pregnancy, 841 
Ectosarc, 116 
Eden, on placenta, ref., 822 
Edsall and Ghriskey, on communicability 
of pneumonia, ref., 606 
Egg albumen for fixing section to slide, 
1028, 1034 
Ehrlich's hypothesis, 176 
Ehrlich, on experimental tumors of mice, 
ref., 351; on immunity, 196; side chain 
hypothesis of, 165; triacid stain for 
blood, 468 
Ehrlich and Lazarus, on diseases of blood, 
ref., 471 
Elaterium poisoning, 422 
Elbe, on calcification of kidney, ref., 753 
Electricity, action of, on bacteria, 138 
death from, 10 
Elephantiasis of penis, 855 
scrotum, 855 
vulva, 794 
Elser, on cerebro-spinal meningitis, ref., 
225 
Elser and Huntoon, on meningococcus in 
blood, ref., 225 
Elsner, on formation of gall-stones, ref., 
744 
Elting, on gonorrhoea, ref., 221 
Embedding tissues, 1031 
Emboli, 28 
air, 34 
fat, 29, 34, 469 
of lungs, 595 
forms of, 29 
liver-cell, ref., 29 
parenchyma-cell, ref., 29 
placental-cell, ref., 29 
sources of, 31 
tumor-cell, 34 
Embolism, 28 
effects of, 29 
of arteries, 571 
brain, 940 
cerebral arteries, 31 
kidney, 748 
mesenteric vessels, 671 
spinal cord, 942 
spleen, 502 
paradoxical, 32 
retrograde, 32 
study of, in living animal, 34 
Emerson, on experimental nephritis, ref., 
769; on pneumothorax, ref., 637; on 
status lymphaticus, ref., 440 
Embryo, age of, to determine, 1023 
malformations of, 320 
size of, 1023 
Emphysema of bladder, urinary, 786 
lung, 597 
interstitial, 599 
vesicular, 597 
Empyema, 199, 638 
excitants of, 639 
Encephalitis, acute, 964 
chronic, 971 
disseminated, 965 
haemorrhagic, 965 
in new-born, 972 
parenchymatous, ref., 965 
suppurative, 965 
Encephalocele, 928 
Encephalomeningocele, 325 
Enchondroma (see Chondroma), 383 
Endarteritis, 559 
obliterating, 560 
of coronary arteries, 537 
Endemic disease, 159 
Endocarditis, 542 INDEX 
1063 
Endocarditis, acute, 543 
bacteria in, 544 
chronic, 547 
ulcerative, 548 
gonorrhoeal, ref., 545 
infective, ref., 545, 547 
malignant, 544 
bacteria in, 544 
mycotic, 544 
stenosis of valves in, 548 
thrombi in, 546 
tuberculous, 548 
ulcerative, acute, 543 
chronic, 548 
malignant, 544 
vegetations in, 543, 546, 548 
verrucous, 543 
Endocardium, degeneration of, 535 
lesions of, 530, 542 
Endometritis, 804 
acute catarrhal, 804 
chronic, 804 
exfoliative, 804 
membranous, 806 
puerperal, 808 
tuberculous, 806 
syphilitic, 807 
Endometrium, hyperplasia, glandular of, 
805 
inflammation of (see Endometritis), 
804 
Endophlebitis, 573, 574 
Endosarc, 116 
Endothelioma, 377 
of adrenals, 517 
appendix vermiformis, 690 
bone, 901 
brain, 977 
dura mater cerebralis, 911 
spinalis, 922 
kidney, 776 
liver, 735 
lung, 634 
lymph-nodes, 498 
lymph-vessels, 577 
nerves, 979 
ovary, 830 
pericardium, 522 
peritoneum, 698 
pia mater cerebralis, 920 
spinalis, 923 
pleura, 641 
salivary glands, 700 
Endothelioma of thymus, 511 
thyroid, 514 
uterus, 813 
vagina, 797 
Endothelium, regeneration of, 75 
Endotoxin, 152 
bacterial, 139 
Energy, cell, 3 
transformations of, in cells, 35 
Engelken, on adenoma of kidney in 
children, ref., 776 
Enostoses, 899 
Entamoeba histolytica, 115 
in colitis, 676 
Enteritis, acute catarrhal, 672 
chronic catarrhal, 672 
exudative, 673 
follicular, 672 
nodular, 672 
phlegmonous, ref., 673 
pseudo-membranous, 672 
streptococcus, ref., 681 
suppurative, 673 
syphilitic, 674 
tuberculous, 673 
Enteroliths, 690 
Enzymes, bacterial, 139 
proteolytic, in phagocytes, 105 
Eosin-haematoxylin stain for nerve 
tissue, 981 
Eosinophile cells, 461 
Ependyma, 924 
cysts of, 927 
inflammation of, 924 
lesions of, 924 
method of hardening, 998 
parasites of, 927 
tumors of, 927 
Ependymitis, 924 
Epicardial nodules, 521 
Epidemic disease, 159 
Epididymitis, 858 
Epignathus, 332 
Epispadias, 324, 781, 853 
Epistaxis, 21, 579 
Epithelial bodies, 514 
cell tumors 395 
pearls, 407 
Epithelioma (see also under Carcinoma), 
405, 406 
adamantinum, 415 
basal-celled, 408 
giant-celled, 410 1064 
INDEX 
Epithelioma, neuro-, 410 
of mamma, 851 
nose, 581 
scrotum, 855 
uterus, 815 
Epithelium, growth of, following injec- 
tions of Scharlach R, 352 
regeneration of, 71 
Eppinger, on pathological relations of 
spleen, ref., 499 
Epulis, 373 
of mouth, 645 
Erdheim, on thyroid, ref., 512 
Erdman, on caisson disease, ref., 11 
Erlanger, on Stokes-Adams' disease, ref., 
549 
van Ermenghem, on intestinal bacteria, 
ref., 681 
Ernst, on cartilage tumors, ref., 383; on 
metastases in chondroma, ref., 384; 
on psammoma, ref., 912 
Erysipelas, 211 
of penis, 854 
vulva, 793 
Erythraemia, 455 
Erythroblastoma, 902 
Erythrocytes (see Blood cells, red), 456 
Erythrocytoma, 902 
Erythrocyto-opsonins, 184 
Esser, on circulatory changes in lungs, 
ref., 595 
Etat mamelonne of stomach, 657 
Ether poisoning, 424 
Etienne, on tuberculosis of endocardium, 
ref., 548 
Euparal mounting medium, 1029 
Ewing, on adipocere, ref., 987; on bacteria 
in smallpox, ref., 304; on blood, ref., 
452; on blood changes in disease of 
liver, ref., 734; on eclampsia, ref., 718; 
on epithelial cell changes in measles, 
ref., 309; on ganglion cells, ref., 243, 
948; on immunity in typhoid fever, 
ref., 245; on lesions of goitre, 433; on 
lymphatic constitution, ref., 440, 448; 
on malarial nephritis, ref., 761; on 
sudden death, ref., 448; on toxic 
hypoleucocytosis, ref., 464; on vaccine 
bodies, 305 
Ewing and Strauss, on precipitin test for 
blood, ref., 182 
Examination, post-mortem, 933 
Exophthalmos, 432 
Exostoses, 386, 899 
Exudates, 23, 199 
autolysis of, 202 
in inflammation,. 87 
role of, 108 
sterile, method of securing, 195 
Exudation, study of, on frog, 111 
Eye, examination, post-mortem, of, 998 
malformations of, 325, 927 
Face, malformations of, 643 
Faeces, typhoid bacilli in, 244, 245 
Falkson, on tumor of pineal gland, 980 
Fallopian tubes, 838 
absence of, 838 
closure of, 838 
cysts of, 841 
dilatation of, 838 
ectopic pregnancy, 841 
examination, post-mortem, of, 1020 
haemorrhage of, 839 
hydrosalpinx, 838 
hyperplasia of muscle wall, 839 
inflammation of, 839 
malformations of, 838 
malpositions of, 838 
preservation of, 1020 
pyosalpinx, 840 
size of, 1020 
changes in, 838 
syphilis of, 840 
tuberculosis of, 840 
tumors of, 841 
Falta, on senile gangrene, ref., 58 
Faltin, on bacteria of urinary passages, 
ref., 786 
Famine fever, 292 
Farcin de boeuf, 232 
Farcy, 226 
Farmer, Moore and Walker, on mitosis in 
tumors, 351 
Farrant, on thyroid hyperplasia, ref., 512 
Fat-acid crystals, technique of staining, 
ref., 44 
emboli, 29, 34 
Fat-acid in blood, 469 
necrosis, 59 
stains for, 44, 1029 
technique of fixation, 44 
tissue, regeneration of, 77 
Fatigue, action of, on neurones, 950 
Fatty degeneration, 40, 41 
infiltration, 40, 43 INDEX 
1065 
Favus, 148 
Feldmann, on chordoma of sacrum, ref., 
385 
Fenwick, on hair balls in stomach, ref., 
666; on sarcoma of stomach, ref., 663 
Fermentation and yeasts, 146 
bacteria in, 139 
Ferments, bacterial, 139 
Fever, 440 
famine, 292 
catarrhal, epidemic, 233 
hospital, 300 
inflammatory, ref., 204 
jail, 300 
Malta, 287 
paratyphoid, 247 
puerperal, ref., 204, 808 
relapsing, 292 
Rocky Mountain spotted, 301 
scarlet, 307 
seven-day, 292 
ship, 300 
spirillum, 292 
splenic, 228 
spotted, 300 
Rocky Mountain, 301 
suppurative, ref., 204 
surgical, ref., 204 
Texas, 122 
tick, 301 
traumatic, ref., 204 
typhoid, 234 
typhus, 300 
yellow, 301 
Fibrin, 86 
Fibrinogen, 452 
Fibroblasts, 74, 93 
Fibroma, 362 
diffusum, 794 
of penis, 855 
durum, 362 
intracanalicular, 365, 847 
molle, 362 
inolluscum, 363 
of appendix vermiformis, 690 
bladder, urinary, 786 
bone, 899 
brain, 976 
bronchi, 591 
dura mater cerebralis, 911 
spinalis, 922 
ependyma, 927 
Fallopian tubes, 841 
Fibroma of gall-bladder and -ducts, 743 
heart, 556 
intestine, 688 
joints, 907 
kidney, 776 
larynx, 585 
liver, 735 
lymph-nodes, 498 
lung, 634 
mamma, 847 
mamma, male, 867 
mouth, 645 
muscle, 875 
oesophagus, 653 
ovary, 298 
penis, 855 
pericardium, 522 
peritoneum, 696 
pharynx, 650 
pia mater cerebralis, 920 
spinalis, 923 
pleura, 641 
salivary glands, 700 
scrotum, 855 
spleen, 510 
spinal cord, 978 
stomach, 662 
testicle, 860 
tongue, 646 
uterus, 809 
vagina, 797 
vulva, 794, 795 
papillare, 809 
pericanalicular, 848 
Fibrosis, 96 
Fibrous tissue, hyperplasia of, 96 
in pulmonary tuberculosis, 630 
Ficker, on flies and typhoid, ref., 245 
Field, on parasites in scarlatina, ref., 307 
Filaria medinesis, 130 
sanguinis hominis, 130 
in kidney, 781 
lymph-nodes, 498 
lymph-vessels, 576 
Filarial lymphatic varix, ref., 130 
Filariasis, 130 , 
First intention, healing by, 82 
Firth, on micro-organisms in air, ref., 
150 
Fischer, on atypical epithelioma, ref., 352; 
on cholera spirillum, ref., 135; on false 
diverticula of intestine, ref., 668 
Fish poisoning, 425 
spinalis, 923 1066 
INDEX 
Fischl, on foetal infection, ref., 158 
Fistula, 90 
branchial, 647 
recto-vaginal, 796 
vesico-vaginal, 796 
Fitz, on cysts of pancreas, ref., 707; on 
dilatation of colon, ref., 671; on pan- 
creas, ref., 706 
Fixateur, 179; ref., 184 
Fixation of immune substance, 173 
tissues, 1029 
rapid, 1028 
tumor tissue, 362 
Fixative, 179 
Flagella of bacteria, 133 
Flechsig, on tables dorsalis, 962 
Fleischer and Loeb, on experimental 
myocarditis, ref., 539 
Flemming's osmic acid mixture, 1030 
Fletcher, on tuberculous cavities in 
liver, ref., 733 
Flexner, on abrin and ricin intoxication, 
ref., 203; on autolysis, 106; on bubonic 
plague, ref., 612: on connective tissue 
in cirrhosis, ref., 727; on dysentery, 
ref., 678; on experimental meningitis, 
225; on experimental pancreatitis, ref., 
705; on fatty degeneration of heart, ref., 
535; on focal necroses in typhoid fever, 
ref., 241; on focal necrosis of liver, ref., 
715; on haemolysis, 174; on hyperplasia 
of heart, ref., 541; on plague, ref., 288; 
on poliomyelitis, ref., 300; on serum 
therapy in meningitis, 226; on specific 
therapy of infections, 196; on syphilis 
of stomach, ref., 659; on terminal 
infection, ref., 158; on thrombi, ref., 
26; on toxalbumin intoxication, ref., 
153; on tuberculous oesophagitis, ref., 
653; on typhoid bacilli in heart, ref., 
244 
Flexner and Amoss, on poliomyelitis, ref., 
299 
Flexner and Anderson, on B. diphtheriae 
in lungs, ref., 284 
Flexner and Jobbing, on serum therapy in 
meningitis, ref., 226; on transplanta- 
tion of tumors, 355 
Flexner and Lewis, on anterior poliomye- 
litis, 299; ref., 969 
Flexner and Noguchi, on anterior polio- 
myelitis, 300, ref., 969; on snake venom, 
ref., 424 
Flexner and Pearce, on experimental pan- 
creatitis, ref., 705 
Flexner and Sweet, on experimental colitis, 
ref., 678 
Flies, as carriers of tuberculosis, ref., 151 
as carriers of typhoid, ref., 151, 245 
Flockemann, on pulmonary syphilis, ref., 
634 
Fliigge, on distribution of bacteria in 
sneezing, etc., 265 
Focal necroses, 203 
Flukes, 123 
Foetal adenoma of thyroid, 398, 432; in- 
clusions, 333 
infections, 157 
Foetus acardiacus, 328 
malformations of, 320 
size of, at various periods, 1023 
Ford, on bacteria in body, ref., 150; on 
intestinal bacteria, ref., 681 
Foreign-body tubercles, 102 
Foreign bodies, injuries from, 11 
substances, disposal of, in body, 98 
disposal of, in body, experiment- 
al study of, 110 
Formalin as tissue fixative, 1029 
Formaldehyde (see Formalin), 1029 
Formative stimuli, 79, 350 
Formol (see Formalin), 1029 
Forsyth, on Haffkine method in plague, 
ref., 289 
Foster, on changes in aorta, ref., 564 
Foulerton, on blastomycetes, 146 
Fox, on paratyphoid, ref., 247 
Fractures, post-mortem, 990 
Framboesia tropica, 293 
Frank, on chorionepithelioma, ref., 820, 
822, 826; on secretions of corpus lute- 
um, ref., 822; on thyroid tissue in 
ovary, ref., 836 
Frank and Unger, on growth of mammary 
gland, ref., 842 
Fraser, on human and bovine tuberculo- 
sis, ref., 888 
Frazier, on cysts of mesentery, ref., 699 
Freeborn, on picro-acid-fuchsin stain, 
1036 
Freeman, on fatty infiltration of liver in 
children, ref., 720; on focal necrosis in 
measles, 309; on spread of typhoid, 
ref., 245; on typhoid and oysters, ref., 
245; on vaccination, ref., 306 
Frenkel and Bassal, on chordoma, ref., 385 INDEX 
1067 
Frieberger and Frohner on infectious dis- 
eases of animals, 319 
Friedemann, on anaphylaxis, ref., 191 
Friedlander bacillus, 216 
Friedmann, on tonsils as portals of entry 
for tubercle bacilli, ref., 650 
Friedrich's ataxia, 963 
Friedrich, on ataxia, ref., 963 
Frog, circulation in, study of, 34 
circulation of blood in, 83 
plates, Thoma's, 111 
study of inflammation in, 111 
Frost, on anterior poliomyelitis, ref., 
300 
Frothingham, on arterial lesions, ref., 
559, 565; on demonstration of Negri 
bodies, 297 
Frozen section of tissues, 1028 
Fuerst, on giant cells, ref., 103 
Fungus, favus, 148 
fission, 133 
mould, 133, 147 
poisoning, 422 
ray, 231 
yeast, 133, 146 
Funk, on vitamines, ref., 318 
Furuncle, 199 
Futterer, on squamous epithelioma of 
stomach, ref., 666 
Gallaverdin, on stricture of intestine, ref., 
671 
Gall-bladder, bacteria in, 742 
calculi of, 743 
dilatation of, 743 
examination, post-mortem of, 1016 
infections of, 742 
inflammation of, 740 
lesions of, 740 
perforation of, 740 
tumors of, 743 
Gall-ducts, abscesses of, 741 
bacteria in, 741, 742 
calculi of, 743 
constriction of, 742 
dilatation of, 743 
examination, post-mortem, of, 1016 
infection of, 741 
inflammation of, 740 
lesions of, 740 
new-formed, in cirrhosis, 727 
occlusion of, 740, 742 
tumors of, 743 
Gall-stones, 743 
composition of, 744 
in pancreatic duct, 707 
role of micro-organisms in, 745 
Gamboge poisoning, 422 
Ganglia, basal, blood supply of, ref., 425 
Ganglion cells(see Neurones),944, ref., 948 
degeneration of, 962, 965, 966 
Gangrene, 57 
diabetic, 435 
dry, 58 
emphysematous, 290 
moist, 58 
of appendix vermiformis, 685 
lung, 599 
pancreas, 705 
vagina, 797 
vulva, 794 
senile, ref., 58 
Gappisch, on actinomyces-like structures 
in tonsillar crypts, ref., 649 
Gas bacillus, 34, 289 
in blood, 34 
pleura, 637 
formation, post-mortem, 987 
B. aerogenes in, 290, 987 
phlegmon, 290 
Gastritis, 656 
acute catarrhal, 656 
chronic, 656 
croupous, 658 
diphtheritic, 658 
exudative, 658 
membranous, 658 
phlegmonous, 658 
suppurative, 650 
syphilitic, 659 
toxic, 659 
tuberculous, 659 
Gay, on complement fixation, ref., 183 
Gay and Rusk, on antibody formation, 
ref., 175 
Gay and Southard, on anaphylaxis, ref.,191 
Gaylord, on origin of fibrin, ref., 637 
Geissler, on tuberculosis of arteries, ref., 
566 
Gemmules, 944 
General diseases, 429 
Genito-urinary organs, examination, 
post-mortem, of, female, 1019, 
1026 
male, 1018, 1026 
new-born, 1023 1068 
INDEX 
Germicides, 138 
Germs, 133 
Gerulanos, on dermoid cysts of penis, ref., 
855 
Ghon and Sachs, on B. aerogenes capsu- 
latus, ref., 290 
Giannettasio, on umbilical tumors, ref., 667 
Giant cells, 67, 102 
in epithelioma, 410 
Giemsa stain, for blood, 316 
for blood and tissues, 1037 
Gigantism, 438 
Gigantoblasts, 459 
Gilbert and Lippmann, on gall-bladder 
infections, ref., 742 
Gilchrist, on blastomycotic dermatitis, 
ref., 146; on fibroma molluscum, 363 
Gilson's mounting medium, 1029 
Glanders, 226 
diagnosis of, 227 
Glands, Nabothian, ectasia of, 805 
Glegg, on hay fever, ref., 580 
Glioma, 387 
of adrenals, 517 
brain, 976 
ependyma, 927 
Glio-sarcoma, 370, 388 
Glockner, on endothelioma, ref., 380; on 
endothelioma of pleura, ref., 642 
Glomerulo-nephritis, 757 
Glomeruli, lesions of, 756 
Glomset, on Dohle bodies, ref., 307 
Glossina morsitans, 118 
palpalis, 118 
Glossitis, 646 
Glottis, oedema of, 582, 1011 
Gluge's corpuscles, 941, 966 
Glycogen infiltration, 44 
technique of staining, 44, 1038 
Glycogenic degeneration, (See Degenera- 
tion, glycogenic), 144 
Glycosuria, ref., 436 
Goitre, 513 
exophthalmic, 432 
Goldberger, on mosquito in yellowr fever, 
ref., 302 
"Golden" coccus, 206 
Golgi, neurone conception of, 943 
Gonococcus, see M. gonorrhoese, 221 
in inflammation of rectum, 683 
peritonitis, ref., 694 
salpingitis, ref., 840 
vaginitis, 796 
Gonorrhoea, 221 
Goodwin and v. Sholly, on meningococcus, 
ref., 225 
Gordinier and Lartigau, on B. typhosus 
in empyema, ref., 639 
Gottstein, on micro-organisms in air, ref., 
150 
Gougerot, on yeasts and moulds, ref., 149 
Gout, 436 
joint lesions in, 905 
Gowers, tract of, 952 
Graafian follicles, haemorrhage in, 827 
Graf, on periarteritis nodosa, ref., 566 
Graham, on displacements of liver, 708; 
on hajmorrhagic disease, ref., 22 
Graham-Smith, on precipitin test for 
blood, ref., 182; on typhoid carriers, 
ref., 245; on xerosis bacillus, ref., 285 
Gram's stain for bacteria. 144 
Weigert's modification, 144 
Granulation tissue, 92 
in wound infection, ref., 152 
Granulations, 92 
exuberant, 95 
Granuloma, infectious, ref., 251, 348, 361 
Grass bacillus, 267 
Graves' disease, 432 
Greenough, on cell inclusions in cancer, 
ref., 350 
Greenough and Hartwell, on cystic hyper- 
plasia of mamma, ref., 845 
Greff, on trachoma bodies, 307 
Gregarinae, 120 
Griffith, on aneurism of coronary arteries, 
ref., 570; on dilatation of colon, ret., 
671 
Grippe, 233 
Grober, on infection of pleura, ref., 640; 
on pleura as portal of entry for bac- 
teria, ref., 614 
Ground water, 141 
Group agglutination, 180 
Grover, on experimental cirrhosis, ref., 
730 
Gruber, on myositis ossificans, ref., 874 
Guarnieri, on smallpox, 305 
Guinea worm, 130 
Guiteras, on mosquito in yellow fever, 
ref., 302 
Gummata, 273 
of bone, 881 
heart, 542 
kidney, 770 INDEX 
1069 
Gummata of pancreas, 706 
ovary, 829 
Gums, tumors of, 645 
Gurd, on gonorrhoeal salpingitis, ref., 840 
Guy and Ferrier, on forensic medicine, 
425 
Guyot, on formation of lymph-vessels in 
pleurisy, ref., 640 
Gwyn, on typhoid bacilli in urine, ref., 
244 
Haasler, on regeneration of bone marrow, 
ref.. 76 
Haemagglutinins, injection of, into ani- 
mals, 715 
Haemangioma, 393 
Haematemesis, 21, 655 
Haematocele, 857 
uterine, 803 
Haematogenesis, defective, 457 
Haematoidin, 53, 457 
Haematolysis, 456 
Haematoma, 21 
of pia mater cerebralis, 919 
polypoid, of uterus, 803 
Haematometra, 800 
Haematomyelia, 939 
Haematomyelopore, 939 
Haematoxylin as staining agent, 1035 
Haematozoon of malaria, 121 
Texas fever, 121 
Haematuria, 21; footnote, 176 
Haemochromatosis, 54 
Haemoglobin index, 474 
Haemoglobinaemia, 454, 456 
Haemoglobin uria, 456 
of cattle, 122 
Haemolymph-nodes, 497, ref., 499 
compensatory hypertrophy of, ref., 
73 
Haemolysins, 171 
auto-, ref., 176 
bacterial, ref., 206 
Haemolysis, 53, 54, 172 
by Staphylococcus pyogenes aureus, 
206 
Streptococcus pyogenes, 209 
tests, technique of, 194 
Haemolytic serum, 171 
Haemopericardium, 518 
Haemophagocytosis, 195 
Haemophilia, 22 
Haem-opsonins, 184 
Haemoptysis, 21 
Haemorrhage, 20 
by diapedesis, 20 
rhexis, 20 
capillary, 935 
forms of, 21 
in new-born, 22 
organs (see various organs) 
intermeningeal, 913 
spontaneous, in spinal cord, 938 
Haemorrhagic diathesis, 22 
infarction, 21 
septicaemia, 289 
Haemorrhoids, 684 
urethral, 792 
vesical, 783 
Haemosiderin, 53, 457 
Haemosporidia, 121 
of malaria, 312 
Haemothorax, 637 
Haemotoxins, 171 
Haffkine, preventive inoculation in 
cholera, 250 
in plague, 289 
Hair ball in stomach, 667 
Halberstcedter and v. Prowazek, on 
trachoma, ref., 307 
Haldane and Smith, on determination of 
amount of blood in body, ref., 455 
Hall, on lesions of bronchial lymph- 
nodes, ref., 592 
Halliburton, on bacterial products, ref., 
152 
Hamburger, on sporotrichosis, ref., 149 
Hamilton, on rupture of heart, ref., 527 
Hamilton and Horton, on pseudo-diph- 
theria bacilli, ref., 285 
Hammar, on accessory lung, ref., 593 
Hand, on tuberculosis of lymph-nodes, 
ref., 592 
Handmann, on weight of brain, ref., 
993 
Hanging, death from, 443 
v. Hansemann, on acute diverticulitis 
ref., 668; on atypical mitosis in tumors, 
350 
Haptines, ref., 168 
Haptophorous group, 167 
Harbitz, on lesions of bronchial lymph- 
nodes, ref., 592; on tuberculosis of 
lymph-nodes, ref., 487; on tuberculosis 
of lymph-nodes, ref., 265 
Hardening of tissues, 1029 1070 
INDEX 
Hare, on medical complications of typhoid 
fever, ref., 244; on tumors of medias- 
tinum, ref., 636 
Harelip, 321 
Harris, on cysts of ureter, ref., 774 
Harrison, on cultivation of tissues, ref., 80 
Hasenfeld, on hypertrophy of heart, ref., 
554 
Hasslauer, on bacteria of nose, ref., 580 
Hastings, Halpin, and Beach, on avian 
tuberculosis, ref., 260 
Hauser, on fibrin formation, ref., 86 
Hay bacillus, 267 
fever, ref., 580 
Hayem's solution, 467 
Haythorn, on pulmonary anthracosis, ref., 
616; on tuberculosis of aorta, ref., 567 
Head, examination, post-mortem, of, 991 
Healing by first intention, 82 
second intention, 94 
of wounds, 91 
Heart, 522 
hypertrophy of, 61 
abnormalities of, 522, 525 
abscess of, 539 
action, irregular, 550 
aneurism of, 529 
dissecting of, ref., 570 
anomalies of, 522 
aorta, insufficiency and stenosis of, 
552 
atrophy of, 528 
bacteria in, 539 
beat, cause of, 549 
block, 549 
calcification of, 535 
chordae tendineae, abnormal, of, 525 
circulation, interference with, 550 
clots, 531, 1005 
degeneration of, 533 
dilatation of, 528, 550, 555 
displacements of, 526 
embolism of, 538 
endocardium, degeneration of, 535 
inflammation of (see Endocar- 
ditis), 542 
examination, post-mortem of, 1004, 
1025 
His bundle, 550 
hyperplasia, fibrous, of, 541 
replacement, of, 540 
hypertrophy of, 550, 554, 555 
hypoplasia of, 439, 526 
Heart, infarction of, 31 
infiltration, fatty, of, 535 
inflammation of, 538 
insufficiency of, 553 
lesions of, in typhoid fever, 242 
malformations of, 522 
malpositions of, 525 
muscle, fatty degeneration of, 534 
myocardium, segmentation and frag- 
mentation of, 536 
parasites in, 556 
pericardial lesions (see Pericardium) 
pigment in, 529 
polypi, 531 
position of, 1004 
preservation of, 1009 
relation of, to circulation of blood, 
15 
reptilian, 523 
ruptures of, 526 
septa, abnormal, 525 
size of, 1004 
stenosis of, 553 
Stokes-Adams' disease, 549 
sudden death in lesions of, ref., 528 
syphilis of, 542 
thrombosis of, 531, 537 
tuberculosis of, 542, 548 
tumors of, 522, 556 
valves, aneurism of, 530 
aortic, insufficiency of, 552 
stenosis of, 552 
changes in, 15, 555 
insufficiency of, 552 
lesions of, 529, 552 
mitral, insufficiency of, 553 
stenosis of, 553 
pulmonary, lesions of, 553 
stenosis of, 552 
tricuspid, lesions of, 553 
Vegetations, 531 
ventricles, hypertrophy of, 552 
left, hypertrophy of, 554, 555 
right, hypertrophy of, 554, 555 
weight of, 1008 
wounds of, 526 
Heat, damage from, 9 
exhaustion, 437 
Heazlitt, on hair-balls in stomach and 
intestine, ref., 667 
H edr ere, on mixed tumors of kidney, ref., 
776 
Heidenhain's iron haematoxylin, 1035 INDEX 
1071 
Hernia, inguinal, 802 
ischiatic, 802 
of brain, 928 
intestine, 670 
uterus, 802 
vagina, 795 
ventral, of uterus, 802 
vesico-vaginalis, 795 
Herpes tonsurans, 148 
of prepuce, 854 
Herrick, on portal pressure in cirrhosis, 
ref., 727 
Herrick and Janeway on trichina, 129 
Herring, on development of glomeruli, 
ref., 756 
Herrmann, on adrenals, ref., 515 
Herter, on chemical pathology, ref., 426 
Herxheimer, on action of tubercle bacillus, 
ref., 253; on adeno-carcinoma of liver, 
ref., 736; on dead tubercle bacilli, ref., 
260; on primary carcinoma of liver, 
ref., 736 
Herxheimer and Reinke, on tumors, 416 
Herzog, on insects as plague carriers, ref., 
289 
Hess, on cysts, ref., 361; on obliteration of 
gall-ducts, ref., 701 
Heterotopia, 346, 929 
false, 929 
Hetsch, on preventive inoculations in 
Asiatic cholera, ref., 250 
Hewitt, on necrosis of renal epithelium, 
ref., 751 
Hill, on potassium hydroxid clearing 
method, ref., 1039 
Himmelberger, on avian tuberculosis, ref., 
260 
Hintz and Lubarsch, on elimination of 
bacteria, ref., 151 
Hirsch, on hypertrophy of heart, ref., 554; 
on streptococcus enteritis, ref., 681 
Hirschfeld, on polycythaemia, ref., 455 
His, bundle of, 550 
Hiss, on cultivation of typhoid bacilli, 
246; on leucocyte extract, 188; on 
staining encapsulated pneumococci, 
220; on staining streptococcus capsules, 
209; on typhoid bacillus, ref., 235 
Hiss and Russell, on B. dysenteriae, ref., 
677; on B. typhosus, ref., 246 
Hiss and Zinsser, on bacteriology, 133; 
on immunity, 196; on tuberculin, ref., 
262 
Heinz, on inflammation, ref., 110; on 
origin of fibrin, ref., 637; on phagocytic 
power of liver endothelium, ref., 721; 
on physiology of blood-vessels, ref., 
564: on physiology of heart, ref., 550; 
on physiology of lungs, ref., 603 
Hektoen, on aortic aneurism, ref., 570; on 
cardiac anomalies, ref., 524; on changes 
in myocardium, ref., 536; on endar- 
teritis in tuberculosis, ref., 559; on 
giant cells, ref., 103; on infectious 
diseases of unknown origin, ref., 319; 
on inoculation of measles, ref., 310; on 
opsonins, 185; on phagocytosis and 
opsonins, ref., 187; on phagocytosis 
of anthrax bacilli, ref., 230; on pneu- 
monia, ref., 220; on yeasts and moulds 
in disease, ref., 149 
Hektoen and Harris, on secondary sar- 
coma of liver, ref., 737 
Hektoen and Perkins, on sporotrichosis, 
ref., 149 
Hektoen and Ruediger, on opsonins, 184 
Helbing, on rhabdomyoma, ref., 390 
Held's stain for nerve tissue, 982 
Hellebore poisoning, 422 
Heller, on pleural lymph-nodes, ref., 603; 
on removal of viscera, post-mortem, 
ref., 990 
Heller and Lepere, on B. pyocyaneus, ref., 
215 
Helly, on blood-forming organs, ref., 471 
Hemicephalia, 324 
Henrici, on carcinoma of lung, ref., 635 
Hepatic artery, lesions of, 711 
Hepatitis, 722 
acute exudative, 722 
interstitial, chronic (see Liver, cir- 
rhosis of), 725 
peri-, 733 
purulent, 722 
syphilitic, 730 
tuberculous, 731 
Hepatization, gray, of lung, 605 
red, of lung, 604 
Hepatolytic serum, 174 
Heppner, on hermaphroditism, ref., 853 
Heredity, relationship of, to disease, 14 
relation of, to tumor growth, 344, 354 
Hermaphroditism, 853 
pseudo-, 853 
Hernia cerebri, 930 
crural, of uterus, 802 1072 
INDEX 
Hodenpyl, on etiology of appendicitis; 
ref., 688; on faucial tonsils, ref., 649, 
on actinomycosis of lung, ref., 230; 
on lung pigment, ref., 616; on spleen, 
499; on tuberculosis of pleura, 641 
Hodgkin's disease, 489 
Hoen, on uvula in abnormal conditions, 
ref., 648 
Hoffmann, on carbonic oxide poisoning, 
425; on dusty trades and consump- 
tion, ref., 616; on hermaphrodi- 
tism, ref., 853; on myeloma, ref., 902 
Hofmeier, on placenta, ref., 826 
Homen, on streptococcus toxin, ref., 211 
Honl, on haemorrhagic infections, ref., 439 
Honsell, on tumors of tonsil, ref., 651 
Hookworm, 128 
disease, 128 
Hopkins, on differentiation of strepto- 
cocci, ref., 209; on phagocytosis of red 
blood cells, ref., 185 
Hormones, ref., 436 
Horseshoe kidney, 325, 746 
Hospital fever, 300 
Hour-glass uterus, 799 
Howard, on B. mucosus capsulatus, ref., 
216; on cardiac hypertrophy, ref., 555; 
on economic loss by insects, ref., 151; 
on extra-intestinal lesions induced by 
typhoid bacillus, ref., 242; on haemor- 
rhagic septicaemia, ref., 291 
Howard and Hoover, on tropical abscess 
of liver, ref., 723 
Howard and Ingersoll, on bacteria in 
nasal inflammation, ref., 580 
Howard and Wolbach, on obliteration of 
bile-ducts, ref., 743 
Howell, on blood, 453; on heart beat, ref., 
549 
Howland and Richards, on liver in chloro- 
form anaesthesia, 716 
Howship's lacunae, 883 
Hoyer's formula for thionin stain, 1038 
Hueter, on congenital tumors of intestine, 
ref., 688 
Huguenin, on bacteria in smallpox, ref., 
304 
Hurdon, on endothelioma of cervix uteri, 
ref., 813 
Hutchinson, on vulnerability of apex of 
lung, ref., 631 
Hutyra, on haemorrhagic septicaemia, ref., 
289 
Hyaline degeneration, 48 
substances, 47 
technique of staining, 48 
Hydatids, 124 
of liver, 738 
Hydraemia, 454 
Hydrarthrosis, 23 
Hydrencephalocele, 928 
Hydrocele, 23, 856 
Hydrocephalus, 22, 924, 925 
acute, 918 
chronic, 925 
congenital, 925 
externus, 928 
internus, 927 
method of removing brain in, 1024 
primary, 926 
secondary, 926 
Hydrochloric acid, 418 
Hydrocyanic acid poisoning, 422 
Hydromeningocele, 928 
Hydrometra, 799 
Hydromyelia, 929 
Hydronephrosis, 772 
Hydropericardium, 22, 518 
Hydroperitoneum, 23 
Hydrophobia, 294 
animal inoculations in, 295 
diagnosis of, 298 
excitants of, 295 
immunization, artificial, in, ref., 304 
Negri bodies in, 295 
Pasteur method in, 297 
preventive inoculation in, 297 
virus of, 295 
Hydropneumothrax, 637 
Hydropic degeneration, 44 
Hydrops cystidis felleae, 743 
Hydrorrhachis, 929 
Hydrosalpinx, 838 
Hydrostatic test, 1025 
Hydrothorax, 22, 636 
Hymen, anomalies of, 793 
Hyperaemia, 16 
active, 16 
of bladder, urinary, 783 
bone, 877 
brain, 934 
kidney, 748 
liver, 709 
lung, 593 
pia mater cerebralis, 913 
spleen, 502 INDEX 
1073 
Hyperaemia of thyroid, 512 
uterus, 802 
vulva, 793 
passive, 16 
Hypernephroma, 777 
of liver, 735 
Hyperostosis, 900 
Hyperplasia, 61 
cystic, of mamma, 845 
fibrous, of heart, 541 
glandular, of endometrium, 805 
nodular, of intestine, ref., 672, 679 
of fibrous tissue, 96 
liver, 734 
lymph-nodes, 488 
neuroglia, 951 
spleen, 504, 508 
thyroid, 513 
replacement, 61, 96 
of heart, 540 
muscle, 874 
Hypersusceptibility, 190 
Hypertrophy, 61 
compensatory, 61, 62 * 
Hypertrophy, compensatory, of heart, 555 
functional, 61 
numerical, 61 
of brain, 931 
heart, 61, 550 
kidney, 62, 747 
liver, 62 
mamma, 847 
muscle, 62, 871 
pineal gland, 980 
prostate, 863 
thymus, 511 
tongue, 646 
tonsil, 649 
pseudo-, 61 
simple, 61 
Hyphae, 147 
Hyphomycetes, 133, 147 
Hypoleucocytosis, 463, 464 
Hypophysis cerebri, 980 
in acromegalia, 438 
tumors of, 980 
Hypoplasia, 321 
Hypospadias, 324, 853 
Hypostasis, post-mortem, 987 
Ice-cream poisoning, 425 
Ichoraemia, ref., 204 
Ichthyosis, 644 
Icterus, 13, 54 
gravis, 716 
Heo-caecal tuberculosis, hyperplastic, 682 
Immune body, 172 
substance, 170, 172 
Immunity, 160 
acquired, 161, 162 
to streptococcus, 211 
tumors, 356 
active, 162 
anti-bacterial, 162, 169 
anti-microbic, 162, 169 
anti-toxic, 162, 163 
bactericidal, 162, 169 
bacteriolytic, 162, 169 
bibliography of, 196 
definition of, 160 
Ehrlich's hypothesis of, 165 
hereditary, 161 
natural, 161 
nature and forms of, 160 
passive, 163 
Immunization, artificial, 161, 162 
artificial, specific characters of, 193 
natural, 161 
of animals to alien substances, 195 
processes involved in, 193 
Incubation period of infection, 156 
Index, haemoglobin, 474 
opsonic, 187, 220 
India ink stain for Treponema pallidum. 
277 
Infantile paralysis, 299 
Infarction, 29 
haemorrhagic, 21 
of heart, 31 
intestine, 31, 671 
kidney, 31, 748 
liver, 30, 711, 712 
lung, 30, 596 
muscle, 873 
placenta, 823 
spleen, 31, 502 
Infarcts, 29 
absorption of, autolytic processes in, 
ref., 30 
anaemic, 30 
haemorrhagic, 29 
location of, 30 
white, 30 
Infection and immunity, 156 
communicability of, 158 
concurrent, 157 1074 
INDEX 
Infection and immunity, condition of 
body in, 155 
of micro-organisms in, 155 
congenital, 157 
definition of, 156, 160 
foetal, 157 
forms of, 157 
haemorrhagic, ref., 439 
incubation period in, 156 
latent, ref., 151 
mixed, 157 
predisposition to, 155 
proofs of, 154 
purulent, ref., 204 
spleen in, ref., 152 
sub-, ref., 151 
terminal, 157 
theory of, ref., 153 
through granulation tissue, ref., 152 
wound, experimental studies on, 
ref., 152 
Infectious diseases, 156, 197 
bibliography of, 319 
classification of, 197 
communicability of, 158 
conditions influencing occur- 
rence of, 155 
definition of, 156, 159 
general considerations, 197 
of animals, 319 
unknown origin, 318 
protozoa in, 317 
Infectious granulomata, ref., 251, 348,361 
Infiltration, calcareous, 50 
fatty, 40, 43 
of adrenals, 515 
heart, 535 
muscle, 871 
pancreas, 703 
glycogen, 44 
hydropic, of muscle, 871 
purulent, 90 
serous, 45 
of muscle, 872 
Inflammation, 81 
bacteria in, 152 
cardinal symptoms of, 87 
catarrhal, 97 
characterization of, 110 
degeneration in, 97 
experimental study of, 110 
exudative, 87, 89 
practical study of, 111 
Inflammation, fibrinous, 97 
general survey of, 107 
haemorrhagic, 97 
in non-vascular tissue, 82 
in organs (see various organs). 
in vascular tissue, 83 
interstitial, 96, 98 
micro-organisms in, 88 
muco-purulent, 97 
mucous, 97 
necrotic, 97 
parenchymatous, 98 
phlegmonous, 200 
practical study of, 111 
productive, 97 
pseudo-membranous, 97 
purulent, 97 
reparative, 97 
resolution in, 90 
resorption in, experimental study of, 
110 
scrofulous, 487 
sero-purulent, 97 
serous, 97 
significance of, 107 
special phases of, 97 
suppurative, 97, 198 
tuberculous, 251 
diffuse, 252, 255 
Influenza, 233 
bacillus, 233 
Infusoria, 115, 120 
Insects as carriers of disease, 151 
of plague, ref., 151 
method of study of, 132 
Insolation, 437 
Intermediary body, 177 
Internal secretions, 427 
Interstitial inflammation, 96 
Intestine, 667 
absorption in, ref., 681 
actinomycosis of, 691 
amoebae in, 676 
anthrax in, 691 
bacteria in, 678, 811 
cloacae, 668 
concretions in, 690 
cysts of, 690 
degeneration of, 671 
dilatation of, 671 
diverticula of, 667 
dysentery, 675 
embolism of, 671 INDEX 
1075 
Intestine, examination, post-mortem of, 
1002, 1014, 1026 
haemorrhage in, 671 
hernia of, 670 
hyperaemia of, 671 
hyperplasia of, in typhoid fever, 235 
nodular, 672, 679 
incarceration of, 668 
infarction of, 31, 671 
inflammation of (see Enteritis and 
Colitis), 672, 675, 682, 683 
intussusception of, 669 
invagination of, 669 
lesions of, in Asiatic cholera, 248 
in typhoid fever, 235, 242 
malformations of, 667 
malpositions of, 667 
mycosis of, 691 
parasites in, 691 
permeability of wall of, for bacteria, 
ref., 681 
polyps of, 688 
preservation of, 1015 
ruptures of, 671 
strictures of, 671 
syphilis of, 674, 683 
transposition of, 667 
tuberculosis of, 673, 682 
tumors of, 688 
ulcers of, 674, 675, 681, 682 
volvulus of, 668 
wounds of, 671 
Intoxication, auto-,153 
septic, 153, 156 
Intussusception of intestine, 669 
Inversio vesicae, 324 
Involution forms of bacteria, 134 
lodin test for amyloid, 1012 
Ipsen, on hypernephroma, ref., 777; on 
intestinal tuberculosis, ref., 674 
Iron haematoxylin solution, 1035 
"masked," ref., 53 
reactions for, ref., 53 
Irons and Graham, on blastomycosis, ref. 
146 
"Irritation forms" of leucocytes, 462 
Ischaemia, 19 
Ischiopagus, 330 
Isolysins, 176 
Itch insect, 131 
Jackson, Porter and Quinby, on throm- 
bosis of mesenteric veins, ref., 671 
Jacob, on carcinoma of stomach, ref., 
666 
Jacoboeus, on modification of Wassermann 
test, 279 
Jacobi, on cysts of omentum, ref., 699 
Jacobson, on hair balls in stomach, ref., 
666 
J acobsthal, on infantile scorbutus, ref., 
438 
Jaeger, on cerebro-spinal meningitis, 225 
Jail fever, 300 
Jalap poisoning, 422 
James, on lesions of stomach as portals 
of entry for bacteria, ref., 659; on 
pneumopericardium, ref., 518 
Jamin and Merkel, in coronary arteries, 
ref., 537 
Janeway, T. C., on hypertrophic pul- 
monary arthropathy, ref., 438 
Janiceps, 330 
Janowski, on suppurative inflammation, 
ref., 202 
Janus, 330 
Jaundice (see Icterus), 13, 54 
Jaw, malformations of, 643 
Jaworski and Korolewicz, on occult haem- 
orrhage in gastro-intestinal canal, 
ref., 655 
Jelliffe, on death from electric currents, 
ref., 11 
Jelliffe and Larkin, on malignant chor- 
doma, ref., 385 
Jellinek, on myeloma, ref., 902 
Jenner, vaccination in smallpox, 304 
Jenner stain for blood, 468 
Jessup, on carcinoma of appendix vermi- 
formis, ref., 690 
Jochmann, on bacterisemia in pulmonary 
tuberculosis, ref., 631; on serum ther- 
apy in meningitis, ref., 226 
Joints, 903 
cartilage, loose, in, 907 
degeneration of, 903 
false, 878 
inflammation of (see Arthritis), 903 
tuberculosis of, 906 
tumors of, 906 
Jopson and White, on sarcoma of large 
intestine, ref., 690 
Jordan, on acute osteomyelitis, ref., 887 
Jordan, Russell, and Zeit, on typhoid 
bacillus in water, ref., 245 
Jores, on arterio-sclerosis, ref., 561 1076 
INDEX 
Jorgenson, on micro-organisms and fer- 
mentation, ref., 146 
Josserand and Bonnet, on myocarditis, 
ref., 538 
Jurgelunas, on granulation tissue in 
infection, ref., 152 
v. Kahlden, on cysts of ovary, ref., 836 
on periarteritis nodosa, ref., 566 
Kahn, on renal calculi, ref., 776 
Kaiserling's fluid, 1039 
Kala-azar, 119, 480 
Kappis, on urogenital tuberculosis, ref., 
770 
Karakascheff, on adrenals, ref., 516 
Karcher, on bacteria in bronchitis, ref. 588 
Karsner and Ash, on experimental in- 
farction of lung, ref., 596 
Karsner and Meyers, on lobular pneumo- 
nia, ref., 612 
Karyokinesis, 65, 67 
Karyolysis, 57 
Karyomitosis, 67 
Karyorrhexis, 57 
Kataplasia, 63 
Kawamura, on lipoids, ref., 44 
Kedrowsky, on emphysematous cystitis, 
ref., 786 
Keen, on surgical complications of ty- 
phoid fever, ref., 244 
Keen and Funke, on carotid tumors, ref., 
517 
Keith and Flack, on His bundle, ref., 550 
Kelly, on cirrhosis, ref., 730; on leu- 
kaemia, ref., 475; on tumors of appendix 
vermiformis, ref., 690 
Kelly and Hurdon, on vermiform appen- 
dix, ref., 688 
Kelynack, on pathology of vermiform 
appendix, ref., 688; on renal 
growths, ref., 777 
Kerr, on statistics of lobar pneumonia, 
ref., 606 
Keyes, on snake poisons, ref., 424 
Kidney, 746 
abscess of, 754 
absence of, 746 
albuminuria, 749 
anaemia of, 748 
arterio-sclerosis, relation of, 769 
atrophied, 766 
bacteria in, 755, 761 
calcification of, 750, 753 
Kidney, calculi of, 774 
casts in, 749 
congestion of, 748 
cysts of, 772 
degeneration of, 751 
dilatation of, 772 
embolism of, 748 
examination, post-mortem of, 1011, 
1026 
excretion of bacteria by, 755 
pigment by, 755 
glomeruli, alterations in, 756 
granular, 766 
horseshoe, 325, 746 
hyaline casts in, 749 
hydronephrosis, 772 
hyperaemia of, 748 
hypertrophy of, 62 747 
infarction of, 31, 748 
infection, ascending, of, 755 
embolic, of, 754 
of, after injury, ref., 152 
inflammation of (see Nephritis), 
753 
lesions of, in malaria, 311 
sublimate poisoning, 51, 750, 
753 
typhoid fever, 243 
lobulation, foetal, of, 747 
lobulated, 326 
malarial parasites in, 761 
malformations of, 746 
malpositions of, 747 
movable, 747 
necrosis of, 750 
parasites in, 781 
pelvis, lesions of, 771 
perinephritic suppuration, 772 
preservation of, 1013 
red, large, 761 
regeneration of, 72, ref., 748 
surgical, 755 
syphilis of, 770 
thrombosis of, 748 
tuberculosis of, 769 
tubules, lesions of, 757 
tumors of, 776 
wandering, 747 
weight of, 1012, 1026 
white, large, 765 
Kinnicutt, on orchitis in typhoid fever, 
ref., 243; on phlegmonous gastritis, 
ref., 659 INDEX 
1077 
Kirchheim, on hypertrophy of breast, ref., 
847 
Kisskalt, on cooling of body and pneu- 
monia, ref., 614; on natural immunity, 
ref., 161 
Kitt, on comparative pathology, 319 
Klebs, on malformations of generative 
organs, ref., 853 
v. Klecki, on elimination of bacteria by 
kidney, ref., 761 
Kleine and Mollers, on inherited immun- 
ity, ref., 161 
Klemperer, on portal of entry of B. tuber- 
culosis, ref., 264 
Klimenko, on permeability of intestinal 
wall for bacteria, ref., 681 
Klopstock and Seligmann, on portal of 
entry of B. tuberculosis, ref., 264 
Klose, on lesions of thyroid, ref., 433 
Klotz, on arterio-sclerosis, ref., 565; on 
calcareous degeneration, ref., 52; on 
formation of fat in cells, ref., 40 
Knox, on epicardial nodules, 521; on 
lipomyoma of uterus, ref., 813 
Knox and Schorer, on rhabdomyoma of 
heart, ref., 556 
Kober, on tuberculosis in cattle, ref., 266 
Kobert, on poisons, 425 
Koch, on B. tuberculosis, 268 
Koch and Bruck, on gonococcus, ref., 223 
Koch-Weeks bacillus, 234 
Kolisko, on blood supply of basal gan- 
glia, ref., 425 
Kolle, on specificity of infectious agents, 
ref., 165 
Kolle and Hetsch, on animal inoculations 
in hydrophobia, ref., 295; on experi- 
mental bacteriology, 196; on tubercu- 
losis, 268 
Kolle and Schurmann, on cholera spiril- 
lum, ref., 249 
Kolle and Wassermann, on immunity, 196; 
on serum therapy in meningitis, ref., 
226 
Kolmer, on B. diphtheriae, ref., 285 
Kossel, on Texas fever, 122 
Kotlar, on cardiac thrombi, ref., 532 
Koplik and Van Arsdale, on acute osteo- 
myelitis in childhood, ref., 887 
Kraus, on regeneration of fat tissue, ref., 
77 
Kraus and Levaditi, on immunity, ref., 
165 
Krehl, on fever, ref., 439, on heart lesions 
ref., 553 
Krompecher, on basal-celled carcinoma, 
ref., 410; on epithelium and endothe- 
lium, ref., 396 
Krumwiede and Pratt, on fusiform bacilli, 
ref., 293 
Kruse and Pasquale, on abscess of liver, 
ref., 724; on necrotic colitis, ref., 681 
Kuhnau, on bacteriology of blood, ref., 
470 
Killble, on bacteria in lymph-nodes, ref., 
481 
Kunkel, on poisons, 425 
Kutscher, on B. typhosus, 247 
Labia, lesions of, 793, 794 
Lachner-Sandoval, on ray fungi, ref., 232 
La grippe, 233 
Lamar and Meltzer, on experimental pneu- 
monia, ref., 614 
Lambert, on sunstroke, ref., 437 
Lambert, R. A., on cultivation of tissues, 
ref., 80 
Lamy and Mayer, on renal secretions, 
ref., 748 
Lando, on pancreas lesions in hepatic 
cirrhosis, ref., 728 
Landsteiner, on sweat-gland adenoma, 
ref., 399 
Landsteiner and Stoerk, on cystitis en 
plaque, ref., 785 
Landry's paralysis, 969 
Lang and Ullmann, on syphilis, ref., 274 
Lang's solution, formula for, 1030 
Langerhans, islands of, degeneration of, 
703 
development of, ref., 704 
hypertrophy of, ref., 704 
Langhans' cells, 820 
Langmann, on haemosporidia, 121; on 
snake poisons, ref., 424 
Lanz and Tavel, on appendicitis, ref., 688 
Lardaceous degeneration, 48 
Larkin, on multiple neuroma, ref., 393 
Larson and Barron, on fusiform bacilli, 
ref., 293 
Lartigau, on atypical typhoid, ref., 243; 
on gonorrheal endocarditis, ref., 545; 
on ileocaecal tuberculosis, ref., 683; 
on M. tetragenus, 216; on pulmonary 
complications in typhoid fever, ref., 
243; on tuberculosis, 268 1078 
INDEX 
Lartigau and Nicoll, on adenoids, ref., 
581; on tuberculosis of tonsil, ref., 650 
Laryngitis, acute catarrhal, 582 
chronic catarrhal, 583 
croupous, 583 
phlegmonous, 584 
pseudo-membranous, 583 
syphilitic, 584 
tuberculous, 584 
Larynx, 581 
amyloid masses in, 586 
cysts of, 585 
examination, post-mortem, of, 1010, 
1025 
foreign bodies in, 442 
haemorrhage from, 582 
inflammation of (see Laryngitis), 
582 
malformations of, 581 
oedema of, 582 
preservation of, 1011 
syphilis of, 584 
tuberculosis of, 584 
tumors of, 585 
Lasio, on regeneration of mucous mem- 
brane of bladder, ref., 785; on repair 
of bladder mucosa, ref., 71 
Lavenson, on pernicious anaemia, ref., 475 
Lawen, on sarcoma of uterus, ref., 813 
Lead poisoning, 421 
LeComte, on adenoma of pancreas, ref., 704 
Le Count, on lymphoma, ref., 497 
Ledingham, on typhoid carriers, ref., 245 
Lee, on technique, ref., 1027 
Leers, on precipitin test, ref., 182, 194 
Legry, on lung stones, ref., 639 
Lehndorff, on chloroma, ref., 376, 479 
Leiomyoma, 388 
of oesophagus, 653 
ovary, 829 
veins, 575 
Leishman, on opsonins, 183 
Leishman-Donovan bodies, 119 
Leishmania donovani, 480 
infantum, 480 
Leith, on phlegmonous gastritis, ref., 659 
Lentz, on dysentery, ref., 678 
Leonhardt, on myxoma of heart, ref., 556 
Leopold and Levi, on moulds, ref., 147 
Lepra, 269 
anaesthetica, 976 
bacilli, 269 
Leprosy, 269 
Leprosy of nervous system, 976 
orchitis in, 860 
Leptomeningitis, 914 
Leptothrix, 136, 232 
in vagina, 797 
Lesser, on action of poisons, 425 
Leucocyte extract, 188 
Leucocytes, 459 
abnormal, 461 
amitosis in, 68 
as phagocytes, 100, 104, 108, 161, 
178, 463 
as pus cells, 201 
basophile, 461 
classification of, 459 
degenerative changes in, 464 
development of, 77 
emigration of, 83 
eosinophile, 461 
ferments of, 87, 475 
formation of, 77 
in abscess, 89 
cytolysis, 178 
exudates, 108 
inflammation, 108 
leukaemia, 475 
malaria, 310 
pus, 201 
suppuration, 198 
irritation forms, 462 
lymphocytes, 459 
large, 462 
method of securing, 195 
mononuclear, large, 459 
myeloblasts, 462 
myelocytes, 461 
normal, 459 
plasma cells, 462 
polynuclear neutrophile, 461 
proportions of, in normal blood, 461 
regeneration of, 77 
transitional, 459 
Leucocythaemia, 475 
Leucocytolysis, 465 
Leucocytosis, 462 
cachetic, 464 
Leucocytosis, hypo-, 463, 464 
in acute lobar pneumonia, 220 
in infection, 463 
mixed, 462 
polynuclear eosinophile, 464 
pathological, 463 
polynuclear, physiological, 463 INDEX 
1079 
Leucolysis, 179 
Leucolytic serum, 174 
Leucomains, ref., 139 
Leucoplakia buccalis, 644 
Leuco-protease, 105 
Leukaemia, 475 
bone marrow in, 897 
in x-ray workers, 11 
liver lesions in, 734 
lymph-node lesions in, 475 
lymphatic, acute, 475 
chronic, 475' 
myelogenous, acute, 476 
chronic, 477 
pseudo-, 489 
spleen in, 509 
Levaditi on silver impregnation method, 
ref., 276 
Levaditi and Roche, on syphilis, ref., 
275 
Levene, on autolysis, ref., 107 
Lewin, on toxicology, 426 
Lewis, on acromegalia, ref., 439; on types 
of B. tuberculosis, ref., 266 
Lewis, on disorders of the heart beat, ref., 
550 
Lewis and Rosenow, on portal thrombosis, 
ref., 712 
Libman, on bacteria in blood, ref., 547; on 
paratyphoid, ref., 247; on sarcoma of 
small intestine, ref., 690 
Lice as agents of infection in Mexican 
typhus, 301 
Liefmann, on hay fever, ref., 580 
Life, chemistry of, 3 
Lightning, death from, 10 
Linck, on chordoma, ref., 385 
v. Lingelsheim, on dysentery, ref., 678; 
on streptococci, ref., 211; on tetanus, 
ref., 287 
Lip, hare, 321, 643 
Lipaemia, 469 
Lipoid degeneration, 43 
Lipoma, 382 
angio-, 382 
arborescens, 907 
molle, 382 
of appendix vermiformis, 690 
bone, 901 
brain, 976 
bronchi, 587 
dura mater cerebralis, 911 
spinalis, 922 
Lipoma of ependyma, 927 
Fallopian tubes, 841 
heart, 556 
intestine, 688 
joints, 907 
kidney, 776 
larynx, 585 
liver, 735 
mamma, 848 
mouth, 645 
muscle, 875 
oesophagus, 653 
penis, 855 
pericardium, 522 
peritoneum, 696 
pia mater cerebralis, 920 
scrotum, 855 
stomach, 662 
testicle, 860 
tongue, 646 
uterus, 813 
vulva, 795 
Lipomatosis, 43 
Liposis, 43 
Lipo-sarcoma, 376 
Lissauer, on experimental cirrhosis of 
liver, ref., 730 
Lissauer, zone of, degeneration of, 958 
Lithopedion, 842 
Little, on B. aerogenes capsulatus in puer- 
peral infections, ref., 290 
Liver, 708 
abscess of, 722 
amoebic, 723 
bacteria in, 723 
metastatic, 724 
multiple, 724 
tropical, 722 
absence of, 708 
accessory, 708 
adrenal tissue in, 515, 736 
agglutinative thrombi in, 715 
anaemia of, 709 
atrophy of, 714 
acute yellow, 716 
- experimental, 718 
biliary passages, lesions of (see Gall- 
ducts), 740 
bronze, 722 
calcification of, 722 
capsule, inflammation of, 734 
chloroform, effect of, on, 716 
cirrhosis of, 725 1080 
INDEX 
Liver, cirrhosis of, anthracotic, 730 
ascites in, 728 
associated lesions in, 727 
atrophic, 726 
biliary, 729 
congenital, 729 
experimental, 730 
hypertrophic, 728 
nature of, 730 
portal circulation in, 727 
congestion of, 710, 748 
cysts of, 737 
cytolysis in, 715 
degeneration of, 716 
displacements of, 708 
examination, post-mortem, of, 1002, 
1016, 1026 
fluke, 575 
foamy, 738 
focal necrosis of, 241, 714 
gall-ducts, lesions of (see Gall- 
bladder and -ducts), 740 
gall-ducts, new-formed, in cirrhosis, 
727 
gas in, 738 
gumma in, 731 
haemorrhage in, 709 
hobnail, 725 
hydatids of, 738 
hyperaemia of, 709 
hyperplasia of lymphatic tissue in, 
734 
hypertrophy of, 62 
infarction of, 30, 711, 712 
infiltration, fatty, of, 719 
inflammation of (see Hepatitis), 722 
jaundice with necrosis of, 715 
lesions of, in eclampsia, 716, 718 
in malaria, 311, 721 
lesions of, in typhoid fever, 241 
in yellow fever, 302 
malformations of, 708 
malpositions of, 708 
metabolism, disturbances of, 718 
movable, 708 
necrosis of, 714 
nutmeg, 710 
parasites of, 738 
perihepatitis, 733, 734 
pigmentation of, 714, 721, 730 
preservation of, 1017 
regeneration of, 72, ref., 717 
reversion of cells, in cirrhosis, 727 
Liver, rupture of, 709 
size of, 1016 
changes in, 708, 1016, 1026 
syphilis of, 730 
thrombosis of, 711, 714, 715 
tubercles, solitary, of, 733 
tuberculosis of, 731 
tumors of, 734 
vessels, lesions of, 711 
weight of, 1016, 1026 
wounds of, 708 
Lividity, cadaveric, 986 
Livingood, on sarcoma of oesophagus, ref., 
653 
Lobelia poisoning, 425 
Lochte, on hyperplasia of spleen, ref., 511 
Locke, on visceral changes following 
burns, ref., 10 
Lockjaw (see Tetanus), 286 
Locomotor ataxia, 957 
Loeb, on artificial parthenogenesis, ref., 79 
Loeb, Leo, on corpus luteum secretion, 
ref., 822; on mixed tumors of thyroid, 
ref., 514 
Loftier, diphtheria bacillus of, 283 
Leffler's stain for bacteria, 145 
Ldhlein, on opsonins, ref., 184 
Lohrisch, on mediastinum, ref., 636 
Lommel, on ciliated epithelium of res- 
piratory organs, ref., 587 
Longcope, on bone-marrow in infections, 
ref., 243; on Hodgkin's disease, ref., 
495; on reduction of complement, 192 
on relation of cirrhosis to chronic pro- 
tein intoxication, ref., 730; on syphilitic 
aortitis, ref., 567 
Longcope and Donhauser, on lymphatic 
leukemia, 462 
Lonicer, on congenital syphilis, ref., 731 
Loomis, on gumma of heart, ref., 542 
Lord, on B. influenzae, ref., 234 
Lossen, on exudative peritonitis, ref., 693; 
on splenic anaemia, ref., 479 
Lothrop and Pratt, on filaria, ref., 131 
Louse, 131 
Low, on appendicitis, ref., 688 
Lbwit, on hypoleucocytosis, ref., 464 
Lubarsch on B. tuberculosis, ref., 257; on 
bone in tonsils, ref., 649; on emboli, 
29; on endothelioma, ref., 380; on foetal 
infection, ref., 158; on portal of entry 
of B. tuberculosis, ref., 264; on tumors, 
416 INDEX 
1081 
Lubarsch's grouping of tumors, 359 
Lucas, on polycythaemia, ref., 455 
Lucas and Prizer, on experimental 
measles in monkeys, ref., 310 
Lildke, on tubercle bacilli in blood, ref., 
618 
Luetin test, 281 
Lithe, on malaria, ref., 316 
Lungs, 593 
abscess of, 611 
absence of, 593 
accessory, 593 
actinomyces in, 612 
anaemia of, 593 
anthracosis of, 601, 616 
apical vulnerability of, ref., 631 
atelectasis of, 596 
autolysis in exudates, 606 
B. diphtheriae in, 284 
bacteria in, 601, 614 
broncho-pneumonia, 608 
brown induration of, 594 
calcification in, 639 
"carnified," 597 
cavity formation in, 628 
chalicosis of, 616 
circulation in, study of, 113 
circulatory changes in, 593, 595 
congestion of, 593, 594 
cysts of, 635 
dust particles in, 600 
embolism of, 34, 595, 596 
emphysema of, 597 
epithelium, inflammation of, 601, 
615 
examination, post-mortem, of, 1009, 
1025 
exudation in ,601, 605 
gangrene of, 599 
haemorrhage of, 595 
hepatization of, 604, 605 
hyperaemia of, 593 
hypostatic congestion of, 612 
infarction of, 30, 596 
inflammation of (see Pneumonia) 
600 
injuries of, 593 
lesions of, in asphyxia, 442 
in typhoid fever, 243 
lobule, ref., 602 
lymph-vessels of, 601 
malformations of, 593 
oedema of, 595 
Lungs, perforation of, 593 
phthisis, 627 
pigmentation of, 601, 616 
pneumokoniosis, 616 
portal of entry for bacteria, 600; 
ref., 614 
tubercle bacilli, 618 
preservation of, 1010 
reaction of tissue in, 618 
resolution, commencing, in, 605 
siderosis of, 616 
stones, 592; ref., 639 
streptothrix in, 612 
structure of, 600 
syphilis of, 633 
thrombosis of, 596 
transposition of, 544 
tuberculosis of (see Tuberculosis, 
pulmonary), 618 
tumors of, 634 
Lupus, 267 
Lusk, on metabolism in diabetes, ref., 435; 
on nutrition, ref., 9 
Lymph, transudation of, 22 
Lymph-follicles, 481 
Lymph formation, ref., 22 
Lymph-nodes, 481 
atrophy of, 481 
bacteria in, ref., 481 
bone in, 487 
bronchial, as portals of entry for 
bacteria, 592 
lesions of, 592 
pigmentation of, 592 
tubercle bacilli in, 592 
degeneration of, 482 
general characters of, 481 
germicidal action of, ref., 151 
haemo-, 498, ref., 499 
Hodgkin's disease, 489 
hyperplasia of, 488 
in leukaemia, 475 
scrofula, 487 
status lymphaticus, 440 
typhoid fever, 240 
inflammation of, 483 
mesenteric, lesions of, in typhoid 
fever, 240 
oedema of, 482 
parasites in, 498 
pigmentation of, 483 
pseudo-leukaemia, 489 
regeneration of, 76, ref., 486 1082 
INDEX 
Lymph-nodes, scrofula of, 487 
suppuration of, 485 
syphilis of, 488 
tracheal, lesions of, 592 
tuberculosis of, 265, 486 
tumors of, 498 
Lymph-nodules, 481 
Lymph-vessels, 576 
dilatation of, 576 
formation of, 76 
inflammation of, 577 
of nose, ref., 580 
syphilis of, 577 
thrombosis of, 28, 576 
tuberculosis of, 577 
tumors of, 577 
Lymphadenitis, 483 
tuberculous, generalized, 488 
Lymphangiectasis, 576 
Lymphangioma, 395, 576 
of liver, 737 
Lymphangitis, 577 
Lymphatic constitution, 439 
tissue in liver, hyperplasia of, 734 
Lympho-adenoma of mediastinum, 636 
Lympho-protease, 105 
Lympho-sarcoma of mediastinum, 636 
Lymphocytes, 459 
large, 462 
Lymphocytoma, 370 
Lymphocytosis, 464 
Lymphoma, 361, 488, 495 
of intestine, 688 
lung, 634 
mediastinum, 636 
Lymphorrhagia, 576 
Lymphosarcoma, 370 
Lynch, on congenital infection, ref., 151 
Lyon, on lipomatosis, ref., 43 
Lytic substances, 171, 174, 176 
MacCallum, on angioma of intestine, ref., 
688; on changes in myocardium, ref., 
536; on haematozoan infection of birds, 
315; on hypertrophy of islands of Lan- 
gerhans, ref., 704; on lesions of goitre, 
433; on metabolism in fever, ref., 441; 
on phlegmonous enteritis, ref., 673; on 
regenerative changes in liver, ref., 717 
on reparative phases of cirrhosis, ref., 
730; on tumors of parathyroids, ref., 515 
MacCalhim and Voegtlin, on parathyroids 
514 
Mace, on typhoid bacilli, ref., 244 
Macfadyen and MacConkey, on tubercle 
bacilli in mesenteric lymph-node, ref., 
674 
Machard, on perforation of gall-bladder, 
ref., 740 
Mackenzie, on diseases of the heart, ref., 
550 
Macrocytase, 179 
Macrogametes, 314 
Macroglossia, 646 
Macrophages, 93, 104 
Maculae tendinae, 520 
M acW illiams, on carcinoma of appendix 
vermiformis, ref., 690 
Madura foot, 232 
Maladie pyocyanique, 215 
Malakoplakie, 785 
Malaria, 310 
aestivo-autumnal type, 313 
avian, 315 
bibliography of, ref., 316 
blood, lesions of, in, 310, 312 
methods of examination of, 316 
chronic, 311 
excitant of, 311 
haematozoon of, 312 
mosquitoes as intermediary host, 
in, 313 
parasite of, 311 
crescent bodies of, 313 
flagellate bodies of, 313 
pigmentation of liver in, 721 
quartan type, 312 
tertian type, 312 
visceral lesions of, 310 
Malformations, 320 
involving single individuals, 321 
involving two individuals, 327 
Malignant pustule, 228 
Mallein, 227 
Mallory, on congestion of liver, ref., 711; 
on excitant of scarlet fever, 307; 
myoglia fibrils, ref., 389; on necrosis of 
liver, ref., 715; on neuroglia fibrils, 388; 
on staining amoebae, ref., 116 
Mallory anilin-blue stain, 1036 
Mallory and Horner, on whooping- 
cough, ref., 317 
Mallory and Wright, on staining fat-acid, 
ref., 44; on technique, ref., 1027 
Mallory and Wright anilin blue stain, 
1036 INDEX 
1083 
Malta fever, 287 
Mamma, 842 
abscess of, 844 
absence of, 842 
accessory, 842 
cysts of, 852 
haemorrhage in, 842 
hyperplasia, cystic, of, 845 
hypertrophy of, 847 
inflammation of (see Mastitis), 843 
male, lesions of, 867 
malformations of, 842 
nipple, inflammation of, 843 
regeneration of, 72 
syphilis of, 846 
tuberculosis of, 845 
tumors of, 847 
ulcers of, 846 
Manasse, on amyloid masses in larynx, 
ref., 586 
Mandlebaum, on primary splenomegaly, 
ref., 508; on teratoma of mediastinum, 
ref., 636 
Manfredi, on germicidal action of lymph- 
nodes, ref., 151 
Mankowsky, on preparation of brain 
sections, ref., 1039 
Mann, on melanin, ref., 55; on micro- 
chemical reactions for iron, ref., 53 
Marchand, on classification of tumors, 
ref., 357; on endothelioma, ref., 380; 
on malformations, ref., 320; on tissue 
regeneration, ref., 77 
Marchi, on degeneration of nerve fibres, 
ref., 954 
Marchi's method of staining nerve fibres, 
981, 999 
Marchiafava and Bignami, on malaria, 
314, ref., 316 
Marcus, on entrance of bacteria through 
intestine, ref., 694 
Marfan, on bronchial lymph-nodes, ref., 
592 
Margulis, on hydrocephalus, ref., 925 
Marie, on spastic paraplegia, 956 
Marine and Lenhart, on lesions of thy- 
roid, ref., 433 
Marinesco, on chromatolysis, 950 
Marrow, bone, in anaemia, 897 
leukaemia, 897 
malaria, 311 
pigmentation of, 877 
Martins, on auto-intoxication, ref., 417 
Martin and Rennie, on cardiac throm- 
bosis, ref., 532 
Marx, on primary sarcoma of liver, ref., 
737 
Maschka, on poisons, 425 
Mastigophora, 115, 116 
Mastitis, 843 
acute exudative, 843 
chronic, 845 
suppurative, 844 
tuberculous, 845 
Mayer, on trypanosomes, 118 
Maximow, on amyloid degeneration, ref., 
50 
McC ampbell, on Mexican typhus, 301 
McCrae, on collodium sacs, ref., 319; 
on mycotic aneurisms, ref., 567; on 
visceral charges following burns, ref., 
10 
McCrae, Fyshe and Ainley, on acute lobar 
pneumonia, ref., 606 
McCrae and Klotz, on fat in liver, ref., 720 
McFarland, on vaginitis, 796 
McNeal and Novy, on cultivation of 
trypanosomes, 122 
McWeeny, on rupture of oesophagus, ref., 
651 
"Measle," 124 
Measles, 309 
inoculation of, 310 
Meat poisoning, 291 
Meckel's diverticulum, 323, 667 
Mediastinitis, 636 
Mediastinum, inflammation of, 636 
tumors of, 636 
Medico-legal autopsies, 1022 
Megaloblasts, 459 
Megalocytes, 458 
Melanaemia, 470 
Melanins, 55 
Melano-carcinoma, 415 
Melano-sarcoma, 370 
Melanuria, 55 
in melano-sarcoma, ref., 372 
Meltzer, on functional provision, ref., 69; 
on oedema, ref., 22; on protection of 
body against bacteria, ref., 151; on pul- 
monary oedema, ref., 595; on pyloric 
stenosis, ref., 655 
Membranes and ventricles of brain, 908 
Membranous dysmenorrhcea, 804 
Mendelson, on apoplexy of thymus, ref., 
511 1084 
INDEX 
Menetrier, on epithelial metaplasia, ref., 
63 
Meningitis, 914 
acute, 914 
basilar, 917 
cellular, acute, 914 
cerebro-spinal, acute, 223 
epidemic, 223 
serum therapy in, 226 
chronic, 917 
exudative, acute, 914 
relation of middle ear to, ref., 917 
spinal, 923 
syphilitic, 919 
tuberculous, 918, 923 
typhoid, ref., 243 
Meningocele, 324 
Meningococcus (see Diplococcus intra- 
celhdaris meningitidis), 223, 225 
Merismopedia, 135 
Merkel, on angioma of liver, ref., 735 
Merkel, on bone in lymph-nodes, ref., 
487 
Merozoites in malaria, 312 
Mesentery, circulation in, study of, 111 
cysts of, 699 
study of inflammation in, 83 
Meslay and Parent, on tuberculosis of par- 
otid, ref., 700 
Mesothelioma, 377 
Metachromatic granules in bacteria, 
134 
Metamorphosis, reversionary, 63 
Metaplasia, 62 
Metastasis of tumors, 341, 350 
Metazoa, 122 
Metcalf and Safford, on carcinoma of 
ureter, ref., 788 
Metchnikoff, on cytolysis, 178; in inflam- 
mation, 108; on immunity, 196; on 
phagocytosis, 104, 106; on protective 
action of skin, ref., 150 
Metchnikoff and Roux, on animal inocu- 
lations in syphilis, 274 
Methylene blue stain, 1037 
for bacteria, 145 
.polychrome, 1037 
Metritis, acute, 807 
chronic, 808 
para-, 808 
peri-, 808 
Metrorrhagia, 21 
Mexican typhus, 301 
Meyer, on obstruction of ven® cav®, ref., 
573; on regeneration of lymph-nodes, 
ref., 76 
Meynert's method of opening brain, 996 
Michaelis, on ostitis fibrosa, ref., 897 
Micrencephalus, 325 
Microbes, 133 
Microcephalia, 928 
Micrococci, 134 
Micrococcus catarrhalis, 226 
gonorrhoe®, 221 
characters of, 222 
melitensis, 288 
pyogenes, 209 
aureus, 205 
tetragenus, 216 
Microcytase, 179 
Microcytes, 457 
Microgametes, 314 
Microgametocytes, 314 
Micron, ref., 134 
Micro-organisms, forms of, 133 
communicability of, 158 
in disease, 150 
fermentation, ref., 146 
inflammation, 88 
mouth, 646 
tumors, 347 
relation of, to infection, 156 
role of, in formation of venous 
thrombi, ref., 25 
ultra-microscopic, 318 
Microphages, 104 
Microsporon furfur, 148 
Microtomes, 1034 
Mieczkowski, on role of micro-organisms 
in gall-stones, ref., 745 
Miescher, tubes of, 121 
Mignot, on role of micro-organisms in 
gall-stones, ref., 745 
Miller, on bacteria of non-pregnant 
uterus, ref., 804; on dead tubercle 
bacilli, ref., 260 
Milne, on repair of liver, ref., 717 
Miloslavich and Namba, on tumors of 
appendix, ref., 690 
Minkowski, on gout, ref., 436 
Minot, on cell development, ref, 69; on 
embryological basis of pathology, ref., 
357; on regressive processes, ref., 35; 
on relation between endothelium and 
mesothelium, ref., 377 
Misick, on teratoma of liver, ref., 737 INDEX 
1085 
Mitchell, on foreign bodies in appendix 
vermiformis, ref., 686; on tubercle 
bacilli, ref., 266 
Mitosis, 65 
abnormal phases of, 66 
in carcinoma, 402 
in tumors, 339 
significance of, 67 
Mitotic figure, 66 
Mitulescu, on tubercle bacilli on books, 
ref., 266 
Moles, hydatid, of placenta, 826 
of placenta, 824 
pigmented, of skin, 372 
Molluscum contagiosum, 415 
Monaster, 65 
Monomorphism in bacteria, 136 
Monsters, 320 
double, 328 
Montgomery, on lung pigment, ref., 592 
Monti and Berggrun, on Von Jaksch 
anaemia, ref., 479 
Moore, on diseases of animals, ref., 157; 
on meningitis, ref., 223; on vaccina- 
tion, ref., 306 
Morbus maculosus neonatorum, 22 
Morj, on sarcoma of thyroid, ref., 514 
Morgan, on heredity, ref., 14; on regen- 
eration, ref., 69 
Morphin poisoning, 422 
Morrow, on leprosy, ref., 270 
Morris, on cysts of mediastinum, ref., 
636 
Morse, on cirrhosis in childhood, ref., 
729 
Moschcowitz, on carcinoma of appendix 
vermiformis, ref., 690; on non-parasitic 
cysts of liver, ref., 737; on tetanus, 
ref., 287 
Moser, on tuberculosis of heart, ref., 542 
Moser and v. Pirquet, on agglutination of 
streptococci, ref., 210 
Mosny, on typhoid and oysters, ref., 245 
Mosquitoes in malaria, 314 
in yellow fever, 302 
Most, on lymph-vessels of nose and 
pharynx, ref., 580 
Mouisset and Mouriquand, on sublimate 
poisoning, ref., 421 
Moulds, 133, 147 
as excitants of pneumonia, 613 
higher, 148 
methods of study of, 149 
Mouth, 643 
bacteria in, 646; ref., 647 
cysts of, 645 
disinfection of, ref., 219 
inflammation of (see Stomatitis), 643 
malformations of, 643 
micro-organisms in, 646 
syphilis of, 644 
tuberculosis of, 644 
Mouth, tumors of, 645 
Much, on immunity, 196 
Mucin, technique of staining, 47, 1038 
Mucous degeneration, 45 
membranes, inflammation of, pseudo- 
membranous, 212 
membranes, regeneration of, ref., 71 
patches in syphilis, 272 
of mouth, 645 
Muhlens, on relapsing fever, ref., 293 
Milhlmann, on body changes, ref., 36 
Muir, on repair of liver, ref., 717 
Muller, on abrin and ricin intoxication, 
ref., 203; on comparative histology of 
lungs, ref., 602; on hypertrophy of 
heart, 554; on natural immunity, ref., 
161; on post-mortem decomposition, 
ref., 987; on thyroid, ref., 512 
Muller's fluid, 1029 
Mummification, 58 
Mumps, 699 
Murphy, on tissue transplantation, 79 
Murray, on heredity in cancer, 354 
Muscle, 868 
atrophy of, 868, 871 
lipomatous, 871 
progressive, 869, 955 
spinal, 955 
bone in, 874 
degeneration of, 871 
embolism of, 873 
haemorrhage of, 873 
hyperplasia of, 874 
hypertrophy of, 62, 871 
pseudo-, 871 
infarctions of, 873 
infiltration, fatty, of, 871 
hydropic, of, 872 
inflammation of (see Myositis), 873 
injuries of, 873 
necrosis of, 868 
ossification of, 874 
parasites of, 875 
pigmentation of, 868 1086 
INDEX 
Muscle, regeneration of, 70 
relation of, to circulation, 16 
rupture of, 873 
syphilis of, 875 
trichinia in, examination of, 131 
tuberculosis of, 875 
tumors of, 875 
Muscles, relation of, to circulation of 
blood, 16 
Musgrave and Clegg, on amoebae, 116; on 
trypanosomiasis, ref., 118 
Musser, Pearce, and Gwyn, on actino- 
mycosis, ref., 232 
Myasthenia gravis, 873 
Mycelium, 147 
Mycetoma, 232 
Mycosis, intestinal, 229, 691 
pharyngis, 647 
Myelin bodies, ref., 44 
Myelitis, acute disseminated, 966 
anterior horn, 967 
central, 967 
chronic, 972, 973 
parenchymatous, ref., 966 
peripheral, 967 
polio-, anterior, 967 
transverse, 966, 973 
unilateral, 967 
Myeloblasts, 462 
Myelocytes, 461, 477, 897 
Myelocytoma, 902 
Myelogenous substances in cells, ref., 40 
Myeloma, 376, 902 
Myelomeningocele, 324 
Myeloplaxes, 901 
Myocarditis, 538 
chronic interstitial, 539 
gonorrhoeal, ref., 538 
interstitial, 538 
suppurative, 538 
syphilitic, 542 
tuberculous, 542 
Myocardium, lesions of, in diphtheria, 
ref., 283 
lesions of (see Heart) 
segmentation of, 536 
Myoglia fibrils, 389 
Myoma, 388 
levicellulare, 388 
of appendix vermiformis, 690 
bladder, urinary, 788 
intestine, 688 
kidney, 776 
Myoma of mamma, 848 
stomach, 662 
testicle, 861 
uterus, 810 
vagina, 797 
striocellulare, 390 
Myomalacia, ref., 538 
Myo-sarcoma, 376 
Myositis, chronic, 873 
interstitial, 873 
ossificans, 386, 874 
poly-, 874 
suppurative, 873 
syphilitic, 875 
tuberculous, 875 
Myxo-chondroma, 383 
Myxcedema, 429 
internal secretions of thyroid in, 
430 
Myxoma, 365 
gelatinosum, 365 
medullare, 366 
molle, 365 
of bone, 899 
brain, 976 
dura mater spinalis, 922 
Fallopian tubes, 841 
heart, 556 
larynx, 585 
liver, 737 
lymph-nodes, 498 
mamma, 848 
mamma, male, 867 
muscle, 875 
oesophagus, 653 
peritoneum, 697 
pia mater cerebralis, 920 
spinalis, 923 
salivary glands, 700 
testicle, 860 
Myxo-sarcoma, 376 
Myxosporidia, 120 
Nabothian glands, 805 
Naegeli, on blood, ref., 452 
on diseases of blood, ref., 471 
on statistics of tuberculosis, ref., 263 
Naevi, vascular, 394 
Nagana, 118 
Naville and Fromberg, on brain emboli, 
ref., 34 
Nebelthau, on intestinal tuberculosis, ref., 
674 1087 
Neck, appearance of, in strangulation, 
443, 989, 1024 
cysts of, 647 
Necker, on statistics of tuberculosis, ref., 
263 
Necrobiosis, 36 
Necrosis, 36, 56 
coagulation, 58, 59 
fat, 59 
of pancreas, 704 
focal, 58, 203 
in inflammation, 97 
liquefaction, 56 
of appendix vermiformis, 685 
bone, 889 
kidney, 750 
liver, 241, 714 
muscle, 868 
phosphorus, of bone, 890 
zonal, of liver, 715 
Negri and Mieremet, on organism in Hodg- 
kin's disease, 497 
Negri bodies, 295 
staining methods for, 296 
impression method, 297 
Neisser, on animal inoculations in 
syphilis, 274; on Staphylococcus pyog- 
enes aureus, ref., 208 
Neisser and Baermann, on animal inocu- 
lations in syphilis, 274 
Neisser and Gins, on B. diphtheriae, ref., 
285 
Neisser and Sachs, on haemolysis tests, 
ref., 182 
Neisser and Scholtz, ref., on gonococcus, 
223 
Nematoda, 126 
Nephritis, diffuse, acute, 756 
degenerative type, 759 
excitants of, 760 
exudative type, 759 
glomerular type, 757 
haemorrhagic type, 759 
interstitial type, 758 
parenchymatous type, 759 
productive type, 759 
variations in type, 759 
chronic, 762 
consideration of, 762 
excitants of, 768 
indurative type, 766 
interstitial type, 766 
parenchymatous type, 763 
INDEX 
Nephritis, diffuse, chronic, variations in 
type, 768 
experimental, ref., 769 
exudative, 759 
general considerations, 753 
glomerulo-, 757 
interstitial, 759, 766 
malarial, ref., 761 
peri-, 772 
productive, 759 
pyelo-, 771 
suppurative, 754 
syphilitic, 770 
tuberculous, 769 
Nephrolytic serum, 174 
Nerve cell, degenerations of, 946 
nature of, 943 
pigment in, 943 
structure of, 943 
fibres, degeneration of, 946 
Marchi's method of staining, 981 
myelin sheath, 944 
Schwann sheath, 944 
tissue, eosin-haematoxylin stain for, 
981 
Held's method of staining, 982 
Marchi's method of staining, 981 
Nissl's method of staining, 982 
preparation and study of, 980 
regeneration of, 69, 951 
Weigert's method of staining, 
981 
tracts, crossed pyramidal, 952 
degeneration of, 953 
direct pyramidal, 952 
degeneration of, 953 
Nerves, degeneration of, 946, 970 
degeneration of neurone, 946 
in tumors, 338, 362 
inflammation of (see Neuritis), 970 
injuries of, 931 
leprous inflammation of, 976 
lesions of, in diphtheria, ref., 283 
morphology of, 942 
preservation of, 1001 
regeneration of, 951 
relation of, to circulation, 16 
sclerosis of, 971 
tumors of, 979 
Nervous system, 908 
artefacts of, ref., 928 
degeneration, primary, of, 955 
secondary of, 953 1088 
INDEX 
Nervous system, degenerations of, 946, 
951 
neurone theory of, 943 
preparation and study of, 980 
regeneration of, 951 
relations of, to circulation of 
blood, 16 
syphilis of, 975 
tuberculosis of, 974 
tumors of, 976 
Netter, on bacteria in exudative pleu- 
ritis, ref., 638; on pneumococcus in 
empyema, ref., 640; on preventive in- 
oculation in plague, ref., 289 
Neuberger, on calcification of kidney, ref., 
753 
Neufeld, on agglutination of streptococci, 
ref., 210 
Neufeld and Handel, on D. pneumoniae, 
ref., 221 
Neufeld and Rimpau, on opsonins, 184 
Neufeld and Topfer, on opsonins, ref., 184 
N eumann, on bacteria of nose, ref., 580 
Neumann and Mayer, on protozoa, ref., 115 
Neurilemma, 946 
Neuritis, acute, 918 
chronic, 973 
exudative, 918 
multiple, 918 
optic, 957 
Neuro-epithelioma, 388, 410 
Neuroglia, 945 
cells, genesis of, ref., 357 
hyperplasia of, 951 
nature of, 945 
types of, 945 
fibrils, ref., 388 
in glioma, 387 
Neuroglioma ganglionare, 976 
Neurolytic serum, 174 
Neuroma, 390 
amputation, 391, 931 
false, 391, 931 
fibrillar, 391. 
ganglioniforme, 390 
of adrenals, 517 
liver, 735 
nerves, 979 
plexiform, 391 
Neurone, degenerations in, 946, 953, 955, 
970 
nature of, 943 
theory of nervous system, 943 
Neurones, action of fatigue on, 950 
toxins on, 948, 970 
degeneration, primary, of, 955 
secondary, of, 953 
motor, cortico-spinal, 952 
degeneration of, 955, 956 
motor, peripheral, 952 
degeneration of, 955, 956 
upper, 952 
nutritional disturbance of, 948 
sensory, lower, 952 
peripheral, 952 
degeneration of, 957 
upper, 952 
systems of, 951 
Neuroryctes hydrophobi®, 296 
Neusser, on status lymphaticus, ref., 440 
New-born, encephalitis of, 972 
examination, post-mortem, of, 1023 
size and characters of, 1023 
tissues, preservation of, 1026 
Newman, on malignant disease of tonsils, 
ref., 651 
Newton, on rupture of heart, ref., 527 
Nicolas and Beau, on spleen in infection, 
ref., 152 
Nichols, on experimental yaws, ref., 293; 
on ganglion cells in typhoid fever, ref., 
243; on tumor transplantation, ref., 351 
Nichols and Richardson, on arthritis 
deformans, ref., 905 
Nicolle, on infective agent in typhus fever, 
ref., 301 
Niles, on pellagra, ref., 318 
Nipple, absence of, 842 
eczema of, 843 
inflammation of, 843 
Nissl's stain for nerve tissue, 982 
Nitric acid, 418 
Nitrobenzol poisoning, 423 
Nocard and Leclainche, on infectious 
diseases of animals, 319 
Nocard and Roux, on ultra-microscopic 
organism, 319 
Nocardia, 136, 232 
Noguchi, on cultivation of spirochetes, 
ref., 292, 647; on cultivation of Tr. 
pallidum, ref., 275; on luetin test, 281; 
on modification of Wassermann re- 
action, 281; on rabies, ref., 296; on 
staining Tr. pallidum, 276 
Noguchi and Cohen, on trachoma bodies, 
ref., 308 INDEX 
1089 
Noma, 644 
of vulva, 794, 797 
von Noorden on diseases of blood, ref, 
471 
Normoblasts, 458 
Norris, C. C., on carcinoma of appendix 
vermiformis, ref., 690 
Norris, Charles, on bacterial precipitins, 
182; on myeloma, ref., 902; on status 
lymphaticus, 440 
Norris, G. W., on tuberculous pericar- 
ditis, ref., 521 
Norris and Larkin, on streptothrix 
pneumonia, ref., 232 
Norris, P appenheimer, and Flournoy, on 
relapsing fever, 292 
North, on septic sore throat, ref., 211 
Northrup, on emphysema of lung, ref., 
598; on reptilian heart, ref., 523; on 
tuberculous bronchial lymph-nodes, 
ref., 487 
Northrup and Crandall, on scurvy in 
infants, ref., 438 
Norton, on persistent thymus, ref., 511 
Nose, 579 
adenoids, 581 
bacteria in, 580 
cysts of, 581 
haemorrhage from, 579 
hay fever, ref., 580 
inflammation of (see Catarrh), 579 
lymph-vessels, of, ref., 580 
malformations of, 579 
mucous membranes of, 579 
polyps of, 581 
tumors of, 581 
Novy, on pathogenic trypanosomes, ref., 
118 
Novy and Knapp, on relapsing fever, ref., 
293 
Novy and McNeal, on Trypanosoma 
lewisi, 117 
Noyes, on accessory adrenals, ref., 515 
Nutmeg liver, 710 
Nutrition, disturbances of, 9 
relationship of, to disease, 9 
Nuttall, on blood relationships, 172, ref., 
181; on role of insects in infection, 
ref., 151 
Nuttall and Shipley, on anopheles in 
malaria, ref., 316 
Nux vomica poisoning, 424 
Nymphse, anomalies of, 793 
Obermeier, spirochaete of, 292 
Occupation, relation of, to disease, 9 
Ochronosis, 55 
Odontoma, 387 
(Edema, 22 
malignant, 291 
of brain, 934 
glottis, 582, 1011 
labia, 793 
larynx, 582 
lung, 593 
lymph-nodes, 482 
pia mater cerebralis, 913 
uterus, 802 
purulent, 200 
Oertel, on classification of nephritis, ref., 
763; on echinococcus in liver, ref., 739; 
on necrosis of liver, ref., 715; on 
tuberculosis and cancer, ref., 267 
CEsophagitis, 653 
(Esophagus, 651 
abscesses in, 653 
cysts of, 654 
dilatation of, 651 
diverticula of, 652 
examination, post-mortem, of, 1010 
foreign bodies in, 652, 653 
haemorrhage in, 651 
inflammation of, 653 
malformations of, 651 
perforation of, 651 
rupture of, 651 
stenosis of, 652 
syphilis of, 653 
tuberculosis of, 653 
tumors of, 653 
ulcer of, 651 
varices in, 651 
Ogata, on blood plates, ref., 466 
O'Hare, on experimental nephritis, ref., 
769 
Oidiomycosis cutis, 146 
Oidium, 147 
albicans, in mouth, 147, 644 
vagina, 797 
Oligocythaemia, 454, 456 
Omentum, cysts of, 699 
examination, post-mortem, of, 1002 
hernia of, 670 
tumors of, ref., 698 
Oophoritis, 827 
acute exudative, 827 
chronic interstitial, 828 1090 
INDEX 
Oophoritis, syphilitic, 829 
tuberculous, 829 
Ophuls, on "acid-proof" bacilli in gan- 
grene, ref., 600; on atypical typhoid, 
ref., 243; on corpora amylacea, ref., 50; 
on nephritis, ref., 763 
Opie, on experimental atrophy of liver 
cells, 718; on filarial lymphatic varix, 
ref., 130; on hsemochromatosis, ref., 
54; on lesions of pancreas, ref., 704; 
on leucocytic exudates after intra- 
peritoneal injection of bacteria, ref., 
694; on proteolytic enzymes in phago- 
cyte, 105; on relation of pancreas to 
diabetes, ref., 435; on thrombosis of 
lymphatics, ref., 577; on zonal necroses 
of liver, ref., 715 
Opie and Meakins, on haemorrhagic necro- 
sis of pancreas, ref., 705 
Opitz, on entrance of bacteria through 
intestine, ref., 694 
Opium poisoning, 422 
Oppenheimer, on bacterial poisons, ref., 
152 
Oppenheimer, B. S., on method of opening 
heart, 1088 
Opsonic index, 187 
in acute lobar pneumonia, 220 
power, determination of, 186 
substances, 183 
Opsonins, 183 
clinical significance of, 186 
fixation of, 185 
in typhoid fever, 246 
Orchitis, 857 
acute exudative, 857 
chronic, 858 
leprous, 860 
syphilitic, 860 
tuberculous, 858 
Oriental plague, 288 
Ornithodorus moubata, 293 
Orthmann, on retro-ovarian cysts, ref., 
841 
Orth's fluid, 1029 
Oshima, on malignant tumors of kidney 
in children, ref., 777 
Osler, on cretinism, ref., 430; on hair balls 
in stomach, 666; oh Madura foot, ref., 
232; on purpura, ref., 439 
Osler and McCrae, on carcinoma of stom- 
ach in young, ref., 664 
Osmic acid, as fixative, 1029 
Ossification, irregular, in rickets, 892 
syphilis, 888 
of bronchi, 592 
Osteitis, 882 
condensing, 885 
ossifying, 883 
rarefying, 883 
suppurative, 885 
syphilitic, 888 
tuberculous, 887 
ulcerative, 891 
Osteoblasts, 876, 881 
Osteo-chondroma, 383 
of mamma, 848 
Osteoclasts, 60, 103, 876, 883 
Osteoid tissue, 878 
Osteoma, 385 
of brain, 976 
bone, 899 
dura mater cerebralis, 911 
lung, 634 
mamma, 848 
peritoneum, 697 
pia mater cerebralis, 920 
muscle, 874 
penis, 855 
testicle, 860 
Osteomalacia, 896 
Osteomyelitis, 886 
chronic, 887 
infectious, acute, 886 
malignant, 887 
Osteophytes, 386, 881, 889 
Osteo-porosis, 883 
Osteo-sarcoma, 373 
Osteo-sclerosis, 885 
Oswald, on lesions of thyroid, ref., 433 
Otis and Evans, on blastomycosis, ref., 
146 
Otto, on cysts of spleen, ref., 510 
Ottolenghi, on bacteria in blood of ca- 
daver, ref., 987 
Ovarian pregnancy, 842 
Ovaries, 826 
absence of, 826 
cystadenoma of, 830 
cysts of, 830, 836, 837 
displacements of, 826 
ectopic pregnancy, 842 
examination, post-mortem, of, 1020, 
1026 
haemorrhage of, 827 
hernia of, 826 INDEX 
1091 
Ovaries, hypersemia of, 826 
hypertrophy of, 62 
inflammation of (see Oophoritis), 
827 
malformations of, 826 
malpositions of, 826 
preservation of, 1020 
regeneration of, 73 
size of, 1020 
changes in, 826 
syphilis of, 829 
teratoma of, 836 
thyroid tissue in, ref., 836 
transplantation of, 78 
tuberculosis of, 829 
tumors of, 829 
weight of, 1020 
Ovula Nabothi, 805, 822, 1020 
Oxalic acid, 418 
Oxyuris vermicularis, 127 
Oysters and typhoid fever, 245 
Pacchionian bodies, 912, 992 
Pachydermia diffusa, 583 
verrucosa, 583 
Pachymeningitis, 909, 922 
acute externa, 909, 922 
interna, 909 
chronic, 909, 922 
interna hsemorrhagica, 910, 922 
syphilitic, 911 
tuberculous, 911, 922 
Packard, on faucial tonsils, ref., 649 
Page, on diphtheria carriers, ref., 285 
Paget's disease, 843 
Palate, cleft, 643 
Paltauf, on status lymphaticus, ref., 440 
Pancreas, 701 
absence of, 701 
accessory, 701 
atrophy of, 702 
autodigestion of, 702 
bacteria in, 705 
calculi in ducts of, 707 
cholelithiasis, effect of, on, 705 
concretions in ducts of, 707 
cysts of, 706 
degeneration of, 703 
diabetes, relation of, to, 435, 703 
displacements of, 701 
ducts, dilatation of, 706 
examination, post-mortem, of, 1017 
fat necrosis of, 704 
Pancreas, foreign bodies in ducts of, 707 
gangrene of, 705 
gummata in, 706 
haemorrhage in, 705 
infiltration, fatty, of, 703 
inflammation of, 705 
Langerhans' islands, degeneration of, 
703 
lesions of, in diabetes, 435, 703 
cirrhosis of liver, 728 
malformations of, 701 
necrosis of, 704 
parasites of, 707 
preservation of, 1018 
size and weight of, 1017 
syphilis of, 706 
tuberculosis of, 706 
tumors of, 706 
Pancreatic duct, malformations of, 701 
Pancreatitis, 705 
Pancreolytic serum, 174 
Pandemic disease, 159 
Papilloma, 364 
of bladder, urinary, 786 
Fallopian tubes, 841 
gall-ducts, 743 
kidney, 776 
larynx, 585 
mouth, 645 
oesophagus, 653 
ovary, 829, 835 
penis, 854 
stomach, 662 
vagina, 797 
vulva, 794 
Pappenheimer, on thymus, ref., 511 
Pappenheim's method of staining tubercle 
bacilli, 258 
Paraffin embedding, 1033 
Paralysis, acute ascending, 969 
infantile, 299 
Landry's, 969 
spinal, infantile, 967 
spastic, 955 
Parametritis, 808 
Paraphimosis, 854 
Paraplegia, ataxic, 962 
spastic, 955 
Parasite, 332 
Parasites, animal, 114 
in blood, 470 
plant, 133 
Parathyroid glands, 514 1092 
INDEX 
Paratyphoid, 247 
Parenchymatous degeneration, 39 
Paresis, general, lesions of brain in, 972 
Paris green poisoning, 421 
Park, R., on osteomyelitis, ref., 887 
Park, W. H., on agglutination tests in 
classification, ref., 181; on B. influenza;, 
ref., 234; on serum therapy, ref., 165 
Park and Krumweide, on types of B. 
tuberculosis, ref., 266 
Park and Williams, on B. dysenteric 
ref., 677; on bacteriology, 133; on 
diphtheria antitoxin, 285; on infection 
of children with bovine tuberculosis, 
ref., 266; on preventive inoculations in 
hydrophobia, ref., 298; on protozoa, 
ref., 115; on typhoid carrier, ref., 245 
Parotid gland, 699 
inflammation of, 699 
tuberculosis of, 700 
tumors of, 700 
Parotitis, 699 
Parovarium, cysts of, 837 
Parsons, on bone lesions in typhoid 
fever, ref., 243 
Passler and Heineke, on relation of hyper- 
trophy of heart to kidney disease, ref., 
768 
Pasteur method in hydrophobia, 297 
Pathological morphology, characteriza- 
tion of, 5 
physiology, characterization of, 5 
specimens, preservation of, 1027 
Pathology, classifications of, 6 
comparative, 319 
definitions of, 3, 5 
divisions of, 5 
general introduction to, 3 
special, 451 
Pawlowsky, on elimination of bacteria in 
body, ref., 151 
Payr, on transplantation of thyroid, ref., 
78 
Pearce, on cytolysins, 175; on degenera- 
tion of heart muscle, ref., 541; on 
experimental cirrhosis, ref., 730; on 
hemagglutinins and liver necroses, ref., 
715; on islands of Langerhans, ref., 704; 
on leptothrix, ref., 232; on oedema, 
ref., 22; on pancreas in congenital 
syphilis, ref., 706; on regeneration of 
kidney, ref., 72; on regeneration of 
liver, ref., 717; on thrombi, ref., 26 
Pearce and Winne, on haemagglutinins 
and liver necroses, ref., 715; on 
thrombi, ref., 26 
Pearce, Hill, and Eisenbrey, on experi- 
mental nephritis, ref., 769 
Pearls, epithelial, 407 
Pearson, on animal immunization against 
tuberculosis, ref., 262 
Pediculus capitis, 132 
vestamenti in Mexican typhus, 301 
Pellagra, 318 
Pellew, on arsenic poisoning, ref., 421 
Penis, 853 
absence of, 853 
balanitis, 854 
calcification of, 855 
calculi of, 855 
condyloma of, 854 
corpora cavernosa, inflammation of, 
854 
cysts of, 855 
elephantiasis of, 855 
enlargement of, 853 
epispadias, 853 
erysipelas of, 854 
examination, post-mortem, of, 1018 
furuncles of, 854 
haemorrhage in, 854 
herpes of, 854 
hypospadias, 853 
indurations of, 854 
inflammation of, 854 
injuries of, 854 
malformations of, 853 
ossification of, 855 
paraphimosis, 854 
phimosis of, 854 
congenital, 853 
syphilis of, 854 
tuberculosis of, 854 
tumors of, 854 
ulcers of, 854 
Pentastomum denticulatum in liver, 739 
lymph-nodes, 498 
spleen, 511 
Periarteritis, 559 
nodosa, 566 
Pericarditis, 518 
acute, 519 
bacteria in, 520 
chronic, 520 
exudative, 519 
fibrinous, 519 INDEX 
1093 
Pericarditis, obliterative, 520 
purulent, 520 
sero-fibrinous, 519 
suppurative, 520 
tuberculous, 521 
Pericardium, 518 
air in, 518 
calcification of, 520 
cysts of, 522 
dropsy of, 518 
examination, post-mortem, of, 1004 
fibroid nodules in, 521 
gas in, 518 
haemorrhage in, 518 
hydro-, 518 
inflammation of, 518 
pneumo-, 518 
tuberculosis of, 521 
tumors of, 522 
Perihepatitis, 733 
Perimetritis, 808 
Perinephritic suppuration, 772 
Periosteum, haemorrhage in, 877 
hyperaemia of, 877 
inflammation of (see Periostitis), 878 
tumors of, 899 
Periostitis, 878 
exudative, 879 
fibrous, 880 
ossifying, 880 
suppurative, 870 
syphilitic, 881 
tuberculous, 882 
Periphlebitis, 573 
Peripneumonia of cattle, organism of, 319 
Perisplenitis, 507 
Peritoneum, 691 
absorption from, ref., Ill, 694 
ascites of, 692 
cysts of, 699 
haemorrhage in, 692 
inflammation of (see Peritonitis), 692 
malformations of, 691 
parasites of, 699 
tuberculosis of, 695 
tumors of, 696 
Peritonitis, 692 
acute, 692 
bacterial excitants of, 694 
cellular, 692 
chronic, 695 
chronic, 694, 695 
exudative, 693 
Peritonitis, gonococcus, ref., 694 
suppurative, 693 
tuberculous, 695 
Perkins, on B. mucosus capsulatus, ref., 
216 
Perkins and Pay, on bacteria in smallpox, 
ref., 304 
Perrone, on appendicitis, 688 
Pertussis, 317 
Pest (see Plague), 288 
Petechiae, 21 
Peterson, on non-malignant rectal stric- 
tures, ref., 684 
Peterson and Haines, on legal medicine, 
425 
Pettit, on concurrent infection in tuber- 
culosis, ref., 631 
Peyer's patches in typhoid fever, 235 
Pfaff, on oesophageal diverticula, ref., 
652 
Pfeiffer, on bacteriolysis, 170; on immun- 
ity, 196 
phenomenon, 170 
Phagocytes, 99, 161 
action of, 105, 111 
counting, 187 
enzymes in, 105 
forms of, 103 
in cytolysis, 178 
Phagocytic count, 187 
Phagocytosis, 98, 183 
by leucocytes, 463 
experimental study of, 110 
Phagolysis, 179 
Pharyngitis, 648 
adenoids in, 648 
catarrhal, 648 
tuberculous, 649 
Pharyngo-mycosis leptothrica, 232 
Pharynx, 647 
abscess in, 648 
adenoids, 648, 649, 650 
as portal of entry for tubercle bacilli, 
650 
cysts of, 647 
diverticula of, 647 
examination, post-mortem, of, 1010, 
1025 
fistulas of, 647 
inflammation of (see Pharyngitis), 
648 
lesions of, 581 
malformations of, 647 1094 
INDEX 
Pharynx, mycosis of, 647 
polyps of, 650 
preservation of, 1011 
tuberculosis of, 649 
tumors of, 650 
Philips, on acute yellow atrophy in 
children, ref., 718 
Phimosis, 854 
congenital, 853 
para-, 854 
Phlebectasia, 572 
Phlebitis, 573 
acute infective, 573 
chronic, 574 
endo-, 574 
peri-, 574 
syphilitic, 575 
tuberculous, 575 
Phleboliths, 27, 533 
Phlegmon, 200 
gaseous, 290 
Phloridzin diabetes, ref., 436 
Phloroglucin as decalcifying agent, 1031 
Phosphorus necrosis of bone, 890 
poisoning, 419, 656 
fat embolism in, 34 
Phthisis, 627 
Pia mater cerebralis, 912 
blood in, 913 
bone in, 921 
cysts of, 921 
haemorrhage in, 913 
hyperaemia of, 913 
inflammation of (see 
Meningitis), 914 
oedema of, 913 
Pacchionian bodies in, 912 
parasites of, 921 
pigmentation of, 914, 921 
structure of, 912 
syphilis of, 919 
tuberculosis of, 918 
tumors of, 919 
examination, postmortem, of, 
992 
methods of hardening, 998 
, spinalis, 922 
bone in, 923 
cartilage in, 923 
haemorrhage in, 922 
inflammation of (see 
Meningitis, spinal), 923 
parasites of, 923 
Pia mater spinalis, tuberculosis of, 923 
tumors of, 923, 977 
Pic and Bonnamour, on arterio-sclerosis, 
ref., 565 
Pic, on hydatid moles, ref., 826; on ochro- 
nosis, ref., 55 
Picro-acid-fuchsin stain, 1035 
Pierson and Ravenel^ on moulds, ref., 
147 
Pigment, anthracotic, 53, 616 
extraneous, 53, 56 
haematogenous, 53 
hepatogenous, 53, 54 
in blood, 470 
metabolic, 55 
of red blood cells, 456 
skin, ref., 55 
Pigmentation, 53 
of adrenals, 516 
bone marrow, 877 
brain, 933 
heart, 529 
liver, 714, 721, 730 
lungs, 601, 616 
lymph-nodes, 483 
muscle, 868 
nerve cells, 943 
pia mater cerebralis, 914, 921 
pleura, 641 
spleen, 501 
Piles, 684 
Pilocarpin exudates, 195 
Pineal gland, lesions of, 980 
Pinworm, 128 
Piroplasma bigeminum, 122 
Pituitary body, 980 
Pituitrin, 439 
Pityriasis versicolor, 148 
Placenta, 822 
apoplexy of, 823 
calcification of, 823 
cysts of, 826 
degenerations of, 823 
haemorrhage in, 823 
infarction of, 823 
inflammation of, 823 
lesions of, 822 
moles of, 824 
polyps in, 824 
structure of, ref., 822 
syphilis of, 823 
tuberculosis of, 823 
tumors of, 824 INDEX 
1095 
Plague, bacillus of, 288 
bubonic, 288 
lobular pneumonia of, 612 
insects and, 289 
insects as carriers of, ref., 151 
oriental, 288 
preventive inoculation in, 289 
pulmonary, 288 
rats and squirrels and, 289 
septicaemic, 288 
swine, bacillus of, 289 
Plant parasites, 133 
Plasma cells, 74, 93, 462 
Plasmodium malariae, 311 
Plasmodromata, 115 
Plant, on yeasts and moulds in disease, 
ref., 149 
Pleomorphism, in bacteria, 136 
Plethora, 16, 455 
Pleura, 636 
air in, 637 
as portals of entry for bacteria, ref., 
614 
calcification of, 639 
cysts of, 642 
echinococcus of, 642 
empyema, 638 
gas in, 637 
haemorrhage in, 637 
hydro-pneumothorax, 637 
hydrothorax, 636 - 
inflammation of (see Pleuritis), 637 
pigmentation of, 641 
pyo-pneumothorax, 637 
tuberculosis of, 640 
tumors of, 641 
Pleural cavities, air in, 637 
tests for, 1003 
examination, post-mortem, of, 
1003, 1009, 1025 
gas in, 637 
Pleurisy (see Pleuritis), 637 
Pleuritic adhesions, 640 
Pleuritis, 637 
acute, 637 
chronic, 640 
dry, 637 
exudative, 637 
fibrinous, simple, 637 
sero-fibrinous, 637 
excitants of, 638 
sicca, 637 
suppurative, 638 
Pleuritis, tuberculous, 640 
with effusion, 637 
Plimmer bodies, 348 
Plotz, on infective agent in typhus fever, 
ref., 301 
Pneumococcal vaccines, 220 
Pneumococco-opsonic index, 220 
Pneumococcus (see Diplococcus pneu- 
moniae), 218 
lanceolatus, 217 
of Frankel, 217 
Friedlander, 216 
Pneumokoniosis, 56, 616 
Pneumonia, 600 
aspiration, 611 
broncho-, 608, 609 
excitants of, 612, 613 
exudates in, 611 
tuberculous, 624 
cheesy, 627 
classification of, 603 
cooling of body as determining, 
614 
crisis in, 219, 606 
croupous, 603 
excitants of, 218 
experimental, ref., 614 
in animals, ref., 614 
exudative, 603 
fibrinous, 603 
haematogenous, 611 
hypostatic, 612 
interstitial, 614 
lobar, acute, 603 
associated lesions in, 606 
bacteria in, 607 
complications of, 606 
concurrent infection in, 607 
delayed resolution in, 607 
diplococcus of, 218 
experimental, 218, 614 
mixed infection in, 607 
statistics of, 606 
suppurative inflammation 
in, 607 
lobular, 608 
excitants of, 613 
exudate in, 611 
"organizing," 607 
"patchy," 608 
"purulent infiltration" in, 608 
pyaemic, 611 
reversion of epithelium in, 615 1096 
INDEX 
Pneumonia, septic, 611 
syphilitic, 633 
tuberculous, 618 
Pneumonitis (see Pneumonia), 600 
Pneumonomycosis, ref., 147 
Pneumopericardium, 518 
Pneumothorax, 637 
Poikilocytes, 457 
Poisoning, examination, post-mortem, 
in cases of, 1014, 1016, 1022 
meat, 291 
Poisons, 417 
abrin, 153, ref., 203, 424 
aconite, 425 
alcohol, 423 
aloes, 422 
ammonia, 419 
animal venom, etc., 424 
arsenic, 420, 656 
bacterial, 139, 152 
bibliography of, 425 
cantharides, 422 
carbolic acid, 423 
carbonic oxide, 424 
chloral hydrate, 424 
chloroform, 423, 716 
colchicum, 422 
colocynth, 422 
conium, 425 
copper, 422 
corrosive sublimate, 421 
croton oil, 422 
cyanide of potassium, 423 
digitalis, 425 
elaterium, 422 
endogenous, 417, 426 
ether, 424 
exogenous, 417 
fungi, 422 
gamboge, 422 
hellebore, 422 
histogenic, 426 
hydrochloric acid, 418 
hydrocyanic acid, 422 
jalap, 422 
lead, 421 
lesions induced by, 417 
lobelia, 425 
morphin, 422 
nitric acid, 418 
nitrobenzol, 423 
nux vomica, 424 
opium, 422 
Poisons, oxalic acid, 418 
Paris green, 421 
phosphorus, 419, 656 
potash, 419 
potassium nitrate, 419 
potassium oxalate, 419 
ptomain, 425 
ricin, 153; ref., 203, 424 
savin, 422 
scammony, 422 
Scheele's green, 421 
soda, 419 
stramonium, 425 
strychnin, 424 
sulphuric acid, 417 
tartar emetic, 422 
tartaric acid, 419 
turpentine, 422 
vegetable irritants, 422 
venom, animal, 153, 424 
veratria, 422 
Polaillon, on lung stones, ref., 639 
Polar body, 65 
Poliomyelitis, acute anterior, 299, 967 
communicability of, 300 
immunity in, 300 
Polycythsemia, 454 
Polymyositis, acute primary, 874 
Polyps, adenoid, 650 
of bronchi, 592 
heart, 531 
intestine, 688 
nose, ref., 580, 581 
pharynx, 650 
placenta, 824 
urethra, 792 
uterus, 803, 810 
Popon, on arsenic poisoning, 421 
Poor and Steinhardt, on rabies, ref., 297 
Porencephalus, 979 
Portal vein, lesions of, 711 
Porter, on coronary arteries, ref., 537 
Posselt, on echinococcus in liver, ref., 
739 
Post-mortem changes in blood distribu- 
tion, 986, 990 
in cholera, 248 
pyaemia, 204 
septicaemia, 204 
contusions, 989 
cooling of body, 988 
cultures, 1021 
decomposition, 987 1097 
INDEX 
Post-mortem discoloration of viscera, 
1002 
examination, 985 
after asphyxia, 442 
drowning, 444 
strangulation, 443 
closure of body after, 1021 
external inspection, 986 
for bacteria, 1021 
internal inspection, 990 
lividity, cadaveric, 986 
medico-legal, 1022 
method of making, 986 
of abdomen, 1001, 1025 
adrenals, 1013, 1026 
aorta, 1018 
base of cranium, 998 
bladder, 1018, 1019, 1026 
bones, 1026 
brain, 992, 1024 
bronchi, 1009 
diaphragm, 1003 
dura mater, 992 
ear, 988 
eyes, 998 
Fallopian tubes, 1020 
gall-bladder, 1016 
-ducts, 1016 
genito-urinary organs, fe- 
male, 1019, 1026 
male, 1018, 1026 
hsemolymph-nodes, 1018 
head, 991, 1024 
heart, 1004, 1025 
internal ear, 998 
intestine, 1002, 1014, 1026 
kidney, 1011, 1026 
larynx, 1010, 1025 
liver, 1002, 1016, 1026 
lung, 1009, 1025 
new-born, 1023 
oesophagus, 1010 
omentum, 1002 
ovaries, 1020 
pancreas, 1017 
pericardium, 1004 
pharynx, 1010, 1025 
pia mater, 992 
pleural cavities, 1009, 1025 
prostate gland, 1018 
solar plexus, 1018 
spinal cord, 999 
spleen, 1013, 1026 
Post-mortem examination of stomach, 
655, 1003, 1015, 1026 
testicles, 1018 
thoracic duct, 1018 
thorax, 1001, 1024 
thymus, 1025 
thyroid, 1010, 1025 
trachea, 1011 
umbilical cord, 1026 
urethra, 1018 
uterus, 1019 
vagina, 1019 
vesiculse seminales, 1018 
vulva, 1019 
putrefactive changes, 987 
fractures, 990 
gas formation, 987 
hypostasis, 986 
identification, 986 
lividity, 986 
marks of violence, 989 
putrefaction, 987 
rigidity, 988 
rise of temperature, 988 
softening of viscera, 1002 
wounds, 990 
Potash poisoning, 418 
Potassium bicarbonate in Muller's fluid, 
1029 
nitrate poisoning, 419 
oxalate poisoning, 419 
Potter, Ditman, and Bradley, on opsonins, 
ref., 187 
Powers, on carcinoma of branchial cleft, 
ref., 651 
Pratt, on coronary arteries, ref., 537; on 
histology of acute lobar pneumonia, 
ref., 606; on paratyphoid, ref., 247; 
on typhoid bacillus, ref., 244 
Preble, on gastro-intestinal haemorrhage 
in cirrhosis, ref., 728; on oesophageal 
varices, ref., 651; on pneumococcus 
endocarditis, ref., 544 
Preble and Hektoen, on multiple neuroma, 
ref., 393 
Precipitating substances, 181 
Precipitin test in forensic medicine, 181 
technique of, 194 
Precipitins, 181 
anti-, 182 
in typhoid fever, 246 
nature of, 182 
Pregnancy, abdominal, 842 1098 
INDEX 
Pregnancy, chorionepithelioma of, 820 
extra-uterine, 841 
interstitial, 842 
ovarian, 842 
toxaemia of, liver in, 718 
tubal, 841 
tubo-abdominal, 842 
vomiting, pernicious, in, 718 
Prepuce, absence of, 853 
lesions of, 854 
Preservation of tissues, 1029 
Pribram, on bacterial haemolysins, 
ref., 153 
Proescher and Reddy, on paratyphoid, 
ref., 247 
Proglottides of tapeworm, 123 
Prolapsus uteri, 801 
Prosopothoracopagus, 330 
Prostate, 863 
abscess of, 866 
atrophy of, 863 
concretions of, 866 
cysts of, 866 
degenerations of, 863 
examination, post-mortem, of, 1018 
hyperplasia of, 864 
hypertrophy of, 863 
inflammation of, 864 
parasites in, 866 
tuberculosis of, 866 
tumors of, 866 
Prostatitis, 864 
Proteids, defensive, 161 
protective, 109 
Proteins, 3 
Proteus group of bacilli, 216 
Prothrombin, 452 
Protoplasmic processes, 944 
Protozoa, 114 
classification of, 115 
cultivation of, 115 
effects of, 115 
in infectious diseases, 317 
tumors, 347 
methods of study of, 122 
modes of transmission of, 114 
Proud flesh, 95 
Prudden, on bacteria in exudative 
pleuritis, ref., 638; on dead tubercle 
bacilli, ref., 260; on experimental tu- 
berculosis, ref., 631; on malignant 
endocarditis, ref., 545; on multiple 
neuroma, ref., 393; on pseudo-hyper- 
trophy of muscle in multiple neuroma, 
ref., 871; on pseudo-membranous in- 
flammation, ref., 212; on rhabdo- 
myoma of parotid gland, ref., 390; 
Prudden and Hodenpyl, on dead tubercle 
bacilli, ref., 260 
Psammoma, 376 
of dura mater cerebralis, 912 
spinalis, 922 
pia mater cerebralis, 920 
Pseudo-diphtheria, 212 
bacillus, 285 
Pseudo-hermaphroditism, 793, 853 
Pseudo-hypertrophy of muscle, 871 
Pseudo-leukaemia, 489 
granulomatous, 491 
infantum, 479 
spleen in, 509 
Ptomain poisoning, 425 
Ptomains, bacterial, 139 
Puerperal fever, 808 
Purpura haemorrhagica, 439 
Pus, 89, 201 
cells, 201 
Pustules, 199 
malignant, 228 
Putnam, on haemorrhagic encephalitis, 
ref., 965 
Putnam and Taylor, on spinal-cord de- 
generation, ref., 963 
Putrefaction, post-mortem, 987 
Pyaemia, 203 
crypto-genetic, 204 
post-mortem changes, 204 
septico-, 204 
Pycnosis, 57 
Pyelitis, 771 
Pyelo-nephritis, chronic, 771 
suppurative, 771 
Pygopagus, 331 
Pylorus, stenosis of, 662 
congenital, 654 
Pyogenic bacteria, 205 
Pyo-pneumothorax, 637 
Pyosalpinx, 840 
Pyo-septicaemia, ref., 204 
Pyramids, anterior, 952 
Pyrexia, 440 
Quarter-evil, 291 
Quenu and Branca, on regeneration of 
intestinal epithelium, ref., 682 
Quinsy, 649 INDEX 
1099 
Rabies (see Hydrophobia), 294 
Race, relationship of, to disease, 13 
Rachitis, 891 
foetal, 896 
Radium, injuries from, 11 
Radziewsky, on bacterial infection, ref., 
153 
Rainey, tubes of, 121 
Ramsay, on tumors of adrenals, ref., 517 
Ranula, 646, 700 
Raschkes, on endothelioma of vagina, 
ref., 797 
Ravenel, on bovine tubercle bacillus, ref., 
260; on entrance of bacteria through 
intestine, ref., 694; on human and 
bovine tuberculosis, ref., 266; on portals 
of entry of B. tuberculosis, ref., 264 
Ravenel and McCarthy, on lesions of 
hydrophobia, ref., 294 
Raviart, on tuberculosis of heart, ref., 
542 
Ray fungus, 231 
Receptors, 166 
v. Recklinghausen, on rachitis, ref., 897 
Rectocele vaginalis, 796 
Rectum, 683 
examination, post-mortem, of, 1018 
haemorrhoids, 684 
.inflammation of, 683 
strictures of, 684 
Reed, on focal necrosis in typhoid fever, 
ref., 241; on Hodgkin's disease, ref., 495 
Reed and Carroll, on excitant of yellow 
fever, ref., 302; on mosquito in yellow 
fever, ref., 302 
Reed, Carroll and Agramonte, on mos- 
quito in yellow fever, ref., 302 
Reed, Vaughan and Shakespeare, on 
typhoid fever in army camps, ref., 245 
Regeneration, 64 
of bladder mucosa, ref., 71 
blood, 77 
blood-vessels, 75 
bone, 76 
bone-marrow, 76 
cartilage, 76 
cells, 68 
impulse to, 79 
connective tissue, 73 
endothelium, 75 
epithelium, 71 
fat tissue, 77 
kidney, 72 
Regeneration of liver, 72 
lymph-nodes, 76 
lymph-vessels, 76 
mammary-glands, 72 
mucous membranes, ref., 71 
muscle tissue, 70 
nerve tissue, 68, 951 
ovary, 73 
salivary glands, 72 
testicle, 73 
thyroid, 72 
Regression in cells, 35 
Reinbach, on colloid, ref., 513; on granula- 
tion tissue, ref., 95 
Reineboth and Kohlhardt, on cooling of 
body and pneumonia, ref., 614 
Relapsing fever, 292 
in animals, 292 
Renon, on aspergillus, ref., 147 
Reproductive organs, female, 793 
male, 853 
Resolution in inflammation, 90 
Resorption, 23 
in inflammation, experimental study 
of, 110 
Respiration, relation of, to circulation 
of blood, 16 
Respiratory system, lesions of, 579 
Reversion, 63 
Rhabdomyoma, 390 
of heart, 556 
muscle, 875 
parotid, 701 
testicle, 861 
Rhabdonema strongyloides, 131 
Rheumatism, acute, 318 
articular, 904 
Rhexis, haemorrhage by, 20 
Rhinitis, 579 
acute catarrhal, 579 
chronic catarrhal, 580 
pseudo-membranous, 580 
syphilitic, 580 
tuberculous, 580 
Rhinoscleroma, 282 
Rhizopoda, 115 
Rhodes, on haemorrhage of larynx, ref., 
582 
Ribbert, on appendicitis, ref., 688; on cell 
regeneration, 79; on cholesteatomata, 
ref., 379; on chordoma, ref., 385; on 
compensatory hypertrophy, ref., 80; 
on fatty degeneration, 41; on liver 1100 
INDEX 
cirrhosis, ref., 730; on metaplasia, ref., 
63; on miliary tubercles, ref., 252; on 
regeneration of lymph-nodes, ref., 486; 
on reversion, ref., 63; on tuberculosis of 
pleura, ref., 641; on tumors, 416 
Ribbert's hypothesis of origin of tumors, 
351 
Richet, on anaphylaxis, ref., 191 
Richter, on ilio-caecal tuberculosis, ref., 
683 
Ricin poisoning, 153, ref., 203, 425 
Ricker, on relationship of yeasts and 
moulds to human disease, ref., 149 
Riocker and Schwalb, on epithelioma, ref., 
408 
Rickets, 891 
foetal, 896 
Ricketts, on blastomycosis, ref., 146; 
on immunity, 196; on infection in 
Rocky Mountain fever, 301 
Ricketts and Gomez, on Rocky Mountain 
spotted fever, 301 
Ricketts and Wilder, on Mexican typhus, 
301 
Riechelmann, on statistics of carcinoma, 
ref., 404 
Rieder, on leucocytosis, ref., 464 
Riesman, on Meckel's diverticulum, ref., 
667; on pulmonary oedema, ref., 595 
Rigor mortis, 988 
Ring worm, 148 
Ritchie, on bacteria in bronchitis, ref., 588; 
on cystic kidney, ref., 774; on im- 
munity, 196 
v. Ritook, on arterial hypoplasia, ref., 
1018 
Roberts, on pellagra, ref., 318 
Robertson, on tonsillar calculi, ref., 649 
Robin, on precipitin test, ref., 182 
Robinson, on pulmonary complications 
in typhoid fever, ref., 243 
Rocky Mountain spotted fever, 301 
Rodet, Lagriffoul, and Aly Wahby, on 
soluble poisons of typhoid bacillus, 
ref., 235 
Roentgen rays, injury from, 11 
Roger, on conditions of disease, ref., 14 
Roger and Garnier, on tuberculosis of 
thyroid, ref., 512 
Rolleston, on carcinoma of intestine, ref., 
690; on diseases of liver, ref., 725 
Rolleston and Crofton Atkins, on pyloric 
stenosis, ref., 655 
Rolleston and Hayne, on congenital 
cirrhosis, ref., 729 
Rolly and Liebermeister, on death of 
bacteria in small intestine, ref., 681 
Rosenau, on anterior poliomyelitis, ref., 
969; on coilodium sacs, ref., 319; on 
viability of B. tuberculosis, ref., 257 
Rosenau and Anderson, on anaphylaxis, 
ref., 190 
Rosenberger, on acid-fast bacteria, ref., 
267; on bacteriology of blood, ref., 470; 
on tuberculosis of mesenteric nodes, 
ref., 674 
Rosenheim, on acute diverticulitis, ref., 
668 
Rosenow, on blood cultures in pneumonia, 
ref., 606; on D. pneumoniae in blood, 
218; on experimental endocarditis, ref., 
545; on leucocytosis in pneumonia, 220 
Ross, on method of counting phagocytes, 
ref., 187 
Ross and Milne, on tick fever, ref., 293 
Round worms, 126 
Roux, on invisible microbes, ref., 319 
Rowley-Lawson, on malarial parasite, ref., 
311 
Ruckert, on bone in tonsil, ref., 649 
Russell bodies, 347 
Russell, B. R. G., on immunity to tumor 
transplantation, 355 
Russell, F. F., on ovarian cysts, ref., 836; 
on preventive inoculation in typhoid 
fever, ref., 246 
Russell and Fuller, on typhoid bacillus 
in water, ref., 245 
Russell, Batten, and Collier, on spinal- 
cord degeneration, ref., 963 
Rutimeyer, on Friedrich's ataxia, ref., 963 
Ruzicha, on theory of vital staining, ref., 
1027 
Sabouraud's medium, 149 
Saccharomyces, 146 
Sacerdotti, on hypertrophy of kidney, ref., 
747 
Sachs, on indurations of corpora caver- 
nosa penis, ref., 854 
Sacral region, tumor of, 359 
teratomata, 333 
Sago spleen, 500 
Sailer and Rhein, on eventration of dia- 
phragm, ref., 692 
Saliva, action of, on bacteria, ref., 150 1101 
INDEX 
Salivary glands, 699 
calculi in ducts of, 700 
ducts of, 700 
inflammation of, 699 
regeneration of, 72 
tumors of, 700 
mixed, 700 
Salpingitis, 839 
Salvetti, on congenital rickets, ref., 891 
Sanarelli, on B. icteroides, ref., 302 
Sand, intestinal, 691 
Saprophytes, 141 
Sarcina, 135 
Sarcocystis muris, 121 
Sarcoma, 366 
adeno-, 376 
alveolar, 375 
angio-, 374 
chondro-, 376 
cysto-, 375 
fibro-, 376 
giant-celled, 372 
glio-, 370, 388 
lipo-, 376 
lympho-, 370 
melano-, 370 
mixed forms, 375 
myelogenic, 901 
myeloid, 372 
myo-, 376 
myxo-, 376 
of adrenals, 517 
appendix vermiformis, 690 
arteries, 571 
bladder, urinary, 786 
bone, 900 
brain. 977 
bronchi, 591 
dura mater cerebralis, 911 
spinalis, 922 
ependyma, 927 
Fallopian tubes, 841 
heart, 556 
intestine, 690 
kidney, 776 
larynx, 585 
liver, 737 
lung, 634 
lymph-nodes, 498 
mamma, 850 
male, 867 
muscle, 875 
nerves, 979 
Sarcoma of nose, 581 
oesophagus, 653 
ovaries, 829 
pancreas, 706 
penis, 855 
pericardium, 522 
peritoneum, 697 
pharynx, 651 
pia mater cerebralis, 921 
spinalis, 923 
pleura, 641 
prostate, 866 
salivary glands, 700 
spinal cord, 977, 978 
spleen, 510 
testicle, 861 
thymus, 511 
thyroid, 514 
tongue, 646 
uterus, 813 
vagina, 797 
veins, 575 
vulva, 795 
osteo-, 373 
osteoid, 901 
parosteal, 901 
periosteal, 900 
round-celled, 369 
spindle-celled, 368 
transplantation of, in mice, 356 
Sarcoptes hominis, 131 
Sarcosporidia, 121 
Sauerbeck, on aggressins, ref., 153 
Savin poisoning, 422 
Sayer, on pneumonomycosis, ref., 147 
Scagliosi, on lesions of myocardium in 
diphtheria, ref., 283 
Scammony poisoning, 422 
Scarlatina, 306 
excitants of, 307 
Scarlet fever, 306 
Scars, post-mortem examination of, 990 
Schaffer, on islets of gastric mucosa in 
oesophagus, ref., 651; on plasma cells, 
ref., 74 
Scharlach R, injections of, effect of, 352 
Schaudinn, on entamoeba histolytica, 115; 
on Treponema pallidum, 119 
Schaudinn and Hoffmann, on Spiro- 
chaete pallida, 274 
Scharlach R stain for fat, 44 
v. Scheibner, on tonsils as portals of entry 
for tubercle bacilli, ref., 650 1102 
INDEX 
Schenck, on sporotrichosis, ref., 149 
Scheller, on influenza bacillus, ref., 233 
Schilder, on glioma of adrenal, ref., 517 
Schizomycetes, 133 
Schlagenhauf er, on sarcoma and car- 
cinoma in same breast, ref., 850 
Schlegel, on actinomycosis, ref., 232 
Schlesinger, on streptococcus haemolysis, 
ref., 209 
Schloss, on blood of children, ref., 461 
Schmidt, on amyloid tumors, ref., 646; on 
pathology of bone, ref., 903; on squa- 
mous epithelium in prostate, ref., 
866 
Schmidtmann, on carbonic oxide poison- 
ing, ref., 425 
Schmoll, on Stokes-Adams' disease, ref., 
550 
Schmorl, on embolism of chorionic cells, 
ref., 821; on staining fat, ref., 44; on 
technique, 1027 
Schnarrwyler, on phlegmonous gastritis, 
ref., 659 
Schone, on tissue transplantation, ref., 
78 
Schorr, on complex tumors of mouth, 
ref., 645 
Schottmuller, on S. mucosus capsulatus, 
ref., 221 
Schridde, on Giemsa's stain, 1037 
Schridde and Naegeli, on fixation of blood, 
ref., 467 
Schulte, Huntington, and Carmalt, on 
salivary glands, ref., 701 
Schultze, on crypts of Lieberkuhn, ref., 
682; on cyst of stomach, ref., 666; on 
degeneration of nervous system, 954; 
on lymphatic leukaemia, 462 
Schulze, on B. tuberculosis, ref., 257 
Schwalbe, on malformations, ref., 320 
Schwann, sheath of, 944 
Schwarz, on disappearance of bacteria 
from blood, ref., 151 
Scirrhus, 411 
Sclerose en plaque, 971 
Sclerosis, amyotrophic lateral, 956 
multiple, of brain, 971 
spinal cord, 973 
of brain, 971 
coronary arteries, 537 
spinal cord, 957 
posterior spinal, 957 
Scolex, 123 
Scorbutus, 437 
infantile, 438 
Scrofula 487 
Scrotum, cysts of, 855 
elephantiasis of, 855 
malformations of, 853 
teratoma of, 855 
tumors of, 855 
varicocele of, 856 
Scudder, on tuberculosis of breast, ref., 
846 
Scurvy, 437 
Sebileau, on orchitis, 860 
Secretions, internal, 427 
in acromegalia, 438 
Addison's disease, 433 
diabetes, 435 
exophthalmic goitre, 432 
myxcedema, 430 
Section cutting, 1034 
Seiffert, on rhabdomyoma of heart, ref., 
556 
Selective filtration, 86 
Seminal vesicles, lesions of, 863 
tumors of, 863 
Setter, on bacteria in healthy bodies, ref., 
150 
Senator, on polycythaemia, ref., 455 
Senility, ref., 36, 38 
Sensibilizing substance, 179 
Septicaemia, 152, 156, 203 
haemorrhagic, 289 
in diphtheria, 284 
plague, 288 
post-mortem changes, 204 
Septic sore throat, 211 
Septico-pyaemia, 204 
Sequestrum, 59 
of bone, 890 
Serum, 86 
antitoxic, 164 
collection of, for tests, 195 
diagnosis of syphilis, 277 
haemolytic, 172 
haemotoxic, 172 
hepatolytic, 174 
inactivated, 172 
injections of, in carcinoma, 356 
leucolytic, 174 
nephrolytic, 174 
neurolytic, 174 
of exudation, 86 
pancreolytic, 174 INDEX 
1103 
Serum, reactivated, 172 
spermatolytic, 174 
therapy, 192 
in diphtheria, 164 
meningitis, 226 
thyreolytic, 174 
Serum-sickness, 190 
Seven-day fever, 292 
Sex, relation of, to disease, 14 
relation of, to tumor growth, 344 
Shaw, on chyliform ascites, ref., 692 
Sheath of Schwann, 944 
Sherrington, on elimination of bacteria 
in secretions, ref., 151 
Shiga, bacillus of, 677 
Ship fever, 300 
Shipley and Fearnsides, on parasites, 
ref., 123 
Shober, on displacements of colon, ref., 
667 
Side-chain hypothesis of Ehrlich, 165 
Siderosis of lung, 616 
Silbermann, on sudden death following 
burns, ref., 10 
Silberschmidt, on peritonitis, ref., 694 
Siler and Garrison, on pellagra, ref., 318 
Simmons, on Hodgkin's disease, ref., 
495 
Simon, on blood, ref., 470; on resolution 
of exudate in pneumonia, ref., 606 
Sinus pocularis, dilatation of, 792 
Sittmann, on elimination of bacteria by 
kidney, ref., 761 
Skin, blastomycosis of, 146 
bronzed, 433 
in yellow fever, 302 
melano-sarcoma of, 372 
pigmentation of, in Addison's dis- 
ease, 433 
protective action of, against bac- 
teria, ref., 150 
tuberculosis of, 267 
Slaughter, on Haffkine method in plague, 
ref., 289 
Sleeping sickness, 118 
Smallpox, 303 
bacteria in, 304 
excitant of, 304 
immunization, artificial, in, 303, 
ref., 304 
protozoa in, 304 
vaccination in, 304 
Smegma bacillus, 267 
Smith, A. H., on carcinoma of thoracic 
duct, ref., 576 
Smith, Th., on adaptation of bacteria, 
ref., 160; on bacterial association in 
infection, ref., 157; on bovine tubercle 
bacillus, 260; on parasitism of B. tuber- 
culosis, ref., 262; on sarcosporidia in 
mice, ref., 121; on transmitted immu- 
nity, 196; on vaccines, ref., 186 
Sm th, W. H., on chronic adherent peri- 
carditis, ref., 520. 
Smith and Kilbourne, on Texas fever, 122 
Soaps, role of, in formation of fat in cells, 
ref., 40 
Sobernheim, on anthrax, 229; on Tr. 
pallidum, ref., 275 
Soda poisoning, 419 
Sodium sulphate in Muller's fluid, 1029 
Sokoloff, on adeno-carcinoma of liver, 
ref., 736 
Solar plexus, examination, post-mortem, 
of, 1018 
Somatochromes, 943 
Soor, 644 
Specimens, preservation of, in gross, 1039 
Spengler, on concurrent infection in 
tuberculosis, ref., 267 
Spermatocele, 857 
Spermolytic serum, 174 
Spider cells in glioma, 387 
Spina bifida, 326, 929 
Spinal apoplexy, 938 
cord, 928 
absence of, 928 
amyelia, 928 
apoplectic clots in, 938 
artefacts of, 928, 999 
arteries of, 933 
asymmetries of, 929 
atelomyelia, 928 
atrophy of muscle of, 955 
blood-vessels, lesions of, 942 
circulatory changes in, 933 
cysts of, 978 
degeneration of, 942 
diffuse, 963 
neurone in, 946 
primary, 955 
secondary, 953 
diastematomyelia, 928 
diplomyelia, 928 
distortions of, 929 
embolism of, 942 1104 
INDEX 
Spinal cord, examination, post-mortem, 
of, 999, 1025 
haemorrhage in, 938 
haematomyelia, 939 
haematomyelopore, 939 
heterotopia, 929 
false, 929 
hydromyelia, 929 
hydrorrhachis externa, ref., 929 
interna, 929 
inflammation of (see Myelitis), 
966 
injuries of, 931 
post-mortem, 999 
lesions of, in tabes, 958 
malformations of, 928 
morphology of, 942 
post-mortem changes in, 999 
preservation of, 1001 
removal, post-mortem, of, 999 
sclerosis of, 971, 973 
segments of, 1001 
spina bifida, 929 
structure of, 942 
syphilis of, 975 
syringomyelia, 978 
false, 940 
thrombosis of, 942 
tuberculosis of, 974 
tumors of, 977 
vascular changes in, 933 
vessel walls, lesions of, 942 
weight of, 1000 
nerve roots, anomalies of, 929 
paralysis, spastic, 955 
infantile, 967 
Spiremes, 65 
Spirillum, 119, 134 
cholerae asiaticae, 247, 249 
reproduction of, ref., 135 
toxic products of, 250 
fever, 292 
of Finkler and Prior, 250 
sputigenum, 251 
tyrogenum, 251 
Spirochaete, 119 
duttoni, 293 
in paresis, 972 
in tumors, 119 
obermeieri, 119, 292 
in spleen, 511 
pallida (see Treponema pallidum), 
119, 274 
Spirochaete pertenuis, 294 
recurrentis, 292 
refringens, 275 
Spleen, abscess of, 504 
accessory, 499, 1014 
anaemia of, 501 
atrophy of, 500 
cysts of, 510 
degeneration of, 500 
displacements of, 499 
embolism of, 502 
examination, post-mortem, of, 1013, 
1026 
haemorrhage in, 500 
hyperaemia of, 502 
hyperplasia of, 504, 508 
hypertrophy of, 62 
in infection, ref., 152 
leukaemia and pseudo-leukaemia, 
509 
malaria, 311 
relapsing fever, 292 
infarction of, 31, 502 
inflammation of (see Splenitis) 504 
lesions of, in cirrhosis of liver, 728 
in typhoid fever, 240 
malformations of, 499 
parasites of, 511 
pigmentation of, 501 
preservation of, 1014 
rupture of, 500 
sago, 500 
size of, 1014 
syphilis of, 506 
thrombosis in, 503 
tuberculosis of, 506 
tumors of, 510 
weight of, 1014, 1026 
wounds of, 500 
Splenectomy, in splenic anaemia, 480 
Splenic fever, 228 
Splenitis, chronic indurative, 505 
hyperplastic, 504 
peri-, 507 
suppurative, 504 
syphilitic, 507 
tuberculous, 507 
Splenomegaly, primary, 508 
Sporangium, 147 
Spores, in bacteria, 136 
yeast, 146 
Sporotrichosis, 149, 232 
Sporotrichum, Beurmanni, 149 INDEX 
1105 
Sporotrichum, Gougeroti, 149 
Jeanselmei, 149 
Schencki, 149 
Sporozoa, 115, 120 
Spotted fever, 300 
Rocky Mountain, 301 
Sputum, methods of staining, 
258 
Staining methods, 1035 
Staphylococcus cereus, 208 
epidermis albus, 208 
pyogenes albus, 208 
pyogenes aureus, 205 
salivarius pyogenes, 208 
Starck, on diverticula, ref., 639 
Starling, on internal secretions, ref., 
427 
St. Arnold, on bony tumors of breast, 
ref., 848 
Stasis, 19 
Status lymphaticus, 439 
Stdubli, on animal parasites in blood, ref., 
470 
Steele, on sarcoma of peritoneum, ref., 
698 
Stegomyia calopus, 302 
Steinhaus, on liver infarcts, ref., 713 
Stengel, on Stokes-Adams' disease, ref., 
550 
Stenosis of aorta, 552 
mitral valve, 553 
pylorus, 654, 662 
right heart, 553 
Stepanow, on celloidin embedding, 1032 
Sterling, Anderson, and Rosenau, on 
anaphylaxis, ref., 190 
Stern, on malignant tumors in childhood, 
416 
Sternberg on " Bacillus X," ref., 302; on 
blastomycosis, ref., 146; on chloroma, 
ref., 376; on lesions of bronchial lymph- 
nodes, ref., 592; on tuberculosis of 
lymph-nodes, ref., 491 
Stiles, on dissemination of carcinoma of 
the breast, ref., 851 
Stillman, on oedema of pia arachnoid, ref., 
913 
Stimson, on preventive inoculations in 
hydrophobia, ref., 298 
Stimulins, 181 
Stober, on blastomycosis, ref., 146 
Stokes, on cysts of vagina, ref., 797 
Stokes-Adams' disease, 549 
Stomach, 654 
absence of, 654 
atrophy of, 656 
bacteria of, ref., 659 
cadaveric changes in, 655 
cysts of, 666 
degenerations of, 656 
dilatation of, 662 
displacement of, 662 
erosions, haemorrhagic of, 662 
etat mamelonne, 657 
examination, post-mortem, of, 655, 
1003, 1015, 1026 
foreign bodies in, 667 
haemorrhage in, 655, 662, 728 
hair balls in, 667 
inflammation of (see Gastritis), 656 
injuries of, 655 
malformations of, 654 
malpositions of, 654 
preservation of, 1016 
rupture of, 655 
syphilis of, 659 
tuberculosis of, 659 
tumors of, 662 
ulcers of, 660 
Stomatitis, aphthous, 644 
catarrhal, 643 
chronic, 644 
croupous, 644 
gangrenous, 644 
parasitic, 644 
phlegmonous, 644 
syphilitic, 644 
tuberculous, 644 
ulcerative, 644 
Stones, lung, 592 
Stramonium poisoning, 425 
Strangulation, 9 
death from, 443 
Straus, on infantile paralysis, ref., 969; 
on tuberculosis, 268; on eclampsia, 
ref., 718 
Strawberry marks, 394 
Streptobacilli, 135 
Streptococci, 135 
anaerobic, ref., 210 
Streptococcus antitoxin, 211 
brevis, 209 
capsulatus, 209 
epidemicus, 211 
erysipelatis, ref., 212 
in intestine, 678 1106 
INDEX 
Streptococcus longis, 209 
mucosus capsulatus, 209, 221 
in pneumonia, 221 
phagocytosis of, 211 
pyogenes, 209 
agglutination of, ref., 210 
artificial immunity to, 211 
bibliography of, ref., 211 
in inflammation, 88 
viridans, 209 
Streptothrix, 136 
Stricture of appendix, 686 
rectum, 684 
urethra, 790 
Stroma reaction in tumors, 355 
Strong, on amoebic dysentery, ref., 116 
Strongylus gigas, 128 
in kidney, 781 
longevaginatus, 128 
subtilis, 128 
Struma, 513 
ovarii, 836 
Strumitis, 512 
v. Strumpet, on primary acute polymyo- 
sitis, ref., 874 
Strychnin poisoning, 424 
Stuhlern, on B. mucosus capsulatus, 
ref., 216 
Subinfection, ref., 151 
Sublimate, corrosive, as fixative, 1030 
poisoning, kidney in, 51, 750, 753 
Sublingual gland, inflammation of, 700 
tumors of, 700 
Submaxillary gland, inflammation of, 700 
Substance sensibilisatrice, 179, 183 
Suctoria, 115 
Sudan III, stain for fat, 44 
Suffocation, 9, 442 
Suggillations, 21 
Sulphuric acid, 417 
Sunstroke, 437 
Suppuration, 89, 94, 198 
Suprarenal bodies (see Adrenals), 515 
capsules (see Adrenals), 515 
Surra, 118 
Susceptibility to disease, 14 
Sutton, introduction to general pathol- 
ogy, 416 
Swelling, cloudy, 39 
white, 25 
Symbiosis, 142 
Symmers, on necrosis of liver, ref., 715 
Syncytium, 820 
Synophthalmia, 325 
Synotia, 321 
Syphilis, 270 
and tabes dorsalis, 9G2 
animal inoculations in, 274 
congenital, 273 
of bone, 888 
constitutional, 272 
diagnosis of, 274 
dioxydiamidoarsenobenzol in, 119 
immunization in, 275 
luetin test, 281 
of adrenals, 516 
arteries, 567 
bone, 881, 888 
brain, 975 
bronchi, 589 
dura mater cerebralis, 911 
endometrium, 807 
Fallopian tubes, 840 
heart, 542 
intestine, 674 
kidney, 770 
larynx, 584 
liver, 730 
lung, 633 
lymph-nodes, 488 
lymph-vessels, 577 
mamma, 846 
mouth, 644 
muscle, 875 
nervous system, 975 
nose, 580 
oesophagus, 653 
ovary, 829 
pancreas, 706 
penis, 854 
periosteum, 881 
pia mater cerebralis, 919 
placenta, 823 
rectum, 683 
spinal cord, 975 
stomach, 659 
testicle, 860 
thymus, 511 
thyroid, 512 
urethra, 792 
vagina, 797 
veins, 575 
primary, 271 
secondary, 272 
serum diagnosis of, 277 
spirochetes in, 119,274 INDEX 
1107 
Syphilis, Spirochaete pallida in, 119, 274 
tertiary, 272 
Treponema pallidum in, 119, 274 
Wassermann reaction, 277 
Syringomyelia, 978 
false, 940 
Tabardillo, 301 
Tabes dorsalis, 957 
lesions of nerves in, 957, 958 
syphilis, relation of, 962 
Taenia cucumerina, 126 
echinococcus, 124 
flavopunctata, 127 
madagascariensis, 127 
mediocanellata, 124 
nana, 126 
saginata, 124 
solium, 123 
Talipes, 326 
Talipomanus, 326 
Tape worms, 123 
Tartar emetic poisoning, 422 
Tartaric acid, 419 
Tattoo marks, 990 
Tawara, on abnormal chordae tendinae, 
ref., 525 
Tavel and Lanz, on peritonitis, ref., 
694 
Taylor, on auto-intoxication, ref., 426; on 
fatty degeneration, ref., 40; on poisons, 
425; on volvulus of Meckel's diverticu- 
lum, ref., 667 
Tchistovitch, on crisis in pneumonia, ref., 
606 
Tendeloo, on retroperitoneal lymph- 
nodes, ref., 697 
Teratoids, 333 
Teratoma, 334, ref., 345, 358 
of liver, 737 
muscle, 875 
ovary, 836 
pineal gland, 980 
scrotum, 855 
testicle, 863 
vagina, 797 
sacral, 333 
Terminal infection, 158 
Terry, on chemical therapy in trypano- 
somiasis, ref., 118 
Testicle, 855 
abscess of, 857 
absence of, 855 
Testicle, atrophy of, 857 
chorionepithelioma of, 822, 863 
cryptorchismus, 856 
cysts of, 861, 863 
epididymitis, 858 
examination, post-mortem, of, 1019 
haematocele, 857 
hydrocele, 856 
hypertrophy of, 62 
inflammation of (see Orchitis), 857 
leprosy of, 860 
malformations of, 855 
malpositions of, 856 
parasites of, 863 
regeneration of, 73 
spermatocele, 857 
syphilis of, 860 
teratoma of, 863 
tuberculosis of, 858 
tumors of, 860 
varicocele, 856 
weight of, 1019 
Tetano-toxin, 286, 287 
Tetanus, 286 
antitoxin, 165 
theory of, 165 
diagnosis of, 287 
in animals, 286 
lesions of, 286 
Tetany following removal of para- 
thyroids, 514 
Tetrads, 135 
Texas fever, haematozoon of, 122 
Thacher, on melanuria, 372 
Thalhimer and Rothschild, on myocarditis 
in relation to Aschoff nodules, ref., 538 
Thayer, on malarial nephritis, ref., 761; on 
venous thrombosis in typhoid fever, 
ref., 243 
Thayer and Hewetson, on malaria, ref., 
316 
Thionin stain, 1038 
Thoma, on arterio-sclerosis, ref., 554, 565; 
on conditions of disease, ref., 14; on 
fissures in cervical region, ref., 647; on 
hypertrophy, ref., 747; on inflamma- 
tion, ref., 110; on malformations, ref., 
320; on waxy degeneration of muscle, 
ref., 872 
Thoma's frog plates, 111 
Thomas and Hibbard, on lesions of myo- 
cardium in diphtheria, ref., 283 
Thompson, on parathyroids, ref., 514 1108 
INDEX 
Thompson and Leighton, on transplanta- 
tion of parathyroids, ref., 515 
Thoracic duct, examination, post-mor- 
tem, of, 1018 
lesions of, 576 
Thoracopagus, 329 
Thorax, examination, post-mortem, of, 
1001, 1024 
Thorel, on lesions of oesophagus, ref., 654; 
on lesions of salivary glands, ref., 700; 
on lesions of stomach, 666; on regenera- 
tion of kidney epithelium, ref., 748. 
Threadworm, 128 
Throat, septic, 211 
Thrombi, 24 
agglutinative, 26 
in liver, 715 
alterations, in, 27 
arterial, 26 
canalized, 26 
causes of, 24 
degeneration of, 27 
forms of, 24, 26 
hyaline, 27, 48 
infective, 26 
marasmatic, of liver, 711 
marantic, 25 
micro-organisms in formation of, 
ref., 25 
mixed, 24 
obstructing, 26 
organization of, 27, 95 
parietal, 26 
primary, 26 
propagated, 26 
red, 24 
secondary, 26 
simple, 26 
softening of, 27 
solid, 26 
stagnation, 25 
venous, 26 
role of micro-organisms in, ref., 25 
white, 24 
Thromboarteritis, 559 
Thrombokinase, 452 
Thromboplastin, 453 
Thrombosis, 24 
causes of, 24, 25 
effects of, 27 
of adrenals, 516 
brain, 940 
coronary arteries, 537 
Thrombosis of dura mater cerebralis, 908 
heart, 531 
kidney, 748 
liver, 711, 714, 715 
lung, 596 
lymph-vessels, 28, 576 
spinal cord, 942 
splenic vein, 503 
veins, 573 
Thrush, 147, 644 
Thymus, 511 
accessory, 511 
examination, post-mortem, of, 1025 
haemorrhage in, 511 
hypertrophy of, 511 
inflammation of, 511 
in status lymphaticus, 440 
malformations of, 511 
new-born, size and weight of, 1025 
syphilis of, 511 
tuberculosis of, 511 
tumors of, 511 
Thyreolytic serum, 174 
Thyroid, 512 
accessory, 512 
degeneration of, 512 
examination, post-mortem, of, 1010, 
1025 
extract in myxoedema, 430 
foetal adenoma of, 398, 432 
goitre, 513 
hyperaemia of, 512 
hyperplasia of, 513 
hypertrophy of, 62 
in Graves' disease, 432 
in myxoedema, 429 
inflammation of, 512 
malformations of, 512 
para-, 514 
parasites in, 514 
regeneration of, 72 
syphilis of, 512 
tissue in ovary, ref., 836 
transplantation of, ref., 78, 429 
tuberculosis of, 512 
tumors of, 513, 514 
weight of, 1011, 1025 
Tic douloureux, 974 
Tick fever, 293, 301 
of cattle, haematozoon of, 122 
Tidy, on post-mortem examination, ref., 
989 
Tilger, on cysts of pancreas, ref., 707 INDEX 
1109 
Tinea circinata, 148 
Tischner, on experimental closure of 
hepatic artery and gall-ducts, ref., 711 
Tissue, calcification in, 51 
changes, regressive, 35 
cicatricial, 93 
fixation of, 1029 
rapid, 1028 
fresh, method of staining, 1027 
frozen section of, 1028 
method of preparation and staining, 
980, 1027 
granulation, 92 
necrotic, disposal of, 59 
non-vascular, injury to, 82 
tension, 79 
transplantation of, 77 
vascular, injury to, 83 
Todd and Wolbach, on tick fevers, ref., 293 
Tongue, 645 
absence of, 645 
cysts of, 646 
"furred," 646 
hypertrophy of, 646 
inflammation of, 646 
malformations of, 645 
tumors of, 646 
Tonsil, calculi of, ref., 649 
hypertrophy of, 649 
inflammation of, 649 
leptothrix in crypts of, 232 
portal of entry for tubercle bacilli, 
ref., 650 
tuberculosis of, ref., 650 
Tonsillitis, 649 
Tooth, on degeneration of spinal cord, 
954 
Tophi, 436 
Toxaemia, 153, 202 
Toxalbumins, 152 
Toxalbumose, 152 
Toxin, binding of, ref., 167 
diphtheria, 164 
fixing of, ref., 167 
molecule, character of, 167 
of Asiatic cholera, 250 
diphtheria, 285 
tetano-, 286, 287 
Toxins, 152 
action of, on neurones, 948 
bacterial, 139 
cellular, ref., 152 
haemo-, 171 
Toxoids, ref., 167 
Toxophorous group, 167 
Trachea, 581 
amyloid masses in, 586 
death from pressure on, 592 
examination, post-mortem, of, 1011 
lesions of, 585 
malformations of, 581 
preservation of, 1011 
tumors of, 585 
Trachoma, 307 
bodies, 308 
granules, 308 
Tracy, on microchemical reactions for 
iron, ref., 53 
Transplantation of organs, 78 
of tissue, 77, 354 
autoplastic, 77 
homoplastic, 77 
of tumors, 354 
technique of, 356 
Transudates, 23 
Transudation, 22 
Trauma, 11 
Trematoda, 123 
Trepinski, on tabes dorsalis, 962 
Treponema pallidum, 119, 274 
demonstration of, 275 
India ink stain, 277 
in paresis, 972 
staining methods, 275 
pertenuis, 294 
Trichina spiralis, 129 
in lymph-nodes, 498 
muscle, 875 
examination of, 131 
Trichiniasis, 130 
Trichocephalus dispar, 128 
Trichomonas vaginalis, 119, 797 
Trichophyton tonsurans, 148 
Triplets, 327 
Trypanosomes, 116 
brucei, 118 
evansi, 118 
gambiense, 118 
lewisi, 117 
pathogenic, 117 
Trypanosomiasis, 117 
Tsetse-fly, 118 
Tubal pregnancy, 841 
Tubercle, 251 
bacillus (see B. tuberculosis), 251, 
257 1110 
INDEX 
Tubercle, conglomerate, ref., 251 
development of, 254 
diffuse, 255 
foreign-body, 102 
forms of, 255 
granulum, ref., 251 
"healed," 622 
miliary, 251, 252, 621, 640 
polyhedral-celled, 255 
solitary, of liver, 733 
tissue, ref., 252 
Tuberculin, diagnostic use of, 261 
therapeutic use of, 262 
Tuberculosis, 251 
agglutination in, 261 
and cancer, ref., 267 
animal, 263 
autopsy findings in, ref., 263 
bacillus of, 251, 257 
bibliography of, 268 
bovine, infection of children with, 
ref., 266 
complex factors in, 262 
concurrent infection in, 266 
diffuse, 252, 255 
dust infection in, 265 
frequency of, 263 
immunity in, 262 
lesions of, 251 
"localized," 251 
lymphoid, 255 
miliary, generalized, 252 
localized, 251 
necrosis, coagulation in, 254 
of adrenals, 516 
appendix vermiformis, 686 
arteries, 566 
bladder, urinary, 786 
bone, 882, 887 
brain, 974 
bronchi, 589, 591 
dura mater cerebralis, 911 
spinalis, 922 
Fallopian tubes, 840 
heart, 542 
ileo-caecal region, 682 
intestine, 673 
joints, 906 
kidney, 769 
larynx, 584 
liver, 731 
lungs, 618 
experimental, 631 
Tuberculosis of lymph-nodes, 486, 265 
lymph-vessels, 577 
mamma, 845 
mouth, 644 
muscle, 875 
nervous system, 911, 922, 923, 
974 
nose, 580 
oesophagus, 653 
ovary, 829 
pancreas, 706 
parotid, 700 
penis, 854 
pericardium, 521 
peritoneum, 695 
periosteum, 882 
pharynx, 649 
pia mater cerebralis, 918 
spinalis, 923 
pleura, 640 
prostate, 866 
seminal vesicles, 863 
skin, 267 
spinal cord, 974 
stomach, 659 
testicle, 858 
thymus, 511 
thyroid, 512 
urethra, 792 
uterus, 806 
vagina, 797 
veins, 575 
predisposition in, ref., 252 
pulmonary, 618 
and pigmentation, 641 
apex in, 631 
broncho-, 624 
cavities in, 626, 628 
classification of, 619 
complex forms of, 627 
concurrent infection in, 631 
diffuse, 627 
distribution of lesions in, 630 
experimental, 631 
exudative, 627 
fibrous tissue formation in, 630 
flies, as carriers of, ref., 151 
focal, 619 
healing in, 630 
miliary, acute, 619 
chronic, 622 
modes of infection, in, 618, 620 
641 INDEX 
1111 
Tuberculosis, pulmonary, secondary le- 
sions in, 629 
statistics of, ref., 263 
tuberculin, 261 
Tubes of Miescher, 121 
Rainey, 121 
Tubo-abdominal pregnancy, 842 
Tumors, 336 
age as factor in growth of, 344 
anaplasia in, 351 
autonomy of, 337 
bacteria in, 347 
benign, 342 
bibliography of, 416 
biological origin of, 347, 350 
cachexia of, 343 
cell anarchy in, 337 
cell inclusions in, 347 
characters of, 336 
classification of, 357 
Lubarsch's, 359 
congenital, 358 
connective-tissue type of, 357 
degenerative processes in, 339 
diagnosis of, 343 
dissemination of, 341 
epithelial tissue type, 358 
etiology of, 344 
excitants of, 347 
intrinsic, 350 
extensions of, 340 
fixation of tissue, 362 
heredity, bearing of, on, 344, 354 
immunity, artificial, to, 356 
local predisponents to, 346 
malignancy of, 342 
malignant, 342 
metastasis of, 341, 350 
metastatic, 341 
micro-organisms as excitants of, 347 
mixed, 358; 
of parotid gland, 700 
muscle tissue type, 357 
nature and characters of, 336 
occurrence and growth of, 344 
origin of, 344 
Cohnheim's hypothesis, 346, 
351 
Ribbert's hypothesis, 351 
parasitic, 347, 355 
protozoa in, 347 
seats of (see under various tissues 
and viscera, and types of tumors) 
Tumors, serum injections in, 356 
sex factor in growth of, 344 
shape of, 340 
size of, 340. 
splenic, 504 
stroma reaction in, 355 
technique of fixation of, 362 
transplantation of, 356 
tissue types in, 338 
transplantation of, 354 ,356 
trauma as factor in occurrence of, 345 
vascular tissue type, 358 
yeasts in, 349 
Turk, on "irritation forms" of leucocytes 
462; on leucocytosis, 464 
Turner, on sarcoma of pia mater and 
spinal cord, ref., 977; on tumor of 
pineal gland, 980 
Turpentine poisoning, 422 
Tuttle, on streptothrix pneumonia, ref., 
232 
Twins, 327 
Typhoid carriers, 245 
fever, 234 
bacillus of, 235 
bibliography of, 247 
blood in, 463 
experimental, 235 
flies as carriers of, ref., 151, 245 
immunity to, 245 
lesions of, 235 
appendix vermiformis 
in, 685 
circulatory organs in, 
in, 242 
digestive organs in, 242 
genito-urinary organs 
243 
intestines in, 235 
liver in, 241 
lymph-nodes, mesen- 
teric, in, 240 
lymph-nodules in, 235 
nervous system in, 243 
Peyer's patches in, 235 
respiratory organs in, 
243 
spleen in, 240 
mixed infections in, 244 
para-, 247 
preventive inoculations in, 245 
secondary lesions in, 242 
septicsemic forms of, 243 1112 
INDEX 
Typhoid fever, toxaemia in, 241 
ulceration of intestine in, 237 
meningitis, ref., 243 
Typhus fever, 300 
Mexican, 301 
lice as agents of infection in, 
301 
mouse, bacillus of, 289 
recurrens, 292 
Tyzzer, on Coccidium oviforme, ref., 121 
Uffenheimer, on permeability, of intestine 
wall for bacteria, ref., 681 
Uffreduzzi, on histology of undescended 
testicle, ref., 856 
Uhlenhuth and Weidanz, on precipitin 
tests, ref., 182 
Ulceration, 58 
of intestine in typhoid fever, 237 
Ulcers, 58 
of intestine, 237, 674, 675, 681, 682 
mamma, 846 
mouth, 644 
oesophagus, 651 
penis, 854 
stomach, 660 
urethra, 792 
phagedenic, of uterus, 803 
Ullmann, on tonsils, ref., 650 
Umbilicus, tumors of, 699 
Uncinaria americana, 128 
duodenalis, 128 
Uncinariasis, 128 
Unna's glycerin-ether mixture, 278 
polychrome methylene-blue stain, 
1037 
Urachus, malformations of, 782 
Ureter, carcinoma of, ref., 788 
cysts of, 774 
inflammation of, 771 
malformations of, 746 
Urethra, cysts of, 792 
dilatation of, 790 
examination, post-mortem, of, 1018 
gonorrhoea of, 792 
haemorrhoids of, 792 
inflammation of (see Urethritis), 791 
malformations of, 790 
malpositions of, 790 
perforations of, 792 
polyps of, 792 
prolapse of, 791 
rupture of, 791 
Uretha, strictures of, 790 
syphilis of, 792 
tuberculosis of, 792 
tumors of, 792 
wounds of, 791 
Urethritis, catarrhal, 791 
chronic, 792 
croupous, 792 
syphilitic, 792 
tuberculous, 792 
Urinary organs, 746 
Urine, typhoid bacilli in, 244, 245 
Uterus, 797 
absence of, 797 
atrophy of, 803 
bacteria in, ref., 804, 809 
bicornis, 798 
chorionepithelioma of, 820 
chorionic villi, 820 
cysts of, 822 
degenerations of, 803 
dilatation of, 799 
displacements of, 800 
double, 798 
elevation of, 801 
enlargement of, 799 
examination, post-mortem of, 1019, 
1026 
flexions of, 800 
haematocele, 803 
haematoma, polypoid, of, 803 
haematometra, 800 
haemorrhage of, 802 
hernia of, 802 
hour-glass, 799 
hydrometra, 799 
hyperaemia of, 802 
hyperplasia of mucous membrane, 
glandular, 805 
infantile, 1020 
inflammation of (see Endometritis 
and Metritis), 804, 807 
inversion of, 802 
Langhans' cells, 820 
malformations of, 797 
malpositions of, 800 
parasites of, 822 
perforation of, 802 
placenta, lesions of, 822 
polyps of, 803, 810 
position of, 1019 
pregnant, inflammation of, 808 
prolapse of, 801 INDEX 
1113 
Uterus, rupture of, 802 
size of, 1020 
changes in, 798 
syncytium, 820 
syphilis of, 807 
tuberculosis of, 806 
tumors of, 809 
ulcer, corroding, of, 803 
versions of, 800 
weight of, 1020 
Vaccination, 304 
Vaccine bodies, 305 
Vaccines, bacterial, 186 
in acute lobar pneumonia, 220 
pneumococcal, 220 
Vaccinia, 304 
Vacuole, 45 
Vacuolization, 45 
Vagina, 795 
absence of, 795 
bacteria in, 79; ref., 804 
closure of, 795 
cystocele, 795 
cysts of, 797 
dilatation of, 795 
double, 795 
examination, post-mortem, of, 1019 
fistula: of, 796 
gangrene of, 797 
hernia of, 795 
inflammation of (see Vaginitis), 
796 
lengthening of, 795 
malformations of, 795 
malpositions of, 795 
narrowing of, 795 
parasites in, 797 
perforation of, 796 
prolapse of, 795 
syphilis of, 797 
tuberculosis of, 797 
tumors of, 797 
wounds of, 796 
Vaginitis, 796 
catarrhal, 796 
gangrenous, 797 
suppurative, 797 
syphilitic, 797 
tuberculous, 797 
Valsalva, sinus of, aneurism of, 530 
Van Gehuchten, on nervous system, ref., 
942 
Van Gieson, on artefacts of nervous 
system, ref., 928; on haematomyelopore, 
ref., 939; on post-mortem examination 
of brain, ref., 998; on sunstroke, 437 
Van Gieson's picro-acid-fuchsin stain, 
1035; stain for Negri bodies, ref., 297 
Varices, oesophageal, 651 
Varicocele, 856 
Variola, 303 
Varix aneurismal, 569 
lymphatic, filarial, ref., 130, 576 
Vaughan, on alkaloidal poisons, ref., 
425; 
on spread of typhoid, ref., 245 
Vaughan and Novy on cellular toxins, ref., 
152 
de Vecchi, on tuberculosis of adrenals, ref., 
434 
Vedder, on beri-beri, ref., 318 
Vein stones, 27 
Veins, 572 
anastomosis of, 18 
calcification of, 573 
degeneration of, 573 
dilatation of, 572 
about umbilicus, in cirrhosis, 
728 
hepatic lesions of, 714 
inflammation of (see Phlebitis), 573 
obstruction of, 18 
parasites of, 575 
perforation of, 573 
portal lesions of, 711 
rupture of, 573 
syphilis of, 575 
thrombosis of, 573 
tuberculosis of, 575 
tumors of, 575 
umbilical, lesions of, 712 
varicose, in labia, 793 
wounds of, 573 
Veit, on chorionic cells, ref., 821 
Vena cava, thrombosis of, 573 
Venom, animal, 153, 424 
Ventricles of brain, lesions of, 924, 925 
tumors of, 927 
Veratria poisoning, 422 
Verploegh, Kehr er, and v. Hoogenhuyze, on 
Hodgkin's disease, ref., 497 
Vibrio cholerae asiaticae, 247, 249 
Massawah, 251 
Metschnikovi, 251 
proteus, 250 1114 
INDEX 
Vierordt, on weight of viscera, etc., ref., 
990 
Vincent, on angina, ref., 293 
Vincent's angina, 293 
Vincent, on internal secretions, ref., 427 
Virchow, on tumors, 416 
Virus, fixed, 295, 297 
of hydrophobia, 295 
Viscera, changes in, following extensive 
burns, ref., 10 
weight of, ref., 990 
Vitamines, 318 
Vogel, on accessory lung, ref., 593 
V olkmann, on mixed tumors of salivary 
glands, ref., 701 
Voluntary muscle, 868 
Volvulus of intestine, 668 
Meckel's diverticulum, ref., 667 
Von Jaksch anaemia, 479 
Von Pirquet and Schick, on anaphylaxis, 
191 
von Volkman, on endothelioma, ref., 380 
Voss, on B. pyocyaneus, ref., 215 
Vulva, 793 
condyloma of, 794 
cysts of, 795 
elephantiasis of, 794 
erysipelas of, 794 
examination, post-mortem, of, 1019 
gangrene of, 794 
haemorrhage of, 793 
hyperaemia of, 793 
inflammation of, 793 
malformations of, 793 
noma of, 794 
oedema of, 793 
syphilis of, 794 
tuberculosis of, 794 
tumors of, 794 
varicose veins in, 793 
Vulvitis, 793 
Wachenheim, on pyloric stenosis, ref., 655 
Wadsworth, on experimental pneumonia, 
218; ref., 614; on mouth disinfection, 
ref., 219; on pneumococcus infection, 
ref., 220; on puerperal infection, ref., 
809; on staining D. pneumoniae, ref.. 
218; on staining encapsulated pneumo- 
cocci, ref., 220 
Wagener, on intestinal tuberculosis, ref.. 
674 
Walker, on renal tuberculosis, ref., 770 
Walker and Swijt, on Wassermann re- 
action, ref., 278 
Waller, law of, 947 
Ward, on influence of parasites on host, 
ref., 123; on thyroid and pregnancy, 
ref., 512 
Warfield, on carcinoma of male breast, 
ref., 867; on meningococcus endocar- 
ditis, ref., 545 
W arrington, on structural alterations in 
nerve cells, 948 
Warthin, on accessory adrenals, ref., 515; 
on carcinoma of gall-ducts, ref., 743; 
on emboli, 29; on fatty degeneration of 
heart, ref., 535; on haemolymph-nodes, 
ref., 497; on multiple carcinoma, ref., 
404; on pancreas, ref., 706 
Warthin and Cowie, on placental and 
congenital tuberculosis, ref., 265 
W aschkewitsch, on lesions of diphtheria, 
ref., 283 
Washbourn, on infective endocarditis, 
ref., 545 
W asielewski, on vaccine bodies, ref., 305 
Wassermann, on congenital transmission 
of infectious agents, ref., 151; on mixed 
infections, ref., 157; on nature of infec- 
tion, ref., 156; reaction in syph- 
ilis, 277 
Watson, on Negri bodies, ref., 296 
Watters, on preparation of museum 
specimens, ref., 1039 
Watzold, on adenoma of liver, ref., 736 
Weaver, on agglutination of streptococci, 
ref., 210; on anaphylaxis, ref., 190 
Weber, on changes in the blood, ref., 456 
Wechsberg, on action of tubercle bacil- 
lus, ref., 253 
Weichselbaum and Ghon, on meningo- 
coccus, ref., 225 
Weidenreich, on fixation of blood, ref., 
467; on lymph-nodes, ref., 73; on 
lymph-nodes, ref., 481; on plasma cells, 
ref., 74 
Weigert, on immunity, 196; on origin of 
tumors, ref., 351; on tumor of hypo- 
physis cerebri, 980; on tumor of pineal 
gland, 980 
Weigert's stain for bacteria, 144 
stain for nerve tissue, 981 
Weil, on anaphylaxis, 191 
Weinberg, on tuberculosis and cancer, 
ref., 267 INDEX 
1115 
Weir, on duodenal ulcers, 675 
Weiss, on bacteria in stomach, ref., 659; 
on intestinal bacteria, ref., 681 
Welch, on adaptation in pathological 
processes, ref., 110; on agglutinative 
thrombi, ref., 27; on B. aerogenes cap- 
sulatus, 289, 290; on bacteria of body 
surfaces, ref., 150; on cardiac hyper- 
trophy, ref., 550; on carcinoma of 
stomach, 664; on cirrhosis hepatic 
anthracotica, ref., 730; on fat embolism, 
ref., 469; on gastric ulcer, 660; on im- 
munity, 196; on pulmonary oedema, 
ref., 595; on staining D. pneumoniae, 
220; on thrombosis and embolism, 
ref., 28; on venous thrombosis, ref., 
573 
W eleminosky, on bronchial lymph-nodes, 
ref., 592 
Welker, on technique of opsonic work, 
ref., 188 
Weller, on carcinoma of bronchi, ref.,591 
Wells, on autolysis, ref., 60, 107; on calci- 
fication, ref., 52; on chemical pathology 
ref., 426; on fat necrosis of pancreas, 
:ef., 704; on infarcts, ref., 30; on nutri- 
tion, 9; on proteolytic enzymes, ref., 
103 
Wells and Scott, on paratyphoid, ref., 
247 
Werigo, on disposal of bacteria in blood, 
ref., 151 
Westenhoeffer, on cerebro-spinal menin- 
gitis, ref., 225; on mode of infection 
by B. tuberculosis, ref., 264; on 
plethora, ref., 455 
Wharton's duct, dilatation of, 700 
Wheeler, on viability of typhoid bacillus, 
ref., 245 
Whipham, on carcinoma of appendix 
vermiformis, ref., 690; on mediastinitis, 
ref., 636 
Whipple, on intestinal lesions in typhoid 
fever, ref., 240; on nodular colitis, ref., 
680 
Whipple and Sperry, on chloroform liver 
necroses, 716 
Whipworm, 128 
White, on blood in septicaemia, ref., 205; 
on S. pyogenes aureus in skin lesions, 
ref., 208; on toxaemia of pregnancy, 
ref., 718 
"White swelling," 25 
Whooping-cough, 317 
Wichmann, on amyloid degeneration 
ref., 50 
Wiener, on melano-sarcoma of rectum, 
ref., 690 
Wiesel, on arterio-sclerosis, ref., 564; on 
lesions of coronary arteries, ref., 537 
Wiesner, on lesions of coronary arteries, 
ref., 537 
Wilder, on sarcoma of bladder, ref., 786 
Williams, on B. diphtheriae, ref., 285; on 
bacteriology of vagina, ref., 804; on 
placental infarcts, ref., 823; on plasma 
cells, ref., 74; on sarcoma of pericar- 
dium, ref., 522 
Williams and Lowden, on parasites of 
scarlatina, ref., 307; on staining Negri 
bodies, 296 
Willis, circle of, 933 
Wilms, on teratoma of ovary, ref., 837; on 
teratoma of testicle, ref., 863 
Wilson, on cell development, ref., 68; on 
mitosis, ref., 67 
Wilson and Chowning, on infective agent 
in Rocky Mountain fever, 301 
Wilson and Kalteyer, on melano-sarcoma 
of skin, ref., 372 
Wilson and Willis, on mixed tumors, ref., 
701; on tumors of kidney, ref., 777 
Winkler, on cysts of appendix, ref., 686; 
on tuberculosis in children, ref., 263 
Winternitz, on tuberculosis of spleen, ref. 
507 
Witte, on perforation of aorta, ref., 557 
Wladimiroff, on characters of glanders 
bacillus, ref., 227 
Wohlgemuth, on ferments, ref., 139 
Woglom, on tumors, ref., 68 
Wolbach and McKee, on trachoma bodies, 
ref., 308 
Wolbach, on filterable viruses, ref., 134; 
on lesions in x-ray examinations, 
ref., 11; on rhabdomyoma of heart, 
ref., 556 
Wolbach and Ernst, on bovine tubercle 
bacillus, ref., 260 
Wolff-Eisner, on anaphylaxis, 191 
Wollstein, on bacilli from whooping- 
cough, ref., 317; on B. influenzae, ref., 
234; on tuberculosis in children, ref., 
265 
Wollstein and Meltzer, on experimental 
pneumonia, ref., 614 1116 
INDEX 
Wood, F. C., on blood, ref., 470; on D. 
pneumoniae, ref., 219; on poisoning by 
nitric acid fumes, ref., 418; on stain for 
blood, 317; on viability of D. pneu- 
moniae, 218; on tumors of salivary 
glands, ref., 380 
Wood, G. B., on faucial tonsils, ref., 649; 
on tonsils as portals of entry for 
tubercle bacilli, ref., 650; on tuber- 
culosis of parotid, ref., 700 
Woodman and Tidy, on poisons, 425 
Wool sorter's disease, 228 
Woolley, on tuberculosis of aorta, ref., 567 
Wormley, on poisons, 425 
Worms, 123 
guinea, 130 
method of study of, 131 
pin, 127 
round,126 
tape, 123 
thread, 127 
whip, 128 
Wounds, granulation tissue in, signifi- 
cance of, ref., 152 
healing of, 91 
post-mortem, appearance of, 990 
Wright blood stain, 468 
method of collecting serum, 195 
method of making frozen sections, 
1028 
Wright, A., on opsonins, ref., 187; on 
) opsonic technique, 188; on preventive 
I inoculation in typhoid fever, ref., 246 
Wright, J. H., on absorption in tonsils, ref., 
649; on actinomyces-like structures in 
tonsillar crypts, ref., 649; on biology of 
actinomyces, ref., 232; on blood plates, 
466; on Madura foot, ref., 232; on 
multiple myeloma, ref., 902; on nasal 
polyps, ref., 580 
Wright and Douglas, on opsonins, 183 
Writer's cramp, 950 
Wrzosek, on infection, ref., 151 
Xerosis bacillus, 285 
Xiphopagus, 329 
X-rays, lesions from, 11 
Yaws, 293 
Yeasts, 133, 146 
in fermentation, 146 
tumors, 349 
methods of study of, 149 
Yellow fever, 301 
excitant of, 302 
lesions of, 301 
mode of infection in, 302 
mosquitoes and, 302 
Yersin's anti-plague serum, 289 
Young, on gonorrhoea, ref., 221; on nerves 
in tumors, ref., 338 
Zahn, on ciliated cysts of pleura, ref., 642; 
on cysts, ref., 361; on statistics of intes- 
tinal tuberculosis, ref., 674; on stenosis 
of oesophagus, ref., 652; on tumors of 
mediastinum, ref., 636 
Zenker's degeneration of muscle, ref., 872 
fluid, 1030 
Ziegler, on Hodgkin's disease, ref., 495; 
on lesions of bones and joints, ref., 
907; on tumors, 416 
Zinsser, on leucocyte extract, ref., 189 
Zooglcea, ref., 135 
Zuber, on bronchial lymph-nodes, ref., 592 
Zuntz, Lowy, Muller, and Caspari, on 
polycythaemia, ref., 455