July - A TEXT-BOOK OF GENERAL PATHOLOGICAL ANATOMY AND PATHOGENESIS BY ERNST ZIEGLER, PROFESSOR OF PATHOLOGICAL ANATOMY IN THE UNIVERSITY OF TUBINGEN TRANSLATED AND EDITED FOR ENGLISH STUDENTS BY DONALD MAC ALISTER, M.A., M.B., MEMBER OF THE ROYAL COLLEGE OF PHYSICIANS ; FELLOW AND MEDICAL LECTURER OF ST. JOHN'S COLLEGE, CAMBRIDGE NEW YORK WILLIAM WOOD & COMPANY 56 & 58 Lafayette Place 1883 Trow's Printing and Bookbinding Company 201-213 East Twelfth Street New York MAGISTRO srro CAROLO LUDWIG EX PIETATE DONALD MAC ALISTER PREFACE. I have first of all, at Professor Ziegler's request, to say something with regard to the German original of the text-book now offered to English students. His first design was to bring out a new and re- vised edition of Foerster's well-known manual of Pathological Anat- omy. But as the revision went on, it became clear that the present state of our knowledge of Pathology could not be fitly represented without recasting and almost rewriting the whole work. It was, therefore, thought better that he should undertake an entirely new text-book, in which the subject should throughout be treated from a modern point of view. The great success of the first edition in Ger- many would seem to show that such a book was needed, and that the author's manner of treating the subject was approved by teachers of Pathology. Professor Ziegler explains that a great part of his text is based upon observations made or verified by himself. Where he has drawn upon other sources he has carefully cited the needful author- ities. " I am not blind to the fact," he adds, " that my statements and criticisms may bear too strongly the mark of my own personal views, and that these views may not be readily accepted by all patho- logists. But I have, nevertheless, held it wiser not to introduce much matter of controversy into the text of a treatise intended mainly for students. Experience leads me to believe that the learner gains a readier and surer grasp of his subject when it is first presented to him as a uniform and coherent system of doctrine, even though the teacher's statement of it should border on the dogmatic. Once this grasp is gained it is easy for the more advanced student to master and PREFACE. VI to appreciate other theories and doctrines. I have given in brackets full references to the literature of each subject discussed, and I have added such indications of its bearing as may prove useful to those who are engaged in pathological research." The present English version was begun a year ago, on the basis of the first German edition. At that time there seemed to be no near prospect of a second German edition. In the first I found a consid- erable number of details which needed amendment or amplification in order to fit the book for the use of English students. The author very generously admitted my criticisms, and gave me full leave to make such changes as I might think useful. The w'ork was well advanced, when a new edition of the first part was called for in Germany, and presently appeared. It embodied most of the improve- ments we had agreed upon, together with valuable additions. These I have now made full use of, so that this volume corresponds through- out to the second German edition. The matter in brackets has had my special care, and I have verified a very large number of the refer- ences. The original contains few allusions to English or French memoirs; I have therefore made it my duty to add full notices of such as throw light on the subjects treated in the text, choosing both original contributions and papers serving as a clue to previous work. This feature, and the careful revision of the main text, will, I trust, help to make the text-book useful to English workers in Pathology, even though they may be familiar with German. The first part-on General Pathological Anatomy-is now pub- lished. It is practically complete in itself, and on some subjects, such as Malformations, Inflammation, Etiology of Tumors, and Bacteria, it gives a fuller account of modern teachings and discoveries than has yet ap- peared in any English manual. The second part-on Special Patho- logical Anatomy-is in course of publication in Germany. It is hoped that the English version of this part may be ready soon after the Ger- man edition is completed. I owe more than I can well express to the kindness of Professor Klein ; he has read through the proof-sheets of this volume, and has sent me many very useful suggestions and criticisms. Without his en- couragement, and that of Professor Greenfield, I should not have ven- tured to undertake the work. I would also gratefully acknowledge the willing help I have received from my friends Professor Cossar PREFACE. VII Ewart, Dr. J. F. Payne, and Dr. S. II. Vines; and from one whose loss I shall never cease to feel-Frank Maitland Balfour. The beautiful drawing of tubercle-bacilli, somewhat inadequately represented by Fig. 80, was kindly sent me by Dr. Heneage Gibbes, of King's College, London. In the multitude of references given I can hardly hope to have es- caped all error. Any corrections or queries which may reach me shall therefore have my grateful attention. DONALD MAC ALISTER. St. John's College, Cambridge, England, December, 1882. CONTENTS. PAGE INTRODUCTION 1 SECTION I. MALFORMATIONS. CHAPTER I. General Considerations (Arts. 1-5) 17 II. Malformations by Arrest in Single Individuals . . . .24 a. Arrested Development of the Embryo as a Whole (Art. 6) . .24 b. Arrested Development of Paris of the Body (Arts. 7-10) . . 25 c. Malformations and Malpositions of the Organs (Art. 11) . .30 III. Double Monstrosities and Malformations 32 a. Cleavage Affecting the Undifferentiated Embryo . . . .32 a. Complete Cleavage of the Axial Structures (Arts. 12-13) . 32 /3. Partial Cleavage of the Axial Structures (Arts. 14-15) . 36 y. Multiple Cleavage, and Overgrowth of the Entire Body (Art. 16) 37 b. Cleavage Affecting the Rudiments of Particular Parts; Con- genital Hypertrophy (Arts. 17-18) 37 SECTION II. ANOMALIES IN THE DISTRIBUTION OF THE BLOOD AND OF THE LYMPH. TV. Anomalies in the Distribution of the Blood within the Vessels -Hyperemia and Anemia (Arts. 19-22) 43 V. Anomalies in the Distribution of the Lymph-(Edema and Dropsy (Arts. 23-25) 48 VI. Escape of the Blood from the Vessels-Hemorrhage (Thrombosis, Embolism, Infarction) (Arts. 26-30) 52 VII. Lymphorrhagia (Art. 31) 57 X CONTENTS. SECTION III. RETROGRESSIVE DISTURBANCES OF NUTRITION. CHAPTER PAGE VEIL Necbosis (Arts. 32-42) 61 a. Coagulative [Hyaline or Fibrinous) Necrosis (Arts. 35-38) . . 63 b. Caseation (Art. 39) ......... 67 c. Colliquative Necrosis or Softening (Art. 40) . . . . .68 • d. Dry Gangrene or Mummification (Art. 41) .... .70 e. Moist Gangrene or Sphacelus (Art. 42) 70 IX. Simple Atbophy and Pigmentaby Degenebation (Arts. 43-47) . 72 X. Cloudy Swelling and Dbopsical Degenebation (Arts. 48-49) . 76 XI. Fatty Degenebation (Arts. 50-54) 79 XII. Mucoid and Colloid Degenebation (Arts. 55-56) . . . .84 XIII. Amyloid Degenebation and Amyloid Concketions (Arts. 57-62) . 87 XIV. Hyaline Degenebation of the Flbbous Tissues (Art. 63) . . 95 XV. Infiltbation of the Tissues with Salts (Arts. 64-66) . . .97 XVI. Fobmation of Pigment in the Tissues (Arts. 67-70) . . . .99 XVII. The Fobmation of Cysts (Art. 71) 105 SECTION IV. PROGRESSIVE OR FORMATIVE DISTURBANCES OF NUTRITION. XVDI. The Cellulab Pbocesses Concebned in Hypebtbophy, Hypebpla- sia, and Regenebation (Arts. 72-83) 109 XIX. Hypebplasia and Regenebation in Pabticulab Tissues (Arts. 84- 89) 122 XX. Metaplasia (Arts. 90-92) 131 SECTION V. INFLAMMATION AND INFLAMMATORY GROWTHS. XXI. The Eably Stages of Inflammations-Exudation (Arts. 93-103) . 137 XXII. Lateb Stages of Inflammation-Recoveby-Regenebation-Gban- ulation-Cicatbization (Arts. 104-111) 149 XXTIT. Impebfect Re-absobption-Fobeign Substances (Arts. 112-116) . 158 XXIV. The Infective Gbanulomata 165 General Characters (Art. 117) ....... 165 Tubercle and Tuberculosis (Arts. 118-127) ..... 166 Syphilis (Arts. 128-130) ......... 182 Leprosy (Art. 131) 186 Lupus (Art. 132) 187 Glanders (Art. 133) ......... 188 Actinomycosis (Art. 134^135) ........ 189 CONTENTS. XI SECTION VI. TUMORS. CHAPTER PAGE XXV. General Considerations (Art. 136-141) 195 XXVI. Tumors Developed in Mesoblastic Tissues-Connective-tissue Tumors 202 a. Fibroma (Art. 142) 202 b. Myxoma (Art. 143) 204 c. Lipoma (Art. 144) ......... 205 d. Glioma (Art. 145) . 205 e. Chondroma (Art. 146) 207 f. Osteoma (Art. 147) 208 g. Angioma (Arts. 148-152) 210 h. Myoma (Art. 153) ......... 215 i. Neuroma (Art. 154) 217 j. Lymphoma and Lymphosarcoma (Art. 155) .... 218 k. Sarcoma (Arts. 156-163) ....... 219 I. Mixed Tumors of the Connective-tissue Group (Aits. 164-165) 230 XXVII. Epithelial Tumors (Art. 166) 233 a. Adenoma (Arts. 167-169) 234 b. Carcinoma (Arts. 170-176) 237 XXVIII. Etiology of Tumors (Arts. 177-181) 253 SECTION VIL PARASITES. XXIX. General Considerations (Art. 182) 265 XXX. The Schizomycetes or Bacteria. Morphology, Development, and Classification (Arts. 183-187) . 267 Biology of the Bacteria (Arts. 188-211) ..... 274 XXXI. Hyphomycetes and Blastomycetes (Moulds and Yeasts) (Arts. 212-224) 316 The Hyphomycetes or Moulds (Arts 213-222) . . . .317 The Blastomycetes or Yeasts (Arts. 223-224) .... 328 XXXII. Animal Parasites 330 Arthropoda (Arts. 225-226)........ 330 Scoledda, or Worms (Arts. 227-249) ...... 333 Protozoa (Art. 250) 353 Index of Authors Cited 357 Index of Subjects 363 INDEX OF FIGURES. FIG. PAGE 1. Croupous (false) Membrane from the Trachea 64 2. Waxy Degeneration of Muscle 66 3. Section through the Uvula in Diphtheritis Faucium . . . .67 4. Section through the Epidermis and Papillae after a Burn . . .69 5. Section of an Atrophied Muscle 74 6. Cloudy Swelling of the Renal Epithelium 76 7. Section through a " Mucous Patch " ....... 77 8. Fatty Degeneration of the Muscles of the Heart 79 9. Amyloid and Fatty Degeneration of the Kidney 80 10. Fat-crystals 83 11. Catarrhal Secretions from Various Mucous Membranes . . . .85 12. Amyloid Degeneration of Liver Capillaries 89 13. Section of an Amyloid Kidney 89 14. Corpora Amylacea 92 15. Calcified Ganglion Cells 98 16. Calcification of the Tunica Media of the Aorta . . . . .98 17. Chalky Concretions 98 18. Blood-pigment 101 19. Indirect Cell-division Ill 20. Development of Blood-vessels by Sprouts and Off-shoots . . . 125 21. Metaplasia of Cartilage into Areolar Tissue 132 22. Inflamed Omentum from the Human Subject 140 23. Section of a Croupous Membrane from the Trachea .... 147 24. Section of Uvula from a Case of Diphtheria 148 25. Granulation-cells in Various Stages 153 26. Pus-cells Becoming Fatty and Shrinking 158 27. Section through a Degenerating Patch from the Brain .... 160 28. Lymphatic Gland Containing Pigment-granule Cells .... 161 29. Tubercle from a Fungating Granuloma in Bone 168 30. Fungating Granuloma with Tubercles from the Calcaneum . . . 171 31. Tuberculous Ulceration of the Large Intestine 172 32. Tuberculosis of a Lymphatic Gland 173 33. Miliary Tuberculosis of the Liver 174 34. Section of a Syphilitic Hard Sore 183 35. Condyloma Latum ani, or ' ' Mucous Patch " 184 XIV INDEX OF FIGURES. FIG. PAGE 36. Gumma of the Liver Undergoing Caseation 185 37. Section of Skin through a Lupus-patch ....... 187 38. Fibroma Molluscum of the Skin 203 39. Cells from a Periosteal Myxoma of the Thigh 204 40. Glioma from the Brain 206 41. Dilated Capillaries from a Simple Angioma of the Brain . . . 211 42. Section of a Simple Hypertrophic Angioma of the Skin.... 212 43. Congenital Cavernous Angioma of the Skin 213 44. Section from a Cavernous Angioma of the Liver ..... 213 45. Subcutaneous Cavernous Lymphangioma 215 46. Section through a Leiomyoma ........ 216 47. Margin of a Sarcomatous Nodule from the Mamma .... 219 48. Sarcoma of the Intermuscular Connective Tissue ..... 221 49. Lymphosarcoma from the Nasal Mucous Membrane .... 222 50. Section from a Fungating Large-round-celled Sarcoma .... 223 51. Sarcoma of the Mamma containing Variously Formed Cells . . . 223 52. Spindle-cells from a Large-spindle-celled Sarcoma .... 224 53. Giant-celled Sarcoma (" Myelogenic " Sarcoma) ..... 224 54. Melanotic Alveolar Sarcoma of the Skin ....... 225 55. Sarcoma Myxomatodes .......... 227 56. Section of Myxosarcoma (Cylindroma) ....... 228 57. Blood-vessels from a Cylindroma ........ 229 58. Osteoid Chondroma of the Humerus ....... 231 59. Papillary Growths Inside a Cyst 235 60. Section from a Papilliferous Cystadenoma ...... 236 61. Margin of a Destructive Adenoma of the Stomach 237 62. Cutaneous Cancer or Epithelium ........ 238 63. Cancer of the Uterine Glands ......... 240 64. Section through a Mammary Cancer 241 65. Bird's-nest Body or " Concentric Globe " 242 66. Glandular Cancer of the Uterus . . . . . . . 244 67. Simple Carcinoma of the Mamma 245 68. Simple Cancer of the Mamma (Scirrhous in Barts) .... 246 69. Colloid Cancer of the Mamma ........ 246 70. Carcinoma Myxomatodes of the Stomach ...... 247 71. Cylindroma Carcinomatodes ......... 248 72. Cancerous Embolus of a Hepatic Capillary ...... 249 73. Metastatic Development of Cancer in a Hepatic Capillary . . . 249 74. Various Forms of Bacteria ......... 270 75. Development of Bacillus Anthracis 272 76. Colonies of Micrococci from the Vocal Cord of a Child .... 290 77. Micrococcus Septicus in Hepatic Capillaries 291 78. Bacillus Anthracis; Liver-cells Unaffected 291 79. Hepatic Abscess ; First Stage 292 80. Bacillus Tuberculosis in Phthisical Sputum 305 81. Fungi from a Favus-patch 317 82. Development by Conidia and Zygospores 319 83. Eurotium Bepens and Aspergillus Glaucus 320 INDEX OF FIGURES. XV fig. PAGE 84. Hair Affected with Favus 327 85. Saccharomyces Cerevisiae 328 86. Female Acarus Scabiei 330 87. Acarus Folliculorum 331 88. Head-end of Pentastoma Denticulatum ...... 332 89. Ascarides Lumbricoides . 334 90. Egg of Ascaris Lumbricoides 334 91. Oxyuris Vermicularis 335 92. Trichocephalus Dispar 336 93. Egg of Trichocephalus Dispar 336 94. Head-end of Dochmius Duodenalis 336 95. Mature Trichinae 337 96. Trichinae Encysted in Muscle . . . . . . . 338 97. Filaria (Dracunculus) Medinensis . 340 98. Embryo of Filaria Sanguinis Hominis ....... 340 99. Distoma Hepaticum 342 100. Distoma Hepaticum 342 101. Distoma Lanceolatum 342 102. Eggs of Distoma Lanceolatum 343 103. Distoma Haematobium 343 104. Eggs of Distoma Haematobium 343 105. Head of Taenia Solium, and Circlet of Hooks 345 106. Immature and Mature Proglottides 346 107. Two Proglottides Showing the Uterus 346 108. Eggs of Taenia Solium 347 109. Cysticercus Cellulosae 347 110. Fragments of a Taenia Saginata 348 111. Head-end of Taenia Saginata Retracted ...... 348 112. Segment of Taenia Saginata . 348 113. Full-grown Taenia Echinococcus 349 114. Brood-Capsules of Echinococcus 350 115. Fragments of a Bothricephalus Latus 352 116. Eggs of Bothricephalus Latus 353 117. Coccidia from the Human Liver 354 PATHOLOGICAL ANATOMY. INTRODUCTION. Life is known to us only in the concrete. It is indissolubly bound to a material substance. This substance, the basis of all the vital pro- cesses, is fashioned out of cells and their derivatives. All living organ- isms are made up of cells and cell-derivatives. The cell by itself appears originally as a microscopic mass of pale slimy finely granular matter, the so-called protoplasm. It usually contains within it a nucleus, that is to say a structure like a tiny vesicle, whose form may be round, oval, rod-like, or irregular, and in whose interior we can make out by proper handling, 1, small definite bodies, the nucleus corpuscles, 2, a net-like framework of nucleus substance, and 3, a clear fluid, the nucleus juice. The young cell is at first naked. Only in its maturer stages does it develop on its surface an optically distinct membrane or other structure according to the special tissue of which it forms a part. The vital activity of the cell is of a threefold kind. It is directed in part toward its self-preservation, in part toward its propagation, and in part toward the ordering of its outward relations. Virchow distinguishes these severally as the nutritive, formative, and functional activities. Many of the functions of the cell (including the chemical changes which always accompany them) cannot be directly observed and are only to be made out by their effects. Others again, like motion, growth, and multi- plication, can be observed in proper specimens under the microscope. Every cell, whether it be isolated or joined with others, is influenced by the nature of its environment. This may work either to further or to hinder some or all of the functions of the cell. To a certain extent in- deed the cell may exist unaffected by this influence in virtue of its own inherent properties, but the range of this independence is very limited. Let the external conditions deviate from the normal by more than a cer- tain small amount and disturbances of the cell-functions at once show themselves. These disturbances may amount to the complete arrest of all sisrns of cell-life, or even to the utter destruction of the cell as such. 1 2 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. An Amoeba observed in a suitable liquid under the microscope mani- fests its vital activity by altering its form. It sends out fine prolonga- tions from its pale finely granular body-protoplasm. It fixes one or other of these to some object in its neighborhood. Then its main mass flows toward them and blends with them again. If there be any fine particles suspended in the liquid and these happen to come within reach of the amoeba as it moves forward, the animal flows round about them as it were, and so takes them up into its substance. Let us now change the external conditions by raising the temperature a few degrees. The result is that the movements, hitherto perhaps slow and languid, at once become more lively-the vital activity of the cell is increased. Raise the temperature higher still-the movements gradually cease. At a certain degree of warmth the cell becomes quite stiff and still, and only when the temperature is allowed to sink to its former level do the original movements gradually reappear. By cooling down the liquid we bring about a like result. The cell gradually ceases to move and becomes a mere inert globule. When the temperature is again raised it regains its power of movement. Now add to the liquid a concentrated solution of common salt-the cell becomes turbid and shrivels up, its outline becoming irregular. Or pass a constant galvanic current through the liquid-the cell takes on a spherical form, becomes inflated, loses its fine granulation, becomes a mere vesicle with clear contents, and finally bursts. These experiments show in clear and simple fashion how in conse- quence of changes in the external conditions the manifestations of life in the cell also change. The change may take the form of temporary in- crease, or of temporary diminution and arrest, or of permanent cessation. When the cell bursts we cannot pretend to doubt that it has ceased to exist as a cell ; it is in fact dead. Even the shrunken salted cell, though its structure may be less affected, must still be regarded as dead, for in no way can we succeed in again obtaining from it any manifestation of life. Permanent cessation of all the functions of the cell is what we mean when we speak of its death.; even though at first sight the anatomical structure of the cell is not destroyed. But in the first experiments the case is very different. When the temperature is raised or lowered in a moderate degree, only one of the cell-functions is suspended, the function of movement. The nutritive activity persists ; hence it is that on readjustment of the temperature the motor activity is re-established. This cannot be spoken of as death. A condition in which there is not cessation of all the functions but only a partial suspension, diminution, increase, or alteration of any kind in some of them we distinguish as a morbid or diseased condition. The no- tion of disease is thus at the outset a physiological notion. We infer it primarily from the appearance of some abnormality among the accus- tomed manifestations of life. Disease is not an entity, capable of per- sonification, of being placed in antithesis to health. The term health INTRODUCTION. 3 merely denotes that the vital functions are being performed in a manner which experience has taught, us to regard as normal. So by disease we merely imply a phase of life whose manifestations deviate in some way from the normal type. Restoration of the functions to the normal type is recovery; cessa- tion of all function is death. The causes of the diminution and extinction of a cell's vital activity may be internal as well as external. No cell is endowed with the power of living on indefinitely. Certain cells or rather unicellular organisms, it is true, have the power of producing a long line of descendants merely by continual subdivision of their own substance, and in this way their vital activity appears to persist for an indefinite time. But life protracted after this fashion has also its limits. In the first place, it is unlikely that all the cells derived by subdivision from the mother-cell should receive at their birth exactly the same share of vital energy. Granting then that in the process of derivation an unequal transmission of the vital proper- ties of the mother-cell to the daughter-cells is possible, we must also admit that the less favored descendants must sooner or later fail in their power to overcome the normal agencies antagonistic to cell-life. But even if this be denied, the life of the cell becomes at once finite so soon as we pass from the simplest unicellular organisms to higher multicellular forms. When division of labor is set up within the organism, and the production of new individuals is no longer a function shared in by all the parts of it, then it follows of necessity that some of the parts, some of the constituent cells, must be destined to perish. How long a cell can live cannot in general be exactly determined. It depends on the properties transmitted to it from the mother-cell. We may say broadly that a cell's life is shorter in proportion as it stands higher in the scale of development, and as its properties are more spe- cialized. Thus for example the ganglion-cells and gland-cells of one of the higher animals are always short-lived, and often fail to produce any progeny at all. On the other hand the number of cell-descendants of a vertebrate ovum, or of an amoeba, is indefinitely large. The death of a cell depending thus on internal causes is a physiolog- ical death. The gradual extinction of function which ushers it in does not fall within the category of disease : it is a phenomenom of age in the cell, a senile change, a senile retrogression. Unlike this senile extinction of the vital processes a true disease is not a consequence of the indwelling and inherited properties of the cell. The efficient causes of a disease are always external. In the observations we made on the amoeba it was heat or cold, an altered surrounding me- dium, or the galvanic current, which brought about disease and death. All these noxious influences are derived from without. And what we have here remarked in a single instance experience shows us to be uni- versal. Autonomous as the cell may seem, it is yet unable, without external impulsion, to heighten its functions above the physiological 4 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. standard, or on the other hand to check or to suppress them. We can therefore give a still more exact definition of the notion of disease. By the term disease we are to understand a deviation of some of the vital manifestations from the normal, the deviation being con- ditioned by external influences. But in considering disease as thus defined we must not limit our attention to the case of a single individual, or we shall find our dictum contradicted by everyday experience. If we could observe under the microscope the successive generations of a unicellular organism, and fol- low with certainty the life-history of each, we should come upon indi- viduals whose functions were abnormally performed, and that although it might be impossible to detect any injurious external influence at work. We should then have to confess that the abnormal behavior was here, as in senile retrogression, conditioned by intrinsic properties. This would in fact be true, yet it would not contradict the above proposition-that disease can only arise through changes in the external conditions. If we had had before us a complete series of the cell's ancestors, and had noted all the phases of their lives, we should have found that the morbid phe- nomena of the last cell, though not immediately traceable to external influences, had yet already appeared in some of the foregoing generations. And there we should have found that external conditions existed which exercised a disturbing influence on the cell's life. The morbid condition of the last cell then had not its origin in the cell's own lifetime. It was acquired from the mother-cell along with existence itself-the cell inherited it. We. must thus distinguish inher- ited from acquired diseases. What we have hitherto said of morbid life and death applies primarily to the individual cell. But the organism with which the physician and the surgeon have to deal is not unicellular. The human body is built up of millions of cells, and these cells differ one from the other in their mor- phological as well as in their physiological properties. Among unicellular organisms each single cell must exercise all the functions of life ; but in many-celled organisms the principle of the division of labor is carried to a high degree of completeness. Different cell-groups have built up organs differing utterly in form and substance ; even the component cells of the same organ are not all of the same nature. Notwithstanding this, we have no reason to suppose that what is true of the single cell is not also true of the various cell-groups. The life of the entire organism as well as of the several organs is bound to the component cells ; it is the activities of the latter which we perceive and accept as the manifestation of life. As disease of the uni- cellular organism is but abnormal action of the single cell, so human dis- ease is but abnormal action of a multiplicity of cells. Naturally the question becomes now much more complex. With the multiplication of the cellular elements, with their differentiation into diverse organs, arises the possibility of local disease. Nay, it is all but INTRODUCTION. 5 inconceivable that, when the complex human organism is invaded by dis- ease, each and every cell should thereupon simultaneously err from its normal function. As a fact, experience shows that every disease has its local seat or seats ; in other words it is not the entire organism ,which is diseased, but only some of its organs, or only individual cell-groups form- ing parts of organs. We speak therefore of organic and of local dis- eases. Which cell-groups become affected in any special case depends upon two factors : on the one side upon the external causes in operation, on the other upon the physiological nature of the tissue affected. A given injury does not affect every cell in the same degree. The vital properties of the cells of multicellular organisms are highly diverse, and so also is their power of resisting diverse influences. An injury that does not affect in the slightest the functions of one cell-group or organ may produce grave disturbances in those of another ; a different injury may paralyze the tissues in one region, and in another stimulate them to increased activity. This difference in behavior can depend only upon causes inherent in the cell and arising from its specific properties. It is the evidence of a specific predisposition of individual tissues to specific disorders. On the other hand the influences which can injuriously affect the or- ganism as such are innumerable, and the manner as well as the seat of their operation exceedingly various. If then we duly regard the great variety of the causes of disease on the one hand, and on the other the equally great diversity of structure and therefore of predisposition among the tissues, we shall not be likely to underestimate the difficulty that in most cases meets us when we try to determine the nature and the origin of a disease in man. Here also it is true that the ultimate cause of disease is external ; but the place and time and manner of its operation are far harder to deter- mine than in the case of unicellular organisms. Sometimes it may be quite impossible to fix the ultimate determining factor, especially when an organ is attacked only in some of its elements and its functions are thus but slightly or imperceptibly affected. There is still another fact to be considered-the propagation of dis- ease from one organ to another. It often happens that an injurious agency which at first produces a morbid disturbance in one organ only, in its further progress invades another. This is brought about either by direct transition from one organ to its neighbor, or by actual transport of morbific matter through the blood-vessels and lymphatics to remoter regions. For example, a poison introduced into the intestine may be able to produce local disorder there; but if it be absorbed into the blood and so be carried to the various organs, it may further have the power of exciting grave functional disturbance in the brain ; a different poison may leave the brain alone and influence the kidneys, and so on. But this propagation of disturbance may take place in another way. Defective performance of its function by one organ is not always without 6 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. influence upon other organs. A morbid condition of one very often in- volves the like in another. Thus disease of the liver and bile-ducts may throw back the secreted bile into the blood, and this impure blood will tend to inhibit the action of the heart. Again disease of certain gan- glion-cells in the spinal cord is followed inevitably by the atrophy of cer- tain muscles. Failing action of the kidneys may bring on the general affection called uraemia. Imperfect action of the lungs may bring on serious changes in the action of the heart. Next to external influences heredity plays an important part in the genesis of disease. Unfortunately its influence is not easy to estimate; and it is often difficult, often impossible, to distinguish the inherited from the acquired. The human organism takes its rise in the maternal propagation-cell, the egg ; and its development dates from the instant when in the act of impregnation the egg receives a specific stimulus from the paternal sper- matozoa. The impulse thereby communicated manifests itself by cell- division and proliferation. According to the laws of heredity, the prop- erties of the paternal and maternal organisms are transmitted to the child that is to be; and it is hence probable d priori that morbid condi- tions of the parents may be likewise transmissible to the child. This as a matter of fact is the case. The transmission shows itself in two ways. In the first place there are actual diseases, such as syphilis, which are be- queathed by the parent to the child. They are such that even in the womb or shortly after birth, or later still in life, they make their appear- ance in like fashion with the parental disease and without the intercur- rence of fresh injury from without. Such are inherited diseases in the narrower sense of the term. They originate in a diseased condition of the ovum or spermatozoon which is transmitted to their cell-progeny, or in a direct transference of some morbific agent from the tissues of the father or mother into those of the newly generated organism. In the higher groups of animals the latter mode of transmission is the most likely one, and it has been actually demonstrated in certain special cases. They are not common. More common than inheritance of a definite disease is inheritance of a morbid predisposition. By this is to be understood a certain debility of an organ or a tissue, not easy to define more exactly. This debility has arisen in the parents in consequence of some primary or inherited disease in them. In such cases an external cause is required to bring about the development of actual disease, and it is by no means necessary that the disease when it appears should be of exactly the parental type. Inherited predisposition is oftenest observed in connection with ner- vous disease, and just in this region is best exemplified the fact that the type of disorder need not be the same in the child as in the parent. It is probable that the external or determining causes have an influence in this modification of type. Distinct from inherited disorders are those which the foetus acquires INTRODUCTION. 7 within the maternal organism after conception. It is true that the foetus is protected by the sheltering womb against manifold injuries to which in later life it becomes exposed. But it must not be forgotten that in this season of development, and especially in its earlier stages, its consti- tution is far frailer than in the mature condition. Nor must we leave out of account that its intimate relations with the maternal organism are in themselves a source of danger. Local changes in the uterus or in the foetal membranes, and disorders of the mother generally, must obviously have an influence on the development and life of the foetus. Experience proves indeed that the child in utero is subject to many and various dis- eases, and often enough perishes unborn. Certain diseases of the mother, such as small-pox, are directly transmissible to the foetus. Others inevi- tably involve its death. As above said, local changes in the uterus and in the foetal mem- branes may also produce disturbances in the growing organism. To the investigator these do not show themselves primarily as disturbances of function ; in the most favorable case he may perhaps be able to distin- guish an abnormality in the movement of the heart or the action of a muscle. All that he finds on examination is the anatomical effect of the disturbance. The foetus is an organism whose function is to grow. If any one part of the developing organism meet with an injury, or if by any means a local disorder anywhere arise, the consequence is a local disturbance of the process of growth. If in other respects the foetus develops normally and ultimately comes to be born, we shall find a corresponding abnormal- ity in the conformation of the affected part. This may consist either in a defect, an overgrowth, an imperfect closure, or a misformation. When the form or structure of a member deviates in this way from the normal, we describe it as a congenital malformation. It is the effect of a morbid process in the period of intra-uterine development, and may concern the whole or a part of the organism or of any one of its or- gans. Inasmuch as it is the effect of intra-uterine disturbance it is to be distinguished from acquired defect, mutilation, malformation, or over- growth. The latter conditions arise in virtue of injuries sustained by the organism after it has become independent of the mother. The question now arises, What are the special questions which fall to the lot of Pathological Anatomy in the investigation of morbid pro- cesses ? Disease is nothing but a phase of life, in which one or more of the physiological processes is running an abnormal course. Is it then possible that the problems of life in disease can hopefully be attacked by anatomical methods ? The observations that can be made during life upon diseased tissues-such as the skin, the epithelia, the eye-show that these methods are practicable ; and the experience gained at the post- mortem table, from the microscope, or through actual experiment, con- firms after death the conclusions drawn from the living subject. All these show that anatomical tissue-changes lie at the bottom of the morbid 8 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. phenomena observed during life ; and that these tissue-changes are for the most part still recognizable after death. In other words they supply the justification for our previous postulate-that the diseases of man have always a local seat in some definite cell-group. Thus the primary and peculiar function of Pathological Anatomy is-to investigate, with all possible exactness and detail, the tissue-changes which are involved in the various forms of disease. The information gathered in this field is already plenteous and im- portant. Formerly diseases were of necessity classified symptomatologi- cally; their names connoted certain groups of outward symptoms. Now, thanks to pathological anatomy, we are able to arrange them according to anatomical characteristics. We find this classification justified in practice by the constant recurrence of well-marked and specifically dis- tinct anatomical changes in diseases whose whole course and character prove them to be in fact specifically distinct. It cannot be gainsaid that as yet Pathological Anatomy has not suc- ceeded in supplanting the clinical or symptomatic order of ideas. It is not yet possible in all cases to connect the morbid action of this or that organ with definite anatomical changes. We still must use the terms " epilepsy," " diabetes," to distinguish certain disorders ; but that only implies that we are not yet able to replace the clinical conception by an anatomical one. It by no means implies that the several diseases are not dependent upon local changes in some special tissue or cell-group. From the fact that we are sometimes unable to discover the seat of an affection we can only infer one of two things. Either the difficulties in the way of discovery are so great that we can only in certain favor- able cases, not yet met with, succeed in overcoming them ; or, that the tissue-change we are seeking eludes our optical appliances, inasmuch as it is not a change of gross structure, but one of chemical constitution and metabolism. This latter must at any rate be true of a vast number f trifling functional disturbances, whose transitory nature and slight in- tensity almost exclude the idea of a recognizable physical alteration of structure. The various morbid tissue-changes which allow us in some measure to infer from the dead body the functional disorders experienced in life are either macroscopic or microscopic. A skilled eye can gather a great deal by mere inspection ; and in this way a large number of diseases can be diagnosed on the post-mortem table. Still it very often happens that naked-eye inspection is insufficient, and it would in reality be much oftener so, if in previous similar cases the microscope had not already yielded us necessary information touching the minuter changes and the processes they involve. Morbid changes have their seat in the cells, and in their derivatives the intercellular substances. It is therefore indispensable to a right un- derstanding of these changes to call in the help of the microscope, and with it follow out the cellular and intercellular processes. INTRODUCTION. 9 As a fact the microscope has in countless cases thrown an utterly un- expected light upon these processes, and the enormous advance of pathological anatomy in the last quarter of a century or so has been brought about simply by the exact attention bestowed upon them. Virchow it was who inaugurated this new method and established it on a firm basis. Microscopic examination of cellular and intercellular changes, in connection with naked-eye post-mortem examination, still remains the foundation on which our knowledge of disease and its nature must be based. The amoeba, which under changed conditions of life becomes languid and finally dies, undergoes before the last event certain visible changes. These enable the observer to follow the process of dissolution if not com- pletely at least through all its more important stages. It is plain that a simple experiment of this kind, made on a single cell, can exhibit but a fraction of the normal and pathological processes that take place among the cells, cell-colonies, and cell-derivatives of complex organisms. The cellular processes which underlie the various diseases are extremely manifold and extremely diverse. He who tries for the first time to penetrate deeper into their nature, and to educe the significance of the changes he observes, will hardly be able to accomplish at once his designs and desires. He must first become familiar with the essential facts of the subject, which have been gathered and sifted out by the fundamental investigations of Virchow and the labors of Foerster, von Reckling- hausen, Klebs, Cohnheim, Eberth, Rindfleisch, and many others. The outcome of their labors is-that pathological processes fall into four great groups. If we follow the morbid processes in the order in which they attack the individual organism from its first beginning to its end, we naturally direct our attention first to those which affect its development. The human being originates from a single cell by a process of con- tinued cell-division. If for any reason a cell-group is not formed which naturally should be formed, the member or organ normally developed from this group will be lacking in the mature organism. A malformation is the consequence ; and it is greater or less according to the number of cells undeveloped, and more or less obvious and striking according to the degree in which the symmetry and harmony of the whole is disturbed. When a structure is thus lacking or incomplete it is described as a Hypo- plasia or Aplasia. The second kind of morbid change ends also in defect of structure ; not however through interference with growth, but through the destruc- tion or degeneration of parts already formed. This may of course oc- cur in the embryonic stage, and result in aplasia, or it may take place at a later stage as atrophy. These destructive or degenerative processes are not always alike ; they may be rapid, or they may be slow and gradual ; they may sometimes be extensive and obvious, sometimes strictly local and not at once perceptible. Changes of this kind are in- cluded under the term Retrogression or Regression. 10 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. In antithesis to these stand other processes distinguished as Progres- sion, Overgrowth, or Hyperplasia. As the names indicate, the characteristic of these changes is an abnormally active growth, a too abundant cell-production. When they occur during embryonic life we have produced the so-called Monstra per excessum ' in other words we have structures excessive in relative size or duplicated. When they occur at a later stage, in the growing, stationary, or declining periods of life, they result in overgrowth of the organism as a whole, or of single organs or their parts, or lastly in so-called tumors. We may describe such changes as constructive or formative. Constructive and retro- gressive disturbances of nutrition are not to be regarded as wholly with- out correlation. On the contrary, progressive processes not infrequently succeed to retrogressive ones, the object here being, if we may speak teleologically, to replace parts which have been lost. In this case the process is described as Regeneration. A fourth type of morbid tissue-change is that known as Metaplasia. Metaplastic processes are such as lead to the transformation of one species of tissue into another. Sometimes they are retrogressive in character, sometimes rather constructive. The most important and most striking instances of this form of tissue-change are afforded by the cells. But the intercellular substances may also, and not infrequently, undergo more or less complete metamorphoses. Thus although we chiefly turn our attention to the cellular processes as after all the most essential, we must not altogether leave out of account the behavior of the intercellular substances. It is needful to note this, for the nature and condition of these substances have certainly some influence on the life of the cells themselves. In each of these processes, retrogressive, constructive, and meta- plastic, the condition of the circulatory system is of special importance. The regular and normal fulfilment of the function of circulation is essen- tial to the maintenance of a tissue in its normal state. Disturbances of the circulation quickly bring about disturbances of function and changes in the tissues. Disturbances of the circulation play a distinct and highly important part in the process known as Inflammation. Unless we desire to limit this term to a single stage of the entire process, we may indeed say that the characteristic phenomena of Inflammation are those connected with the circulatory mechanism. Pathological Anatomy has not fulfilled all its task when it has inves- tigated the morphology of morbid change in cells and tissues. It must go on to determine the genesis, and the causation of morbid processes. If we would obtain a satisfactory insight into the significance of the special changes that come before us, we must make it a first principle to compare these changes with each other, and with the known facts of physiology bearing on tissue-formation and degeneration. As our pres- ent ideas of the origin of specific forms of life only became possible after we had subjected animals to comparative examination and acquired an INTRODUCTION. 11 exact knowledge of their embryology, so also must we study disease comparatively and investigate with exactness the processes of histogene- sis, if we are to attain a satisfactory understanding of morbid phe- nomena. The appropriate objects for investigation will in the first instance consist of the morbidly altered tissues taken from the human subject ; but there will remain many questions for whose complete an- swer we must needs have recourse to experiments upon animals. The pro- found importance of these we may gather from the fact-that our knowl- edge of such diseases as can be artificially produced in animals is far more complete and thorough, than in the cases where the artificial methods have as yet failed us. A knowledge of the etiology of the several forms of disease is of the very highest import. It is beyond dispute that a perfect understand- ing of the causes of disease and their mode of action is the end and goal of all research in morbid anatomy ; and it is the clear duty of patholo- gists to devote their energies to its attainment. If we could but define a disease, not according to its symptoms or its morbid anatomy, but strictly by referring it to its causes, we should gain far more than a clear comprehension of the affection ; we should have done much to settle the therapeutic treatment. It has long been known that certain diseases arise in consequence of the settlement of certain plants and animals in the human organism. Only of late years have we learned that the domain of these parasitic dis- orders, as they are called, is of wide and far-reaching extent. Formerly we were acquainted with such vegetable and animal parasites only as are relatively large in size and easy to detect; in the last twenty years our improved optical instruments have made us aware of a great number of minute and hitherto unperceived species of parasitic organisms. The Schizomycetes, or Bacteria, especially have been recognized in recent years as the causes of certain most grave diseases. The observations now before us make it probable that the " bacterial " affections are very widely diffused. These investigations are of deep interest, and have vastly increased our store of facts concerning the diseases in question. It must not, however, be forgotten that the study of parasitic fungi can only make real and well-grounded additions to our knowledge of the as- sociated diseases, can only in any measure yield us a true theory of them, can only lead us to a full understanding of the entire morbid process, when it has succeeded in making out the manner in which the fungi act, and the causal relation existing between fungus and disease. Fungi have been detected in a large number of diseases, but only in a few cases have we gained an insight into their mode of affecting the organism. The mere presence of a fungus in the system cannot be de- scribed as disease. Disease only begins when, owing to the presence of the fungus, changes take place in the tissues of the organism which in- duce disturbances of their functions. Here then a wide field lies open to research. The detection of fungi in the diseased organism is but 12 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the first step toward discovery of the cause of the disease and its mode of operation. It is a long way from this first step to the full and com- plete explanation of the entire process. This hiatus in our knowledge must not be too little thought of. The smallest contribution to the fill- ing up of the gap is at least as welcome as the discovery of a new fun- gus-perhaps even more welcome. The pathologist must keep his attention well-fixed in this direction. Even though it may lie beyond his present powers to follow the processes in which morphological change is no longer detectible, and molecular transformation recognizable only by the chemist takes its place, there nevertheless remains a vast region still accessible to his means of research. In dealing with fungi we have to do with formed elements, with cells in fact. The changes they pro- duce are changes in cells and their derivatives ; and in so much as re- lates to cellular processes and changes in formed protoplasm we have matter within the scope of anatomical investigation. The path along which etiological research has to proceed is twofold -examination of the altered human organ on the one hand, experiment on the other. The former in this case cannot lead us to much. Experi- ment is by far the more promising way. If a given fungus disease can be produced in animals, it becomes at once possible to follow its spread and operation step by step ; we are limited only by our instruments and modes of examination. It is thus in our power, in comparatively short time, to acquire information which not even centuries of post-mortem investigation would suffice to educe. This method of research is con- fessedly of somewhat limited reach. To say nothing of the technical difficulties which meet the investigator, the number of microparasitic dis- eases capable of transmission from man to the lower animals is small ; or they run a course so different that their identity is not easily established. For such diseases therefore we are compelled to forego this valuable aid. If we will not decline the task altogether we must adopt another method; we must endeavor to make out experimentally the biological properties of the several fungi, as they are found in the human body. If we are successful, we have made it at least possible to form an idea of their mode of working upon the system. Of recent years both methods have led to brilliant results. But there are sources of disease other than parasitic-such as high temperature, cold, chemically active substances, etc. These must not be overlooked. Though they are for the most part not themselves amena- ble to anatomical methods, their effects upon the tissues are. Knowledge of the morphology, the genesis, the etiology of morbid changes is thus the aim and object of pathological anatomy. Its methods are post-mortem examination, direct or microscopic, on the one hand; experiment on the other. On comparing the domain of the pathological anatomist with that of the clinical observer, it will not escape our notice that there is a gulf betwixt them. One has to do with death, the other with life; one with 13 INTRODUCTION. what has been, the other with what is and is to be. To bridge this gulf is the t^ask of pathological physiology ; hers it is to bind into one the scat- tered facts which pathological anatomy has gleaned; to discover and make sure the link that connects the morbid change with the disordered function. Standing with firm foot on the ground of anatomical research, and leaning on experiment as her staff, it is her part to explain to the physician the phenomena he has observed at the bedside of his patient. She analyzes the complex of clinical phenomena into its elements, and from them reconstructs the natural types and species of disease. Through her mediation anatomical research joins hands again with prac- tical medicine. SECTION I. MALFORMATIONS. CHAPTER I. GENERAL CONSIDERATIONS. 1. By congenital malformation we mean an anomaly in the form and make of the body as a whole, or of individual parts of it, referable to a disturbance of normal intra-uterine development. The degree of mal- formation may be very different in different cases. When the deviation from the normal is slight, affecting perhaps only a single part, we speak of it as a simple anomaly. The term malformation is not usually em- ployed unless the misformed part or organ seriously disturbs the balance and harmony of the bodily form as a whole, seeming in fact to be ill- matched with the rest of the organization. When the deviations from the normal are very considerable the affected individuals are spoken of as monsters. Monsters fall into two great groups-the single and the double. In single monsters we have malformation occurring in a single individual. One or more parts of the organism may have been arrested in growth, and are therefore incomplete or wanting ; thus we have monsters by defect {monstra per defectum). Or the structure and disposition of the parts may deviate from the normal, and thus we get monsters by perversion {monstra per fabricam alienam). Double monsters are of several kinds. Two nearly similar individ- uals may have one or more parts in common; or a properly formed indi- vidual may have attached to it the ill-developed body of a second as an appendage; or lastly particular members may be doubled, or simply ex- aggerated in size {monstra per excessum). [The literature of malformation is rich both in comprehensive treatises and in accounts of individual cases. The following sketch is based on the works of Foerster (" Die Missbildungen des Menschen," Jena, 1865); Gurlt (Article "Monstrum " in the " Encyclopiidisches Wdrterbuch der medici- nischen Wissenschaften," vol. xxiv., and "Virch. Arch.," vol Ixxiv.); Ahlfeld ("Die Missbildungen des Menschen," Leipzig, 1880); and Peris (" Lehrbuch der allgemeinen Pathologie," Part ii., 1879). Foerster, Gurlt, and Ahlfeld give summaries of the ancient and modern literature of the subject. The student may also consult Vrolik's article on "Tera- tology " in " Todd's Cyclop, of Anatomy," and Lowne's " Catalogue of Teratological Specimens," Royal College Surgeons, London, 1872.] o 18 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. 2. The human organism is developed from the ovum. This is a cell of definite and regular structure, which is set into activity by the impulse of impregnation. The rudiments of the several parts are produced by continued segmentation of the primordial cell. The morphological form of the embryo begins very early to appear, and depends ultimately on certain regular evolutionary processes which the several rudimentary or- gans undergo. These processes are histologically recognizable as lateral or central proliferations of the cell-complex, and the resulting outgrowths forthwith become differentiated into specific forms. The factors deter- mining the special direction development is to take do not, in the first instance at least, lie in the external relations of the ovum, in its environ- ment. They are rather to be sought in the inherent and inherited prop- erties of the segmentation-cells. But at the same time the external rela- tions are not without influence on the subsequent course of development. If these are abnormal, the process of embryonic growth may be thereby altered, arrested, or perverted. Theoretically speaking the origin of a malformation may be of either of two kinds. On the one hand, the primary rudiment (in other words, the ovum) may have inherited a tendency to abnormal growth; on the other, a normal embryo may in the course of development be affected by disturbing influences from without which check its progress toward the perfectly developed form. Experience indicates that both events occur. The recurrence of hereditary malformations in a family (such as excess of fingers or toes) can only be explained by the supposition that the abnor- mal tendency exists from the first in the embryo, having been transmitted to it from one or other parent. On the other hand the absence of one or more limbs, deficiency of the cranium, etc., observed only in isolated cases, are to be accounted for in a satisfactory way only by assuming that ex- ternal causes of injury have affected the growing foetus. [Disturbing influences acting on the otherwise normal embryo play a far more important part than heredity in the genesis of malformations. This might be inferred from the fact that the term malformation has come to connote exclusively gross and obvious anatomical relations. These gross anatomical anomalies arise generally from external causes. The pathological peculiarities transmitted congenitally from parent to child manifest themselves less in anomalies of external form that in deficient or perverted function of the tissues, or in morbid predispositions. Such anomalies are to be detected only by minute anatomical examination, or they are incapable of anatomical demonstration at all.] 3. Monstrosities by defect, as they occur in man, are of many kinds. Many of them affect most gravely the shape and fashion of the human form ; others, of trifling character and affecting none but internal organs, can only be recognized by anatomical examination. The con- MALFORMATIONS. 19 figuration of the body is most prejudicially affected by defective closure, whether total or partial, of the larger body-cavities (pleural, peritoneal, or cerebro-spinal); or, on the other hand, by defective development of the extremities. The causes of malformation in any given case can only be approxi- matively determined, or referred to this or that hypothetical injury ; nevertheless we can generally indicate the direction in which the cause of the defect is to be sought. Monstrosities by defect are commonly malformations by arrest ; they owe their existence to a local hindrance to the development of a normally constituted embryo. It is but seldom, and then chiefly in cases where the entire body is affected (as in dwarfs), that we can attribute the effect to iieredity ; even of such cases the hereditary ones form by no means the majority. The influences which check and hinder growth are to be sought in al- teration, injury, or disease of the uterus, or in disease of the foetus itself. To the first class belong defective development or disease of the mem- branes and placenta (uterine or foetal), adhesion of the amnion to the foetus, abnormally small quantity of liquor amnii, tumors of the uterus, concussions of the uterus with separation of the membranes, hemorrhages in the membranes or in their neighborhood, etc. As concerns the foetus itself, its development may be disturbed by inflammatory affections which it acquires by transmission from the mother (small-pox, scarlatina, endo- carditis), or by inherited disease such as syphilis. In the earlier stages of development abnormal twists or flexures of the embryo may be enough to cause very serious hindrances to growth. The influences we have cited may act in various ways. Many arrest growth mechanically by simple pressure ; others hinder the circulation so that the foetus, or some of its parts, receive too scanty a supply of blood, and thus the growth is retarded. Other affections, such as the inflammations, actually destroy parts already formed and so render their further growth impossible. Not infrequently several factors may act at the same time, or the malformation of one organ, like the heart, may in- volve detriment to the proper development of the others. The point of time at which the disturbing influence makes itself felt may of course vary greatly, and so by consequence will vary the intensity of its effect. The earlier the injury the greater is usually its effect. The loss of a few cells in the earlier stages of growth may involve the absence of an entire organ or limb ; while later on, after the general form is nearly complete, the same loss might not be noticeable at all. Malforma- tions, in the narrower sense of the term, originate for the most part in the first three months of foetal life. By the. end of that time the general form of the body and its members is well defined. Later disturbances give rise rather to changes that manifest themselves after birth as con- genital disorders ; they are therefore more fitly regarded as the anatomi- cal basis of foetal diseases than as true malformations. 20 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [Geoffroy St. Hilaire ("Histoire generale et particuliere des anomalies de 1'organisation chez 1'homme et les animaux," Paris, 1832-37) rejects altogether the doctrine of the primary perversion of the embryo (Haller and Winslow) and refers the malformations by arrest entirely to mechani- cal influences. Panum (" Untersuchungen uber die Entstehung derMiss- bildungen," Berlin, 18G0) on the whole agrees with him, although he grants the possibility of a primary perversion. He produced malforma- tions in embryo chicks by varying the temperature of the incubator, and by varnishing the egg-shells. Dareste (" Recherches sur la production artificielle des monstruosites," Paris, 1877) made like experiments, and pro- duced malformations by arrest by placing the eggs vertically, varnishing the shells, raising the temperature above 45° C., and by warming the eggs in an irregular manner. He has lately (" Comptes Rendus," 1882) shown that abnormalities may be produced by prolonging the interval between the laying and the incubation of the egg. On the significance of adhesions of the amnion to the foetus see Jensen, "Virch. Arch.," vol. xlii.; Fuerst, "Arch, ftir Gynakologie," 1871 ; Peris, " Allg. Pathol.;" Dareste, "Comptes Rendus," 1882. If a malformation is to be produced, the original injury must of course not be too grave, otherwise the embryo would die outright. Above all things it is neces- sary that the apparatus of circulation should be maintained in working- order. If the embryo dies, it is either expelled with its membranes from the uterus ; or it is absorbed, in which case the membranes undergo, further changes before they are finally expelled. A malformed foetus then can never sink below a certain minimum of development without perishing prematurely ; unless indeed it manages to prolong its existence by attaching itself as a kind of parasite to a second simultaneously de- veloping foetus. Compare Art. 13.] 4. The malformations of single individuals, which we with Foerster have distinguished as monstra per fabr team alienam or monstrosities, by perversion, consist exclusively of abnormalities in the viscera of the thorax and abdomen. To this class belongs the Situs transversus or right- and-left reversal of the position of the thoracic or abdominal viscera, or both. In this case we usually find, in addition to the change of position,, other changes in the forms and relations of the misplaced organs. Here also we include the various malformations (mostly by defect) of the heart and great vessels. Lastly, we must mention the numerous malformations- of the genital apparatus, especially those distinguished as true and false hermaphroditism. The genesis of these malformations is in general to be referred to the factors cited in Art. 3. They are for the most part to be reckoned among the malformations by arrest.1 [1 For further details on this subject see the chapters relating thereto in the Special Pathological Anatomy.] MALFORMATIONS. 21 5. Double monstrosities, monstra duplicia, have the entire body, or a part of it, duplicated. The duplicated parts are sometimes equally well developed, sometimes unequally. In the latter case one part is stunted, and appears as a parasitic appendage to a well-formed individual. We thus distinguish between equal and unequal double monstrosities. Older theories had it that double monsters arose through the adhesion of two originally distinct ova (Meckel, Gurlt, G. St. Hilaire). It was even assumed that the membranes of two separate ova might disappear at the point of contact, and then that the two foetuses might become fused together, so to speak. This view is no longer upheld. All double monsters originate from a single ovum and are fashioned on a single blastodermic vesicle. According to Koelliker, the first rudiment of the embryo appears as a round opaque white spot on the wall of the blastodermic vesicle. This is the embryonic area (area embryonalis), formerly misnamed the germi- nal area. The embryonic area originates in a thickening of the epiblast (ektoderm), produced by a proliferation of the cells of this outer layer of the bilaminar blastodermic vesicle. The embryonic area next becomes pear-shaped. At the same time there appears at its posterior extremity a rounded thickening, which is continued into a somewhat conical pro- longation. This thickening is the earliest rudiment of the primitive streak, in other words, it is the region of the epiblast or ektoderm from which the mesoblastic layer is to begin to grow. From the primitive streak the mesoblastic layer spreads between the epiblast and hypoblast till it extends over the whole of the embryonic area, and at length passes its boundaries. It thus forms a marginal zone, called the vascular area (area vasculosa), around the embryonic area. When the primitive streak has existed for some time, there appears in front of it the medullary groove. Thereupon the embryonic area becomes differentiated into a vertebral zone adjoining the medullary groove, and an outer lateral or parietal zone. The various parts and members of the embryo are pro- duced by the progressive development of both zones. The genesis of a double monster may be accounted for in various ways. In the first place it is conceivable that two embryonic areas may arise on the surface of a single blastodermic vesicle. These as they grow may come into contact, and fuse with each other to a greater or less ex- tent. Another possibility is-that in the same embryonic area two primitive streaks may appear, and subsequently two medullary grooves ; these may remain distinct, or may in part become blended. Thirdly, we may suppose the primitive streak to be single, while the medullary groove is developed in duplicate either throughout or in some part of it. Finally, it may happen that in certain cases the duplication occurs at a still later stage, affecting either single ^>arts of the vertebral or parietal zones, or the rudiments of the several organs as they develop from these zones. Each of these hypotheses assumes that at some time or other a 22 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. duplication occurs in parts which normally are developed as single. In the first, the date at which duplication appears is that at which the embryonic area is first formed. In the others, the duplication takes place within the embryonic area itself. In the first three cases, the duplication occurs in structures which are axial ; in the fourth, it may be limited to parts which are lateral. We are compelled to accept the hypothesis that a duplication of some part or parts of the blastodermic vesicle or embryonic area can take place, if we are to account for the genesis of double monsters. The only question is-how far it is possible for a duplication which has already taken place to disappear again, owing to subsequent fusion. For ex- ample, it may be asked-whether from two originally distinct embryonic areas nothing but separate homologous twins can ever develop ; or whether the twin rudiments can unite again at some later stage. This question cannot as yet be definitely answered, so far at least as concerns embryos of the age at which the blastodermic layers have become com- pletely differentiated. On the other hand, it may readily be believed that two embryonic areas which are actually in process of formation may encroach on each other and so unite. Here we have to do not with a fusion of two formed and separate structures, but merely with a group- ing or arrangement of cells (due to identical processes) taking place round two centres close to each other, instead of round a single one. It is perhaps best, in dealing with the genesis of the double malformations, to avoid assuming the occurrence of secondary fusion or reunion of pri- marily distinct rudiments ; and to refer them all to incomplete cleavage or duplication. The ultimate causes of such cleavage are unknown to^ us ; it is likely that they are partly internal and partly external. [The views of different authors on this subject (the genesis of double monstrosities) are very various. Some, like Foerster, Virchow, Oellacher, Ahlfeld, and Gerlach, pronounce for the theory of cleavage. Others, such as Schultze, Panum, and Marchand, think that rudiments already more or less completely distinct may reunite. According to Rauber, two or more primitive streaks may be formed on a single embryonic area ; and these may meet at some point in their length and there fuse together. This is the li Radial " theory. Marchand maintains that two rudimentary embryos are formed, and then unite. The duplication of the embryo is, he thinks, referable to causes anterior to the segmentation, inherent therefore in the ovum before impregnation, or involved in the process of impregnation itself. In support of this hypothesis he adduces some recent observations on invertebrates, which make it probable that the admission of two spermatozoa to the ovum may lead to the formation of two centres of segmentation. In other cases it is said that two blasto- dermic vesicles may be formed, and give rise to a double monstrosity. L. Gerlach lately attempted to produce double monsters experimentally. He varnished over a number of hen's esfffs before incubation, leaving MALFORMATIONS. 23 nothing uncovered but a Y-shaped space over the region of the primitive streak. Out of a number of trials he obtained, on one occasion, a duplicitas anterior (Art. 14), in addition to various other malformations. He infers that in chicks at least it is possible to produce double mon- strosities by artificial means. See Foerster, " Die Missbildungen des Menschen," Jena, 1865 ; Panum, " Untersuchungen fiber Entstehung der Missbildungen," Berlin, I860, and "Virch. Arch.," vol. Ixxii. ; Dbnitz, "Reichert's Archiv fur Anat. u. Physiol.," 1866 ; Dittmer, " Reichert's Archiv," 1875 ; Ahlfeld, " Archiv fur Gynakol., vol. ix., and "Die Missbildungen des Menschen," Leipzig, 1880 ; Rauber, " Virch. Arch.," vol. Ixxi. ; Marchand, " Realencyclopadie der gesammten Heilkunde," Art. " Missbildungen ; " L. Gerlach, " Sitz- ungsberichte d. phys. med. Soc. zu Erlangen," 1880 ; Cleland, Journal of Anatomy, 1874.] CHAPTER II. MALFORMATIONS BY ARREST IN SINGLE INDIVIDUALS. a. Arrested Development of the Embryo as a Whole. 6. If the development of the embryo as a whole be interrupted, one of two results will follow. When the disturbance is grave the further development of the embryo is rendered impossible ; it either ceases to live forthwith, or it dwindles away and ultimately perishes unborn. A slighter disturbance may not exclude a certain amount of development, and as a result there is born a foetus whose general form is normal, though in size it is small and puny. A dead foetus cannot remain for long un- changed ; sooner or later it undergoes certain retrograde alterations. In most cases, foetus and membranes are expelled from the womb, and this constitutes abortion. In other cases, that is to say, in the earlier stages of its development, the embryo may be absorbed and so disappear, the membranes undergoing a different fate. Most commonly they are ex- pelled at once ; but at times they remain and. pass through further changes. In this latter way is generally formed the so-called fleshy mole (mola carnosa ; otherwise clot- or blood-mole). This is a flesh- like mass consisting of membranes and altered blood-clots. The clots form the greater part of the mass ; they are the result of hemorrhages from the maternal placenta, and are not infrequently the efficient cause of the death of the foetus. In other cases, the villi of the chorion undergo a peculiar degeneration, increase in size, and at length form a mass of club-shaped or spherical translucent cysts. These give the ovum at first sight the appearance of a bunch of grapes (whence the German name Traubenmole, or grape- mole). The manner in which cyst grows out of cyst, and the absence of stems uniting the pedicles, render this comparison somewhat inexact. In England this " cystic degeneration " of the membranes is often described as a hydatidiform mole. A still rarer product of completely arrested development is the so- called lithopaedium. The foetus dries up into a kind of mummy, while its superficial parts and the tissues inclosing it become calcified. This effect is oftenest found when the situation of the ovum is abnormal. The second result of a general arrest of growth is dwarfing of the MALFORMATIONS. 25 entire body {Afikrosomia or Nanosomia). Sometimes in dwarfs the pro- portion between the several parts is abnormal ; for example, the head is often inordinately large. b. Arrested Development of Parts of the Body. 7. Malformations depending on imperfect closure of the cerebro-spinal cavity. (1) Acrania ^Ilemicephdlus, Cranioschisis) is a frequent malforma- tion ; it consists in an entire absence of the bones and integuments form- ing the vault of the skull. In most cases the brain is also lacking (Anen- cephalia}, and the base of the skull is covered with a vascular mass of connective tissue, enclosing a variable number of cyst-like structures. More rarely there is found a pocket-like fold of dura mater, containing some brain-detritus. The forehead being imperfectly formed the eyes project strongly, and give these monsters a toad-like appearance. The parietal bones are entirely absent. The tabular portions of the occipitals, temporals, and frontals, may be wanting in whole or in part. If the supra-occipital be also wanting, while the upper cervical vertebrse remain unclosed, the monstrosity is spoken of as Cranio-rachischisis. In such cases the upper part of the spinal cord is also wanting or rudimentary. The production of Acrania is referred by G. St. Hilaire, Foerster, and Panum to the collection of fluid in the cerebral vesicles prior to the fourth month of gestation {Hyclroce^yhalus}. Dareste and Peris dispute this view, on the ground that in Acrania the base of the skull is generally convex toward the brain, and cannot have been subjected to pressure tending outward such as hydrocephalus would produce. They therefore regard the cause of Acrania to be some pressure exerted on the cranium from without. Peris maintains that this external pressure may be ex- erted by the head-fold of the amnion ; this may, he thinks, be stretched too tightly over the cranial flexure, and so arrest the proper development of the cranial vault. Quite recently Lebedeff has offered a new explanation of Anenceph- alia and Acrania. He thinks these are due to the production of an ab- normally sharp cranial flexure in the embryo. This occurs when the cephalic extremity grows at an unusual rate in the longitudinal direction, or when the head-fold of the amnion is retarded in its development. In consequence of the sharp flexure the closure of the medullary plate to form the medullary canal is prevented ; or else the medullary canal al- ready formed is obliterated. This explains very easily the subsequent absence of the brain, and of its membranous and bony coverings. The cystic structures found upon the base of the skull Lebedeff believes to originate from the folds of the medullary plate, which sink into the sub- stance of the mesoblast, and are then constricted off from the main mass. 26 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. (2) Hernia Cerebri and Spina bifida are terms used to describe minor deficiencies in the walls of the skull or of the vertebral column, through which the contents of their respective cavities protrude. In the case of the skull, a sacculation appears on the surface, which contains either fluid (Meningocele), or brain-substance (Encephalocele), or both (Hydroencephalocele). The fluid may lie either in the subarachnoid tis- sue, or in the dilated and sacculated ventricle; in the latter case it is en- closed on all sides by brain-substance (Hydrocephalus externus and in- ternus). Hernia cerebri is oftenest found in the occipital region, and at the root of the nose. The size of the sac, as also the size of the opening in the skull-wall, are very various. The malformation known as Spina bifida is generally limited to the sacral and lumbar regions of the vertebral column. The herniated sac is covered by the integuments, and contains either fluid only (Hydrorachis externa or Spinal meningocele), or fluid with a thin layer of cord-sub- stance (Hydrorachis interna or Hydromyelocele). In the latter case, the central canal is dilated by the fluid.1 (3) Cyclopia or Synophthalmia is a malformation in which the orbits form a single continuous cavity. This may be either very small, containing a mere rudiment of an eye or none at all, or larger in size and containing one eye or two lying close together. The nose is wanting, or represented by a snout-like projection just beneath the common orbit. When the brain is examined, we find instead of the cerebral hemispheres an undivided pointed vesicle running from behind forward ; the optic nerve is often either absent or single, and the olfactory nerve is likewise wanting. The other parts of the brain may also exhibit various malfor- mations. The malformation as a whole depends on the defective develop- ment of the primary cerebral vesicle, in consequence of which the optic vesicles remain either unevolved or in close contact with each other (Peris). Dareste thinks the cause is arrested development of the head- fold of the amnion. [References: Foerster, loc. cit.; Dareste, Zoe. cit.; Peris, "Allgemeine Pathologie," ii., 1879; Lebedeff, "Virch. Arch.," vol. Ixxxvi.; Marchand, loc. cit.; Ackermann, "Die Schadeldifformitat bei der Encephalocele con- genita," Halle, 1882.] 8. Fissural malformations depending on imperfect union of the bran- chial arches. (1) Cleft palate (Cheilo-gnatho-palatoschisis). In this deformity a fissure extends from the upper lip through the alveolar process of the su- perior maxilla, the superior maxilla itself, and the palate. The hard palate is cleft along its line of junction with the vomer; in the soft palate the ['An interesting series of cases of Spina bifida will befound described in the Medi- cal Times and Gazette, 2, 1858.] MALFORMATIONS. 27 fissure passes along the middle line ; in the alveolar process it goes be- tween the exterior incisor and the canine tooth. If the fissure is bilateral, there appears a yawning aperture above the mouth, which is wider and deeper according to the stage at which the development of the vomer, intermaxilla, and lip was arrested. Very often the fissure affects only the upper lip {Labium leporinum, hare-lip) ; less often the palate alone, or the palate and superior maxilla. The slightest degree of fissure is probably represented by a slight notch or scar in the upper lip, or in another direction by a bifurcation of the uvula. Even slight fissures of this kind may, however, be bilateral. These varieties of fissure depend on an imperfect union of the supe- rior maxillary and palatal processes of the first branchial arch with the nasal process of the frontal, the intermaxilla, and the vomer. This union should normally take place in the third month. In some cases the cause of the cleft has been found to be a morbid adhesion of the amnion to the face. The malformation may be hereditary. (2) Schistoprosopia and Aprosopia. If the development of the first branchial arch, and of the nasal process of the frontal, be still more seriously interfered with, we have instead of the middle of the face a mere gaping cavity. Cleft-palate has become cleft-face. In extreme cases, eyes and nose being also absent, there may be no face at all. (3) Agnathia, or absence of the inferior maxilla, is due to arrested development of the inferior maxillary process of the first branchial arch. In consequence of this deficiency the lower half of the face seems cut away, and the ears come almost into contact with each other {Synotid). In special instances the superior maxillary process is also rudimentary, and the malformation is accompanied by Cyclopia, with imperfect cere- bral development. (4) In consequence of the partial persistence of a branchial cleft, we sometimes meet with fissure of the neck, the so-called Fistula colli congenita. This oftenest takes the form of an opening a little above and external to the sterno-clavicular joint; more rarely the opening is in the middle line, or higher up in the neck. Generally there is but one opening ; sometimes, however, there are two symmetrically placed. The fistular canal is for the most part narrow and lined with mucous mem- brane; it passes upward and inward, and as a rule ends caecally; now and then it opens into the trachea or the pharynx. Sometimes such fistulee have dilatations, or these may take the form of closed cysts filled with fluid {Hydrocele colli congenital, or of cavities containing epidermoid cells and cellular detritus {Atheromata}. Fistula? and cysts of this kind are usually formed in the site of the third or fourth branchial cleft. Their hereditary character has been established in nume- rous instances. [On cervical fistula see Heusinger, "Virch. Arch.," vols. xxix. and xxxiii., "Deutsche Zeitschrift fur Thiermed.," ii., 1875; Rehn, " Virch. 28 A TEXT-EOOK OF PATHOLOGICAL ANATOMY. Archiv," vol. Ixii.; Neumann and Baumgarten, "Arch., fur klin. Chirur- gie," xx.; Virchow, "Virch. Arch.," vol. xxxv.; Schede, "Arch, fur klin. Chirurgie," xiv.] 9. Fissural malformations depending on imperfect closure of the pleuro-peritoneal cavity. The abdominal surface of the embryo, which is that directed toward the blastodermic vesicle, begins about the third or fourth week to close in by converging marginal growth. This at first takes place only from the anterior and posterior ends, but afterward at the lateral borders also. At the end of this stage the only communication between the intestinal cavity and the vitelline or umbilical vesicle is by means of the omphalo- meseraic or vitelline duct. In the sixth week the duct becomes obliter- ated, but it happens not infrequently that the part next to the intestine persists as Meckel's diverticulum; this takes the form of a cylindrical or club-shaped sacculation of the ileum. Clefts of the abdominal wall. The complete closure of the body- cavity occurs in the eighth week, but this is liable to several forms of interruption. The slightest degree of abnormality is that in which a peritoneal protrusion, containing a coil of intestine, persists at the site of the umbilicus. This, forms a hemispherical bulging, from the apex of which the umbilical cord arises {Hernia funis'). This malformation is common; the sac is usually small; it is less usual for the hiatus in the abdominal wall to be considerable. Cases, however, occur in which a fissure extends for nearly the entire length of the anterior belly-wall {Gastroschisis or Fissura abdominalis)', this may even extend to the thorax {Thoraco-gastroschisis). In the latter case the development of the laminae laterales toward the umbilical vesicle must have been very early arrested. It is even possible for the funis to be absent altogether, and then the umbilical vessels pass direct to the placenta. Occasionally the fissure is altogether unclosed; in other instances a kind of hernial sac is formed by the peritoneum and the amnion stretched over it. Now and then we find that the abdominal wall is duly closed in the neighborhood of the umbilicus, while a fissure persists either above it or below it. If below it, the fissure is usually associated with imperfect closure of the allantois and so of the urinary bladder. The internal mu- cous surface of the bladder in this case appears externally, and is pressed forward and everted by the intestines behind. The genital groove re- mains unclosed, and the external genitals are ill-developed. This is known as Inversio, Ectopia, or Ecstrophia vesica?. Clefts of the thoracic wall. If the fissure is small and merely affects the sternum, it is described as Fissura sterni ; if it is wider, so that the heart is covered only by membrane and integument and pro- trudes, it is called Ectopia cordis. The efficient causes of these imperfections of development are seldom demonstrable. It may be that they depend in part on morbid adhesions MALFORMATIONS. 29 of the borders of the laminae laterales to the amnion. Very frequently they are found in individuals affected with malformations in other parts, such as the genitals or anus. [See Buhl, " Klinik der Geburtskunde von Hecker und Buhl," 1861; Wedl, " Wiener med. Jahrbuch," 1863 ; Ahlfeld, " Arch. f. Gynak.," v.; Peris, " Allg. Pathologie," ii., 1879. On intestinal diverticula see Lock- wood, Pritish Medical Journal, 1882; Roth, " Virch. Arch.," vol. Ixxxvi.] 10. Aplasia of the extremities and of the hip- and shoulder-girdles. Defects in the development of the limbs are by no means rare. Different classes are distino-uished according to the decree of malforma- tion. (1) Amelus. Limbs entirely wanting or replaced by wart-like stumps. Trunk generally well-formed. (2) Peromelus. All the limbs stunted. (3) Phocomelus. Limbs consisting merely of hands and feet, sessile upon the shoulders and pelvis. (4) Micromelus (Microbrachius, Micropus). Limbs regular in form, but abnormally small. (5) Abrachius and Apus. Absence of upper limbs, while lower are well-formed; and vice versa. (G) Perobrachius and Peropus. Arms and thighs normal; forearms and hands, legs and feet malformed. (7) Monobrachius and Monopus. Absence of a single upper or lower limb. (8) Sympus, or Siren-monster. Lower limbs coalescent, being first rotated backward so that the external surfaces .come into contact. The pelvis is usually malformed, as also the external genitals, bladder, urethra, and anus. Feet may be wholly absent or represented by single toes (Sympus apus) ; or there may be one (aS. monopus) or both feet (aS. dipus) at the end of the undivided extremity. (9) Achirus and Perochirus. Absence or stunted growth of the entire hand or foot is seldom observed. More frequently we find absence of single fingers or toes (Perodactylus); or coalescence of two or more {Syndactylus or li webbing "). (10) Of the several bones those most commonly wanting are the radius, fibula, patella, clavicle, and scapula. [See Foerster, loc. cit.; Gruber, "Ueber angeborne Defecte der Hand:" "Arch. f. Anat. u. Phys.," 1803 ; Voigt, "Ueber congenitalen Radiusdefect:" "Arch. d. Heilk.," 1863; Julliard, "Sympodia:" " Gaz. med. de Paris," 1869. Many cases of malformation of the limbs have been attributable to constriction and even amputation by folds or bands of the foetal membranes, or by loops of the umbilical cord. Compare Abelin and Blix, "Jahresber. der gesammt. Med.," 1863 ; Bambeke, 30 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. " Annal. de la Societe de Med. de Gand," 1861 ; Baker Brown, " Ob- stetrical Transactions," viii., 1867. Dareste explains the formation of the siren-monster by supposing that the tail-fold of the amnion has pressed too tightly on the caudal end of the embryo.] c. Malformations and Malpositions of the Organs. 11. We have seen that the form of the body as a whole is liable to manifold irregularities, resulting from disturbances in its development. The several organs may likewise, and from like causes, deviate in form and structure from the normal. Especially is this the case with the genital organs and with the heart, which very often exhibit anomalies depending on arrested development. But malformations affecting the alimentary canal, the kidneys, the lungs, or the brain, are by no means rare. These will more naturally fall to be discussed in connection with the pathological anatomy of the respective organs. Very frequently, too, we meet with malposition of the organs. This reaches its highest degree in the so-called Situs transversus (or inversus) viscerum ' this is a right-and-left reversal of the viscera, the contents of the thorax and abdomen being transposed as if reflected in a mirror. It occurs in single as well as in double monsters. But apart from the viscera, malpositions also occur in connection with the extremities. Under this head must specially be mentioned congen- ital dislocations, or displacements of the articular ends of bones from their sockets ; and also abnormal positions of the feet, the hands being less often misplaced. According to the position of the foot we distinguish four types : (1) Pes varus (commonly though less strictly called Talipes varus), or club-foot. The inner border of the foot is directed upward, the outer downward ; the heels inward ; the astragalus projects strongly outward ; the scaphoid bone lies beneath the inner malleolus. The calf-muscles and tendo-Achillis are shortened. (2) Pes valgus, or flat-foot. The outer border of the foot is directed upward, the inner downward ; the sole outward. The peronei and extensor muscles are shortened. (3) Pes equinus, or (as we might call it) tip-foot. The heel is drawn upward ; the tendo-Achillis shortened. (4) Talipes calcaneus, or hook-foot. The toes are drawn up toward the front of the leg. The tibialis anticus, the peroneus longus and brevis, and the extensors, are shortened. [References on Situs transversus:-K. E. Von Baer, " Entwickel- ungsgeschichte, i., p. 51 ; Valsuani, " Annali univ. di med.," February, 1869 ; Gruber, "Arch. f. Anat. u. Phys.," 1865; Buhl, " Mittheil. Munch- ner pathol. Inst.," 1878 ; Hickman, " Trans. Path. Soc.," 1869 ; Valli- enne, " Etude sur les transpositions viscerales," Paris, 1881. MALFORMATIONS. 31 Transposition of the abdominal viscera alone is much more uncom- mon than complete transposition of all the viscera. References on Congenital Dislocation: Hueter, " Gelenkkrankheiten," second edition ; Konig, " Lehrb. der Chirurgie," ii. ; Grawitz, "Virchow Archiv," vol. Ixxiv. ; Krbnlein, " Deutsche Chirurgie," part 26, 1882. The ordinary surgical text-books give details concerning the various congenital deformities of the hands and feet. On the genesis of club- foot see "Adams's Jacksonian Essay," London, 1873.] CHAPTER HI. DOUBLE MONSTROSITIES AND MALFORMATIONS. a. Cleavage Affecting the Undifferentiated Embryo. a. Complete Cleavage of the Axial Structures. 12. Forms in which the development of the segments is equal. (1) Homologous twins; these are produced when the development of the divided rudimental embrvos goes on without check or hindrance. Homologous twins are always of the same sex. Each twin is enclosed in its own amnion, though portions of the membranes may disappear where the two are in contact. The placenta is almost always single and common. , (2) Thoracopagi. If the two rudimental embryos lie near or in con- tact with each other, a double monster may result. If portions of the trunk, that is of the thorax or abdomen, are coalescent, the monster is described as Thoracopagus. As the umbilicus and umbilical cord are single and common, the term Omphalopagus is sometimes applied to it. The various forms of this monstrosity are named from the extent to which coalescence is carried. Xiphopagi are those in which the ensiform processes are united by a cartilaginous bridge. The peritoneum passes for some distance into the connecting structure (the well-known Siamese twins were xiphopagi). Sternopagi are xiphopagi with a common thoracic cavity. The ster- num may be double or single ; the heart also double or single, in which latter case it is malformed ; the alimentary canal is in part common ; the liver double, though the two organs are connected by processes of gland- substance. Two of the upper limbs may be coalescent (Thoracopagus tribrachius), or two lower limbs and the pelves (Th. tripus). If the heads as well as the breasts and bellies have coalesced, we have a Prosopo- thoracopagus, Cephalo-thoracopagus, or Syncephalus. If a face be formed on the posterior aspect of the head as well as on the anterior, the monster is described as Janus-headed or Janiceps. Generally one of the faces is a mere rudiment (Janiceps asymmetros). The liver of the right- hand twin is usually " perverted " in position ; more rarely this is the case with the other viscera also. Thoracopagi are the commonest kind of double monsters. MALFORMATIONS. 33 (3) Craniopagus is a pair of twins whose heads are adherent. They are distinguished as frontal, parietal, or occipital according to the local- ity of the adhesion. They are rare. (4) Ischiopagus is a monstrosity in which the twins are united only at the pelvis. The spinal column and pelvis is duplicated, but the latter forms but a single wide girdle of bone, in which the two sacra are at op- posite sides. This double pelvis carries two or four limbs. The trunks arise distinct and bent away from each other. [In preparing this systematic survey of the double monstrosities use has been made chiefly of Ahlfeld's work, " Die Missbildungen des Men- schen," Leipzig, 1880, and of the chapter in Peris's " Allgemeine Pathol- ogie." Both treatises give references to the literature of the subject. The genesis of all these double forms seems most easily explained by supposing that two embryonic areas are formed on the surface of a single blastodermic vesicle, and that these as they grow come into contact and coalesce at some part or other of their periphery.] 13. Forms in which the development of the segments is unequal. These forms fall into two groups. In the first, the nutrition of one twin is somehow cut off, and it dies without alteration of its external form. In the second group, the nutriment of one twin is derived from the other. As a result the form of the first or parasitic twin is more or less affected. The parasite may be more or less intimately incorpo- rated with the " autosite " or host, as the foetus is termed which finds nutriment both for itself and its neighbor. Or again, the parasite may be connected only with the placenta of the autosite. The following varieties have been distinguished. (1) Foetus papyraceus. If the umbilical vessels at their attach- ment to the common placenta come too close to each other, arterial anas- tomoses are formed between them ; the blood-current in one system may become more powerful than in the other, and thus the main stream is diverted toward the more powerful. The circulation in one of the foetuses is checked, and that foetus sooner or later perishes. The secretion of its liquor amnii ceases at the same time. The dead foetus becomes more and more compressed by the growing one, and may ultimately become reduced to a thin flattened remnant. In other cases, the death of one of the foetuses is determined by hemorrhage into the villi of the chorion, or by torsion, knotting, or compression of the umbilical cord. (2) Acardiacus. This is a monster devoid of a heart ; it is always very imperfectly developed. The rudimentary foetus is either free, and connected with the well-developed one only through the placenta ; or it is adherent to the well-developed one and blended with it to a greater or less extent (cf. Teratoma). In the first case the acardiac twin is in fact an allantoid or placental parasite ; its umbilical vessels are connected with those of its host, and its blood is kept in circulation by the host's 3 34 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. heart. According to Claudius, Foerster, Ahlfeld, and others, the mon- strosity results from the later development of the allantois in one foetus than in the other. The retarded allantois is prevented from reaching the chorion, and is compelled to insert itself into the expansion of the other allantois. The course of the circulation in the parasite being in- verted, its heart is either wanting or rudimentary. The lungs, trachea, pericardium, diaphragm, sternum, vertebral bodies, and ribs, are absent or undeveloped ; as are also the liver and the upper limbs. The only or- gans which are fairly developed are, at most, those of the abdomen and pelvis. We frequently find in such cases an over-development of the sub- cutaneous connective tissue, giving rise to shapeless unorganized masses or tumors. The different varieties of acardiac monsters are (a) Acardiacus amorphus. This form is rare, and consists of a shapeless lump covered over with skin and containing mere rudiments of organs. (5) A. acormus. Head developed ; thorax and abdomen absent or rudimentary. Very rare. (c) A. acephalus. Head absent ; thorax rudimentary ; pelvis and at- tached members developed. This is the commonest variety. (cZ) A. anceps. Trunk well developed ; head and limbs rudimentary ; heart also rudimentary. Rare. (3) Thoracopagus parasiticus. Should one of the foetuses of a thoracopagous monster be imperfectly developed, it will hang from the other in the form of a mere stunted appendage. The parasite is con- nected with the autosite by the ensiform cartilage, and the abdominal wall as far as the umbilicus ; it is therefore often spoken of as Epigas- trius. It is seldom completely developed, i.e., provided with all its mem- bers. In the majority of the cases on record, the parasite has been an Acardiacus acephalus or acormus, and its vascular system a mere out- lying region or extension of the host's. This monstrosity is very rare. (4) Epignathus. This is an amorphous acardiac monster connected with the mouth-cavity of the well-developed twin-foetus. From this cavity protrudes a shapeless skin-covered mass, made up of cartilage, connective tissue, gland-tissue, brain-substance, teeth, bones, intestinal elements, muscles, skin, and foetal down. In very rare instances the epi- gnathus is attached to some other region, such as the orbit. (5) Teratoma. Teratomata are tumor-like formations which are made up of a great variety of very different tissues, and so are distin- guished from ordinary new-growths. Some of them contain rudimentary skeletal elements, such as those of the spine, pelvis, etc.; as well as rudi- ments of various organs, like the brain, intestine, different glands, kid- neys, and muscles. Others contain tissue-formations of various kinds, such as muscular tissue, cartilage, skin, bony substance, gland-tissue, cysts, etc.; but no definitely formed masses which can be regarded as representing any special organ or member. The former tumors are un- MALFORMATIONS. 35 doubtedly to be viewed as remnants of parasitic foetuses which have failed altogether to develop ; they are in fact Acardiaci amorphi in very close relation with the well-developed twin. With regard to the latter class of tumors, this view is not so certain. It is more likely that they depend in part for their origin on some disturbance or arrest of the de- velopment of a single foetus, or on an aberration in germine (cf. Etiology of Tumors, Arts. 178, 179). Regarded thus, the monstrosities Epigastrius and Epignathus become teratomata whenever the degree to which they are developed is less than a certain limit. Teratomata occur, however, most commonly in the form of large tumors attached to the extremity of the coccyx ; they are then spoken of as sacral teratomata, or teratoid sacral tumors. If the out- ward shape suggests that of a foetus or a part of one, it is not hard to diagnose the case as an unequal form of double monstrosity. This is described as Epipygus (see Art. 14). When the tumor is of no defi- nite shape, the diagnosis is not so obvious. In this case anatomical examination alone can settle the question, according to the principles just laid down. It is not to be forgotten, however, that new-born infants are liable to have tumors of the sacral region, which are not unlike tera- tomata, but which are really of the ordinary fibroid (or it may be the epi- thelial) kind. (6) Inclusio fcetalis. In the form of foetal parasitism just described, it usually happens that the parasite is more or less included and over- grown by some of the tissues of the autosite. This inclusion may be car- ried to a still greater extent. Teratoid tumors may be so completely en- veloped by the body of their host, that they may be scarcely or not at all perceptible upon the exterior. This form of parasitism is spoken of par excellence as Inclusion. According to the region in which the teratoma is enclosed we distinguish the varieties : («) Inclusio abdominalis (or Engastrius}. (b) Inclusio subcutanea. (c) Inclusio mediastinalis. (d) Inclusio cerebralis (or Teratoma glandules pinealis). (e) Inclusio testiculi et ovarii. What has above been said of the teratomata applies also to these inclu- sions. In most cases so described, we have to do not with the enclosure of one foetus by another, but with a pathological growth within the body of a single aberrant foetus. [Peris has brought together the literature of acardiac monstrosities in his " Allgemeine Pathologie," Part ii., p. 319. The above theory concern- ing their origin, put forward by Claudius ("Die Entwickelung der herz- losen Missgeburten," Kiel, 1859), and accepted by Foerster and Ahlfeld, is held by Peris to be inadequate. He thinks with Panum (" Virch. Arch.," vol. Ixxii.) that one twin-foetus may be seriously mutilated by constricting bands derived from the membranes, or by the funis ; that anastomoses may 36 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. be formed between its umbilical vessels and the placental circulation of the uninjured twin ; and that thereupon the latter may, as it were, undertake the nutrition of the mutilated twin, which thus assumes the condition of a parasite. In support of this view he refers to an observation of Orth's (" Virch. Arch.," vol. liv.), who remarks that even a decapitated foetus has in some such way continued to grow. See also Houston, Dublin Medical Journal, 1836. Ahlfeld brings together the literature of Epignathus in the " Archiv fur Gynakologie," vii. Since then papers on the subject have been pub- lished by Sonnenburg (" Zeitschrift f. Chir.," v.) ; Verneuil ("Jahresb. der ges. Med.," 1875) ; Wasserthal ("Epignathus," Inaug. Diss., Dorpat, 1875) ; and others. With respect to teratomata the following references may be given- Virchow, " Virch. Arch.," vol. liii. (Terat. of the Mediastinum) ; Arnold, '"Virch. Arch.," vol. xliii. (Terat. of the Cranial Cavity); Weigert, " Virch Arch.," vol. Ixv. (Terat. of the Pineal Gland) ; Braune, " Doppel- bildung und angeborne Geschwiilste der Kreuzbeingegend," 1862. Mrith special reference to sacral teratomata see Depaul, " Jahresb. der ges. Med.," 1869; Reichel, "Virch. Arch.," vol. xlvi.; Liitkemuller "Oest- reich med. Jahrb.," 1875 ; Bohm, "Berlin, klin. Woch.," 1872; Ahlfeld, " Arch. f. Gynak.," viii., xii.] Partial Cleavage of the Axial Structures. 14. Duplicitas anterior. The later the cleavage of the rudimental embryo is in appearing, the less extensive are its consequences. It may thus happen that part at least of the axis of the embryo remains un- divided. Cleavages of the cephalic end (Duplicitas anterior) are the most common ; those of the caudal end are rare. The slightest degree of anterior cleavage is indicated by duplication of the pituitary body. Next in degree come the clefts of the face (Diprosopus), of which there are numerous varieties gradually increasing in severity from mere dupli- cation of the mouth-cavity to the formation of two distinct and complete faces (Diprosopus distomus, diophthalmus, triophthalmus, tetrophthal- mus, triotus, tetrotus). D icephalus is a monstrosity consisting in duplication of the head and upper part of the vertebral column, and is either dibrachius, tribrachius or tetrabrachius. The latter form has two hearts and two pairs of lungs, and is capable of living. Dicephalus parasiticus is very rare. The stunted foetus has always a part of its vertebral column in common with the full-grown one. The highest degree of anterior cleavage is called Pygopagus. The twins are then united solely by the sacrum and coccyx. The urinary and sexual organs may be either single or double. The equal form of this monstrosity is somewhat uncommon ; the twins are capable of living. MALFORMATIONS. 37 The unequal form is more common, if we may regard as pygopagi some of the monsters described above (Art. 13) as epipygi and sacral teratomata. [A pair of living pygopagous twins, born in South Carolina in 1851, has been exhibited as " the two-headed nightingale." An anatomical description will be found in the British Medical Journal, 1869, by Simpson, and in the "Berl. klin. Woch.," 1873, by Virchow. The cavities of the pelves were completely distinct, the sacral region alone being common.] 15. Duplicitas posterior. A monster in which the pelvis and lumbar portion of the spinal column are duplicated is described as Pipygus. The duplicated parts are very seldom equally developed ; much more commonly one remains rudimentary (Pipygus parasiticus}. In the slighter cases of this malformation, only individual parts of the pelvic bones or contents are duplicated. The lower extremities are duplicated, or there are but three of them (Polymelia}. If the rudimen- tary pelvis is not visible externally, the supernumerary limb looks as if it sprang from a normal pelvis. It is usually very ill developed. 16. Homologous triplets are produced when the rudimental embryo has undergone a complete threefold cleavage, and its subsequent develop- ment has been unchecked. They lie inside a single chorion, and the amnion may also be single ; though cases occur where each foetus has its own amnion. Frequently one or two of the triplets are malformed (Acar- diacus). In consequence of a second partial cleavage in an embryo already completely divided, there may be formed a double monster together with a single ordinary foetus-the whole being enclosed in a single chorion. This combination is not infrequent. Tricephali^ or three-headed monsters, arise from a second partial cleavage of an embryo already partially cleft ; they are extremely rare. Of multiple cleavage occurring at both extremities of the embryo only a single instance is on record. If the rudimentary embryo is of abnormal size, and undergoes no form of cleavage, the entire body becomes excessively developed. New- born infants weighing as much as ten kilogrammes (twenty-two pounds) have been met with. In other instances, the abnormally rapid or exces- sive growth has not begun until after birth. y. Multiple Cleavage, and Overgrowth of the Entire Body. b. Cleavage affecting the Rudiments of Particular Parts ; Congenital Hypertrophy. 17. Cleavages affecting the rudiments of separate organs, and the multiplication of these organs or their elements which ensues, vary in significance according to their mode of origin. Some of them must be 38 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. regarded as conditioned by mechanical influences. Others are demon- strably due to heredity. Others still are referable to atavism, or the tendency of a higher type to revert to the organization of a lower. (1) Duplication in the limbs. Cleavage of an entire limb, with- out duplication in the limb-girdle, has not been observed in the human species. Duplication of hands or feet is very rare. On the other hand, the duplication of fingers or toes (polydactylism) is a very common oc- currence. The additional member is sometimes a mere appendage of skin ; in other cases it contains bones, and has the form of a perfect digit. The number of fingers on one hand may be as high as ten. Cleavage affecting the carpal or tarsal bones is rare. (2) Duplication of the mammary glands {Polymastia). This occurs not very infrequently, and in men as well as women. The super- numerary mamma may lie close beside the normal one ; or it may be remote, having its seat on the abdomen, groin, or shoulder, at times even on the back. Double nipples are less often met with than supernumerary mammse. [See Leichtenstern (" Virch. Arch.," vol. Ixxiii.), and Mitchell Bruce (Journal of Anatomy, 1879).] (3) Supernumerary bones and muscles. These are very com- mon. Extra vertebrae may occur in any region of the spinal column. Connected with the coccyx they may give rise to a tail-like appendage, though all so-called tails are not referable to multiplication of vertebrae. Multiplication of the ribs (by the formation of cervical or lumbar ribs), and bifurcation of the ribs, are not infrequent. Multiplication of the teeth is no rare occurrence. [On supernumerary vertebras and ribs see Weicker (" Arch. f. Anat.," 1881), Struthers (Journal of Anatomy, 1875), and Turner (Journal of Anatomy, 1870). On so-called tails see Ecker (" Arch. f. Anthrop.," xi.), and Leo Gerlach (" Morphol. Jahrb.," vi.).] (4) Duplication (or multiplication) of the thoracic and abdominal viscera. This is commonest in the cases of the spleen, pancreas, ure- ter, and pelvis of the kidney. It is rare in the lungs, ovaries, liver, kid- neys, testes, and bladder. 18. Congenital hypertrophy, or excessive growth of individual parts. Abnormal enlargement of one side only has more than once been observed. Excessive size of the head without hydrocephalus is rare, whether symmetrical or unilateral. Undue enlargement of one limb or part of a limb is more common. A hand or foot, a finger or toe, may thus grow to an excessive degree and so give rise to very serious defor- mity. The symptoms of excessive growth are generally apparent at birth. Sometimes the effect depends on a general hypertrophy of all the MALFORMATIONS. 39 elements of the member, sometimes on a mere over-development of adi- pose tissue. Like the limbs, other organs also may reach abnormal dimensions by augmentation of their normal elements. This is the case with the thyroid gland, the tongue, the mammae, the kidneys, the bladder, the uterus, the clitoris, the labia pudendi, and the penis. [Full references to the literature of congenital hypertrophy are given in Kessler's " Inaugural-dissertation uber einen Fall von Macropodia lipomatosa," Halle, 1869. Compare also Reid {Monthly Journal Medical Science, 1843) ; Curling (" Medico-Chirurgical Trans.," xxviii.) ; Trelat and Monod (" De 1'hypertrophie unilateral : " " Arch. gen. de med.," 1869) ; Friedreich (" Congenital Unilateral Hypertrophy of the Head " Virch. Arch.," vol. xxviii.). Cases of congenital hypertrophy of the limbs are reported by Busch (" Arch. f. klin. Chir.," vii.) ; Freidberg ("Virch. Arch.," vol. xl.) ; Little ("Trans. Path. Soc.," 1866) ; Fischer (" Der Riesenwuchs : " "Deutsche Zeitsch. f. Chir.," 1880); Anderson {St. Thomas's Hospital Reports, London, 1882). A good instance of hered- itary polydactylism is given by Lucas, Guy's Hospital Reports, London, 1881.] SECTION II. ANOMALIES IN THE DISTRIBUTION OF THE BLOOD AND OF THE LYMPH. CHAPTER IV. ANOMALIES IN THE DISTRIBUTION OF THE BLOOD WITHIN THE VESSELS-HYPEREMIA AND ANAEMIA. 19. It is the office of the blood to convey nutriment to the organs and tissues. The cells and cellular structures, of which these are built up, cannot long continue to exist unless they are kept supplied with fresh nutriment. For this reason most tissues are furnished with blood-vessels, and those which are not so furnished are in intimate relation with others which are.. The demand for blood on the part of a tissue is not at all times equally great. Hence the supply may also undergo a corresponding increase or diminution, and with the incoming supply varies also the amount of blood actually present in the tissue. If a vascular organ happen thus to con- tain an unusually large amount of blood it is called hypersemic; if it contains less than usual it is anaemic. The regulation of the amount of blood, which an organ receives under physiological conditions, is effected by modifying the resistances offered by the arterial system. This modification of the resistances again is ef- fected simply by means of changes in the calibre of the arteries. The quantity of blood contained in the entire body is insufficient to fill all the vessels at the same time. It is thus possible to increase the supply to any one organ only by diminishing the amount sent in other directions. The calibre of the arteries is altered by help of the elasticity of their walls and the contractility of their intrinsic non-striated muscles, and this apart from the action of changes in the blood-pressure otherwise conditioned. The intrinsic muscles of the arterial wall constitute the active regulating element. Their activity is dependent partly upon influences which di- rectly affect them, and partly upon nervous impulses. These latter are transmitted to them from centres some of which are intravascular, and some situated in the medulla oblongata. They may act so as to contract the vessels, or to dilate them, as the case may be. If the amount of blood in an organ deviates beyond the physiological limit from the mean or usual amount ; or if there is a deviation depend- ent on factors other than the physiological ones ; or if a deviation persists for an undue length of time, we have to do with a hypermmia or anaemia which is pathological. Such pathological deviations are produced by 44 A TEXT-BOOK OE PATHOLOGICAL ANATOMY. agencies only in part identical with those which regulate the normal blood-supply of the organ. [In this book, which deals with pathology, we can only sketch in the broadest outline the general physiology of the circulation. For further details we refer the reader to the chapters on the subject in the classical work of Cohnheim (" Vorlesungen uber allgemeine Pathologic," second edition, Berlin, 1882). Many of the physiological remarks in the text are derived from these chapters. A summary of the main facts will be found in Foster's "Text-book of Physiology."] 20. Hyperaemia of an organ shows itself to the eye as a more or less intense reddening and turgescence. The redness will be bright or dark (livid) according as the contained blood is rich or poor in oxygen. In organs which are themselves strongly colored, the redness may be more or less masked, and its exact tint modified. The reddening and turgescence are produced simply by the dilatation of the blood-vessels of the part, and their repletion with blood. Hyperemia is not easily observed in the dead body ; what is seen represents at best but partially the degree of hyperaemia which may have been present during life ; and that only in some organs. At death the greater number of the vessels, and especially the arteries and capillaries, empty themselves of their contents. This is partly due to the contrac- tion of their walls ; partly to the rigor mortis of the tissues in which they have their course. The contraction of rigor presses out the blood con- tained in them much as the pressure of the finger makes a reddened hyperaemic spot become pale. It may thus come to pass that a membrane, which during life was hyperaemic and red, may after death appear pale and colorless. Or the only reminder of the pre-existing hyperaemia may consist of engorged veins and venules, which, on mucous membranes at least, run in purple branching tree-like courses over the surface. 21. Hyperaemia may be either active (congestive) or passive (mechan- ical). The first form depends on increased flow of blood to the part, or congestion; the second on diminished flow from the part, producing engorgement. Active hyperaemia is either idiopathic or collateral. The former is the more important, and depends on a relaxation of the muscular fibres of the arteries. This relaxation is brought about by paresis of the vaso- motors ; or by stimulation of the vaso-dilators ; or it may be by direct weakening or paralysis of the muscular fibres themselves (such for example as is produced by heat, contusion, or atropia). Collateral hyperaemia is merely the consequence of diminished blood-supply to some other part. It ensues first in the immediate neighborhood of the anaemic part ; but afterward the diverted blood may be conveyed to more remote organs, which happen to stand in need of it. ANOMALIES IN THE DISTRIBUTION OF THE BLOOD. 45 The causes of passive Hyperaemia are of a different kind. The veins are normally devoid of tonus. The resistances offered to the ven- ous blood-current are chiefly due to gravitation. They are chiefly over- come by means of the action of the muscles ; in part also by the aspira- tion toward the thorax which takes place during inspiration. When the muscles are inactive and the respiration feeble, these important forces are no longer available ; the blood then tends to stagnate in the veins, and collects especially in those parts which are most dependent. This condition is often misnamed hypostasis, or gravitative hyperasmia. En- feebled action of the heart favors its appearance. Uncompensated val- vular disease acts in the same way ; the blood is imperfectly propelled into the arteries, and so tends more and more to accumulate in the heart itself and in the venous system. A further very common cause of passive hypenemia is the interposi- tion of abnormal resistances in the course of the venous current. Of this nature are obliteration of veins by compression, ligature, coagulation of the contained blood, or thickening of the walls. The forms of engorge- ment depending on narrowing or obliteration of veins are very various. Often they are scarcely or not at all perceptible, inasmuch as neighboring veins may dilate sufficiently to provide for the complete drainage of the part. This has, however, its limits. When, for example, in the arm the greater number of the great veins are occluded ; or when in the leg the femoral vein is stopped up at Poupart's ligament ; or again, when the main renal vein is obliterated, it becomes impossible for the blood to find adequate exit ; the current becomes slower and slower, and the blood goes on accumulating in the engorged region. When the process is directly observed in the expanded tongue of the frog, the red blood-cells are seen to become tightly packed together, and to fill completely the lumen of the dilated veins and capillaries. This appearance is due to the fact that, as a consequence of the engorgement, an increased quantity of liquid plasma transudes under pressure from the vessels. In the systemic circulation the engorgement is confined to the veins and capillaries ; the arterial blood-pressure remains unaffected by it. In the pulmonary vessels, on the other hand, where there is no very marked tonus (Cohnheim), the engorgement is propagated through the arteries to the right heart, and there gives rise to increased blood-pressure. Congested tissues are bright red in color, engorged tissues on the other hand are dark purple or livid ; though it must not be forgotten that if air be allowed access the livid color may speedily change to a brighter red. [True hypereemia must, of course, not be confounded with post-mortem staining of the tissues. The arteries after death squeeze out by the con- traction of their walls the greater part of the blood they contain. This passes into the veins, and being affected by gravity, most readily into the parts that are lowest. Such a pseudo-hyperremia is called a hypostasis. 46 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. Reddened patches on the skin due to such post-mortem movement of the blood are called livores. They appear three hours or more after death, and commonly upon the back and sides of the trunk and the posterior surfaces of the limbs and neck. If there be already an ante-mortem en- gorgement of these parts, it will appear more intensely after death. In order to observe the process of the engorgement which ensues when the circulation is disturbed, we may conveniently make use of the tongue or the foot-web of a frog which has been curarized (Cohnheim, " Virch. Arch.," vol. xl.). The object must be spread out under the microscope on a proper holder. For example, the tongue may very simply be arranged by turning it out over a cork ring glued to the stage of the instrument, and stretching it with common pins stuck into the cork. When the circula- tion is normal the pulsating arterial stream, as well as the continuous ve- nous stream, are seen to be bordered by a zone of plasma. If now en- gorgement be induced by ligature of the efferent vein of the tongue, the stream becomes slower-the zone of plasma in the veins disappears-and both veins and capillaries become tightly crammed and dilated with the red-blood cells as they accumulate. After a time the tongue begins to swell up, as it becomes infiltrated with the transuded liquid. The frog's tongue and foot-web are also very well adapted for study- ing the changes of the circulation in congestive hyperaemia, and in anaemia.] 22. Pathological anaemia is dependent upon oligaemia, or upon ischaemia. In oligaemia there is a general deficiency of blood through- out the body ; the anaemia of the several organs is due less to defective distribution by the vessels than to the inadequate quantity of blood they contain. Ischaemia, on the other hand, can give rise only to local anaemia ; it always implies a diminution of the blood-supply to the affected part. Ischaemia may of course coexist with oligaemia. Pathological diminution of the blood-supply to an organ is often due simply to an abnormal increase of the normal resistance offered by the arterial channels ; in other words, to powerful contraction of the circular muscular fibres of the arteries. In other cases, the resistances are path- ological in character : such are, for example, compression, diminution of th& lumen owing to morbid changes in the vessel wall, deposits on the inner surface of the vessel, etc. The result of diminishing the calibre of an artery is, in the first in- stance, to slow and to weaken the blood-current behind the constricted point. If the artery be completely occluded, the circulation behind the obstacle comes at once to a standstill. Yet the later consequences of such obstructions to the circulation are by no means always identical. Everything depends on the question whether the arteries behind the point of obstruction have anastomoses of fair size connecting them with other arteries ; whether in fact a collateral circulation is possible. If it be possible, the disturbance of the circulation at first produced is quickly ANOMALIES IN THE DISTRIBUTION OF THE BLOOD. 47 compensated by an increased blood-supply through the collateral arteries. The compensation will be the more rapid and complete as the collaterals are larger and more dilatable. The case is different, however, when the obstructed artery has no arterial anastomoses beyond the obstruction, when it is terminal, as it is called. The diminution of the current beyond the obstruction cannot be compensated for, and the affected region becomes in the first instance nearly or wholly deprived of blood. This state of things may alter after a time, however. When the movement and pressure of the blood beyond the obstruction have sunk to a minimum, the propelling forces become at length insufficient to maintain the flow. The specifically heavier red blood-cells become stationary, and accumulate in the capillaries and veins. In this way the anaemic region becomes again filled wfith blood, but with blood which is stagnating, not circulating. The same thing happens when a terminal artery is completely occluded. The blood from the anastomosing capillaries is slowly urged backward under slight pressure into the anaemic region. Finally, there may be a reflux from the veins themselves sufficient to give rise to an accumulation of blood in the vessels of the anaemic region. This reflux will occur when in the latter vessels the blood-pressure has sunk to zero, and the usual resistances to reversed flow in the veins (such as gravity, or the presence of valves) are not in action. A further cause of anaemia in an organ may be the excessive deter- mination of blood to other organs. The entire amount of blood available may thus be inadequate to supply the non-congested organs. This is de- scribed as collateral anaemia. All anaemic tissues are pale. At the same time they are limp and non-turgescent, and any proper color which they may possess becomes well marked. CHAPTER V. ANOMALIES IN THE DISTRIBUTION OF THE LYMPH-(EDEMA AND DROPSY. 23. The lymph which bathes the tissues is merely a transudation from the blood, mingled with the products of tissue-change. The trans- uded liquid is taken up by the lymphatics from the lymph-spaces of the tissues, and carried back into the venous system through the thoracic duct. Every change in the circulation, which determines an increased transudation of liquid from the blood, leads by consequence to an in- creased saturation of the tissues. This increased saturation is generally balanced by an increased discharge through the lymph-channels. But this compensating action has its limits. If the transudation from the blood-vessels still increases, there at last comes a time when the satura- tion of the tissues with liquid can no longer be kept down, and so it rises above the normal degree. The condition in which fluid collects in the substance of the tissues is called oedema. When the fluid collects in the greater cavities of the body we have hydrops or dropsy. The liquid transudation in oedema and dropsy has never the same composition as blood-plasma ; it is always markedly poorer'in albumen. Tissues which are the seat of oedema swell up ; but the degree of swelling depends in great measure upon the structure of the tissue. The skin and subcutaneous cellular tissue may, in virtue of their structure, undergo extreme distention; an oedematous limb may thus become enormously swollen. It looks pale, is doughy to the touch, and " pits " on pressure with the finger. It is customary to describe oedema of the integumentary structures as anasarca. If an anasarcous part be cut into, the fibrous bundles of the tissue are seen to be separated from each other by clear liquid, which trickles away from the cut surfaces. Other structures, like the kidney, are much less capable of containing large quantities of liquid than are the integuments. When an oedemat- ous kidney, therefore, is cut into, very little liquid flows from it ; but the cut surface looks moist and glistening. The lung can hold a very considerable quantity of liquid. Owing to its narrow accommodation in the thorax, it cannot of course become very greatly distended. But it has within it a multitude of air-cavities, and these fill with liquid when oedema invades it. From these the liquid, ANOMALIES IN THE DISTRIBUTION OF THE LYMPH. 49 generally frothy with air-bubbles, may be squeezed when the lung is cut. The amount of blood contained in cedematous tissues is variable, and so therefore are their color and appearance. Cavities which are the seat of a dropsical effusion contain a greater or less quantity of a clear, generally pale-yellowish, seldom quite color- less, liquid. It has an alkaline reaction, and at times curds of fibrin may be found in it (Art. 35). Compressible organs situate in the dropsical cavity may be flattened, and the cavity itself enlarged. . If the effusion of liquid be general throughout the body we speak of it as general dropsy; if limited to the abdominal cavity it is called ascites. 24. Three varieties of oedema may be distinguished, according to their mode of origin : these are-the oedema of engorgement, inflamma- tory oedema, and hydnemic oedema. The oedema of engorgement, as the name implies, depends upon a disturbance of the circulation. If from any cause the outflow of blood from the veins is hindered, the blood tends to accumulate in the capil- laries and venules (Art. 21). If the degree of obstruction exceeds a cer- tain limit, the plasma seeks a lateral exit and escapes from the vessels. The amount of liquid thus escaping is proportionate to the discrepancy existing between the inflow and the outflow. The escaped liquid is always poor in albumen, poorer even than the normal lymph. It contains, however, a certain proportion of red blood- cells, depending on the intensity of the engorgement. The immediate consequence of increased transudation is an increased flow through the lymphatics. Often enough this may be quite sufficient to convey away all the liquid which escapes. If it is insufficient the liquid collects in the tissues and the result is cedema or dropsy. Obstruction to the outflow through the lymphatics does not usually bring about cedema ; direct experiments have demonstrated this. In the first place, the lymphatics of most parts of the body possess ample anas- tomoses, so that it is not easy for a stagnation of the lymph to occur. Even when the thoracic duct is occluded collateral channels may be opened up and the circulation restored. Furthermore, when in a limb, for example, the whole of the lymphatic outlets have been closed, if no more than the normal amount of transudation from the blood-vessels goes on, no cedema is produced. The blood-vessels themselves have the power of taking up again the lymph they have produced. If the thoracic duct be completely occluded, and no collaterals are opened up, then oedema is the result ; it takes the form of ascites. At the same time the larger lymphatics become greatly distended with accumulated lymph. Though lymphatic engorgement alone is inadequate to produce oedema, it may possibly increase an oedema which has already been pro- duced by increased transudation from the blood-vessels. 4 50 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. 25. The quantity and the nature of the liquid which escapes from the capillaries and veins depend not only on the intravascular pressure and the resistances to the flow, but also to a great extent on the character and condition of the vessel-wall. Alterations in the amount of transudation may thus be referable, not to disturbance of the circulation, but to changes in the vessel-wall, and especially in their endothelial lining. The vessel-wall may in fact be made more permeable for the corpuscular as well as for the liquid constituents of the blood by various causes. One of these is long-standing engorgement, involving incomplete renewal of the blood-supply to the vessel. More serious causes of injury are persist- ent ischaemia, imperfect oxygenation, chemical changes in the blood, very high or very low temperatures, and traumatic lesions. What the exact inj'uries are which these bring about we are not as yet able to say ; but it may fairly be imagined that they amount to a loosening of the con- nections between the endothelial cells of the intima (Arts. 9G-98). It is in virtue of such alterations in the vessels that inflammatory and hydrae- mic oedema are produced. As regards inflammatory oedema no doubt can exist that it orig- inates in some vascular change. It occurs as an independent affection, in the form of a more or less local and circumscribed swelling with drop- sical effusion ; but it may also, as a secondary phenomenon, accompany other processes, like severe inflammation. In the latter case it is often characterized as collateral oedema. Inflammatory oedema is distinguished from the oedema of engorgement by the fact that in the former the exu- dation is very much richer in albumen and white blood-cells ; it is also common for coagulation to take place in the dropsical tissues. Hydraemic or cachectic oedema is very near akin to inflammatory oedema. It was formerly believed that hydraemia, in which the blood is impoverished of its solid constituents, and hydraemic plethora, or over- dilution of the blood with water, might directly give rise to increased transudation from the vessels. It was conceived that the vessel-wall acted like other animal membranes, through which liquids poor in albu- men filter more readily than liquids rich in albumen. This is incorrect. Cohnheim and his pupils have shown that the vessel-wall is not to be regarded as a dead membrane ; it is a living organ. When hydraemia is artificially produced it is not followed by oedema. Even hydraemic plethora produced by overfilling the vessels with diluted blood, though it does lead to increased transudation, does not do so till the dilution has been car- ried to an extreme degree. Even then the oedema does not make its appearance at the parts which are the usual seat of hydraemic oedema in man. We must therefore look for another explanation of the oedema of cachexia and of nephritis (in which disease the function of the kidneys is disturbed). According to Cohnheim, they owe their origin, as we have said, to a change in the vessel-wall. This change is due to the watery character of the blood, or to some deleterious substance circulat- ing in it. ANOMALIES IN THE DISTRIBUTION OF THE LYMPH. 51 Hydraemic oedema, we say, is near akin to inflammatory oedema ; but it is not identical with it. This appears from the fact already alluded to -that the liquid effused in the former is much poorer in albumen than that in the latter, and that it contains considerably fewer of the corpus- cular elements. [The doctrine of oedema in its present form is essentially due to the work of Cohnheim and his school. This is true as well of the theory of oedema from engorgement as of the theory of hydraemic and inflammatory oedema. It was he who made out the nature of the disturbances of the circulation involved in passive hypertemia, as well as the conditions which govern the morbid alterations of the vessel-wall. (See Cohnheiin's " Vorles. ub allg. Pathologic," second edition, 1882, and his "Untersuch- ungen uber die embolischen Processe," Berlin, 1872.) The researches on the consequences of hydraemia and hydraemic plethora were carried out by him in collaboration with Lichtheim ("Virch. Arch.," vol. Ixix.). Solutions of common salt were injected into the vascular system of dogs, but no oedema was produced by this dilution of the blood. When the blood-plasma is increased in amount, almost all the secretions (urine, saliva, bile, intestinal juice, etc.) are forthwith increased. The current of lymph in the lymphatics is also increased, but not in all parts ; nota- bly not in the limbs. In extreme hydraemic plethora the abdominal organs become oedematous, but never the limbs. On inflammatory transudation and oedema, see also Lassar (" Virch. Arch.," vol. Ixix.).] CHAPTER VI. ESCAPE OF THE BLOOD FROM THE VESSELS.-HEMORRHAGE. (THROMBOSIS, EMBOLISM, INFARCTION.) 26. Hemorrhage or extravasation implies an escape of blood (with all its constituent elements) out of the vessels into a tissue, or upon a free surface. It may be arterial, venous, capillary, or from all the ves- sels together, in which latter case it is termed " parenchymatous." Such an extravasation into a tissue takes on various appearances according to the quantity of blood which has escaped ; and special names are given to some of these. When the quantity is small and forms more or less sharply defined red or brown spots, these are called petechiae or ecchymoses; when larger and less defined they are sugillations or sanguineous suffu- sions. If the affected tissue is completely infiltrated by the escaped blood, we speak of it as a hemorrhagic infarct. If the blood forms a tumor or swelling, it is called a haematoma or blood-tumor. Hemorrhage in quantity always causes serious changes in the tissue invaded ; not infrequently (as in the brain) the tissue is stretched, torn, and disintegrated. If the bleeding take place from the free surface of an organ, the blood flows away either altogether or into the cavity which is bounded by the free surface. Certain hemorrhages have received names from the localities in which they occur. Thus bleeding from the nasal mucous membrane constitutes epistaxis; vomiting of blood is heematemesis; bleeding from the lungs gives rise to haemoptoe or haemoptysis; from the uterus to metror- rhagia ; from the urinary organs to haematuria. A collection of blood in the uterus is called haematometra, in the pleural cavity haemothorax, in the tunica vaginalis of the testicle haematocele, in the pericardium haemopericardium. Fresh effusions of blood have the color characteristic of arterial or of venous blood, as the case may be. In the course of time the extravasation undergoes certain well-marked changes. Especially remarkable are the changes of color seen in ecchy- moses and sugillations of the skin, which pass through tints of brown, blue, green, and yellow. Ultimately the extravasation is absorbed (Arts. 68 and 112-116).' ANOMALIES IN THE DISTRIBUTION OF THE LYMPH. 53 27. The escape of blood from the vessels occurs in two distinct ways. A large and sudden hemorrhage always implies a solution of continuity in the vessel-wall. This has been distinguished as hemorrhage by rup- ture {per rhexin, per diabrosin) or, clinically, as apoplexy. Such solu- tions of continuity are the only causes of arterial bleeding; but from veins and capillaries bleeding may occur in another way, namely by what is called diapedesis. In this process the blood passes through a vessel- wall in which no rent exists. The escape is not sudden but gradual. The blood-cells slip through the vessel-wall one after the other. Liquid escapes at the same time ; but it is not simply plasma, for it contains less albumen (Arts. 24, 25). These hemorrhages often remain small and cir- cumscribed; but occasionally the process continues for a longer time, and then the infiltration of the tissue with blood-cells may go on to a serious extent. It must not be supposed that hemorrhage by apoplexy (or rup- ture) is always large, or hemorrhage by diapedesis always small. A rent in a capillary or a small vein will give rise to no great loss of blood; while the hemorrhage from long-continued diapedesis may reach an alarming magnitude. In a given case it is often by no means easy, often indeed quite impossible, to decide whether hemorrhage has occurred by rupture or by diapedesis. [The process of diapedesis may be observed under the microscope. For this purpose the mesentery or the foot-web of a frog is used (Cohnheim). If the veins of outflow have first been ligatured, the capillaries and veins of the membrane are seen to be crammed with blood. After a certain time the red blood-corpuscles begin to escape from the capillaries and veins (compare Cohnheim, " Allgemeine Pathologic," i., and " Virch. Arch.," vol. xli.). The process is to be regarded as one of filtration (Her- ing, " Sitzungsberichte der Wiener Akademie," 57, 1868). As a result of the arrested outflow the blood seeks to escape laterally ; it is in fact squeezed through the vessel-wall. We owe to Arnold some very beautiful researches upon the diapede- sis of red blood-corpuscles, as well as of other particulate substances in- troduced into the vessels ("Virchow's Archiv," vols. Iviii., Ixii., Ixiv.). Arnold at first thought it must be admitted that at the points of escape of the particles holes or slits occur, which he called stigmata and stomata ; afterward, however, he recognized the supposed openings to be merely ag- gregations of the intercellular or cementing substance of the endothelial cells. Under pathological conditions this substance becomes loose, and readily permits the corpuscular elements of the blood to pass through. Some beautiful physical experiments in illustration of the processes in- volved in diapedesis have been lately described by Hamilton (" Proc. Roy. Soc. Edin.," vol. xi.). See also Schklarewsky, "Pfliiger's Arch.," vol. i.).] 28. The cause of rupture of the vessel-wall is either traumatic injury, or disease of the wall itself. In all so-called spontaneous hemorrhage we 54 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. must take it for granted that the latter cause is in action. Newly formed vessels are likewise very easily torn. Increased blood-pressure of course tends toward rupture of the vessel-wall, but it never actually produces it if the vessel be perfectly sound. Diapedesis comes into play when the pressure is raised in the veins and capillaries, and also when, coeteris paribus, the vessel-wall becomes more permeable. It is very rapidly set up by obstructing the outflow of venous blood. The nature of the change in the vessel-wall which results in greater permeability is not yet completely understood ; but it is known at least that the exciting cause of the change is a disturbance in tissue-nutrition (Art. 25). Thus it may be produced by temporarily checking the blood-supply of the vessel, or by direct injury to the vessel- wall. Moreover, certain poisons introduced into the blood may lead to the change. The vessel-wall must, in fact, be directly or indirectly damaged. Sometimes the defective structure of the vessel-wall is congenital. There are persons who show a great tendency to bleed upon small occa- sion. These are called " bleeders," and are said to exhibit the hemor- rhagic diathesis or haemophilia. What we may describe as an acquired hemorrhagic diathesis is ex- hibited in the diseases known as morbus maculosus or purpura, and scurvy ; as well as in many of the infectious fevers and toxaemic affec- tions, such as septicaemia, spotted typhus, small-pox, plague, icterus gravis, yellow fever, nephritis, phosphorus poisoning, etc. In some cases of haemophilia neonatorum and of endocarditis, collections of bacteria have been found to be the originating cause of hemorrhage. Such hemor- rhages are sometimes slight, sometimes very serious. They occur chiefly in the skin, mucous membranes, and serous membranes.. Similar hemorrhages also occur sometimes in connection with troubles of the cen- tral nervous system, chiefly in the stomach and the lungs. [Full references to the literature of haemophilia are given by Legg, (" Haemophilia," London, 1872, and St. Bartholomew's Hospital Reports, 1881), and by Immermann (" Ziemssen's Cyclop.," vol. xvii.). Hemorrhages occurring in connection with brain affections have been observed in the human subject, and have also been experimentally pro- duced in animals (Jehn, " Allg. Zeitschrift f. Psychiatric," 1874 ; Char- cot, "Lemons sur les maladies du systeme nerveux," i., 1875 ; Ebstein, "Arch. f. exper. Path.," ii.). Ziegler has twice noted serious hemorrhages of this kind in epileptics. In one case three-fourths of each lung was completely filled with blood. He has likewise met with extensive hemorrhage into the lung in a pa- tient who died of traumatic softening of the brain.] 29. The obstruction of arteries and veins plays the chief part in the production of irregularities in the circulation, and of hemorrhages. This ANOMALIES IN THE DISTRIBUTION OF THE LYMPH. 55 obstruction may arise in various ways, from without by ligature or com- pression, from within not infrequently by thrombosis. By this term is meant the formation of a coagulum or blood-clot within the vessel during life (Arts. 35 and 252-255). This coagulation occurs for the most part when the circulation is already weakened or arrested, and the vessel-walls diseased. The result is that the lumen of the vessel is first narrowed, and then as coagulation proceeds is blocked altogether. In the former stage the thrombosis is called concentric or incomplete; in the latter it is obstructive. Thrombi are formed oftenest in the veins, but thev occur also in the arteries and in the heart. If a thrombus becomes loosened from the vessel-wall, and so gets into the blood, it is carried on by the current. Tn this way it may pass from the systemic veins into the pul- monary arteries, or from the heart and greater arteries into the smaller ones. It becomes then wedged in at the point where its size corresponds with the section of the vessel ; and then by adapting its form to that of the lumen, or by setting up fresh coagulation on its own surface, it speed- ily blocks the vessel altogether. A thrombus thus swept into the vessel from a distance is called an embolus. It is generally situated at the bifurcation of an artery. The consequences of embolism are very various. Often enough the tissue concerned is very slightly affected ; in other cases it may undergo anaemic necrosis (Art. 33); in others still what is called embolic infarc- tion. 30. The bleeding which sometimes ensues upon thrombosis of a vein is, as we have seen in Arts. 27 and 28, the immediate result of arrested outflow through the natural channels. The consequences of the closure of an artery have already been touched upon in Art. 22. The immediate consequences are these-First of all, the circulation is brought to a stand- still, and the region beyond the block becomes anaemic. If the arterial twigs of this region are connected directly with some other unobstructed artery, the latter forthwith dilates and conveys a sufficient quantity of blood to irrigate the starved region. The circulation is thus speedily re- established. If, however, the vessels of the region possess no such collateral con- nections, the region itself is altogether deprived of fresh blood, and sooner or later perishes (Art. 33). If the embolized artery be, as Cohnheim calls it, a terminal artery, having no arterial anastomoses, a scanty influx of blood to the tissues from the contiguous veins and capillaries may still be possible. It is in this way that a hemorrhagic infarct is produced. The capillaries of the anaemic region become gradually filled with blood, partly derived from the capillaries of neighboring regions, partly from slow reflux out of the veins. The blood oozing in from the neighboring capillaries is under a very low pressure. This pressure is insufficient to propel the blood out of the obstructed capillary system into the corresponding veins again. The blood therefore stagnates, and the capillaries become ever more and 56 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. more engorged. Of course, whatever reflux takes place from the veins can only carry blood into the capillary system; it cannot suffice to drive the blood through the capillaries. In consequence of this engorgement, due to lack of propelling power, diapedesis is soon established, just as in complete obstructions of the venous outflow. The escape of blood is further aided by the disorganiza- tion of the vessel-wall, set up by the cessation or serious diminution of its supply of nutriment. The ultimate result of the diapedesis is the infil- tration of the entire tissue with blood, and the formation of a firm, gen- erally conical, hemorrhagic patch. Embolic infarcts of this kind are found chiefly in the lungs, the spleen, and the kidneys. As to their final fate see Art. 37. [The fundamental experiments on thrombosis and embolism were ori- ginally made by Virchow (" Gesammelte Abhandlungen," Frankfurt a. M., 1856). Virchow referred the production of the embolic infarct to increased flow in the arteries of the contiguous regions, consequent on the ischaemia of the region considered. This involved an increased lateral pressure within the vessels, and so increased tendency for the blood to escape. Cohnheim (" Untersuchungen uber die embolischen Processe," Berlin, 1872), examining directly the results of embolism in the frog's tongue, established the existence of the reflux from the veins, the gradual refilling of the capillaries, and the escape of blood by diapedesis. The efficient cause of the diapedesis he considered to be an ischaemic disorganization of the vessel-wall. Litten (" Untersuchungen fiber den hamorrhagischen Infarct," Berlin, 1879) regards the reflux from the veins as non-essential, and refers the refilling of the capillaries to the influx from continuous regions. Even disorganization of the vessel-wall is, according to him, unessential to the production of an infarct; inasmuch as diapedesis is completely accounted for by the mere fact of engorgement (as is seen when the veins are obstructed). Diapedesis is for this reason increased when it chances that the blood coagulates in the vein of outflow from the embolized region.] CHAPTER VII. LYMPHORRHAGIA. 31. Lymphorrhagia occurs when a lymphatic vessel is ruptured and the contained lymph is effused into the tissues around. The pressure in the lymphatics is very low, scarcely higher, that is to say, than that in the contiguous tissues. An escape of lymph from the vessel can therefore occur only when a cavity already exists at the place of rupture, or when one is made by the same injury which rent the vessel. Thus in wounds, for example, we see lymph and blood escaping together ; but the flow of the lymph can be arrested by interposing a very slight resistance. If the opening in the surface be not closed up after the rupture of a lymphatic, so that lymph continues constantly to escape, as sometimes happens in the case of ulcers, we have lymph-fistulse formed. Such fistulee may lead to the loss of very considerable quantities of lymph. The most impor- tant lesion of this kind, as well as the most likely to be dangerous, is rupture of the thoracic duct. This has occasionally been observed as a consequence of a wound ; but more commonly of engorgement from closure of the lumen of the duct by inflammation or tumor. The lymph escaping into the thoracic or abdominal cavity gives rise to chylous hydrothorax or chylous ascites. [References :-Curnow, " Lectures on the Lymphatic System," Lancet, 1, 1879 ; Day and Hill, "Trans. Clin. Soc.," 1869 ; Cayley, "Trans. Path. Soc.," 1866. ] SECTION III. RETROGRESSIVE DISTURBANCES OF NUTRITION. CHAPTER VIII. NECROSIS. 32. Everything that lives comes sooner or latA- to an end-it dies. Death makes its appearance so soon as the vital energy of the organism, infused into it when it was first engendered, is exhausted in antagonizing external resistances. Besides this death of the organism as a whole, or somatic death, we recognize what we must regard as a localized death ; a death, that is to say, of individual cells or cell-groups, which we call necrosis. The occurrence of local death or necrosis in a cell-group or entire organ is only in special cases associated with recognizable changes in structure. The slight histological changes the cells undergo in dying are not always enough to indicate with certainty the exact factor which has caused life to cease. The naked-eye appearances of the larger organs do not always betray the fact that some part of them has become necrosed. Even the cessation of the obvious functions of an organ may leave us in doubt whether, as in necrosis, the cessation is permanent, or whether the functions are merely suppressed for a time. Thus we can only subject necroses to anatomical examination, when death of the tissue involves change in its structure either consequent or antecedent. The latter occurs only to a limited extent ; the former (i.e., change consequent on necrosis) on the other hand is invariably found after a longer or shorter interval. The varieties of necrosis are in fact distinguished from each other according to the nature of these consecu- tive tissue-changes. 33. The injuries which .lead to local death are divisible into three groups. The first includes those which destroy the tissue by their me- chanical or chemical action. Thus external violence may crush a fin- ger ; sulphuric acid may destroy a patch of skin ; and fungous parasites may disorganize the structure of a gland in which they are permitted to grow. A second group of injuries may be classed as thermal. If the temperature of a tissue be maintained at 54° C. to 58° C. for any time, the tissue is inevitably killed. Higher temperatures act still more rapidly. The lower limit within which life may be maintained is 16° C. to 18° C. A third cause of necrosis is arrest of nutrition. This produces " an- aemic necrosis," and occurs very frequently in the human subject. 62 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. All causes which seriously interfere with the circulation of a part, and bring about permanent arrest of its movement, or stasis, may lead to the death of the affected tissue. Such causes are thrombosis, embolism, clos- ure of the vessels by disease or ligature, pressure on the tissue, inflamma- tion, hemorrhag-e, etc. The arrest of the circulation need not, however, be permanent ; it is enough if it persists longer than a certain time- necrosis still ensues. It is unimportant whether or not hemorrhage then takes place (Art. 30); this will only affect the external appearance of the part. Hemorrhagic infarction is thus pathologically equivalent to anaemic necrosis plus hemorrhage. It is of course possible that mechanical, chemical, and thermal agen- cies may act together. Not infrequently they come into play successively in the same case. The effect of a given injury in producing necrosis depends not merely on the normal character and strength of the tissue, but also to an essen- tial extent upon its condition for the time being. A tissue whose nutri- tion has suffered in consequence of deficient or vitiated blood-supply, general marasmus, or hydrmmia, is much more apt to necrose than when it is in its normal state. Thus in old patients, and in those suffering from uncompensated valvular disease of the heart, very slight injuries are enough to induce necrosis of the limbs. In emaciated typhoid patients the slightest pressure on the skin over the trochanter, elbow, sacrum, or heel, suffices to bring on gangrenous necrosis of the skin and subcutan- eous tissues. Such necroses are described as senile or marasmic gangrene, and decubitus ^bed-sores j or decubital necroses. [The time required to produce necrosis by interruption of the blood- supply is different in different tissues. Brain tissue, renal epithelium, and intestinal epithelium, die within two hours (Cohnheim, " Allgem. Pathologie "). Skin, bone, and connective tissue, continue to live over twelve hours. In general it may be laid down-that tissues which exer- cise special functions die much more quickly than those which, like con- nective tissue, possess only the faculty of self-preservation, so to speak.] 34. The course of the necrosis the character of the tissue-changes it involves) is influenced by such circumstances as the nature of the tissue, its locality, and the form and cause of the necrosis. Not less important are the amount of blood and proper fluid or juice contained in the tissue, and the access or exclusion of air and of putrefactive ferments. Moreover, there may be antecedent tissue-changes which are not with- out influence on the necrotic process, such, for example, as fatty degen- eration, inflammation, and hemorrhage. We thus see that even if the necrotic process be in itself simple, i.e., associated with only slight histolog- ical change, the consecutive changes it involves may yet be very manifold. We proceed to discuss the chief forms which have been observed. A constant result of the death of a portion of a tissue is more or less RETROGRESSIVE DISTURBANCES OF NUTRITION. 63 severe inflammation in the surrounding portions. This is most severe when decomposition sets in in the dead portion. By means of this in- flammatory zone, the necrosed region is in a way marked off and isolated from the rest. The inflammation is hence described as definitive, and the zone as the line of demarcation. The process is more fully treated in Arts. 112-116. Among the various terminations of necrosis we may distinguish four main types. We exclude special complications, such as the development in the necrosed tissue of specific irritant matters. In the first class, the dead tissue is absorbed and replaced by newly formed normal tissue (re- generation, Arts. 72-80). In the second, the dead tissue is likewise absorbed, but is not replaced by normal tissue ; an inflammation in situ is followed by the formation of fibrous tissue, which fills up the gap in whole or in part (healing by scar or cicatrix, Arts. 112-116). In the third, the necrosed tissue is only partially absorbed, a part remaining as a caseous mass ; this later on becomes in general calcified and enclosed in a capsule of connective tissue (caseation and calcification, Arts. 112-116). The fourth issue is the formation of a cyst. The dead tissue is absorbed, and in its place there is developed a small amount of fibrous tissue, but only over the boundary of the vacated space. In other cases, this space becomes filled with fluid, which is thus encysted. This hap- pens oftenest in the brain. a. Coagulative (Hyaline or Fibrinous) Necrosis. 35. Necrosis accompanied by coagulation occurs in two ways. In certain of the vital fluids like the blood and lymph, and in fluids which have escaped from the vftsels, granular, fibrous, or homogeneous coagula are formed ; that is one kind of necrosis. In the other, cells and cellular structures as they die become solid and firm, and coalesce into peculiar homogeneous or hyaline masses. The granular, fibrous, and hyaline masses which make their appear- ance when blood coagulates are albuminoid bodies ; and we speak of them in general terms as fibrin. This fibrin takes the form of flakes or curds, shreds, lumps, or membranes. If red blood-cells are enclosed in the meshes of the fibrin as it separates, the clots are soft and dark red in color. If coagulation does not take place in the plasma till this has separated from the red blood-cells, the clots produced are pale yellowish, soft, gelatinous, watery, translucent, and somewhat tenacious ; after a time they contract and so become drier and tougher. In lymph, mere flakes only are formed. According to current theories, coagulation of the blood, or of the lymph, occurs when the white corpuscles die and dis- solve in the plasma. Alex. Schmidt affirms that the plasma contains fibrin- ogen only. To bring about coagulation, that is the formation of fibrin, the presence of fibrinoplastin and of a ferment is necessary. Both of these are supplied by the white corpuscles as they dissolve in the plasma. 64 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. Inflammatory effusions or exudations may coagulate as blood does, and so yield masses containing a large amount of fibrin. These may lie on the surface of the inflamed tissue in the form of false membranes (Fig. 1). The fibrinous masses may be made up of granules, of delicate fibres, of coarse-meshed trabeculae (Fig. 1, c), or of homogeneous flakes. [Alexander Schmidt's researches on blood-coagulation are to be found in his paper :-11 Die Lehre von den fermentativen Gerinnungen," Dorpat, 1876. Montegazza has pursued similar investigations-(Moleschott's " Untersuchungen zur Naturlehre," 1876). For other papers, see Gam- gee's "Physiological Chemistry," vol. i., chap. 2. Wooldridge ("Proc. Roy. Soc.," 214, 1881, and "Du Bois-Reymond's Arch.," 1881) has re- cently published the results of a research conducted in Prof. Ludwig's laboratory at Leipzig^ in which he seeks to make out that coagulation is mainly due to the action of deleterious liquids on the blood-cells. In Fig. 1.-Croupous (false) Membrane from the Trachea. + 250. a, section through the false mem- brane ; &, upper layer of the mucous membrane, infiltrated with pus-cells dl; c, fibres and granules of fibrin; d, pus-cells. shed blood the plasma "dies" and becomes deleterious in this sense ; its action on the cells, especially the white cells, makes them break up and coalesce into a coagulum. A ten per cent, salt solution would have the same effect. The factors of fibrin are said to be furnished by Hayem's haemato- blasts, and by Bizzozero's " Blutplattchen." The latter have been re- cently described (" Centralb. f. d. med. Wiss.," 2, 1882) as small, very transient, delicate, colorless discs. According to Bizzozero it is the breaking up of his " Blutplattchen " which alone determines coagulation. The true significance of these bodies is not yet determined. They are perhaps mere decolorized red blood-cells. Full discussions on the subject of fibrin and its origin are to be found in Virchow's " Gesammelte Abhandlungen," 1856. The intra-vascular coagulation of the blood is treated more adequately in Art. 252. It is possible that, in the coagulation of liquids contained in cellular tissues, the fibrinoplastic substance is yielded by the tissue-cells. These latter either dissolve altogether, or they permit their protoplasmic contents to escape in the shape of simple homogeneous masses.] RETROGRESSIVE DISTURBANCES OF NUTRITION. 65 36. In the second form of necrosis with coagulation, the knowledge of which we owe chiefly to Weigert, the circumstances and the appear- ances presented are essentially different from those of the first. Here, as before, we have to do with the death of tissue occurring under special conditions, and resulting in the formation of coagulated albuminoids ; but the coagulation takes place not in a liquid but in the substance of formed tissue-elements, in cells and cellular or intercellular structures. If by reason of arrested nutrition, or by the action of chemical or thermal agencies, a definite segment of an organ be caused to die, and if then a moderate amount of lymph happen to flow through the necrosed segment, we have the conditions which give rise to coagulation within the tissue. The lymph contains fibrinogen, the cells contain fibrinoplas- tin ; between them fibrin is produced. Cohnheim introduced the term coagulative necrosis to describe this special form of local death. Sometimes at least it may be fitly spoken of as hyaline necrosis. In this process the cells alter their appearance in various ways. The ultimate effect is always the destruction of the cells as such. The varieties of morphological change observed in coagulating cells and tissues are dependent, partly on diversity of structure in the tissues, partly on the quantity of fibrinogen effused. The manner in which ne- crosis has been brought about is indifferent ; but the dying of the tissue must not be too protracted, or degenerative processes, such as fatty change, may intervene and render the cells non-coagulable. [The chief investigations on this subject of coagulative necrosis are those of Weigert. A summary of his results is given in " Virch. Arch.," vol. Ixxix. The proof of the fact-that interfusion of lymph may cause the destruction of cells and the disappearance of their nuclei-was ef- fected by introducing hardened pieces of tissue into the abdominal cavity of rabbits. These tissues were transformed in the manner described. Similar cell-changes to those produced in coagulative necrosis, and more especially the disappearance of nuclei, may also result from mere putrefaction. Coagulative necrosis may also be found combined with other retrogressive changes, such as fatty degeneration.] 37. Among the numerous cases in which coagulative necrosis takes place must be mentioned embolic infarction. A certain time after the obstruction of an artery of the kidney or spleen, there is found lying beneath the capsule an opaque yellowish-white conical patch. This patch consists of necrosed kidney- or spleen-tissue, with perhaps fragments of disorganized and completely decolorized blood-clot. If the patch be microscopically examined in unstained sections, its structure will be found almost normal, though paler than the surrounding parts. The difference becomes, however, sharply defined when the section is stained, for the necrosed part is incapable of taking up color. The cells are strikingly pale and transparent, and their nuclei are either gone, or 5 66 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. swollen up and unstained. In later stages the outlines of the cells be- come blurred, the nuclei vanish, and the cell-contents are metamorphosed into a finely granular fibrinous mass. Later still this mass disintegrates and is absorbed (Art. 115). If the infarct was originally hemorrhagic, the effused blood, like the tissue-elements, is changed into a colorless granular, or it may be homogeneous, mass. [Minute investigations into the nature of hemorrhagic infarction have recently been made by Litten (" Untersuchungen uber den haem. Infarct," Berlin, 1879) and Guillebeau (" Die Histologie d. haem. In- farctes," In. Diss. Berne, 1880). According to Litten, renal infarcts are generally anaemic, i.e., not accompanied by hemorrhage. Guillebeau, on the contrary, says that both renal and splenic infarcts are generally hemorrhagic, but become very quickly decolorized. Ziegler inclines to the latter view, though he has examined recent infarcts in which he was unable to demonstrate either hemorrhage or its traces.] 38. The so-called waxy degeneration of muscle (Zenker) is also an instance of coagulative necrosis. Muscle-fibre invariably coagulates after death, but generally preserves its striation. Under various influ- Fig. 2.-Waxy Degeneration of Muscle, x 250 (From a case of typhoid fever.) a, normal muscle- fibre ; b, degenerate muscle-fibre broken up into flaky lumps; c, regenerative cells lying inside the sarco- lemma; d, connective tissue infiltrated with cells. ences, however, as e.g., after bruising, forcible extension, raising of the temperature, or febrile disease, the muscle substance is here and there disintegrated, and the contractile myosin coagulates into a lustrous homogeneous mass (Fig. 2, b}. This mass breaks up into shining flaky lumps. To the naked eye muscles so affected have a dull semi-opaque lustre, and look not unlike the muscles of fish. Coagulative necrosis very often occurs in the course of inflammatory RETROGRESSIVE DISTURBANCES OF NUTRITION. 67 processes. It is hardly ever quite absent where there has been copious exudation. In such cases it may take one of two forms. Either the effused fluid dissolves up the contained cells and then coagulates (Art. 35, Fig. 1, and Art. 102) ; or the tissue-cells themselves coagulate, forming homo- geneous lumps or fibrous reticulated masses. To give an example, the ordinary stratified epithelial cells (Fig. 3, a) of the pharynx and soft pal- ate in diphtheritis faucium (diphtheria) solidify into a peculiarly formed trabecular mesh-work (Fig. 3, c). Similar changes in the epithelium are observed in various cutaneous inflammations, such as small-pox. The ag- Fig. 3.-Section through the Uvula in Diphtheritis Faucium. x 75. (Aniline staining.) a, normal epi- thelium ; b, normal areolar tissue ; c. necrosed epithelium transformed into a coarse mesh-work; d, areolar tissue infiltrated with fibrin and leucocytes ; e, blood-vessels ; f, hemorrhage ; g, heaps of micrococci. gregations of cells which accumulate in simple inflammation may also solidify into pale hyaline flakes or granular masses. Such solidifications occur, for example, in typhoid infiltration of Peyer's patches and of the lymphatic glands, and in the cellular exudations which fill the pulmonary alveoli in caseous broncho-pneumonia. The formation of continuous hya- line masses out of cellular material may be typically seen in diphtheritic desquamation of mucous membranes (Arts. 103 and 425) ; the entire in- filtrated tissue sometimes solidifies in this manner. The ground-substance of connective tissue, hyaline membranes, the walls of blood-vessels, etc., are all liable to be transfused with coagulable liquid, and then to coagulate into homogeneous masses. S. Caseation. 39. Caseation (or tyrosis) is a pathological transformation of tissue, whose product somewhat resembles in appearance firm new Cheshire cheese on the one hand, or soft cream cheese on the other. The name 68 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. refers merely to the outward appearance of the product ; the process which leads to its formation is by no means always the same. In the first form of caseation-in which the degenerated tissue is firm, tough, yellowish-white, and somewhat translucent-the process is one of coagulative necrosis. This occurs most frequently in tissues which are rich in cells ; for example, in the foci of tuberculous disease, in cellular tumors, and in inflamed lung. A tissue which has become completely caseous is always devoid of nuclei, and is either homogeneous or finely granular. The transformation of a tissue into a firm cheesy mass may occur in one of three ways. The tissue may gradually assume as a whole a more and more homogeneous appearance, losing its nuclei the while. Or detached homogeneous masses may first be formed, which later on fuse together into a continuous mass. Or lastly, the tissue-cells may first dissolve and be replaced by granules and granular fibrils of fibrin ; these last then close up and coalesce into a dense uniform mass. The last process is chiefly observed in the caseation of the cellular exudations of pneumonia ; the first chiefly in tissues which, in consequence of chronic inflammation or tuberculosis, are the seat of a fibro-cellular hyperplasia. It should be noted that caseating masses originally homogeneous may, by subsequent transformation, take on a more granular appearance. The softer form of caseation changes the tissue to a dull white. The chief part of the mass is made up of granular fatty and albuminous detri- tus. Neither cells nor cellular structures are any longer recognizable. This form of caseation is generally the result of a fatty disintegration of cellular tissues or exudations (Arts. 50-54), which have lost water by absorption. The tissue thereupon becomes inspissated, and its opaque appearance is due to the formation in it of minute oil-globules. The firmer and softer forms of caseous change are not very sharply distinguished. At times both forms may be found together in one organ. It is even possible for the firmer form to be transformed, by processes physical or chemical, into the softer. The ultimate fate of caseous foci is either softening and liquefaction with absorption (Arts. 112-116), or calcification. c. Colliquative Necrosis or Softening. 40. Colliquative necrosis, in which the affected tissue "becomes as it were liquefied, is closely akin to coagulative necrosis. In each case the necrosed parts become saturated with liquid. Colliquation may thus either precede or follow upon coagulation. For example, the coagulation of the blood and formation of a clot is preceded by the liquefaction or solution of certain cells contained in the blood. A similar process may be observed in the case of blisters following upon burns. The first change perceived is an enormous swelling up of the epidermal cells overlying the papillse (Fig. 4, d) ; the cells being wholly or in part killed by the action of the heat. This swelling up depends on the ab- RETROGRESSIVE DISTURBANCES OF NUTRITION. 69 sorption by the dead cells of the liquid which transudes from the papillary vessels. It becomes at length so extreme that the cell-substance dis- solves completely and the cell-membrane itself disappears. Not until the tumefaction and colliquation have reached a certain point-i.e., when the cell is distended to a mere vesicle, or has gone altogether-do the granular fibrils which indicate coagulation begin to appear (f, g, h). In some tissues this coagulation after colliquation does not occui-. Thus in anaemic necrosis (softening) of the brain we have simply disintegration and liquefaction of the brain-substance. The several con- stituents of the tissue break up, and dissolve in the liquid which is poured out from the vessels. They are then absorbed, and the liquid Fig. 4.-Section through the Epidermis and Papillae after a Burn, x 250. The preparation (carmine- stained) is from a cat's paw which had been burned with melted sealing wax. a, horny layer; b, rete Mal- pighii; c, normal papilla ; d, swollen epithelial cells (in some the nucleus is still visible, in others not); e, interpapillary cells (those below are uninjured, those near the surface are swollen and stretched); f, fibrin- ous mesh-work (composed of cells and exudation; cell-structure altogether lost) ; g, swollen cells without nuclei; A, interpapillary layer of cells stripped off and destroyed ; k, subepithelial exudation (coagulated) ; i, depressed papilla, infiltrated with cells and disappearing. becomes gradually clear again ; but there is no coagulation. The reason of this probably is-that brain-substance contains but few coagulable matters, and on the other hand that the effused lymph, not being the re- sult of acute inflammation, contains but little fibrinogen or fibrinoplastin. The same thing is at times to be observed in other tissues, as for instance in so-called " softening of the heart," when the muscle-substance has already undergone fatty degeneration. Here the antecedent degenera- tion has notably diminished the amount of coagulable matter in the muscular tissue. But colliquation of the tissues may follow upon coagulation as well as precede it. It is a very frequent occurrence for coagulated exudations (as in croupous pneumonia) or thrombi to break down and liquefy. This liquefaction of coagulated masses is always accompanied by certain 70 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. chemical changes, the efficient causes of which are frequently of the nature of organized ferments (Art. 42). d. Dry Gangrene or Mummification. 41. Dry gangrene is commonly the result of necrosis in parts which are exposed to the air. Typical examples are afforded by the so-called senile gangrene of the extremities, especially of the toes and feet ; and likewise by the necroses of the same parts following upon frost-bite. In the first case, the necrosis is determined by defective blood-supply, partly owing to general feebleness of the circulation, and partly to local changes in the blood- vessels. The affected part is generally engorged with blood when necrosis sets in, and thus exhibits a dark or livid coloration. The engorgement is due to stagnation of the blood-current from mere feebleness of propulsion. After the death of the part, the coloring-matter of the blood transudes and gives the tissues their dark-red appearance. At the same time the tissues begin to dry up by evaporation. This drying process is notably accelerated when the epidermis separates, as happens when the engorge- ment has been extreme, and in frost-bite. The part becomes first leathery, and then perfectly hard, brittle, and black. Under the micro- scope the tissue-elements are seen to be shrunken and withered. Dry gangrene or withering is a physiological process as it affects the stump of the umbilical cord in infants. Between the sound tissue and the gangrenous there is formed an inflammatory line of demarcation (Art. 115). Dry gangrene may at times occur as a later stage of moist gangrene. e. Moist Gangrene, or Sphacelus. 42. Moist gangrene is necrosis followed by decomposition and putrefaction of the necrosed tissue. If septic organisms reach a dead tissue which is rich in blood or other liquid, it very soon begins to de- compose. The organisms may reach the part either directly from the air (as in gangrene of the skin or lungs), or through the channel of the circulation (as in gangrene of the testis, or of the foot). Parts which are exposed and abound in blood-vessels, such as the foot, become livid from diffusion of the coloring-matter of the blood. The epidermis frequently rises in blisters and bullae. Soon the putrefying tissue begins to stink, and then to disintegrate. Slight mechanical causes readily give rise to wounds, and in these the tissue is seen to be infiltrated with discolored blood, and it is brittle or even tinder-like. Corresponding to the obvious naked-eye disintegration of the structure are the profound chemical changes which take place (Arts. 191, 192) ; and the final result is the total destruction of the tissue as such. Not infrequently gases are RETROGRESSIVE DISTURBANCES OF NUTRITION. 71 evolved during the process, giving rise to so-called gangrenous emphysema {gangrene gazeuse). The rapidity of the destructive pro- cess depends greatly on the nature of the affected tissue. Bone pre- serves its form for a long time in the midst of a gangrenous mass, while the soft parts perish very quickly. The microscope shows that in this process of decay septic organisms are always present (Arts. 192 et seq.). Blood-corpuscles quickly cease to be distinguishable, inasmuch as they break up and dissolve, or here and there become transformed into granular pigmented masses. Other cells become turbid, lose their nuclei, break up, and disappear. Fat-cells disintegrate, and the oil they contain mingles in small globules with the gangrenous mass. The fibres of the connective tissue swell up, grow turbid and ill-defined, and finally dissolve. Elastic tissue, tendon, and cartilage hold out for a long time, but ultimately perish in like manner. In general terms we may put it-that gangrene involves the gradual solution of the solid constituents of the tissue, and results in the forma- tion of a dirty gray, grayish-black, or grayish-yellow, opaque, semi-fluid mass, mixed with shreds and remnants of various structures. The various normal elements of the tissue thus disappear in succession ; while new crystalline products of chemical decomposition appear instead, such as fatty needles of margarin, needles of tyrosin, spherules of leucin, " sar- cophagus-crystals " of triple phosphates, and granules of black or brown pigment. In the later stages of putrefaction, mould-fungi at times make their appearance on parts exposed to the air (Art. 221). [Further details of the tissue-changes in gangrene may be found in Demme, " Ueber die Veranderungen der Gewebe bei Brand," Frankfort, 1857 ; and in Rindfleisch, " Pathological Histology" (Sydenham Soci- ety). See also Chauveau, " Necrobiose et gangrene," Paris, 1873 ; Paget, " Surgical Pathology." Putrid decomposition, and therefore also gangrene, can arise only through the agency of micro-organisms. Furthermore, the presence of a certain proportion of water in the tissue is essential. If the tissue dry up, the development of septic organisms ceases, or is at least seriously retarded ; and with it also the process of decomposition. The chemical products of the gangrenous decomposition of the tissues are hydrocar- bons, ammonium sulphide, sulphuretted hydrogen, valerianic acid, buty- ric acid, etc. ; and ultimately carbonic acid, ammonia, and water.] CHAPTER IX. SIMPLE ATROPHY AND PIGMENTARY DEGENERATION. 43. In treating of malformations, we showed that in consequence of arrested development members, organs, or parts of organs may be ill- grown, misformed, or altogether wanting. Or if the plastic energy that determines growth be deficient, the entire organism or some of its parts may be dwarfed and stunted. Defective development of this kind, i.e., aplasia or hypoplasia, may occur after birth as well as before it. So long as the organism continues to grow, so long as new parts or organs con- tinue to be formed in it, so long is its growth liable to be checked by external or internal influences. We may often observe this hypoplasia in the child. At birth it may have been anything but puny, yet under the operation of external causes, such as defective nutrition, various kinds of disease, or others less easily recognized, it latex* on shows signs of imperfect development in some of its systems or organs. The consequence is a dwarfing of the entire frame or of its parts, very often associated with faulty structure and function of the viscera. This hypoplasia makes itself especially evident when the bones are badly developed, as also when the heart and great vessels, the genital organs, or the central nervous system are undergrown. The association referred to is observed, for example, in cretins, whose bones are generally ill-grown ; and in chlorotic females, where with hypoplasia of the vascular system there is also some imperfection of the generative functions. Now atrophy is not to be confounded with such hypoplasias or aplasias. In atrophy we have to do not with defective development, but with retrogressive change in parts originally well formed and well grown. 44. The life of an organ, like that of an individual, is limited in its duration. The active cell-growth of the period of development is suc- ceeded by a stage in which the formative activity is less marked. In the latter stage the equilibrium between cell-growth and cell-decay is main- tained with but slight oscillations to one side or the other. In old age this equilibrium is disturbed, and decay has the upper hand. An involution (the reverse of evolution) of the entire organism and of its parts takes place. Thus a man ultimately dies, even when there is no question of disease, so soon as the advancing involution of his RETROGRESSIVE DISTURBANCES OF NUTRITION. 73 vital organs reaches a stage at which they can no longer efficiently per- form their functions. But besides this general retrogression, or senile decay, there is a physiological retrogression of particular organs, which takes place much earlier in life. The generative organs in woman lose their functional power long before extreme old age. The thymus gland has undergone complete degeneration by the age of adolescence. Various tissues, like the hyaline cartilage which is the first rudiment of bone, are in their very nature temporary structures. The several tissues then, like the organism itself, inherit but a measured lease of life. Considered anatomically, retrogression shows itself in an organ by diminution of its size; microscopically, by diminution and ultimate disap- pearance of its constituent elements, especially of the elements which are special to it. 45. An organ, toward the close of its life, undergoes what we have called a physiological retrogression. But analogous retrogressive pro- cesses may occur, as it were prematurely, under pathological conditions. Their result w'e describe as simple atrophy. This pathological atrophy is distinguished, like the other, by shrinking of the organ affected, or by diminution in size and number of its essential elements. In the case of dense parenchymatous organs like the liver, kidney, heart, or brain, the shrinking is the first thing which is likely to strike us. If the shrinking has been uniform the surface remains smooth; if it has been irregular the surface looks uneven and granular, and the exter- nal form of the organ may be altered. On the other hand, atrophy of bone shows itself rather by thinning of the trabeculae and widening of the medullary cavities, than by any general diminution in size. So too in the lungs, we recognize the occurrence of atrophy by the increased size of the air-spaces, and the loss in part of the alveolar septa. Compared with the shrinking and loss of substance, the pigmentary change so often associated with atrophy is of minor importance. It is a secondary, non-essential phenomenon in the process. It depends either on the fact that the normal pigmentation of the tissue becomes more pro- nounced as the essential elements disappear ; or on an actual deposition of pigment associated with the atrophic process ; or lastly on some altera- tion in the amount of blood contained in the tissue. 46. The shrinking of an atrophied organ is due to the fact that its elements dwindle and disappear. Here, as in the case of senile involu- tion, it is the proper and specific elements of the organ which suffer the most; and the supporting framework of connective tissue the least. It is in fact very frequently observed that the connective structures remain perfectly intact or even increase and grow, while the specific elements have already disappeared. Thus in the illustration (Fig. 5) of a muscle undergoing atrophy, the contractile substance (a) contained within the sarcolemma has distinctly dwindled (J). But the connective tissue sepa- 74 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. rating the fibrillse remains undiminished ; the nuclei of its cells seem even to have multiplied. Similar appearances are readily observed in atrophied liver-tissue. There every one of the gland-cells may have vanished, and yet there may be no diminution in the amount of the connective-tissue framework. So Fig. 5.-Section of an Atrophied Muscle, x 300. (From a case of progressive muscular atrophy; Bis- marck-brown staining.) a, normal muscle-fibre; b, atrophied muscle-fibre ; c, perimysium internum, in which, the nuclei as at c, are seen to be increased in number. too in preparations of brain and spinal cord, the ganglion cells may have altogether disappeared, without any visible change in the neuroglia. [Adipose tissue is peculiar in its mode of atrophy. The fat in the cells breaks up into small oil-globules which are absorbed; the empty cells return to their first condition of ordinary connective-tissue cells. At times the disappearance of the contained fat is followed by prolifera- tion of the nuclei (atrophic proliferation). If serum transude into the tissue after the fat has gone, the tissue becomes gelatinous in appear- ance (serous atrophy). If, lastly, pigment be deposited in the atro- phied fat-cells, the tissue becomes yellow or yellowish-brown (pigment- ary atrophy). See Flemming, " Archiv f. mikroskop. Anatomie," vii., and " Virch. Arch.," vol. lii.] 47. Atrophy may result from various causes. It has already been indicated (Art. 44) that the tissues may themselves possess inherent properties which determine their retrogression and decay. The efficient cause of this form of atrophy (described as active atrophy) is that the cells are no longer able to assimilate properly the nutriment brought to them. Atrophy like this, depending on internal conditions, seldom oc- curs as a pathological process. Only the so-called atrophy of inaction and trophoneurotic atrophy should perhaps be classed as pathological. Atrophy of inaction occurs in organs that are subject to the direct influence of the nervous system, and perform their specific functions in obedience to nervous influence. Such are glands, nerves, and muscles. If a muscle or a gland be condemned to inaction for any length of time, it is apt to undergo atrophy. It is not unnatural to infer that the atro- phy depends on the absence of functional activity in the cells, and to RETROGRESSIVE DISTURBANCES OF NUTRITION. 75 frame the hypothesis that nutrition and functional activity go hand in hand and fall off together. A typical instance of trophoneurotic atrophy is seen in the rapid disappearance of the muscles in cases where their proper nerves have been injured, or where there is disease of the anterior horns of gray mat- ter in the cord. It appears that certain ganglion-cells in the anterior horns have a powerful influence on the nutrition of the muscles in con- nection with them. The disappearance of these cells, or the severance of their connection with the muscles, involves inevitably the atrophy of the latter. Leaving these cases out of account, we may fairly refer all other forms of premature atrophy to defective nutrition. The process of the atrophy is the same whatever be the particular factor underlying the de- ficiency. This factor may be general anaemia, local change in the nu- trient vessels, defective assimilation, or any other disorder of the kind ; but it can at most determine the site and extent of the atrophy, not the process. Atrophy of this kind, occasioned by diminished nutrition, is distinguished as passive atrophy. Atrophy consequent on pressure is brought about, partly by mechanical hindrance of the cell-functions, partly by direct injury to the tissue, partly by interference with the cir- culation. [Cohnheim (" Handbuch d. allgemeinen Pathologie ") includes atro- phy of inaction among the passive atrophies, and maintains that it de- pends on diminished blood-supply. It is not easy to believe that this explanation is in all cases adequate. Without undervaluing the impor- tance of the blood-supply, there seems to be no objection to the theory that the assimilative power of an active working cell may be greater than that of one which is at rest.] CHAPTER X. CLOUDY SWELLING AND DROPSICAL DEGENERATION. 48. The term cloudy swelling or parenchymatous degeneration is due to Virchow (" Virch. Arch.," vols. iv., xiv.). He describes by it a certain swelling up of the elements of a tissue by imbibition or accre- tion ; and defines it as a form of hypertrophy with a tendency to degen- Fig. 6.-Cloudy Swelling of the Renal Epithelium, x 800. (Preparation treated with chromic acid and ammonia.) a, normal epithelium; &, cloudy swelling commencing; c, advanced degeneration; a, loose de- generate epithelium. eration. The degenerative side of the process is the more important one. Histological investigation shows that the process consists in the forma- tion of free granules in the substance of the affected cells, which may, for example, be those of the renal epithelium, of the liver, or of the heart-muscle. These free granules are to be regarded, from their micro- chemical reactions, as albuminoid bodies ; they are soluble in acetic acid and insoluble in alkalies or ether. Their presence gives the cell a turbid RETROGRESSIVE DISTURBANCES OF NUTRITION. 77 or cloudy appearance, and its normal form and structure quickly disap- pear. Thus in cloudy swelling of the renal epithelium (Fig. 6), the cells lose their longitudinal markings and the processes which normally pro- ject into the lumen of the tubule {a). The cell as it swells becomes rounder, and dark granules appear within it (6, c). The process depends on a degeneration of the cell-protoplasm. The cell becomes infiltrated with liquid, and a partial separation of its solid and liquid constituents takes place. The degenerative process often ceases when it has reached Fig. 7.-Section through a 11 Mucous Patch " (condyloma latum ani). x 100. (Aniline-brown staining.) a, horny layer of the epidermis; b, rete Malpighii; c, corium ; d, horny layer swollen up and infiltrated with leucocytes; e, swollen cells of the rete Malpighii; f, swollen epithelium infiltrated with cells; g, de- generate epithelial cells, into which leucocytes have made their way ; h, granular coagula; i, swollen papilla, infiltrated with cells; k, corium infiltrated with cells and fibrin ; I, lymphatic vessel; m, sweat-gland. a certain stage, and the cell returns to its former normal condition. In other cases, the cell-substance perishes and breaks up into granular de- tritus. Frequently the process is associated with fatty degeneration (Art. 50). Cloudy or granular degeneration is of very common occurrence. It is found in the parenchymatous organs, such as the liver, kidneys, and. heart, in most cases of infectious disease ; but chiefly in scarlet fever, ty- phoid fever, small-pox, erysipelas, diphtheria, septicaemia, etc. The af- fected organs have a cloudy, dull, often grayish look ; in the severer cases they look as if they had been boiled. They contain an abnormally small quantity of blood, and are doughy in consistence. The minuter structure of the organ is blurred or altogether destroyed. 78 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. There is a certain morbid change in connective-tissue cells which may be classed under this head. It is frequently observed in cedematous or inflamed connective tissue. The affected cells swell up, and dark sphe- rules form in the nucleus as well as in the cell-protoplasm. These sphe- rules, with which the cells are often tightly crammed, are distinguished by their power of taking up an intense color when stained, especially with aniline dyes ; in this they behave like micrococci. Their significance is not understood, though their formation may probably be regarded as evi- dence of a retrogressive change. 49. The term dropsical degeneration fairly describes a morbid change observed chiefly in epithelial cells. They imbibe liquid and be- come sodden and swollen. The process is near akin to cloudy swelling and degeneration, though the changes in the dropsical cells are of a somewhat peculiar nature. The imbibed liquid causes the cell to appear translucent (Fig 7, e). The granules of the protoplasm are pushed asunder, and often crowded toward the periphery ; so that the cell comes to resemble some- what a vegetable cell (/'and g). It becomes at the same time vacuolated, the spherical vacuoles containing clear liquid. The nucleus also swells up, and at length appears as a distended vesicle with clear contents. Changes of this kind may be seen in the cells of dropsical tissues and in inflammation. In inflammation it is chiefly the epithelial cells that ex- hibit marked changes (Fig. 7, g), In stained preparations the dropsical cells remain brighter than the healthy ones. CHAPTER XI. FATTY DEGENERATION. 50. If parenchymatous degeneration (Art. 48) go beyond a certain point, it often passes into fatty degeneration, that is to say, fat-glo- bules form in the disintegrating cells. This variety of fatty degeneration is, however, of limited occurrence, compared with the other varieties to which the organism is liable. Fat, as we know, occurs in the body in considerable amount even under normal conditions. Certain regions, and especially certain tissues of the fibrous type, like the subcutaneous and subserous structures, the marrow, etc., are always rich in fat. The fat is, as it were, stored up in these special regions, being either derived from without, or formed on the spot in the cells of the tissue itself. Increase of the quantity in store, whether due to increased supply or diminished expenditure, does not rightly come under the title of fatty degeneration. We distinguish it as lipomatosis (obesity,adiposity). Within limitsit must be deemed physiological ; when excessive it may pass into the domain of pathology. In such extreme cases, fat is found in cells which normally contain none. The fatty deposit takes the form of oily drops, which soon coalesce into larger spherules ; until at length a single large fat-globule occupies the entire cell. Fatty infiltration of this kind affects chiefly the cells of the connective tissue in particular regions, and the liver-cells. True fatty degeneration must of course be distinguished from lipoma- tosis or fatty infiltration. The fat which occurs in the former is not fat in store, so to speak ; it is fat resulting from the disintegration of albumen in the affected cells. Inasmuch as fat is normally formed from the albumen of the cells, and is consumed as it is formed, we are driven to suppose that in fatty degeneration either the disinte- gration of albumen is increased, or the consumption of the fat produced is impeded. Both these things may occur, but it is specially to be noticed that in fatty degen- eration the lost albumen is not replaced, so that the pro- duction of fat is associated with atrophy. 51. A cell undergoing fatty degeneration always shows larger or smaller oil-drops in its interior. These are colorless, bright, dark contoured, insoluble in acetic acid, soluble in alcohol and in ether. Fig. 8. - Fatty Degeneration of the Muscles of the Heart. + 350. 80 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. In perosmic acid they stain black. The number and size of the oil-drops in the interior of a cell vary greatly ; the size even of the largest is not usually great. Thus, for example, in fatty degeneration of the muscle of the heart, we find more or fewer according to the degree of the degen- eration (Fig. 8). But they are all small and seldom coalesce into larger drops ; they never form very large ones. In fatty degeneration of the kidney (Fig. 9) the appearances are similar ; but the size of the oil-glob- ules is not so regular (c, e). Fra. 9.-Amyloid and Fatty Degeneration of the Kidney. + >300. (Preparation treated with Muller's fluid and perosmic acid.) a, normal capillary loop ; b, amyloid capillary loop (Art. 57); c, fatty epithelium of the glomerulus ; c„ fatty epithelium of the capsule ; d, oil drops on the capillary walls ; e. fatty epithelial cells in situ ; f, loosened fatty epithelial cells: g, hyaline coagula (forming " casts ") ; h, fatty cast in section; i, amyloid artery; k, amyloid capillary ; I, infiltration of connective tissue with leucocytes; m, round-cells (leucocytes) inside a uriniferous tubule. When the degeneration becomes more advanced, the fatty epithelial cells are shed and become disintegrated (f). The oil-globules they con- tain are thus set free and accumulate in the tubules (Ji). Fatty degeneration may occur in connective-tissue cells as well as in epithelial cells. If it affect entire cell-groups or systems, it may be recognized even by the unaided eye ; and the more readily as the degen- eration is more advanced, the proper color of the tissue less marked, and the amount of blood present less considerable. Colorless transparent structures, like the intima of the heart (endocardium) and great vessels, take on an opaque white appearance ; the cortical tissue of the kidney becomes grayish white or, when the fatty change is greater, opaque yellowish white ; the heart-muscle becomes yellowish ; and voluntary muscle pale yellowish brown. If complete disintegration of the tissue follow upon fatty degenera- tion, and if the mass of detritus lose water and become condensed, the RETROGRESSIVE DISTURBANCES OF NUTRITION. 81 fatty change passes into caseation (Art. 39) ; and the tissue assumes a dull white cheesy appearance. Like the cells of solid organs, the cells of organic liquids such as pus, and those of coagulated exudations, very often undergo true fatty degen- eration ending in their complete destruction as cells. [In tissues undergoing fatty degeneration, as also in liquids whose cells are degenerating, there are very frequently found cells crammed full of fat-granules. They are referred to as " fat-granule cells." Their origin is only in part traceable to fatty degeneration of the cells themselves. They are rather to be looked upon as migratory corpuscles which have taken up the fatty products of disintegration, and so have become transformed into granule-carriers (Art. 114). See Reinhardt, " Virch. Arch.," vol. i.] 52. The cause of fatty degeneration is to be sought in an alteration in the constitution of the blood, i.e., of the nutriment supplied to the cells. Deficient supply of oxygen plays a chief part in it. To this must be ascribed, on the one hand, the disintegration of albumen and the forma- tion of fat ; on the other hand, the fact that the fat produced is not straightway consumed. If to the lack of oxygen there is added a deficiency of proper nutri- ment, so that the albumen which is used up by transformation into fat is not replaced, the amount of albumen in the affected part must of course diminish. Corresponding to the case just indicated, we find fatty degeneration taking place in conditions which are associated with general or local anaemia. For example, if the blood becomes diseased in such a way (an- aemia, leukaemia) that its power of taking up oxygen is diminished, and its nutritive value lowered, fatty degeneration is found to occur in the most widely different organs. The same thing comes to pass in particu- lar organs which happen to receive too little blood, either in consequence of disease in the afferent vessels, or because the outflow of blood from them is checked tand its renewal hindered. Lastly, organs like the mus- cles which for any reason are left unexercised, and so fail to undergo an adequate amount of tissue-change, are very apt to become fatty. Various poisons, such as phosphorus, arsenic, and the ferments which produce fevers, may, like imperfect oxygenation, lead to disintegration of the albumen of the tissues and so to fatty degeneration. [We still seem far distant from an exact understanding of the origin and the ultimate fate of the fat which is formed in the body in physiolog- ical and pathological conditions. Iloppe-Seyler (" Physiolog. Chemie " ) inclines to think that fat cannot be formed directly from albumen. He regards it as not unlikely that glycogen is first formed, and from the glycogen fat. Voit (" Zeitschr. f. Biol.," v., and li Neues Rep. f. Phar- macie," xx.), on the other hand, thinks it quite certain that fat may be formed at once from albumen; compare Quain, " Medico-Chir. Trans.," 6 82 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. vol. xxxiii. According to Hermann, it is probable that certain products derived from the disintegration of albumen are normally utilized in re- generative processes. If the oxygen needed for regeneration is wanting, these products cannot be utilized and disintegrate still further ; the ex- penditure of fresh material is thus increased. Binz and Schulz (" Arch, f. exper. Path.," vol. xiv.) hold that the cells, in their avidity for oxygen, take it up from the blood so long as the blood continues to part with it ; when it ceases to do so the cells attack each other, and act as mutual reducing agents. The lateral " chain " of the albumen-molecule (the chain which includes the nitrogen, on the theory of these chemists) is thus broken ; the consequence is increased production of urea and of fat. They explain in this way the fatty changes observed in carbonic oxide poisoning. Bence Jones (" Lectures on Pathology, etc.") accounts for the proneness of the liver to become fatty in a somewhat similar way. See also Ranvier (" Societe anat.," 1868). On the effect of phosphorus in inducing fatty change, see Voit and Bauer (" Zeitschr. f. Biol.," vii.), Lewin (" Virch. Arch.," vol. xxi.), Ran- vier (" Soc. de Biologie," 1866).] 53. It is generally, though not always, easy to decide whether the fat present in the cells of an organ is a product of degeneration, or simply a deposit by way of storage. It is commonly stated that the fat of degen- erative atrophy appears in the form of minute non-coalescent drops ; while deposited fat occurs in large drops which readily run together. This is true of most tissues, but not of all. It is true, for example, of striated muscle, heart-muscle, non-striated muscle, neuroglia, etc. But when the renal epithelium becomes fatty, fat-globules of very considera- ble size are sometimes formed. In the liver again, the fat of degenera- tion may form either small or large drops (the latter in phosphorus- poisoning). On the other hand, what wo may call storage-fat is, in the first in- stance, deposited in very minute globules ; while the great globules of fatty deposits, when about to undergo reabsorption, break up again into minuter globules. But if the distinction is not always clear from the histological appear- ances, we may get more certain information by considering the site in which the fat is found. The appearance of fat-globules in tissue-cells normally free from fat, in circumstances which preclude the idea of a determination of fat to the tissue, is evidence that fat has been formed in loco from the cell-albumen, and therefore that the cells have so far become disintegrated. Difficulty can thus arise only in the case of or- gans, such as the liver, which may normally be the seat of fatty deposit, and on the other hand are prone to fatty degeneration. In such organs it is often hard to say how much of the fat they contain has been pro- duced in loco, how much has been brought to them from without. There is a. further complication, for the fat of degeneration is sometimes carried RETROGRESSIVE DISTURBANCES OF NUTRITION. 83 away from its original seat, and deposited in other spots in the form of a fatty infiltration, or of storage-fat. 54. When fat is present in considerable quantity it happens not infre- quently that crystalline products separate out from it. The so-called "fat-crystals" appear as feathery needles, grouped together in tufted bunches (Fig. 10, 6). They are often described as needles of margaric acid. Whether they really contain margaric acid is doubtful. It is known that equal parts of palmitic and stearic acid would give a mixture having the same composition as is ascribed to margaric acid; and further that palmitic, stearic, and oleic acids in combination with glycerin (as tripalmitin, tristearin, and triolein) form the chief components of ordi- nary animal fat. It is therefore doubtful whether margaric acid or tri- margarin really exists as a distinct component of animal fat at all. These fat-crystals may form in fatty products of disintegration as well as in normal fat-cells. In the latter case they are only produced post-mortem. Fig. 10.-Fat Crystals, x 300. a, cholesterin-tablets; 6, free tuft of margarin needles; c, tuft inclosed in fat-cells; d, feathery needles of " margaric acid" or margarin. In masses of fatty detritus it is very common to find what is called cholesterin (properly cholestearin). This forms thin transparent rhom- bic tablets (Fig. 10, a), often notched at the angles. If these tablets are present in quantity, they may often be recognized by their lustre with the naked eye alone. They are soluble in hot alcohol, ether, and chloro- form, in oils, and in the sodium compounds of the two bile-acids (glyco- cholic and taurocholic). Treated with sulphuric acid the crystals become purplish red, rusty, or violet at their edges. The same coloration appears still better on treatment with iodine. Nothing is known of the mode in which cholesterin is formed. It is said to exist as a normal constituent in the brain (Gamgee). [Schulze and Barbieri (" .Tourn. f. prakt. Chern.," 25, 1882) regard cholesterin as an intermediate product of vegetable metabolism and a constant component of vegetable cells. Cholesterins of various composi- tion are known, so that the term seems to indicate rather a chemical genus than a definite substance.] CHAPTER XII. MUCOID AND COLLOID DEGENERATION. 55. The mucoid degeneration of the tissues has its physiological type in the mucus-secretion of the mucous membranes and mucous glands. As is well known, the epithelium of the mucous membranes contains so-called goblet-cells (Eimer). These look like goblets filled to overflow- ing with a transparent substance. This latter is mucus formed from the cell-protoplasm. The epithelial cells of the mucous glands are similar. They swell up when about to secrete mucus ; the central parts become transparent, and the granules of the protoplasm become aggregated into groups or strings. The so-called mucus-corpuscles in the salivary secre- tion, with their glassy contents and tremulous granules, are merely leuco- cytes which have undergone mucoid metamorphosis. The mucous sub- stance formed from the protoplasm of the cell may be extruded, and the cell may recover ; in other cases the cell perishes. The same process of mucus-formation takes place under pathological conditions. For example, in catarrh of the mucous membrane we find that the increased secretion of mucus depends on an increased mucus- forming power in the lining epithelial cells, as well as in the cells of the mucous glands. Investigation shows that in cylindrical epithelium the goblet-cells (Fig. 11, 6) are increased in number. In the secretion also we may find cells in a state of complete mucoid degeneration ; they are transformed into glassy masses containing a few scattered granules (3 and 5). In other cells (7) the mucus may take the form of lumps of various sizes, enclosed within the unchanged cell-protoplasm. The epithelia of pathological tissues may, like the normal ones, undergo mucoid change. Typical goblet-cells are occasionally found in the epithe- lial lining of ovarian and intestinal cysts. In certain forms of cancer, the majority of the epithelial cells undergo mucoid degeneration. The fibrous tissues, like the epithelia, are also liable to undergo mucoid degeneration. Thus connective tissue, cartilage, bone, adipose tissue, marrow, sarcomatous tissue, may all become mucoid, and so assume a jelly-like translucent appearance. In these tissues it is usually the ground-substance which is transformed. The fibrous constituents lose their structure and become homogeneous. The tissue-cells may persist, RETROGRESSIVE DISTURBANCES OF NUTRITION. 85 or become fatty, or they may take part in the mucoid change. The final product is a hyaline mass recalling the original tissue only by virtue of a few stray fibrous shreds, or single cells, or groups of cells, scattered through it. Mucus swells up readily in water ; acetic acid makes it coagulate ; alcohol makes it turbid, white and opaque. Fig. 11.-Catarrhal Secretions from various Mucous Membranes. + 400. A, from cylindrical epithelium; B, from the mouth ; C, from the bladder. 1, round-cells (pus corpuscles); 2, large round-cells with clear nuclei from the nose ; 3, mucoid cylindrical cells from the nose : 4, Spirillum from the nose ; 5. mucoid ciliated cells from the nose; 6. goblet-cell from the trachea; 7, round-cells with mucus-masses from the nose; 8, epithelial cells containing pus corpuscles from the nose : 9, fatty cells in chronic laryngeal and pharyngeal catarrh ; 10, cells from sputum containing soot-pigment; 11 and 12. squamous epithelium from the mouth ; 13, mucus-corpuscles ; 14, micrococci: 15. Bacterium termo ; 16, Leptothrix buccalis; Yl, Splrochnta denticola ; 18, superficial cells from the bladder ; 19, deeper layer; 20, pus corpuscles ; 21, Schiz<mycetes or bacteria. 56. Colloid degeneration is closely akin to mucoid degeneration ; for here too the essence of the process is the metamorphosis of an albu- minoid substance. The details of the chemical changes which occur are not known. The material which constitutes the colloid substance is de- rived from the epithelial cells. In aged persons, a certain amount of colloid change in the thyroid gland may be regarded as physiological. The parenchyma of the gland is full of large and small spherules, which on sec- tion have a translucent sago-like appearance. They are generally yellowish or brownish in color, and of the consistence of firm jelly. If the colloid change has gone on to a pathological extent, this translucent substance may form the greater part of the mass of the gland. It may even lead to a marked increase in its size, forming a colloidal goitre. Microscopic 86 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. examination shows that the colloid mass is homogeneous. It encloses but few cellular elements, and these for the most part at the periphery, where the colloid change is in progress. Sometimes a large continuous patch of degenerate tissue may be produced by the coalescence of smaller ones. The formation of the colloid substance is indicated by the appear- ance of minute homogeneous spherules in the cells of the acini. These spherules escape from the cells, or become free when the cells themselves break up. When they come into contact, they coalesce to form the homogeneous colloid substance. Colloid spherules, exactly like those just described, are found in the tubules of morbidly altered kidneys. At times large masses of coalescent spherules occur in cystic degeneration of the tubules. In the prostate gland similar formations also occur. Colloid substance is distinguishable from mucus by the fact that acetic acid does not induce coagulation, while alcohol and chromic acid produce no turbidity. [In Virchow's opinion, the homogeneous spherules, while contained in the cells, are not actually composed of true colloid substance. The latter is formed from them after they run together, in virtue of a special chemical transformation. Virchow describes the spherules as modified protoplasm. Colloid substance is probably a resultant of several albuminoid bodies. See Virchow ("Virch. Arch.," vol. i.), Wagner (" Arch. f. phys. Heilk.," 1856, 1866), Eberth (" Virch. Arch.," vol. xxi.).] CHAPTER XIII. AMYLOID DEGENERATION AND AMYLOID CONCRETIONS. 57. Amyloid degeneration is a peculiar degenerative process, which is apt to affect the connective tissues, and is progressive in char- acter. It leads to the deposit of a special albuminoid body (the amyloid substance) in the affected tissues ; these therefore increase in bulk and assume under the microscope a peculiar uniform semi-translucent appear- ance. The affection may occur in any of the organs, but it is specially common in the spleen, liver, kidneys, intestines, and lymphatic glands. When sufficiently intense the morbid change is recognizable with the naked eye ; the part looks semi-translucent, so that it is described as li waxy " or " lardaceous," i.e., like the fat of fried bacon. If the change is confined to scattered patches, as it often is in the spleen, these look like grains of boiled sago or tapioca; hence the name "sago-spleen." In other cases, the process affects the spleen-tissue uniformly. The whole organ grows large and firm to the touch, while the section presents the peculiar translucent lardaceous appearance. Like appearances are found in the liver. The kidneys, too, may undergo considerable increase in size, and present in patches or throughout the lardaceous character, becoming at the same time firmer in consistence. In other cases the translucent patches are so small as not to be readily noticed ; the possi- ble presence of amyloid substance is, however, often indicated by changes of another kind, such as fatty degeneration. In the intestine the degen- eration is seldom recognizable without optical or chemical examination. The same is true of the organs that are less liable to the change, such as the heart, the great vessels, the thyroid gland, etc. 58. The amyloid substance so deposited in the tissues in uniform shiny patches exhibits a peculiar reaction with iodine, and with some of the aniline colors. A solution of iodine in water, or better in potassium iodide and water, when poured on the tissue to be tested, stains the amy- loid substance a dark brownish red or mahogany color. If added to a section under the microscope the staining is a bright brownish red, while the unaffected tissue remains pale yellow. Where the degeneration is extreme, the tissue may become almost woody in consistence, and then the staining may be violet or blue or greenish. If the ordinary iodine- stained tissue be treated with very dilute sulphuric acid, the amyloid 88 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. patches take on a darker brown, or become violet, blue, or greenish ; but the reaction is generally imperfect. Methyl-aniline or aniline-violet stain the amyloid substance bright ruby-red, and the healthy tissue blue or dark indigo. The peculiar iodine-reaction was first observed by Virchow, the dis- coverer of the amyloid substance. This reaction led him to consider the amyloid substance as a non-nitrogenous body allied to cellulose and starch. Cellulose, when treated with iodine and strong sulphuric acid, is stained bright blue. Starch with iodine alone gives an ultramarine tint. For this reason Virchow called the new body "amyloid." It was not until some years later that Friedreich and Kekule proved the amyloid substance to be nitrogenous, to be, in fact, an albuminoid body. The special reaction of the amyloid substance enables us to detect its pres- ence in the tissues, even when to the eye it is not differentiated from them. In examining fresh specimens in a cursory way, the only precau- tion necessary is to see that the surface is washed free from blood ; the red color of the blood blended with the yellow of the iodine may simulate the characteristic brownish-red staining. The amyloid substance is very slightly acted on by acids or alkalies. Alcohol and chromic acid do not alter it at all ; and it has the power of withstanding putrid decomposition for a long time. It is not dissolved by gastric juice at the temperature of the body. [Amyloid degeneration was not altogether unknown before Virchow's researches. Rokitansky had previously introduced the names bacon-liver or lardaceous liver, waxy liver, bacon-spleen, sago-spleen. But it was Virchow who first investigated the nature of the amyloid substance, first of all in amyloid concretions (Art. Cl), afterward in degenerated tissues ; and he discovered the iodine reaction ("Virch. Arch.," vols. vi., viii.). Friedreich and Kekule first showed that the substance was nitrogenous ("Virch. Arch.," vol. xvi.), which was confirmed by Rudneff and Kuehne ("Virch. Arch.," vol. xxxiii.). The literature of the subject is fully given by Kyber, who has also made numerous additions to our knowl- edge regarding its occurrence (" Die ainyloide Degeneration," Dorpat, 1871, and " Virch. Arch.," vol. Ixxxi.). Jurgens first described the color-reaction with iodized methyl-aniline ("Virch. Arch.," vol. Ixv.) ; Cornil studied the reactions with other aniline colors (" Arch, de phy- siol.," 1874). Dickinson showed that a characteristic blue color is im- parted to the amyloid substance by sulphate of indigo.] 59. The amyloid substance is either formed or deposited in the fibrous textures of the blood-vessels, and in the walls of the smaller ves- sels especially. If a microscopic section of an amyloid liver be so treated as to bring out the minuter changes in its structure, it is not hard to show that the seat of the affection is in the capillary walls, that is, in the peri-endothe- RETROGRESSIVE DISTURBANCES OF NUTRITION. 89 lial fibrous tissue. The endothelium is thickly coated on its outer aspect with a uniform glassy layer, here and there broken up into lumps (Fig. 12); this is the amyloid deposit. The liver-cells may remain unchanged between the amyloid masses, or they may be misshapen and partly atrophied. They very often contain fat. If the afferent vessels be examined, it will be found that they too exhibit amyloid patches, especially in their middle coat. The appearances in an amyloid kidney are exactly similar (Fig. 13). A good section shows as before that the formation of the homogeneous deposit occurs mainly in the vessel-walls. The walls of the vascular loops in the glomeruli (b), are greatly swollen and homogeneous in structure, and the arteries (i), veins, and capillaries (k) of the parenchyma show traces of amyloid deposit. In other parts, such as the intestinal mucous membrane, the appear- ances are of the same kind. The vascular system, however, is not invari- ably the chief seat of deposit ; the connective tissue is often chiefly and Fig. 12.-Amyloid Degeneration of Liver Capillaries, x 300. (Section treat- ed with perosmic acid.) Fig. 13.-Section of an Amyloid Kidney, x 300. (Treated with Muller's fluid and perosmic acid.) a, normal capillary loop; ft, amyloid capillary loop; (, fatty epithelium of the glomerulus; c15 fatty epithe- lium of the capsule; d, oil-drops on the capillary wall: e, fatty epithelial cell in xitu ; f, loosened fatty epithelial cells; g, hyaline coagula (forming •* casts"); A, fatty cast in section ; i, amyloid artery ; k, amy- loid capillary; I, infiltration of connective tissue with leucocytes; m, round-cells (leucocytes) inside a uri- niferous tubule. directly affected. In the lymphatic glands and the spleen (Eberth), it is the fibrous trabecular network which suffers most ; in striated muscles the 90 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. perimysium internum and the sarcolemma (Ziegler). In glandular organs with a tunica propria (p.g., the mucous glands and kidneys), this latter may undergo degeneration and become greatly thickened. [The above account of the common seat of amyloid deposit differs essentially from that given in various text-books (e.y., Rindfleisch's) and memoirs. Most authors assert that in glandular organs the chief seat of amyloid formation is in the gland-cells, that is, in the epithelial elements. Ziegler has not succeeded in convincing himself that this is the case. In no one of seven specimens of amyloid liver could he find, on the carefullest examination, that the liver-cells had undergone amyloid degeneration. The cells were always recognizable, though at times greatly atrophied and compressed by the interposed deposits. The examination of mucous glands and kidneys yielded like results. He is therefore constrained to agree with Wagner (" Arch. d. Heilkunde," ii., 1861), Eberth (" Virch. Arch.," vol. Ixxx.), Heschl (" Wiener Sitzungsberichte," vol. Ixxiv.), and others-who regard the connective tissue as the primary seat of amyloid formation, and deny that the epithelium is commonly concerned in it. Ziegler does not go so far as to say that epithelial cells are incapable of amyloid change ; but he is sure that even in extreme cases of amyloid dis- ease they may remain unaffected. The notion that the liver-cells are com- monly affected is due to the fact that they have been overlooked among the amyloid flakes and patches which surround them. The iodine method is probably to be blamed for this, for it fails to bring the liver-cells dis- tinctly into view. Ordinary staining-reagents and perosmic acid are much more useful in this respect than iodine. Ziegler had recently an opportunity of examining a very interesting case of amyloid disease. The patient was a woman of about fifty, who had died of heart-failure. On post-mortem examination it was found that the heart, all the mucous membranes, the peritoneum, tongue, and lungs were amyloid. The pericardium and endocardium were everywhere thickened and beset with numerous translucent gristly nodules as large as millet-seeds. Similar nodules in vast numbers were found in the peri- toneum, and in lesser number in the heart-muscle, the muscularis mucosae of the intestine, the mucosa and submucosa of many of the mucous mem- branes, and in the lungs. In addition to these nodules the heart-wall (and especially that of the auricles) was traversed by thick seemingly fibrous bands. The submucosa of the small intestine was for the most part transformed into a firm bacon-like tissue. The nodules and also the dense thickenings were composed of a uniform substance, either struc- tureless or showing traces of coalescent homogeneous blocks. This was deposited in the walls of the vessels, and in the connective tissue. The vessel-walls were in some places thickened ten- to twenty-fold. When the margins of the affected patches were examined microscopically, it seemed as if the homogeneous substance had been directly produced from the ground-substance of the connective tissue, by a process of swelling RETROGRESSIVE DISTURBANCES OF NUTRITION. 91 and condensation. Some of the homogeneous masses yielded the iodine reaction, others did not.] 60. The consequences of amyloid degeneration, as regards the func- tional efficiency and general condition of the affected organ, show them- selves in two ways. On the one hand the structure is profoundly altered, on the other the epithelial elements of the organ become secondarily dis- eased. Amyloid change is essentially a degeneration. . The connective tissues are permanently altered, for the amyloid substance being but slightly soluble does not disappear again when once deposited. It is ob- vious that a foreign element of this kind must seriously interfere with the functions of the affected organs, such as the kidney, or intestine. The morbid change in the vessel-wall often leads to narrowing and closure of the vessel, and so to permanent disturbance of the circulation. These are not without effect on the epithelial elements ; they speedily become fatty. And inasmuch as the fibrous framework of the organ is at the same time increasing in size and volume, the gland-cells are com- pressed and so tend to disappear altogether. In the liver such misshapen and atrophied cells, as well as others in a state of fatty degeneration, are very often met with. In the kidney the fatty changes in the epithelium (Fig. 13, form a striking and characteristic accompaniment of amy- loid degeneration. In the spleen and lymphatic glands the lymphoid cells are likewise apt to perish, atrophied and fatty, under the pressure of the swollen and al- tered trabecular network. In muscle the contractile substance vanishes, as the amyloid masses in the connective tissue increase and multiply. 61. Amyloid degeneration, as above described, is generally a process affecting several organs at the same time ; or when it happens to affect only one, it takes the form of a change extending throughout the entire organ. But in addition to this diffused form we find a more local one, presenting the appearance either of circumscribed foci of degeneration, or of amyloid concretions. These localized amyloid formations occur, so far as we know, only in tissues which have already undergone morbid change. They are espe- cially apt to follow in the wake of inflammations, either early in the process of granulation, or later when cicatricial tissue has been formed. They are also found in tumors which are undergoing retrogressive change. Small single foci may be formed in the affected tissue, or they may be confined to the walls of the vessels. In other cases the greater part of the tissue degenerates together ; nodular patches are formed, con- sisting almost wholly of amyloid substance, and often assuming a woody hardness of texture. Such formations have been observed in the con- junctiva when altered by old inflammation, in syphilitic scars of the tongue and larynx, in diseased lymphatic glands, in ulcers of the leg, in tumors of the larynx and stomach, and in cartilage in the course of de- generation (Virchow). 92 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. In many cases homogeneous bodies exhibiting the amyloid reaction are obviously formed in the exudation-products of inflammation or hem- orrhage. For example, the so-called tube-casts of the kidney, formed in the tubules by a singular transformation of transuded liquid and shed epithelium, show not infrequently the amyloid reaction if they have lain long in situ. In the remains of old hemorrhages amyloid bodies have often been found (Fig. 14, b). They often enclose a foreign substance, such as a crystal of hsematoidin. These bodies are called amyloid con- cretions or corpora amylacea. They are found under normal conditions n the central nervous system, especially in the ependyma of the ventri- Fig. 14.-Corpora Amylacea. + 400. a, stratified concretion from the prostate ; b, corpus amylaceum from an old hemorrhagic infarct of the lung; c, corpora amylacea from the spinal cord. cles. It was here that Virchow first discovered them. They take the form of small more or less clearly stratified spherules (Fig. 14, c). At times they may be found abundantly in morbidly altered brain-substance, and in cerebral tumors. Corpora amylacea are also very common in the prostate gland. They lie in the lumen of the acini and are of consider- able size ; often indeed they may be recognized by the naked eye as brown grains upon the surface of a section. They are distinctly stratified (Fig. 14, a), except toward the centre. These localized amyloid formations, and especially those originating in tube-casts and old extravasations of blood (Fig. 14, 6), serve to prove that amyloid substance may arise from a direct metamorphosis of the al- bumen of blood and of epithelium. The prostatic concretions, when they really are amyloid (and this is not always the case), are probably to be regarded as modified cell-products. fA large number of memoirs have dealt with the question of localized amyloid change. Kyber (loc. cit.), Leber (" Arch, fiir Ophthalm.," xix., xxv.), Hippel (ibid., xxv.), von Becker ("Amyl, degen. tarsi," Helsingfors, 1870) refer to amyloid formations in the eyelid. Friedreich (" Virch. RETROGRESSIVE DISTURBANCES OF NUTRITION. 93 Arch.," vols. ix.,) x. and Zahn {ibid., vol. Ixxii.) found amyloid bodies in the lung; Langhans in cancer-nodules {ibid., vol. xxxviii.); Burow (" Langen- beck's Arch.," xviii.) in tumors of the larynx, etc. On prostatic concretions see Paulizky (''Virch. Arch.," vol.xvi.). Ziegler discovered amyloid bodies in syphilitic scars (" Virch. Arch.," vol. Ixv.), in a hemorrhagic infarct of the lung which had healed, and in a cancer of the stomach. 62. As to the causes and the nature of amyloid degeneration, there is little to say that is quite definite or quite certain. We know, of course, in what circumstances it is apt to occur, namely in cachectic con- ditions of the system. On the other hand, we do not know to what al- terations in normal metabolism the morbid process owes its special char- acter. The forms of cachexia which lead to extensive amyloid change are in particular tuberculosis, syphilis, chronic destructive ostitis or periostitis, chronic dysentery (cceliac flux), and leukaemia ; while the cancerous cachexia seldom tends to favor it. Amyloid degeneration may, however, occur without previous disease. Some of Cohnheim's researches show (" Virch. Arch.," vol. liv.) that the degeneration may become developed in two to three months. Amyloid change extending to several organs is a local disorder con • ditioned by general causes. The amyloid substance does not exist in the blood, yet the material out of which it is developed is derived from the blood. It would appear that reduced vital activity of the tissues dependent on general cachexia favors the formation of the substance. We may, per- haps, provisionally picture to ourselves the formation of this peculiar sub- stance, as due to a combination of an albuminoid body from the blood with certain components of the tissues ; or we may regard it as a modification of the albumen of the blood, separating out from the latter in consequence of some abnormal metabolism in the cachectic patient. In local amyloid formations, the substances metamorphosed are partly albumen from the blood (concretions formed in extravasations), partly albumen derived from epithelial cells (tube-casts and prostatic concre- tions). In the latter case the special metamorphosis is effected, without the co-operation of living tissue, in albumen which has lain for a time in the tissues without being of them. Here the conditions must be of a purely local nature. [Virchow ("Cellular Pathology") and Kyber ("Virch. Arch.," vol. Ixxxi.) have compared the amyloid degeneration of tissues to the process of chalky deposit, and the comparison seems a good one. In both cases we probably have a tissue whose nutrition is somehow lowered ; a sub- stance brought to the tissue by the blood ; and an intimate combination between this substance and a substance pre-existing in loco. Wagner (" Handbuch d. allgem. Pathologic," 1874, p. 417) considers the lardace- ous material we have described to be due to a retrogressive metamorpho- sis of albuminoids, forming; in fact an intermediate stasre between these bodies and fat. Dickinson argues that it is of the nature of fibrin (blood- 94 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. albumen) "modified by loss of alkali or gain of acid" (" Trans. Path. Soc.," 1879). A statistical analysis of the causes of amyloid degeneration is given by Hennings (" Inaug. Diss., Kiel," 1880). He makes out that phthisis and suppuration of bone hold the first rank among the etiological condi- tions. The spleen is oftenest diseased ; after that follow in order the kid- neys, liver, intestine, stomach, suprarenal capsules, pancreas, lymphatic glands, thyroid gland, aorta, lungs, ovaries, uterus. Somewhat similar analyses-are given by Fagge (" Trans. Path. Soc.," 1876) and Turner (ibid, 1879).] CHAPTER XIV. HYALINE DEGENERATION OF THE FIBROUS TISSUES. 03. Hyaline (or vitreous) degeneration of the fibrous tissues re- sembles amyloid degeneration in its superficial appearance as well as in its seat ; but it does not give the special and peculiar reactions of the amyloid substance. It occurs chiefly in the adventitious tissue of the ar- teries. The adventitia becomes transformed into a shining, translucent, strongly refracting substance, increasing at the same time in thickness. Water has no effect on this substance ; iodine stains it pale yellow ; ether and chloroform give no reaction. It thus resembles in many re- spects the colloid substance. It is specially common in the vessels of the brain and of the lymphatic glands (Wieger). Apart from the blood- vessels a hyaline thickening is also observed in the stroma of tumors, in inflammatory hyperplasias, especially in those of hereditary syphilis (such as occur in the liver, for example), and in structureless membranes like the hyaloid membrane of the eye. As to the nature of the change noth- ing is known. Disturbances of the circulation (Wieger), and inflamma- tions of the affected regions, have been mentioned as exciting causes. [Wieger, under the guidance of von Recklinghausen, has lately ex- amined and described the hyaline degeneration of the lymphatic glands ("Virch. Arch.," vol. Ixxviii.). It seems to be very common in these or- gans. Memoirs on the hyaline degeneration of the cerebral vessels have been published by Arndt ("Virch. Arch.," vol. xli.), Neelsen ("Arch. d. Heilkunde," xvii.), Eppinger (" Vierteljahrsschrift f. pract. Heilk.," Prague, 1875), Lubimoff ("Arch. f. Psychiatric," 1874), and others. The degeneration is found in the central nervous system in connection with various disorders. Peters has quite recently (" Virch. Arch.," vol. Ixxxvii.) made a series of researches in von Recklinghausen's laboratory on hyaline degenera- tion, and he manages to bring under this head all sorts of diverse changes and processes. Thus he includes under it inflammatory coagulations within and without the blood-vessels, coagulative necrosis of the epithelia in diphtheritic inflammation, homogeneous coagulation in exuded fluids, the formation of false membranes, the mucoid metamorphoses of the epi- thelial cells of mucous membrane, and thrombi in lymphatic vessels, 96 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. -in brief everything that has a hyaline look. This is a mere uncritical agglomeration of things that have nothing in common. We may perhaps be unable to distinguish with certainty the exact chemical and physical processes which lead to the formation of homogeneous masses in the va- rious tissues and liquids ; but this does not justify us in affirming that no distinction is at all possible. The case referred to in Art. 59 has great interest, as bearing on the discrimination of hyaline degeneration in fibrous tissues. It shows that hyaline change is near akin to amyloid change ; and that in the former as in the latter an albuminoid may be deposited in the tissues in the form of solid lustrous masses. Whether the hyaline degeneration of the ves- sel-walls, observed in various conditions, has always the same significance -is as yet an open question. Gull and Sutton (" Medico-Chir. Trans.," 1872) have described a "hyalin-fibrous" degeneration of the blood-vessels in connection with chronic renal disease. Klein ("Trans. Path. Soc.," 1877) has described and figured hyaline changes in the arterioles in typhoid fever and in scar- latina.] CHAPTER XV. INFILTRATION OF THE TISSUES WITH SALTS. 64. Petrification or incrustation is a process of transformation characterized by the deposit in a tissue of various salts derived ultimately from the blood. In by far the greater number of cases the deposit consists of carbon- ates and phosphates of calcium, with a small quantity of the magnesium salts ; it is in fact calcareous or chalky. As we know, calcareous deposition takes place in special regions as a normal physiological process. The formation of true bone is always pre- ceded by the deposit of calcareous salts in the cartilaginous structures first laid down. This deposit takes the form of minute granules, which on magnification look like grains of dust or irregular crumbs, and they are seen to lie chiefly in the matrix-substance and cell-capsules of the car- tilage. If the grains lie thick together, they give the part a whitish color and a firm consistence. In the same way as under normal conditions, but in the most various regions of the body, we may have a morbid deposition or precipitation of calcareous salts in the tissues. Experience shows that the tissues af- fected are either already necrosed, as in the case of caseous lymphatic glands, dead parasites, thrombi, and dead foetuses (lithopredia),-or have been seriously stinted in their nutrition. This latter is the case in fatty degeneration of the tunica media of the arteries, or in fatty degenera- tion of tumors such as uterine fibroids. The cause of calcareous depos- its is thus a local one. The calcium-salts dissolved in the blood are not simply precipitated and retained by the tissue, but they proceed to form solid compounds with the albuminoids. Commencing calcification is not recognizable by the naked eye. When the deposit becomes more dense the tissue turns white. At the same time it often becomes extremely hard and cannot be cut with the knife. In other cases it becomes in color and consistence more like mortar. [Litten affirms (" Der haemorrhagische Infarct," 1879) that calcifica- tion depends on a necrotic modification of albumen, possessing a special chemical affinity for lime-salts. Kyber asserts (" Virchow's Archiv," vol. Ixxxi.) that the lime-salts combine with the fatty acids, as well as with the albuminoids.] 65. Calcification invades the cells of a tissue as well as the ground- 7 98 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. substance. Thus ganglion-cells (Fig. 15) which have ceased to live in consequence of some brain-affection may become impregnated with lime- salts. Shining calcareous spherules are formed, which fill out the contour of the cell and its prolongations. Fig. 16. Fig. 15. Fig. 15.-Calcified Ganglion Cells. (From the brain of a hemiplegic idiot with unilateral hydrocephalus.) Fig. 16.-Calcification of the Tunica Media of the Aorta. When an artery is affected, the cells as well as the ground-substance become calcified. Small shining granules are deposited in the latter, which at length thickly infiltrate the tissue (Fig. 16). Simple calcifica- tion does not produce any alteration in the apparent structure. The tissue is petrified as it stands, so to speak, without destruction or trans- formation of its form and texture. It is thus easy to distinguish histol- ogically between calcification and ossification. In tissues altered by inflammation, such as tuberculous lymphatic glands, fibrous false membranes or adhesions, as well as in certain tu- mors of the brain (psammomata), we find at times so-called chalky concretions. They are stratified bodies having an or- ganic basis, in which lime-salts have been deposited. Fig. 17 represents some of these concretions: a, comes from an omen- tum thickened and deformed, and adhe- rent, in consequence of chronic inflam- mation ; b, from a tuberculous lymphatic gland. The several layers of the strati- fied concretion have a uniform shining appearance. 66. In gout we find deposits of urates, chiefly of urate of sodium, together with carbonates and phosphates. The deposition is apt to occur paroxysmally, especially in the metatarso-phalangeal joint of the great toe, but not infrequently in other joints also. Shining white masses (chalk-stones or tophi) are thus formed in the ligaments and cartilages of the joints, and even in the bones. These may also occur in the arte- ries, endocardium, skin, and kidneys. The deposit is usually in the form of needle-like crystals (Rindfleisch), or amorphous granules. It is said that the cells are the first to exhibit the deposit, the ground-substance being invaded secondarily (Cornil and Ranvier). Fig. 17.-Chalky Concretions, a, con- cretions of an inflamed omentum; ft, from a lymphatic gland altered by inflammation. CHAPTER XVI. FORMATION OF PIGMENT IN THE TISSUES. 67. The fibrous as well as the epithelial tissues, in certain regions, contain a normal pigment. It lies within the cells in the form of yel- low, brownish, or black granules ; or the cells may seem more or less uniformly impregnated and stained. Of the pigmented epithelia the best examples are the deepest layer of the rete Malpighii, and the retinal epithelium. In the former the granules are mostly yellow or brown, in the latter they are black (melanin). When the coloration of the skin is more marked, pigment is found in the other cellular layers of the rete. Among fibrous tissues the pia mater, the choroid, the sclerotic, and the cutis are the most frequently pigmented ; and brown or yellow granules are like- wise found in the connective-tissue cells of the heart-muscle. These pigmentations may become more marked under pathological conditions. Thus in Addison's disease, in the course of a general disor- der leading to profound cachexia and associated as a rule with changes in the supra-renal bodies, the normal pigment of the skin increases and the consequent color-changes are very pronounced (cutis cenea or bronz- ing). So too in atrophic conditions of the heart, the normal pigment is markedly increased. In the voluntary muscles also, when they pass into atrophy, yellow pigment is frequently discoverable. The highest degree of pathological pigmentation is met with in mor- bid new growths, such as tumors (nsevi, melano-carcinomata, melano- sarcomata). The amount of pigment may become so great that the tissue looks uniformly and intensely black. The pigment lies usually within the cells of the tissue, less often in the intercellular substance. In either case, as above remarked, it may take the form of yellow, brown, or even black granules ; or of diffuse staining of the protoplasm. Of its mode of formation we know nothing. It is possible that the coloring-matter is derived from the blood, but we are unable to determine in what way the derivation is effected. [Laycock (Medico- Chir. Review, i., 1861) discusses and classifies the various forms of morbid pigmentation ; he gives full references to previous papers on the subject. Gussenbauer has lately attempted (" Virch. Arch.," vol. Ixiii.) to re- 100 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. fer the production of melanin in pigmented tumors to a modification of the coloring-matter of the blood. He thinks the blood-vessels of the tumor become here and there thrombosed ; the coloring-matter of the blood escapes from them by diffusion, saturates the tissue, and is ulti- mately precipitated in granular form. Langhans (" Virch. Arch.," vol. xlix.) had previously sought to derive the pigment of tumors from cells containing blood-corpuscles (Art. 68). According to Kunkel (" Sitzungsb. der phys. med. Gesell.," Wiirz- burg, 1881), it is possible to isolate from melanotic tumors a pigment containing iron. This argues that the pigment is derived from the blood ; but we cannot as yet say by what process it is produced. It is not re- lated to haematin, bilirubin, or hydrobilirubin, as the spectroscope shows. It seems doubtful whether the escape of the coloring-matter from the blood-vessels always occurs in the way described by Gussenbauer. The diffused staining of individual cells may perhaps suggest that the color- ing-matter first infiltrates the cell, and then breaks up into granules.] 68. Htematogenous pigments are such as are demonstrably derived from the coloring-matter of the blood. They generally originate in blood which has escaped from the vessels. More rarely the change to pigment occurs in blood which is still circulating. As is well known, the color- changes recognizable by the eye take place very quickly in small extra- vasations as well as large. In the skin, such extravasations become first brown, then blue, then green, then yellow. Where small hemorrhages have occurred in the deeper tissues, such as the peritoneum, pleura, or lungs, we find, even long afterward, brown, or gray, or black spots and patches. Larger hemorrhages (apoplexies) into the substance of the brain or lungs take on after a time a rusty brown color ; and still later leave only a dirty yellow or yellowish brown staining. All these color- changes correspond to definite chemical and physical transformations of haamoglobin. Wherever in the tissues or in a cavity of the body a hemorrhage may have occurred, there ensues a series of changes in the escaped blood of which the following are the most important. One part of the blood, including red cells as well as plasma, may be re-absorbed by the lymphatics and carried off unchanged. Another portion of the corpuscles may become in a way dissolved ; their haemoglobin diffuses from them into the surrounding tissues, and the pale residual stroma breaks up and disappears. It is this diffused and altered coloring-matter (or haematin) which gives rise to the color- changes in cutaneous extravasations, as it passes through various trans- formations. The transformed pigments (which are similar to the biliary coloring-matters) are partially re-absorbed and at length excreted in the urine (urobilinuria) ; another part crystallizes in the tissues, and forms the orange or ruby-red rhombic tablets and needles known as haematoidin- crystals (Fig. 18, JR). These are very frequently found as the residue RETROGRESSIVE DISTURBANCES OF NUTRITION. 101 of old hemorrhages, such as occur in the brain ; they may remain a long time in the tissues without change. A third portion of the corpuscles shrink up or crumble down into brown granular masses. This is especially the case in the large extra- vasations forming so-called haematomata. These masses become in part transformed into brown amorphous pigment. This lies free in the tissues, and often becomes darker in color with age. A fourth, and that the greater portion of the corpuscles and the pro- ducts of their disintegration, is taken up by leucocytes (Art. 114), which gather in large numbers round the seat of extravasation and even pene- trate into it. The cells become in this way corpuscle- and pigment- carriers (Fig. 18, A, a and b). The transformation of the heematin into Fig. 18. + 500. A. Cells containing red Blood-corpuscles; in ft the fragments are few but large, in & and c they are numerous and minute. B. Rhombic Tablets and Needles of Haematoidin. brown pigment is completed within these cells, the corpuscles breaking up into minute granules (Fig. 18, -4, b and c). The pigment may be set free again by the disintegration of the carrier-cells. Probably the cells have also the power of eliminating it, without themselves perishing. These various modes of transformation of the blood-corpuscles very frequently go on at the same time in the same extravasation. Their ulti- mate result is, in the first instance, a local discoloration, due to pigment partly amorphous and partly crystalline in character. Secondary pig- mentation of remote organs such as the lymphatic glands, the spleen, and the liver, may follow upon this, owing to absorption of the pigment by the lymphatics. The formation of pigment in blood which is actually circulating is not carried beyond the first stage (the breaking up of the red corpuscles) within the vessels (Arts. 262 and 268) ; the completion of the process is effected outside the vessels. The pigments just described are only in part organic derivatives of the-coloring matter of the blood (like hsema- tin and hsematoidin). A considerable part is composed of an inorganic iron-compound ; namely, the hydrated sesquioxide (Kunkel). This is especially the case in large extravasations, where the haemoglobin is de- composed on the spot. The contained iron being thereupon set free in the form of oxide, remains where it is and forms yellow or brownish flakes. 102 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [It may be of use to mention that haemoglobin is the unchanged coloring-matter of the blood as it exists in the living corpuscles. Hasma- tin is the colored constituent obtained when haemoglobin is decomposed (e.g., by boiling) ; the other constituent being a proteid body. Hcema- toidin is formed when the decomposition is carried still further ; it is identical with bilirubin (see Gamgee, "Physiol. Chem.," i_, 2). The first exact researches into the nature of the blood-pigments were made by Virchow (" Virch. Arch.," vols. i., ii., iv., and vi., and " Cellu- lar Pathology "). He sought to show that haematoidin is to be regarded as the typical final resultant of the transformations of haemoglobin within the human body. He assumed that the haemoglobin escaped into the tissues unchanged, and was then, by a secondary process, transformed into granules and crystals, either within or without the cells. Langhans ("Virch. Arch.," vol. xlix.), on the other hand, maintained that the transformation of the red corpuscles into pigment could only take place inside the carrier-cells. Cordua (" Ueber den Resorptionsmechanismus von Blutergiissen," Berlin, 1877) has convinced himself by his investiga- tions that the formation of pigment from haemoglobin may take place partly outside the carrier-cells, partly within them. Ziegler's researches, carried out upon specimens from dead bodies and upon extravasations experimentally produced, lead him to agree with Virchow and Cordua. Peris pointed out ("Virch. Arch.," vol. xxxix.) that the haematogenous pigments all yield the reaction of ferric oxide when treated with ferro- cyanide of potassium and hydrochloric acid. Even when the pigment has become black it still exhibits the reaction. Kunkel was the first to show (" Virch. Arch.," vol. Ixxxi., and " Zeitschr. f. phys. Chemie," iv., v.) that the brownish red flakes found in old extravasations are not always composed of haematoidin. Sometimes these flakes contain no organic coloring-matter at all, but consist entirely of hydrated ferric oxide. The urobilin (hydrobilirubin), which appears in the urine when free absorption of large extravasations takes place, is derived either directly from haemoglobin, or from haematoidin. Further details on the disintegration of the blood under normal and pathological conditions, and the pigmentations connected therewith, are to be found in the Special Pathological Anatomy, Arts. 262 and 268. A distinction must be made between the true slate-colored pigmenta- tion of the tissues dependent on certain blood pigments, and the slaty discolorations seen in corpses (pseudo-melanosis), chiefly in the intestinal canal and its neighborhood. These discolorations, usually in the form of indefinite and diffused gray patches, are due to the formation of ferrous sulphide ; combination takes place between the iron of the haemoglobin present and the sulphuretted hydrogen evolved in commencing decom- position.] 69. Biliary pigmentations. If the excretion of bile be in any way hindered, it passes over into the general circulation, and biliary pigments RETROGRESSIVE DISTURBANCES OF NUTRITION. 103 are thus carried to the various organs. The yellow staining of the tis- sues so brought about is called icterus or jaundice. When jaundice persists for some time the tint becomes olive-green or dirty grayish green. The bile in the tissues is usually diffused through them indefinitely ; more rarely granules and ruby-red crystals occur. Crystals are chiefly found in the tissues in the so-called icterus neonatorum, or jaundice appearing within a few days of birth. These crystals take the form of ruby-red rhombic tablets, and are composed of bilirubin ; they are iden- tical with haematoidin-crystals. In the jaundice of adults crystals are seldom found ; generally the pigment is more granular, and yellow or brown. This is especially the case when it occurs in the cells of the liver, and in the uriniferous tubules. In addition to the hepatogenous jaundice which depends on reabsorption of bile, there is said to occur also a hsema- togenous form resulting from a disintegration of blood within the blood- vessels ; this is however disputed by many observers. [The hypothesis of a haematogenous jaundice was based on certain experimental phenomena by Ktihne (" Virch. Arch.," vol. xiv.). He in- jected dog's blood, in which the corpuscles had become dissolved, into the vessels, and then found bile-pigments in the urine. Kunkel ("Virch. Arch.," vol. Ixxix.) questions the decisiveness of these experiments. Since bile-pigments are formed in the liver by the disintegration of red corpuscles, the process of pigment-formation would be intensified by Kiihne's injections, and the surplus bile produced might in part pass into the blood again. Orth has a paper (" Virch. Arch.," vol. Ixiii.) on the deposition of bilirubin-crystals in the jaundice of infants. The most various theories have been started from time to time to account for icterus neonatorum. Birch-Hirschfeld has recently (" Virch. Arch.," vol. Ixxxvii.) treated the question afresh. He maintains that the benign form of jaundice (i.e., jaundice not depending on septic infec- tion or profound anatomical change in the liver), is the result of oedema of the capsule of Glisson. This oedema arises in consequence of venous en- gorgement in the region of the remnant of the umbilical vein and vena portae. This explanation seems somewhat far-fetched. May not the jaundice simply depend on an overgreat resorption of bile from the meconium ?] 70. Pigmentation of the tissues by extraneous substances. Any substance optically distinguishable from a tissue, which becomes in any way incorporated with it and remains for a time unchanged, may give rise to a special coloration of the tissue. The number of such substances is of course large, and the manner of their incorporation various. The commonest avenues of entrance are surface-wounds, the air-passages, and the alimentary canal. The most familiar instance of wound-staining is tattooing, common among civilized peoples as well as among savages. The way in which 104 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the colored tattoo-marks are produced is this : the skin is first wounded by scratches or punctures, and then insoluble granular coloring-matters, such as charcoal, cinnabar, etc., are well rubbed in. Where the skin is broken the colored particles penetrate and infiltrate the cutaneous tis- sues. One part remains where it is, so that the skin continues perma- nently pigmented ; another part is carried off to the lymphatic glands, which also become pigmented. The lungs and their lymphatic glands may become very deeply pig- mented by the long-continued inhalation of foreign matters, such as coal- dust, soot, particles of iron or rust, etc. In consequence of prolonged inhalation of coal-dust, for example, the lung-tissue may become perfectly black (miner's lung). Among the pigmentations arising from matters taken up in the ali- mentary canal, we must mention the so-called argyrism (argyria). This is a staining of the tissues consequent upon long-continued internal use of salts of silver. The skin in such cases may assume an intense brownish-gray color ; and the internal organs may also be more or less discolored. The silver is deposited as fine granules in the ground-sub- stance of the different tissues. CHAPTER XVII. THE FORMATION OF CYSTS. 71. A cyst is an excavation bounded by an envelope of fibrous tissue or other more complex structure, and enclosing contents distinguishable from the envelope. According to its mode of origin the inner surface of the envelope may be lined with epithelium or with endothelium. Epithelial cysts arise by the dilatation of pre-existing epithelial cavi- ties. The commonest instance of this is the glandular cyst, which ensues upon closure of the gland-duct. The secretion collects behind the ob- struction, and the gland dilates to a cyst filled with altered secretion. Cysts of retention, as these are called, are chiefly met with in the uterus, intestine, mamma, kidney, and skin. In the case of ductless organs, like the Graafian follicles and the thy- roid, dilatation of the cavities ensues whenever the secretion is morbidly increased. Cysts may also be formed in glandular structures occurring in morbid new growths. Various canals, moreover, which are normally clothed with epithelium, may, in consequence of obstruction and local dilatation, develop into epithelial cysts. Such canals are, for example, the bile-duct, congenital cervical fistulfe, the vermiform appendix, and the ureter. Endothelial cysts arise primarily by dilatation of pre-existing cavities in the connective tissues, such as bursse, tendon-sheaths, obstructed lym- phatics, etc. In other cases they are owing to the collection of fluid in new-formed or false membranes. The contents of these cysts vary with their mode of origin, but consist generally of mere lymph. These might also be described as cysts of retention, in a special sense of the term ; they are really exudation-cysts. The cavities which are formed in the substance of a solid organ by softening and disintegration of a defined region are very frequently de- scribed as cysts. Such cysts occur, for example, in the brain, and they usually contain semi-liquid detritus of the brain-substance. Similar cavities arising in tumors by the same process are also called cysts. In order to emphasize the difference between such cysts ajid cysts of reten- tion, the former may be spoken of as cysts of disintegration. Lastly, a species of cyst may be formed around a foreign body which has become lodged in the tissues ; round a parasite like a hydatid, for 106 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. example (Art. 245). It is the result of a new tissue-formation in the neighborhood of the foreign body. [The student should consult the admirable lectures on li Cysts " in Paget's " Surgical Pathology ; " they contain many references of value. To the varieties in the text we might add-cysts of extravasation, or blood-cysts, resulting from hemorrhage into closed cavities (e.g., hae- matoma, haematocele) ; and dermoid cysts, which are congenital (Art. 178). The various neoplastic cysts or cystoid tumors will be referred to under their proper headings in Section VI. ; and, so far as they affect particular organs, in the Special Pathological Anatomy.] SECTION IV. PROGRESSIVE OR FORMATIVE DISTURB- ANCES OF NUTRITION. CHAPTER XVIII. THE CELLULAR PROCESSES CONCERNED IN HYPERTROPHY, HYPERPLASIA, AND REGENERATION. 72. In treating of the malformations, we had occasion to speak of excessive development of the organism as a whole, and of its constituent parts-of over-size and over-growth. When a tissue manifests an abnor- mal tendency to overgrowth, it is said to hypertrophy. This term tacitly implies that the structure of the overgrown tissue continues to cor- respond with that of the normal. The overgrowth first described implies an excessive development of the organism, or organ, in the embryonic stage of existence. Such forms of overgrowth form, however, but a part of the class of tissue-changes described as hypertrophies. In adult life, as in infancy, certain organs are very apt to hypertrophy, that is to increase abnormally in size while preserving their normal structure. Such hypertrophies are to be met with in the voluntary muscles, the heart-muscle, the unstriped muscles of the alimentary canal, bladder, and ureters, in the kidneys, thyroid gland, skin, etc. The increased size of a hypertrophied organ depends on two factors. The several elements of the organ may increase in size, or they may in- crease in number. With Virchow we may distinguish between simple hypertrophy, i.e., elementary overgrowth in the stricter sense of the term, and numerical hypertrophy or hyperplasia, i.e., an increase in the number of constituent cells or cellular structures in the organ or tissue. Thus a muscle may very greatly increase in bulk by mere in- crease in size of each fibre of it ; while the number of fibres remains the same. Of course, hypertrophy and hyperplasia may go hand in hand in the same tissue ; indeed it is hard to conceive of a hyperplasia which has not been preceded by a hypertrophy, at least of some of the cells. When an increase in the number of cellular elements occurs at a part where tissue has already been destroyed by some retrogressive process, we speak of it as regeneration. We assume that the formation of new tissue does not go on beyond the normal limit, but suffices merely to re- place what has been lost. 73. Hypertrophy, hyperplasia, and regeneration are dependent ulti- mately upon certain cellular processes. The formation of new tissue can 110 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. only take place through the agency of the cells. The intercellular sub- stance, unaided by the cells themselves, has no power or potency to pro- duce new tissue. The cells which go to form new tissue arise by subdivi- sion from pre-existing cells. New cells are never generated from plastic exudations, as was formerly supposed. Hypertrophy, i.e., increased size of a cell, is in general consistent with the maintenance of the properties of the cell. The formative pro- cess which results in hypertrophy is confined to the addition of new con- stituents similar in kind to those already present ; the cell simply grows. We know but little of the structural changes which this growth involves. It is, however, sometimes noticed that the cell-protoplasm becomes more granular ; or that the granulation alters as its amount increases ; the nu- cleus also changes more or less its appearance. Our knowledge concerning the process of cell-multiplication, or pro- liferation (as it is called, though the term is not a happy one), is more minute. Researches, most of them very recent, have shown that multi- plication is attended by peculiar changes in the structure of the cell and of its nucleus, which affect the disposition of their several constituents. Movements within the nucleus are usually the first sign that cell-division is about to take place. These issue in subdivision ®f the nucleus. Then sooner or later the protoplasm as a whole is set in motion, and this ends in the complete subdivision of the cell itself. 74. The fully developed nucleus of a cell is not homogeneous, but possesses a very peculiar structure. This is clearly to be made out, by appropriate handling, under the higher powers of the microscope. A resting nucleus, i.e., one which is not about to subdivide, consists of an external capsule or membrane (Flemming, " Virch. Arch.," vol. Ixxvii.), and certain contents. The latter are divisible into a denser highly re- fractive nuclear substance, and a rarer colorless nuclear juice, or inter- mediate substance. The nuclear substance contains-first, certain nu- cleoli or nucleolar corpuscles, and secondly, scattered granules and filaments. Frequently the filaments are aggregated into a framework or network (Fig. 19, a), which may be brought out very distinctly by proper reagents. When the cell is about to subdivide the nuclear network undergoes a series of typical changes of form, ending in the division of the nucleus into two equal portions. According to Flemming, the first stage of nucleus-division is the solution and disappearance of the nucleoli; while the nuclear substance takes the form of a ravelled coil of sinuous filaments (Fig. 19, i); this is the " coil-form " of the mother-nucleus. The nuclear membrane itself seems to break up and furnish filaments to the coil. From this stage onward the nuclear figure alone takes up the staining reagent (hence the nuclear substance is sometimes spoken of as chromatin). The filaments then become thicker and the coil looser ; its continuity is broken here and there, and at length it passes into the " wreath-form " FORMATIVE DISTURBANCES OF NUTRITION. 111 (c). In this the filaments are arranged in a loose series of central and peripheral loopings, the centre of the figure being unoccupied. From this is fashioned a " star-form," or aster {d), with free double rays, the peripheral loops of the wreath-form dividing at their ends. The double rays next divide longitudinally, and the whole star-form contracts. The filaments of the single-rayed star (e) thus formed next gather into an equatorial group, which soon divides into two equal polar segments (y). This division is effected by the development of a transparent equatorial plate (y) often studded with fine points (Strasburger's cell-plate). The two segments, which are the rudiments of the daughter-nuclei, move Fig. 19.-Indirect Cell-division (from Flemming; diagrammatic), a, cell with resting nucleus; 6, coil form of mother-nucleus; c, wreath-form showing the central and peripheral loops, some of them broken through; d, star-form with free rays, showing the filaments in the act of splitting; e, fine-rayed star-form; f, nucleus with equatorial plate; division into polar segments; g, half-barrel or half-spindle form ; the points in the middle are Strasburger's equatorial cell-plate; A, star-form of daughter-nucleus; i, wreath-form; k, coil- form ; I, resting nucleus with network. asunder toward opposite poles and form the "half-barrel" or "half-spin- dle " figure (Eberth's and Maizel's " creel-form," or " basket-form"). The half-spindle form of the daughter-nucleus passes into a star-form (A), and this into a wreath-form (i) by the fusion of the ray-ends. The wreath- form shrinks and its filaments become more ravelled, till at length it takes the coil-form (&). This becomes looser and more regular, and so finally the daughter-nucleus fashions itself a nuclear network (T), and passes into the resting state corresponding to the resting state of the mother-nucleus. In the stage of the star-form and the wreath-form of the daughter- nucleus, constriction of the cell-protoplasm commences (l), and ends with the completion of the coil-form (k). During the active stages of the subdividing process the nuclear juice or intermediate substance does not stain, though it stains in the resting state. During subdivision the nucleus is surrounded by a clear areola. The whole process takes place rapidly ; it ends with the complete constriction and severance of the cell-proto- 112 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. plasm. The above mode of subdivision is called indirect or karyokin- etic ^Kapvov, a kernel). [According to a recent communication of Flemming's' (" Arch. f. ' mikrosk. Anat.," xx.), the intermediate substance of the nucleus contains (in stained preparations, and presumably also in the living state) a deli- cate prolongation or continuation of the nuclear network. The fine granulation observed in the intermediate substance with lower magnify- ing powers is really but an optical section of the meshes and filaments of the finer network. The nuclear membrane is merely the peripheral ex- pansion of the nuclear network. Most important and valuable researches on the changes in cells and nuclei during subdivision have been made by Flemming (" Arch. f. mikrosk. Anat.," xvi.-xx.) and Strasburger (" Zellbildung und Zelltheil- ung," Jena, 1880). The former has worked upon animal cells, the latter upon vegetable cells. Strasburger's description of the process of nucleus division is not quite the same as Flemming's. He distinguishes a nuclear substance (chromatin), and a nuclear juice (achromatin). The capsule or nuclear membrane, as well as the granules, network, and nucleoli which lie in the interior, belong to the nuclear substance. When the nucleus sets about subdividing, its granulation becomes coarser, and the granules run together into convoluted filaments ; the nucleolar corpuscles and cap- sule also take part in forming the filaments. These filaments have the power of stretching or streaming out into the cell-protoplasm. Then follows an elongation of the nucleus and, at the same time, of the fila- ments, so that the whole assumes a spindle-like shape, and two poles be- come distinguishable. The filaments shrink up toward the equator, and so form the nuclear disc, the entire nuclear substance going to make it. From this account it appears that the nuclear disc consists entirely of shortened rodlets or filaments. On both sides of this equatorial disc ap- pear slender striae or filaments, the so-called spindle-filaments, and these together with the nuclear disc make up a secondary spindle-form of which the disc constitutes the equatorial zone. The spindle-filaments converge at the poles, or end freely. The material of which they are made is fur- nished by the cell-protoplasm. They are not taken up by the nuclear substance ; indeed they are eliminated again as the subdivision proceeds. The daughter-nuclei originate in the nuclear disc. This parts asunder at the equator, and the two halves draw apart toward the poles. These halves become the daughter-nuclei ; they are still connected by a few fine spin- dle-filaments. A row of granules now makes its appearance in the equa- torial plane ; this is the cell-plate, and in this the new cell-wall is formed. Protoplasm appears on each side of it, in which the spindle-filaments are merged-and thus the process of division is completed. Strasburger's account of cell-division in the vegetable kingdom would seem to indicate that a certain difference exists between that and the ani- mal kingdom. Flemming, however, has shown in a recent paper that the FORMATIVE DISTURBANCES OF NUTRITION. 113 physical processes involved in karyokinetic subdivision are in all cases essentially the same, at least in so far as they are to be made out opti- cally. He thinks the apparent differences are not so great as Strasburger conceives them to be. It is of great interest to note the fact established by Flemming-that in the segmentation of the ovum the process of nucleus-division follows throughout that which we have described as the karyokinetic mode (Balfour, " Comp. Embryology," i., 3). This mode of nucleus-division has often been observed and described as occurring in pathological proliferations. The chief memoirs are by Eberth ("Virch. Arch.," vol. Ixvii.), Arnold ("Virch. Arch.," vols. Ixxvii., Ixxviii.), Flemming (loc. cit.), Martin ("Virchow's Archiv," vol. Ixxxvi.), Drasch ("Wiener Sitzungsber.," 1881), Klein [Quart. Journ. of Mier. Science, 1878 and 1879). Priestley gives a summary of the early researches in Quart. Journ. of Mier. Science, 1876 ; Cunningham reviews the more recent ones in the same journal, January, 1882.] 75. These structural changes in the nucleus point unmistakably to the energetic internal motions which affect its molecules in the process of growth. Our knowledge of the molecular changes in the cell-protoplasm is unfortunately more meagre and incomplete. Here, however, it is also possible to make out by proper means-that the protoplasm assumes a special structure, and that various movements and transmutations of form occur amongst its component elements. Thus in certain cases nucleus-division is accompanied by lively rotary movements in the pro- toplasm. Such transformations and transpositions explain certain phe- nomena which are frequently observed-for example, the formation of a transparent areola round the subdividing nucleus, of radiating lines of granules making up the so-called " karyolytic " figure, etc. Such radiating lines of granules have especially been seen in the process of impregnation of the ovum. They occur in the neighborhood of the male and female pronuclei, and have been described as the aster (Balfour, " Comp. Embry- ology," vol. i., ch. 3). Flemming, as well as Strasburger, assigns to the cell-protoplasm an essential part in the process of subdivision. Stras- burger even asserts that it is the penetration of the protoplasm into the nucleus which calls forth a reciprocal activity in the latter, and so gives it an impulse toward subdivision. Whether this be true or not we cannot at present decide, inasmuch as no penetration of the protoplasm into the nucleus has ever been directly observed. The ordering of the granules into radiate figures, like the other movements of the protoplasm hitherto observed, takes place, as a rule, simultaneously with the process of nucleus- division. In some cases, however, it may precede, in others it may suc- ceed, the latter. Thus, according to Gruber (" Zool. Anzeiger," 1880) the infusorian Euglypha alveolata first gives rise to a daughter-cell, then the nucleus becomes subdivided and migrates into the daughter-cell ; while at the same time active movements become visible in the cell-protoplasm. 8 114 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. A special form of cell-division is that which takes place after an antecedent conjugation. It is common among the infusorians. [In order to make out the nuclear figures, the cell must be examined either in the living state or after treatment while still living with a rapidly fixing solution. If this is not done the process of subdivision is completed as the cell gradually dies. There is no general rule of proceed- ing which will apply to the examination of all cells.] 76. The indirect process of cell-division just described will serve as a pattern of the processes which occur in pathological cell-formation. No satisfactory demonstration has been given of the theory that cell- division may occur in another way, namely by direct constriction of the cell without interior structural change. Nor has it been certainly es- tablished that a nucleus or cell can arise de novo out of an indifferent blastema (or homogeneous matrix), at any rate within the domain of pathological cell-formation. Virchow's aphorism, Omnis cellula e ceUula, is, in this domain at least, most fully and completely confirmed. But though we maintain that, so far as we know, cell-division is always indirect, never direct, we do not imply that every cell-division proceeds exactly according to the scheme we have indicated. On the contrary, the examination of different specimens shows that the form and construction of the nuclear figures are by no means always the same ; deviations within certain limits may occur. But while the figures formed by the nuclear filaments may differ con- siderably, the principle and plan of the process is fundamentally the same. Even the simultaneous formation and development of three or four daughter-nuclei is but a modification of the general process. The subdivision of the cell-protoplasm usually follows immediately upon the division of the nucleus ; but the connection of the two pro- cesses is by no means inevitable. Not infrequently the nucleus subdivides while the cell does not. The result is the formation of binucleated, or finally of multinucleated cells, the so-called giant-cells. These giant- cells may afterward break up into uninucleated cells, the protoplasm gathering itself around the several nuclei and dividing along the bounda- ries of the regions so defined. Sometimes this happens in a peculiar way. The protoplasm of the daughter-cell separates from that of the mother-cell, but in such wise that it remains surrounded by the latter on all sides ; the one cell includes the other. Virchow has called such cells brood-cells. They do not occur frequently. They have been thought commoner than they really are-inasmuch as leucocytes which have penetrated into a large ordinary cell have been taken for a brood of daughter-cells. The process of cell-division takes a peculiar form also in the formation of cell-buds, or gemmation. The mother-cell shoots out a longer or shorter process ; this then receives a nucleus ; and lastly divides off from the parent (see under New Blood-vessels, Art. 86). The FORMATIVE DISTURBANCES OF NUTRITION. 115 peculiarity is chiefly in this-that the movements of the protoplasm (evidenced by the protrusion of the bud) precede the nucleus-division. The new nucleus, derived, as in all other cases, by subdivision from the mother-nucleus, migrates into the bud after it is already marked off from the parent. [Until quite lately the process of nucleus-division was described (after Remak) somewhat in this fashion : The nucleus lengthens out, becomes indented and constricted in the middle, and at last divides (compare Rind- fleisch, " Pathological Histology," vol. i., p. 71 ; Cornil and Ranvier, " Manual of Path. Hist.," vol. i., pp. 9, 83). The constricted bean-shaped nuclei found in some preparations were regarded as in the preliminary stages of subdivision ; and the multiplication of the nucleoli was regarded as the first step in the actual process. This view must now be given up. The various shapes of the nuclei depend partly on actual contractions, partly on shrinkage during the hardening process. Increased size of the nucleus may perhaps have a relation to its imminent subdivision ; the mere multiplication of its nucleoli has certainly no such relation. The older theories of direct nucleus-division have been discredited by the latest researches ; so also have the still older views concerning the formation de novo of cells and nuclei. (See Strasburger, op. cit., where full references to the literature of this subject are given.) The question whether or not the white blood-cells subdivide is as yet unsettled. Indirect nucleus-division has not been observed in them. See Klein, " Centralb. med. Wiss.," 1869, Quart. Jour, of Mie. Sei., 1875, and " Handb. of Phys. Lab.; " Ranvier, " Traite technique d'histologie," p. 161. On " endogenous gemmation," by which brood-cells are produced, see Virchow, " Cellular Pathology," and Klein, " Wiener Sitzungsber.," 1871, and " Anatomy of Lymphatic System," vol. i., London, 1875.] 77. The formation of new cells is the first step toward hyperplasia as well as toward regeneration. They yield the formative tissue out of which the definitive structures are developed. As the processes of cell- division in pathological new-formations are closely analogous with those of normal multiplication, so also do the succeeding formative processes run parallel with those of normal growth. If epithelium or fibrous tissue is to be fashioned out of the indifferent tissue which results from cell- division, the process of transformation is exactly the same as occurs in the normal development of the organism from embryonic tissue. So far as investigation in this region has yet extended, we find the law of the specific nature of the tissues to be everywhere obeyed. The cell-progeny of the embryonic cells which went to form any given layer of the blastoderm can go to build up such tissues only as are normally de- rived from that layer. An epithelial cell can in no possible circumstances form bone or cartilage ; a connective-tissue corpuscle cannot bring forth an epithelial cell or a gland-cell. This law has frequently been called in question ; the specific distinction between the various tissues was for- 116 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. merly not recognized or not accepted. Thus Virchow, to whom we owe the fundamental principles of cellular pathology as regards new-forma- tions, held that connective tissue might serve for the matrix of the most various structures. This view is no longer tenable ; observed facts con- strain us to believe that a tissue cannot give rise to new tissue other than of its own kind or kindred. Epithelial tissues are, generally speaking, built up by the cementing together of formative cells in a way which is characteristic of epithelium everywhere ; the cells are in juxtaposition, the intercellular cementing substance is subordinate. In fibrous tissue, on the other hand, the inter- cellular material derived from the cells is the chief constituent, and gives to the tissue its characteristic properties. 78. A morbid growth is the product of various factors. If a cell is to grow and multiply it must first be endowed with the faculties necessary to growth and reproduction. In other words, it must have the power to take up from the blood a greater quantity of nutriment, to assimilate this, and apply it to the formation of new protoplasm. This property of the cell Virchow has called the nutritive and formative excitability (Irri- tabilitat')} a term which implies that it is some stimulus or excitation from without which stirs up the cell to increased assimilation. We must, therefore, begin by inquiring of what kind the stimuli must be that can thus excite the cell to intenser activity. When, in embryonic development, a part or organ grows to an abnor- mal size and thus becomes so to speak gigantic, we may refer the phenom- enon to several possible originating causes. The primary rudiment of the part may have been unusually large ; the embryonic cells may have been endowed with an abnormal share of vital energy ; they may have had specially favorable chances of nutrition ; the resistances to prolifera- tion may have been abnormally slight. It is not, in general, an easy task to decide which of these factors has in a given case determined the result. It is, of course, always possible that several factors have been .working to- gether. In the hypertrophies of later life (including the hyperplasias and re- generations), which are demonstrably conditioned from without, and so do not depend on pre-existing or embryonic factors, the question of eti- ology is so far simplified. We must direct our attention to the other possible factors, namely increased vital energy, increased supply of nutri- ment, or diminished resistance to growth. It is, however, not to be for- gotten-that the cause of the increased activity of the cell may be of the nature of a stimulus from without, which acting directly upon the cell excites it to more intense productiveness. We may assert then in gen- eral terms that, when the nutritive and formative activities of a cell are morbidly increased, the effect is due to augmentation of the physiological stimuli or diminution of the physiological resistances to growth, or to the direct influence of external stimuli. 79. Experience has shown that many tissue-cells, even when they FORMATIVE DISTURBANCES OF NUTRITION. 117 seem, by their close connection with their neighbors, to be as it were firmly built into the tissue of which they form a part, still retain for a time the power of growth and subdivision, or, in other words, of multipli- cation. This is especially the case with cells whose protoplasm has not undergone any serious metamorphosis. As to the conditions governing such multiplication, experience alone can inform us. Many observers (Stricker, Boettcher, Neumann, etc.) assert that ex- trinsic stimuli, that is to say physically or chemically active substances, have the power of exciting the cell to proliferate. Thus caustics and the actual cautery applied to tissues are said to induce in them cell-mul- tiplication by direct action. There seems to be no certain observation which either establishes or confirms the assertion. Researches made in this direction have shown that the action of such external agencies is in the first instance destructive ; that in caustic corrosion, for example, not only does the tissue which is directly attacked perish, but that in its neighborhood undergoes secondary degeneration as well. It has further- more been uniformly observed that formative changes do not begin to ap- pear until a certain time after the injury ; it is therefore very unlikely that they are directly brought about by it. Lastly, they do not commence at the injured spot, but in its neighborhood. From these considerations it appears that the proposition, often enunci- ated as if it were self-evident-" The stronger the external stimulus, the greater the proliferation"-cannot be accepted as true. We can at most admit that very slight stimuli, sufficient merely to excite the cell without injuring it, may perhaps call into play its power of multiplication ; but nothing has been experimentally established concerning the nature, the action, or the mode of application, of such stimuli. [The researches on the reaction of cells to external stimuli have been made chiefly with the view of determining the source of the migratory cells in inflammation (Art. 99). Stricker and his pupils affirm that the stimulus of inflammation excites the affected cells to rapid multiplication. The tissue-cells and their appendages swell up (it is said) under this ex- citation, and subdivide into new cells and non-nucleated lumps of pro- toplasm (Stricker's "Vorles. fiber allg. Pathol.," Vienna, 1878 ; and "Pathology of Inflam.:" "Internal. Encyclop. of Surgery," vol. i., 1882). Cohnheim (" Lehrb. d. allg. Pathol."), Key, Retzius, Eberth, and others have failed to make out any such consequence of inflammatory ir- ritation. Even if the meaning of the word stimulus be extended to include any mechanical or chemical agency which can influence the cell, we cannot adduce any undoubted observation serving to establish Stricker's view.] 80. If, then, it be true that external injurious agencies are not com- petent to induce multiplication in cells, we must have recourse to the normal vital stimuli if we are to explain the process of pathological cell- 118 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. growth. For the due growth and multiplication of a cell certain exter- nal conditions must be fulfilled. Above all it is necessary to provide for a certain degree of warmth, and a certain modicum of proper nutritive material. In addition to this there must be no obstacle in the way of multiplication. These are the external requirements. The internal con- dition is the inherent faculty of the cell to assimilate the nutriment of- fered to it. In a tissue not undergoing transformation, the factors favoring pro- liferation and those which inhibit it must be in a state of balance. If this balance be disturbed toward the side of the proliferous forces, the cells proceed to grow and to multiply. The factors in question resolve themselves on analysis into three. In the first place, it is conceivable that the capacity of the cell to as- similate nutriment may be increased. Such increase can only be condi- tioned by an increase in the normal stimuli required for the preservation of the cell. Such stimuli are warmth, for many cells light, for the mus- cles motor impulses, for glands special excitations from the nervous sys- tem, etc. Increased stimulation of this kind may as a fact lead not only to intensified functional metabolism in the tissue concerned, but even to hypertrophy of its elements. Such hypertrophies, which we may call functional hypertrophies or hypertrophies of action, are specially common and remarkable in muscles and glands (heart-muscles, bladder-muscles, kidneys, etc.). As we have said, they are referable in part at least to in- creased vital activity in the cells, consequent upon increased physiologi- cal stimulation. A second possible factor is increase in the supply of nutriment. This plays a chief part in hyperplastic processes, at any rate. A third is the removal of the normal checks to growth. Its effect is most evident in the processes described as regenerative. If we attempt in particular cases to make out to which of these fac- tors cell-multiplication is due, we are led to see that it is rare for any one factor alone to be the efficient cause. The remarkable regulating me- chanism of the vessels is so adjusted, that when the function of a tissue is increased its blood-supply is increased to correspond. In like manner, when the smallest fragment of tissue is removed, the slight loosening of the surrounding- texture is enoug-h to aug-ment the stream of transudation from the vessels. In consequence of these adjustments, increased supply of nutriment plays a great part in all the formative disturbances of nu- trition. , [Cohnheim, in his " Allgemeine Pathologic," has insisted on the im- portance of increased supply of nutriment even more strongly than we have done. According to his view it is the sole influential factor, com- pared with which the intrinsic activity of the cell is quite secondary. We are unwilling to condemn the cell to play so passive a part, but rather agree with Virchow, who (" Cellular Pathology ") lays it down that FORMATIVE DISTURBANCES OF NUTRITION. 119 -"the cell is not nourished, but nourishes itself." Functional hyper- trophy is therefore not to be looked upon as the mere consequence of the increased blood-supply to the active organ. If the assimilative activity of the cells were not augmented, the mere presence of a greater supply of nutriment would be valueless. See Samuel's " Allg. Path.," 1879 ; Pag- et's " Surgical Pathology," Leet. 3.] 81. We shall more readily comprehend the activity of the tissue-cells, i.e., their behavior under various conditions, and the changes they pass through-now at rest, and now manifesting intense formative energy- if we consider first the vital manifestations of an organism that is unicel- lular. In later chapters we shall have frequently to speak of unicellular micro-organisms, of bacteria and yeast-plants, and their mode of life. If we reflect on the conditions essential for the multiplication of such or- ganisms, we note that the nature of the nutrient fluid is (next after the ad- justment of the temperature) the factor of highest importance. In suit- ably composed fluids the fungi develop much more luxuriantly than in those that are ill-suited. But we are not thereby justified in assuming that the cell plays a merely passive part, that all it has to do is to take up the nutriment offered to it. The cell is, on the contrary, active, and its activity has a special influence on the liquid itself. It has the power to in- duce certain chemical changes in the liquid,to decompose certain substances contained in it, and to change their condition so as to adapt them for as- similation by itself. The cell does not merely take in and give out mate- rial ; it acts " catalytically " on its environment. This is proof at least that the cell possesses a high degree of spontaneity-that it has the power of making more available for its own sustenance the various forms of nutriment that come in its way. It is also of great interest to remark that the cell is ultimately limited in its formative activity by its own products. When the amount of nu- triment present is abundant, the activity of the cell comes to an end, not through the exhaustion of the supply, but through its contamination with certain products of cell-metabolism. Many of the substances engendered in fermenting liquids by the action of fungi tend to check the growth and multiplication of the fungi themselves ; when present in quantity they may put a stop to multiplication altogether. The alcoholic fermen- tation, and the multiplication of the yeast-plant which produces it, come to an end when a certain proportion of alcohol has been generated in the fermenting liquid. In septic putrefaction the bacteria generate com- pounds, such as carbolic acid, which are destructive to themselves. If we may apply these facts of fungus-physiology to the cell-physiology of higher organisms, we find that they illustrate first of all this principle- that the quantity and quality of the nutritive material at the disposal of the cell have a profound influence upon its behavior. And secondly, this other-that the cell has nevertheless an intrinsic power of utilizing this material, and of appropriating what is suitable to itself out of various 120 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. combinations. Lastly, the limits imposed on the multiplication of fungi by the products of their own activity jnay help us to understand how the formative activity of the cells of complex organisms may be temporarily checked. We cannot indeed regard the intercellular substance of the connective tissues as equivalent in significance to the products of the chemical changes induced by the bacteria. Yet the comparison may at least enable us to conceive how cell-growth may tend to limit and to check itself, without the interposition of extrinsic resistances. In the connective tissues the formation of the intercellular substance is the lim- iting factor, in the epithelia it is the cohesion or cementation of the in- dividual cells into a firm and single whole ; just as in yeast-fermentation it is the formation of alcohol. When the alcohol is withdrawn in the latter case the multiplication of the yeast-fungus goes on again. So, likewise, if the intercellular substance be dissolved away from a connect- ive tissue, or if the continuity of the epithelial mosaic be loosened or inter- rupted, the faculty of multiplication is again awakened in the constituent cells ; or if (as in the epithelia) it has never been dormant, it is at once intensified. [In the human organism temperature is not a factor of such impor- tance as it is in regard to unicellular organisms. In the former the tem- perature is approximately uniform ; change of temperature cannot there- fore play any great part in promoting cell-growth. Even changes in the quality of the cell-nutriment can have but a small part of the significance here that it has in the case of fungi living in a nutrient solution ; such grave changes as may be artificially produced in the character of the so- lution do not occur in the body. Quantitative variations are thus of the greater importance.] 82. It often happens in an organ which is the seat of hyperplastic proliferation that the different elements do not take an equal share in the process. Thus an enlarged gland may in one case owe its increase in size entirely to additions of gland-substance, in another to increase in the fibrous constituents. We may have a glandular hyperplasia, or a fibrous hyperplasia. This may happen in any organ which is composed of more than one kind of tissue. The inequality in the relation of the two tissues may be so extreme, that while one is highly hyperplastic the other may not merely fail to increase, but may even undergo atrophy. In the latter case it is generally the specific elements (ganglion-cells, nerves, gland-cells, muscles, etc.) which atrophy, while the fibrous elements in- crease and multiply. A very frequent cause of such unsymmetrical hyperplasia of the fibrous tissue is inflammation (which see). Inflamma- tion plays a chief part in pathology ; only too frequently its disastrous result is fibrous hyperplasia of the affected organs, involving atrophy of their essential elements. What is true of hyperplasia holds also for regeneration. When part FORMATIVE DISTURBANCES OF NUTRITION. 121 of a tissue has been destroyed, the regeneration which ensues is by no means always complete and perfect. In the human organism at least, the power of restoring or regenerating a lost part is very limited. Parts of any appreciable size when once lost are never replaced. This is true, for example, of a limb, a finger, a piece of liver, or of brain-substance. All highly specialized structures, and their specific elements, show but slight traces of regenerative power. Thus in adults it is highly probable that ganglion-cells are never reproduced, if once destroyed. Glandular epithelium is only restored when the loss is very trifling, and when some of the essential cells still remain intact within the gland-unit (acinus or tubule). When a gland is wounded and its texture broken into ever so little, the wound in healing fills up not with gland-substance, but with fibrous tissue. Pathological vicarious tissue of this kind is described as cicatricial or scar tissue. It is the result of an inflammatory process (Art. 108), or of multiplication among the connective-tissue cells. With nerves and muscles the case is much the same. Deficiencies of any size are filled up with scar-tissue. The connective and epithelial tissues are more favorably circum- stanced. The latter especially have the power of reproducing wide areas of lost surface. Among the fibrous tissues, the periosteum is remarkable for its regenerative power; while cartilage is replaced very imperfectly, if at all. 83. When, by a process of proliferation, a new tissue is produced whose elements are normal in type, though the type is not that of the matrix-tissue, we speak of the formation as a heteroplasia. In one sense a cicatrix in an organ like the liver is a heteroplasia, inasmuch as fibrous tissue replaces the proper liver-tissue. And even when the fibrous tissue of the cicatrix is compared with that of the liver, we must still regard the cicatrix as heteroplastic ; the characters of the two tis- sues are markedly different. This is true of fibrous hyperplasias in gen- eral, and in particular of those consequent on inflammation. Owing to the generic resemblance of the normal and pathological tissues, however, it is not usual to reckon these among the heteroplasias. The special field of heteroplastic formations lies among the tumors or morbid growths. A tumor, in the limited sense of the term, is a forma- tion of new tissue. It may resemble more or less the matrix-tissue from which it grows, but it always possesses certain characteristics which dis- tinguish it from the surrounding structures, and which justify us in speaking of it as heteroplastic. CHAPTER XIX. HYPERPLASIA AND REGENERATION IN PARTICULAR TISSUES. 84. The morphological changes which take place in the hyperplasia and regeneration of the epithelia are comparatively simple. Epithelium can arise only from epithelium ; the several varieties even do not usually pass into each other. Eberth's researches (" Virch. Arch.," vol. Ixvii.) have shown that the nuclear transformations in epi- thelial cells during their reproduction are quite analogous to those figured in Flemming's scheme. The disappearance of the nucleoli and nuclear membrane, the formation of filaments, of two semi-spindle forms (or, as Eberth calls them, " creel-forms "), of star-forms, etc., are all observed in the epithelial cell, within a clear areola of cell-protoplasm. The star-forms likewise, as they move asunder poleward, become trans- formed into nuclear networks in the midst of the clear intermediate sub- stance of the daughter-nuclei. Arnold describes (" Virch. Arch.," vol. Ixxviii.) nuclear figures observed in tumor-cells, which in details seem rather to correspond with Strasburger's version of the phenomena. The subdivision of the cell-protoplasm occurs either during the later stages of nucleus-division, or after it is complete. In other cases processes are first thrown out by the subdividing epithelial cell, and into these daughter- nuclei then migrate. The budded processes become independent cells by separation from the mother-cell. Small losses of lining epithelium are in general replaced quickly by means of regenerative multiplication. Glandular epithelium, like that of the kidney, may also be quickly reproduced when lost, provided only the structure of the basis-tissue (from which the cells derive their suste- nance) is not altered or destroyed. Hyperplastic multiplication of epi- thelial cells is very common, especially in tumors. Epithelial cells have also the power of remaining alive for a time when separated from their proper matrix. They may in this way be transferred from one basis-tissue to another. Thus epithelial cells from the skin of one person may be transplanted to the surface of a granulat- ing wound in another, and there grow and multiply (Reverdin's skin- grafting). This is a simple and convincing proof of the independence or autonomy of the cell, and of the importance of its inherent powers in reference to its nutritive and formative activity. FORMATIVE DISTURBANCES OF NUTRITION. 123 [The regeneration of epithelium has of late years been made the sub- ject of numerous researches. Most observers agree that epithelium can arise only from epithelium ; only a small number, like Burkhard (" Virch. Arch.," vol. xvii.), Cornil and Ranvier ("Man. Path. Hist.," vol. i.), and Rindfleish (" Gewebelehre," fourth edition, p. 128 ; " Pathological His- tology," vol. i., p. 106) assert that epithelium may be formed from con- nective-tissue cells. No convincing proof of the assertion is alleged ; while the fact that cutaneous wounds begin to skin over only at spots where epidermal cells still remain tells strongly against it. Arnold ("Virch. Arch.," vol. xlvi.) believes that in epithelial regen- eration a plasma is effused into which nuclei subsequently migrate. Klebs ("Arch. f. exper. Path.," iii.), von Wyss ("Virch. Arch.," vol. Ixix.), Cohnheim (" Virch. Arch.," vol. Ixi.), and Eberth (loc. cit.) have failed to confirm this, but found on the other hand that regeneration was effected by subdivision of the old epithelial cells. Klebs observed in the young- cells phenomena suggesting contractility and the power of locomotion ; Waldeyer has made a like observation in the case of epithelial tumor- cells. The first communication on epithelial transplantation and skin- grafting was made by Reverdin (Soc. de chirurgie, December 13, 1869 ; Brit. Med. Journ., 2, 1870 ; " Arch. gen. de med.," 1872. His method has since been extensively employed with a view to the speedier skinning over of wounded surfaces (" Int. Ency. of Surgery," vol. i.). Schweninger has shown (" Ueber Transplant, von Haaren," Munich, 1875) that the mere laying on of hairs, which have been plucked out with the outer root- sheath adhering, suffices to set up epithelial proliferation on granulating surfaces. Griffine (" Virch. Jahresber.," 1876) has shown that, when ciliated cylindrical epithelium is lost, it is first replaced by ciliated squamous epi- thelium ; this is then gradually transformed into the cylindrical variety.] 85; New fibrous tissue is invariably developed from cells, and the process is the same as that by which normal fibrous tissue is formed. The formative cells have been named fibroblasts. They are derived by proliferation either from the stationary cells of the connective tissue, or from migratory leucocytes, i.e., white blood-cells which have escaped from the vessels. The development of the latter will be treated when we discuss inflammatory new-formations. Fibroblasts are cells with large vesicular nuclei and nucleoli, and are capable of active subdivision and multiplication. By proper handling it is possible to make out the nuclear figures, but the subject has not been sufficiently investigated to afford means for a detailed description of the process of subdivision. The cell-protoplasm is pale and highly granular ; the size of the cell varies, on the average it is about that of an ordinary squamous epithelial cell. They are often described as epithelioid cells. Not infrequently multinuclear cells are met with, the so-called giant-cells. The form of the fibroblasts is extremely variable. In the earlier stages 124 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. they are rounded, later on they become club-shaped, spindle-shaped, star- shaped ; in short they assume every possible shape and form. When they have accumulated in any spot and begin to address them- selves to the formation of tissue, they become connected with each other by means of their processes and projections ; or they arrange themselves in a compact mass of densely packed multiform cells. The intercellular substance which gives the fibrous tissues their char- acteristic texture is derived from the cell-protoplasm. The ends and lat- eral borders of the cells become fibrillated ; or the boundaries between the cells disappearing, a homogeneous mass of protoplasm is formed, and in this fibrils are afterward developed. A great many of the formative cells are used up in this way ; some, however, retain their nucleus and a part of their protoplasm, and form i cxed connective-tissue corpuscles of the new tissue. (Cf. Art. 108.) According to the greater or less compactness with which the forma- tive cells are deposited and grouped, the new tissue is firm and dense, or loose and reticular. Fibrous tissue, rather than areolar, is that most commonly developed, especially as a consequence of inflammation. It may become hyperplastic, either by itself, or accompanied by hyperplasia of contiguous tissues such as the epithelia. In respect of the diffusion or extension of the hyperplastic process, it is of some importance to dis- tinguish between diffuse or indefinite hyperplasia, and that which is limited to definite areas ; the latter leads to tissue-formations which re- semble tumors. (See under Tumors, Sect. VII.) Adipose tissue is formed from normal or pathologically developed connective tissue, or from mucous tissue, by the deposition of fat in the interior of the cells. Mucous tissue, characterized by the mucous consistence of its ground-substance, is generally derived from an existing tissue by meta- plasia (Art. 90) ; it may also be formed from new proliferating cells. Neuroglia is developed by the multiplication of the neuroglia-cells. [The structure and development of the connective tissues, both nor- mal and pathological, have been the subject of many researches. The origin of the ground-substance has given rise to controversy. Some con- sider it to arise outside the cells, others from within them. A third theory again, while admitting its external origin, supposes that the fibrils are produced in it by the formative power of the cell as if they were a kind of plastic secretion. The view of the text only applies to the for- mation of fibrous tissue from new-formed embryonic or indifferent tissue. It does not apply, for example, to the formation of fibrous tissue by metamorphosis of the basis-substance of a different tissue, such as bone (see under Metaplasia, Arts. 90-92). For further details the reader is re- ferred to the following : Virchow (" Virch. Arch.," vol. xiii.), Neumann ("Arch, fur Heilk.," 1869), Aufrecht ("Wiener med. Wochenschr.," 1868), Rindfleisch ("Pathological Histology," vol. i., p. 92), Ziegler FORMATIVE DISTURBANCES OF NUTRITION. 125 ("Untersuch. uber path. Bindegewebs-und Gefassneubildung"), Peris ("Handbuchd. allg. Path.," i.),Tillmanns (" Virch. Arch.," vol.lxxviii.).] 86. The formation of new blood-vessels plays a chief part in hyper- plasias of every kind. Wherever fibrous tissue, bone-tissue, gland-tissue, or any other is produced in quantity, new blood-vessels must of necessity be developed. In no other way is it possible to keep the new-formed tissue adequately supplied with nutriment. For this reason new blood-vessels Fig. 20.-Development of Blood-vessels by Sprouts and Off-shoots. (From preparations of inflammatory gran illation-tissue.) a, b, c, d, various forms of vascular off-shoots ; some solid (b, c), others in process of excavation (a. b, d); some single (a, d), others branched (by c); some with nuclei (6, c), others without (a, d). Formative cells from without have attached themselves to the off-shoot d. begin to be formed at a very early stage in all new growths, and they must be regarded as the chief factors in the formative process. New blood-vessels are developed out of off-shoots which start from the walls of existing blood-vessels. The first change observed is the formation of a conical sprout or pro- jection on the outer surface of some capillary vessel. From the top of this runs off a fine filament of protoplasm, which gradually lengthens. The granular mass forming the projection increases in size, growing out into an irregular process or off-shoot. This is at first solid; but nuclei soon begin to appear among its granules. The off-shoot may become attached to another vessel; it may unite with a second off-shoot ; or it may return back into the vessel from which it starts, forming an arch of 126 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. protoplasm (Fig. 20, c). From the solid off-shoot other secondary off- shoots may start (Fig. 20, b, c). Sometimes their extremities become club-shaped (c). The originally solid off-shoot becomes by and by exca- vated, by liquefaction of its central parts. The excavation quickly be- comes continuous with the lumen of the vessel (a), or the wall of the lat- ter bulges into the excavation. In either case the blood from the parent vessel penetrates the new one, and distends it. The excavation proceeds and extends onward to the point of junction of the new vessel with an- other, so that at length a new pervious capillary loop is formed. The off-shoot, as it starts from the wall of the parent vessel, is in effect a sprouted bud from an endothelial cell ; when it subsequently receives a nucleus it becomes an independent cell. The new blood-vessels are there- fore intracellular channels,'produced by the excavation of elongated or filamentous cells. For a short time after the opening up of the new capillary channel the vessel-wall remains homogeneous in structure. Soon the protoplasm begins to gather round the nuclei of the wall, which in the meantime have been multiplying by subdivision. Cells become in this way distin- guishable, and presently the capillary-wall appears in its perfected form as a mosaic of flat endothelial cells. (As Arnold and others showed, the boundaries between the cells may be rendered apparent by injecting the vessels with solution of nitrate of silver.) By this time the wall has gen- erally reached a considerable thickness. This is in part owing to the fact that ordinary formative cells attach themselves in numbers to the vessel-wall; they then dispose themselves along its length, and thus tend to give it needed strength (Fig. 20, cl). So far as we have been able to make out, the process of forming new blood-vessels nearly always passes through the stages described. It is only at times that another stage is interpolated in which spindle-shaped, club-shaped, or branching formative cells become connected with the off- shoots from the capillary walls, and develop into new vessels by central excavation in the same way as the off-shoots themselves develop. [The subject of the formation of new vessels has a special interest in reference to the theory of cell-multiplication. We have in this case to do not with symmetrical subdivision, but with gemmation; and moreover the initial movement is set up, not as usual in the nucleus, but in the cell- protoplasm. The protoplasm of the endothelial wall-cells throws out a non-nucleated process ; the subdivision and migration of the nucleus is subsequent to the movement in the protoplasm. The author has verified the above account in the course of his re- searches on granulation-tissue and on tumors (Ziegler, " Ueber path. Bin- degewebs- und Gefassneubildung," Wurzburg, 1876), Stricker ("Wie- ner Sitzungsberichte," 1865-1866), Golubew ("Arch. f. mikro. Anat.," 1869), and Arnold (" Virch. Arch.," vols. liii., liv.), have described the above mode of development of new vessels as observed in tadpoles' tails, FORMATIVE DISTURBANCES OF NUTRITION. 127 Travers in the foot-web of the frog (" On Inflammation," etc.). It is the only mode which certainly occurs in pathological formations. For this reason we have not given the customary enumeration of the primary, secondary, and tertiary modes formulated by Billroth (" Untersuch. u. d. Entwig. d. Blutgef.," Berlin, 1856) and Rindfleisch (" Pathological His- tology," vol. i., p. 89). In the primary mode the embryonic cells become directly transformed into red blood-cells on one hand, and into the parie- tal cells of a vessel on the other. The embryonic cells in fact arrange themselves into cords ; the axial ones become blood-cells, the peripheral ones cohere as elements of the containing vessel-wall. This process takes place in the mesoblast of the embryo, but not in pathological for- mations (Klein, " Wiener Sitzungsberichte," 1871 ; Quart. Jour, of Mie. Sei., 1872 ; Balfour, li Comp. Embryology," vol. ii.). In the secondary mode (Billroth, O. Weber, Rindfleisch) spindle-shaped cells cohere to form cylinders in such wise as to enclose a continuous canal. This notion seems to rest on a mistake, occasioned by the fact that in granulation-tissue, for example, the vascular off-shoots are very quickly surrounded and wrapped about with spindle-shaped formative cells ; and this gives the offshoots the appearance of strings of cells. The so-called tertiary mode is that given in the text. Compare the description by Paget (" Surgical Path.," Leet. 10).] 87. Proliferation in cartilage may be either a regenerative or a hyperplastic process. The reproduction of cartilage-cells at the margin of a breach is effected by'the cells first enlarging, and then undergoing subdivision of nucleus and protoplasm. Nuclear figures are observed. In this process many of the cells attain to great dimensions and may contain as many as twelve nuclei apiece (Ewetzky). The cells are rounded or branched, stellate or spinous. The capsular membranes disappear as the cells enlarge and multiply. Later on the cells or cell- groups become surrounded by the characteristic hyaline matrix-substance. In hyperplastic proliferation the process is similar. The cells multiply and stretch the capsules, or cause them to give way and disappear ; in like manner the intercellular matrix is distended or destroyed. Subse- quently the new-formed cells generate for themselves fresh capsules and matrix-substance. When a breach in cartilage is not repaired by multiplication of the cartilage-cells, fibrous tissue, developed from fibroblasts, usually fills up the gap. In other cases bony tissue is developed as well. Cartilage may arise not only from cartilage, but from other allied tissues, such as growing periosteum in particular, perichondrium, marrow, bone, fibrous tissue, and epithelium. The metamorphosis is sometimes effected directly, as from perichondrium or marrow, sometimes through the intermediate stage of granulation. In the latter case an indifferent tissue is first formed, which is rich in single cells ; these then become transformed into hyaline matrix-substance and cartilage-cells. Cartila- 128 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. ginous new growths are most commonly found in connection with the skeletal structures ; in other regions they are rare. [Memoirs on the formation and proliferation of cartilage have been published by Virchow (" Onkologie," i.), Goodsir (" Anat, and Path. Obs.,'* 1845), Redfern {Month. Journ. of Med. Science, 1851), Ewetzky ("Ent- ziindungs-versuche am Knorpel," Eberth's " Arbeiten," iii.), Wartmann (" Recherches sur 1'enchondrome," Geneva, 1880), Kassowitz (" Die normale Ossification," Vienna, 1881). Further details will be given in the section on the Special Pathological Anatomy of the Bones.] 88. The bones have a very marked power of regeneration and of hyperplastic proliferation. The seat of this power is not so much in the osseous tissue itself as in those tissues which normally possess the power of bone-production ; these are the periosteum in particular, and in a less degree the marrow. In very many cases the periosteum alone performs the office of replacing a loss of bony substance. Many osseous hyper- plasias are essentially the work of the periosteum. Cartilage has also some power of reproducing bone. Fibrous tissues unconnected with the skeleton very rarely give rise to bony tissue. Such abnormal bone-formation is, however, not unknown in certain cartilaginous and fibrous structures, such as the dura mater, the laryngeal cartilages, the intermuscular septa, and inflammatory fibrous tissues. The formation of new bone may occur in various ways, but it follows in general the lines of the normal process of ossification. The simplest mode is perhaps that in which the periosteum (or medullary tissue) gives rise to osteoblasts («.e., large multinuclear formative cells resembling fibroblasts). These come into contact and cohere, and then imbibing calcareous salts are transformed partly into homogeneous matrix-tissue, partly into bone-corpuscles. In other cases the formation of bone is pre- ceded or accompanied by the formation of granulation-tissue. Owing to this the exact mode in which the bone-substance is generated may be somewhat masked ; but close investigation shows that here also os- teoblasts are produced in the first instance, and that these are afterward transformed into bone. The proliferating periosteum very often produces cartilage to begin with. Part of this cartilage may then pass directly into bone by a peculiar transformation. Or the cartilage may be replaced by a medullary tissue abounding in cells ; and from this, by the agency of osteoblasts, the bone-substance may ultimately be produced. Normal cartilage behaves in the same way as that produced by pro- liferation of the periosteum. Like the latter it may be transformed into medullary tissue and bone-trabecuhe. We have thus, in addition to the osteoblastic mode of bone-formation, a second or metaplastic mode, by which an already existing tissue is transformed into bone. As we have said, this occurs most frequently in cartilage ; but other fibrous and FORMATIVE DISTURBANCES OF NUTRITION. 129 sarcomatous tissues, by taking up calcareous salts, may in like manner be changed into bone. Their basis-substance is transformed into bony matrix-tissue, and their cells into bone-corpuscles (Arts. 90-92). [Further discussion of the subject of pathological bone-formation will be found in the Special Pathological Anatomy. The recent memoirs of the following authors will serve to illustrate the main questions : Kblliker (" Die normale Resorption des Knochengewebes," Leipzig, 1873), Steudener (" Beitrage zur Lehre von der Knochenentwickelung," Halle, 1875), Strelzoff ("Die Histogenese der Knochen," Zurich, 1873), Maas (" Ueber Wachsthum und Regeneration der Rbhrenknochen : " " Langen- beck's Arch.," xx.), Ziegler ("Virch. Arch.," vol. Ixxiii.), Wolff (" Unters. iib. d. Entwick. d. Knoch.," Leipzig, 1875), Busch (" Deut. Zeitschr. f. Chir.," vol. viii.), Kassowitz ("Die Ossification," Vienna, 1881), Macewen (" Proc. Roy. Soc.," vol. xxxii.).] 89. Tn muscular fibre, striated and non-striated, regeneration and hyperplasia start primarily from the existing muscle-cells. Non-striated muscular fibres may possibly be developed from connective-tissue ceils also. New muscular cells are produced by ordinary nucleus- and cell- division. In striated muscle, the so-called muscle-corpuscles grow into large cells, losing, meanwhile, their contractile substance, and multiply- ing their nuclei. They become elongated and spindle-shaped, and then become converted into striated fibres. It is highly probable that no other cells have the power of generating striated muscle-cells, but on this point opinions differ. Wounds in muscle are filled up by cicatricial tis- sue, when the superficial muscle-corpuscles have been destroyed. Nerves and nerve-cells have but slight power of reproduction. It is very questionable whether ganglion-cells can be regenerated at all in adult individuals. We have no knowledge of ganglionic hyperplasia. In the case of nerves themselves, both regeneration and abnormal multiplication occur, though only to a slight extent. In nerve-regenera- tion the axis-cylinder and sheath of Schwann are the first to be formed, and then the medullary sheath. New nerves are developed only from existing nerves ; at any rate very serious doubts attach to the statements which have been made in the opposite sense. Opinions differ as to the part played by the cells of the neurilemma and by the existing axis- cvlinder. fThe statement that non-striated muscular fibres may be developed from connective-tissue cells has been made by more than one observer (J. Arnold, " Virch. Arch.," vol. xxxix.; E. Neumann, "Arch. d. Heil- kunde," x.). It appears certain that cells having at least the structure and appearance of non-striated muscle-cells are so developed ; but no proof has been given that they have corresponding physiological proper- ties. 9 130 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. With regard to striated muscle and its regeneration, Kraske, the latest writer on the subject, asserts positively that new muscle is pro- duced only from existing muscle-elements. Ziegler's observations are in accordance with this. An embryological argument may be brought against the possibility of deriving voluntary muscle from connective-tis- sue. According to the Hertwigs ("Die Coelomtheorie," Jena, 1881) the striated muscle-fibres of vertebrates are of epithelial origin ; they arise from the epithelia of the body-cavities. They are thus in their genesis and descent distinct from the connective tissues. (Cf. Balfour, "Comp. Embryology," vol. ii., ch. 22.) On the striated muscle-cells of tumors see Art. 153. On the repair of nerves see Paget, " Surg. Path." Leet. 11 ; and Ranvier, " Hist. d. Syst. nerv.," 1878. CHAPTER XX. METAPLASIA. 90. A tissue is said to undergo metaplasia when it is transformed into another of a diverse kind ; and that without passing through an in- different blastema stage, with the characters of embryonic or formative tissue. In the foregoing chapter we have more than once pointed out that, of the several tissues belonging to the connective group, one may pass into another by simple modifications, partly affecting the cellular ele- ments, partly the ground-substance. Such modifications are of the nature of metaplasias. They are confined to the connective tissues-fibrous tissue, cartilage, bone, mucous tissue, and adipose tissue, are so to speak potentially convertible. No such relation holds between fibrous tissue and epithelium or muscle. The processes involved in metaplasia have their physiological and embryological prototypes. Hyaline cartilage, for example, is specially prone to transformation ; its matrix-substance often undergoes a mucoid softening- on the one hand, or a change to fibrous tissue on the other. C5 7 O Hyaline cartilage is, in fact, at best a transitory structure in man ; it dis- appears in ossification, partly by retrogressive changes, partly by trans- formation into other tissues such as medullary tissue and true bone. Simple areolar and adipose tissue are likewise prone to change ; the pan- niculus adiposus or subcutaneous fat of the adult is in the foetus a mu- coid tissue. Pathological metaplasias are, however, still more common than such physiological metamorphoses. [The term metaplasia is due to Virchow, who has also fully investi- gated the significance of the processes included under it (" Virch. Arch.," vols. viii., Ixxix., " Gesammelte Abhandlungen," 1856, pp. 500, 509 ; " Cellular Pathology," and fourth German edition, p. 70). The subject seems to have awakened but little attention ; it well deserves it, however, for metaplasia plays no small part in pathological change.] 91. One of the commonest metaplasias of a connective tissue is that by which cartilage is transformed into mucoid tissue or into areolar tissue. 132 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. The first step in the process is the liquefaction or dissolution of the matrix into a mucous or limpid mass (Fig. 21). The capsules also dis- solve away and the cartilage-cells are set free (c). These change their form (6), becoming spindle-shaped or branching; and they then cohere into a cellular reticulum such as is met with in mucous tissue. The matrix- substance does not always become true mucus ; it may pass into a liquid of different composition. Such changes are met with in the cartilages of diseased joints. The areolar tissue may subsequently become filled with marrow-cells or with simple fat ; in the last case the tissue is trans- formed into mere adipose tissue (e.g., in rheumatic polyarthritis). Cartilage also changes very readily into osseous tissue. Part of it becomes transformed into bony trabeculae, part into medullary tissue. The latter is effected through the intermediate stage of areolar tissue ; Fig. 21.-Metaplasia of Cartilage into Areolar Tissue, x 400. (From a case of fungous arthritis; hsematoxylin staining.) a, hyaline cartilage; b. tissue made up of branching cells; c, cartilage-cells, set free by dissolution of the matrix, becoming converted into connective-tissue corpuscles. the former by the deposition of calcareous salts in the matrix, itself sim- ultaneously undergoing change into gelatin ; while the cartilage-cells pass into osteoblasts and bone-corpuscles. It often happens that the cartilage-cells proliferate abundantly during this process ; it is not then strictly speaking a pure metaplasia. Fibrous tissue, like cartilage, may also be transformed into mucoid tissue and bone. The changes in this case are similar to those described in the other. The fibres and fibrillae disappear as the tissue becomes mucoid tissue ; when it becomes bone, calcareous salts are deposited in the ground-substance. Here too cell-multiplication is not uncommon. Conversely, osseous tissue may pass into fibrous tissue or cartilage, especially the former, as happens very frequently in senile bone-affec- tions. The ground-substance of the bone becomes decalcified and fibril- lated, while the bone-corpuscles become connective-tissue cells. FORMATIVE DISTURBANCES OF NUTRITION. 133 The fibrous structures found in tumors are, like the normal ones, liable to metamorphosis into others of the same class. The metaplastic pro- cesses resemble those in normal tissues. The highly cellular sarcomatous tissue is very prone to transformations ; and these are generally such as to show that it is allied to the connective-tissue group. 92. Metaplasia is to be distinguished from the simple degenerations as well as from the proliferative processes. In degeneration no new tis- sue is formed, and what exists perishes. In proliferation new tissue is formed from a cellular matrix or blastema, which is the result of cell- multiplication. Metaplasia stands in a measure between these. New tissue is formed ; but there is no cell-multiplication, or if there is it is quite subordinate. From many points of view metaplasia seems related to the retrogres- sive processes. The transformation of a tissue into mucoid tissue is near akin to mucoid degeneration. The new or transformed tissue is more- over not infrequently an unstable and perishable one. On the other hand, proliferation is no uncommon accompaniment of metaplasia, which is thus brought into relation with the progressive or formative disturb- ances of nutrition. The factor of greatest importance, as regards the further development of the transformed tissue, is the behavior of the blood-vessels. If good vascularization is effected, the tissue continues to live and grow ; if not, then retrogressive changes are apt to set in. SECTION V. INFLAMMATION AND INFLAMMATORY GROWTHS. CHAPTER XXL THE EARLY STAGES OF INFLAMMATION-EXUDATION. 93. Inflammation is a term implying a whole series of processes partly vascular and partly textural ; and these processes admit of a great variety of combinations. Inflammation being thus a complex of many elements, we are unable to give a definition of it that shall be brief and at the same time exact. We might say, indeed, that one or other element (such as that relating to the vessels) is characteristic of inflammation ; but the whole content of the term cannot be fully indicated without de- scribing the processes to*which the term is applied. From the time of Celsus, i.e., from the first century a.d., four car- dinal symptoms of inflammation have been recognized : namely rubor, tumor, dolor, color-or redness, swelling, pain, and heat. To these we may generally add a fifth, the funct io laisa, i.e., impairment or arrest of the function of the inflamed part. These cardinal symptoms are, as a fact, very easily and very fre- quently to be made out ; especially in cases where the inflammation is sudden and intense. In other cases, and especially in chronic inflamma- tions, one or other of the symptoms is generally absent, or beyond the reach of observation. The constitution of the inflamed tissue may also modify the symptoms ; its texture and composition maybe such that the redness, for instance, or the pain, or the swelling, may be absent. 94. Galen rightly attributed the redness to an increased afflux of blood, and the swelling to an increased exudation from the vessels. The vascular changes, which thus take the form of hyperagmia, have been the subject of special attention during the last twenty or thirty years. Many investigators indeed have regarded the vascular changes as constituting the essential feature of the inflammatory process. Andral defined inflammation simply as hyperaemia. Henle, Stilling, Vacca, Lubbock, and others referred the dilatation of the vessels, the accumulation of blood in them, and the resulting exudation, to par- alysis of the vessel-walls from excitation of the sensory nerves (the neuroparalytic theory) ; Hoffmann, Eisenmann, Jos. Heine, Budge, Bruecke, Cullen, and others, to spasmodic contraction of the vessels (the neurospastic theory). In the latter case, the contraction of the arteries and the consequent slowing of the blood-current were supposed to lead 138 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. to an afflux of blood through the neighboring vessels, but in an inverse direction. The result of this vascular disturbance was engorgement and exudation. In opposition to these neuropathic theories, some authors, like Haller, Vogel, Koch, Emmert, Simon, Paget, etc., explain the inflammatory dis- turbance of circulation and nutrition by supposing that the normal attraction of the tissues for the blood is somehow intensified. Virchow has formulated this "theory of attraction " with the greatest precision. In his view, the tissue-cells are excited by the " inflammatory stimulus " to increased activity ; they thereupon attract to themselves more nutri- ment, and so are impelled to grow and multiply. The hyperaemia and vascular dilatation are the result of this intenser attraction. The essen- tial and efficient factor in inflammation is thus the application of a " stim- ulus " to the cells, which excites them to increased activity. Numerous experimental researches during the last twenty years (amongst which those by Cohnheim are perhaps the most fundamentally important) have shown that neither the neuropathic nor the attraction theory can be maintained. Mere dilatation or mere contraction of the vessels does not bring about the disturbances of the circulation character- istic of inflammation. The changes observed in the tissue-cells at the beginning of inflammation do not bear the character of productive or formative disorders of nutrition. There is no evidence of any influence exerted by the tissues on the vessels and the blood, which is at all of the nature of attraction. The changes in the tissue-cells are partly concom- itant with those in the circulation, partly antecedent to them, and partly subsequent. The vascular disturbance is not dependent on any peculiar influence exerted upon the vessels ; it is the result of injury or deteriora- tion (Samuel) of the vessel-walls, with or without an actual lesion of the tissues. To simplify the explanation of the entire process of inflamma- tion, it will therefore be well to consider separately the vascular changes, and the textural changes. [For an account of the contributions which English pathologists (no- tably Hunter, Goodsir, Bowman, Lister, and Burdon Sanderson) have made to our present knowledge of Inflammation, the student should con- sult Paget (" Surgical Pathology," Leets. 13-18), Simon and Burdon Sanderson (Arts, on " Inflammation," Holmes's " Syst. of Surgery," vols. i. and v.), and Burdon Sanderson (" Lectures," Lancet, 1, 187G, and " Lumleian Lectures," Lancet, 1, 1882). References to the work of others will be found below.] 95. The vascular changes. Cohnheim's researches were the first to make us accurately acquainted with the vascular disturbances con- nected with inflammation. He showed that these disturbances may be directly studied under the microscope. The object is usually some trans- parent vascular membrane belonging to a living animal. The most con- INFLAMMATION AND INFLAMMATORY GROWTHS. 139 venient is the frog's mesentery, which from its fineness is well adapted for microscopic examination. The frog, paralyzed with curare, is laid on its back on a large object-stage. The abdominal cavity is opened by means of a cut along the left side, and a loop of intestine is carefully drawn out. This is then spread over a thin circular cover-glass (10-12 mm. in diameter) surrounded by a thin ring of cork stuck to the stage with Canada balsam. The intestine is readily fixed to the cork ring by means of fine pins. If it is not desired to make a protracted examina- tion, it is enough to fasten a cork ring (4-6 mm. thick) to a large object- stage with sealing-wax, and to spread out the intestine over that. The preparation need not be covered with a cover-glass. If no strain is thrown on the mesentery, and it as well as the frog is kept properly moist, the vascular changes may be observed for hours together. [Further details of the method are given by Cohnheim in his various memoirs on inflammation and embolism (" Virch. Arch.," vol. xl. ; "Neue Untersuch. tlb. Entztlnd.," Berlin, 1873 ; "Untersuch. tib. d. embol. Processe," Berlin, 1872). The foot-web and tongue of the frog are also very convenient objects. The latter is to be turned out, spread over a cork ring, and fastened down with fine pins. Inflammation is then produced by a drop of acid, or by clipping out a fragment with the scissors. For the study of the inflammatory process on a large scale the rabbit's ear is well adapted. Inflammation may be set up by rubbing it with croton oil (Samuel, "Berl. klin. Woch.," 24, 1866, and " Der Entziind- ungsprocess," Leipzig, 1873). The mesentery or omentum of a warm- blooded animal may also be employed, if proper precautions are taken to maintain the body-heat, etc. See Stricker and Sanderson, " Handbook for Phys. Lab.," 1870; Thoma, "Virch. Arch.," vol. Ixxiv.] 96. The exposure of the mesentery to atmospheric air quickly sets up inflammation. The earliest vascular change is a general dilatation of the vessels, first of the arteries, then of the capillaries and veins. The flow of the blood through the widened channels at first becomes more rapid; but sooner or later the speed diminishes, and at length the flow becomes slower than the normal. The individual blood-cells, which at first were indistinctly seen as they hurried past, become recognizable, especially in the veins and capillaries. In these latter the blood begins to accumulate more and more as the current slows. In the veins the peripheral layer of the current, usually containing plasma only, begins to be filled with white blood-cells. These have left the axial stream, and float slowly on with the slower peripheral current ; or, fastening them- selves to the wall, they remain immovable or oscillate to and fro. This is described as the marginal or peripheral disposition of the white blood- cells (Fig. 22, d). At this stage the red cells take the place of the white in the capillaries. 140 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. Before long the peripheral disposition of the cells is associated with another appearance. Here and there white blood-cells throw out pro- cesses which pass into the vessel-wall (e). Soon the processes appear outside the vessel (e), and thereupon the whole protoplasmic mass of the cell passes through the wall. The white cells in this way escape, mi- grate, or extravasate from the vessel (vein or capillary) by diapedesis. The first white blood-cells which migrate are quickly followed by Fig. 22.-Inflamed Omentum from the Human Subject. a, normal fibrous trabecula: ft, normal endo- thelium ; c, small artery ; d. vein with white blood-cells peripherally disposed ; e, white blood-cells migrated or migrating ; /, desquamated endothelium ; multinuclear cell; g, migrated red blood-cells. others, and in six to eight hours the veins and capillaries are surrounded by a multitude of white cells, or leucocytes, which gradually distribute themselves through the tissue by active locomotion. From the capillaries, in which the circulation becomes very irregular and often stops altogether, there escape red blood-cells (g), as well as white. If the mesentery be slightly strained so that the circulation is brought to a stand-still (stasis) at some point, the migration ceases there. Blood-cells do not escape from the arteries. Associated with the escape of the formed elements of the blood, there is always an escape of liquid. This is not in general directly percepti- ble, but is evidenced by the accumulation of liquid which takes place in the substance and on the surface of the mesentery. This escaped liquid is comparatively rich in albumen, and thus differs essentially from the exudation which follows upon simple vascular en- gorgement. Moreover it coagulates readily, especially when it is effused on the surface of the mesentery. INFLAMMATION AND INFLAMMATORY GROWTHS. 141 [This description of the inflammatory process as observed in the mesentery applies also to that produced elsewhere, as in the frog's tongue, by caustics. In the latter case the process is not observed in the cauterized piece (which is in fact dead), but in its neighborhood. Thoma ("Virch Arch.," vol. Ixxiv.) has shown that the process in warm-blooded animals is identical with that in cold-blooded animals. W. Addison (" Trans. Prov. Med. Asso.," 1842-45) observed the escape of the white blood-cells from the vessels so early as 1842. Waller {Phil. Mag., vol. xxix.) described the phenomenon more fully in 1846. The discovery was, however, completely forgotten until Cohnheim made it anew in 1867. Caton {Journ. Anat. Phys., 1871) showed that the white cells escape even from healthy vessels, at least in the amphibia. The peripheral disposition of the white blood-cells is a purely mechan- ical phenomenon (Weigert, Article " Entztlndung," " Realencyclopadie der ges. Heilkunde "). It was first observed by Williams (" Gulstonian Leet.," 1841). Schklarewsky (" Pfliig. Arch.," vol. i.) has shown that a similar effect is produced when a slow stream of liquid, containing fine powders of various densities in suspension, is made to pass through a nar- row tube. When the stream flows at a certain rate the lighter particles cling to the periphery, the heavier ones are hurried on by the axial cur- rent. This is what happens in the case of blood. When the current is slowed to a certain extent, the white cells go to the periphery ; when it be- comes still slower (as in engorgement) the red cells go there also. (See also Appert, "Virch Arch.," vol. Ixxi.; Hamilton, "Proc. Roy. Soc. Edin.," vol. xi.). The chemical composition of inflammatory exudations and inflamma- tory lymph has been investigated by Hoppe-Seyler (" Virch Arch.," vol. ix.), Reuss (" Deutsch. Arch. f. klin. Med.," xxiv.), F. A. Hoffmann ("Virch. Arch.," vol. Ixxviii.), and Lassar ("Virch. Arch.," vol. Ixix.).] 97. The effects of the process just described are easy to follow. The inflamed tissue becomes red, swollen, and hot ; we have the inflammatory flush, and the inflammatory exudation or infiltration. The pain felt is referable to pressure, tension, or chemical irritation, acting on the sensory nerves in the tissue. It is plain, too, that the function of the part must be injuriously affected ; the accumulation of exuded matter and the im- perfect and disordered nutrition of the part are enough to account for that. The vascular disturbance is beyond doubt the most important and most characteristic factor in the entire process of inflammation. The other tissue-changes involved are not to be overlooked or undervalued ; but it is the disturbances in the circulation which give inflammation its special character, and determine its course. The question as to the es- sential nature of inflammation is thus almost reduced to the question of the causation of these vascular disturbances. The slowing of the blood-current, the dilatation of the vessels, the peripheral disposition of the white blood-cells, the migration of these from 142 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. capillaries and veins, and the migration of the red cells from the capillaries, are all of them referable to a molecular alteration in the vessel-walls (Samuel). Mere paralytic dilatation does not give rise to slowing of the current, or to peripheral disposition of the white cells ; mere slowing of the current is not followed by extravasation of the cellular elements of the blood. Increased activity of the neighboring cells will not explain exudation, for white and red blood-cells will escape from the vessels into a tissue whose cells are already dead. Cohnheim has shown that if the circulation through a vessel is interrupted for a certain time (in frogs, from thirty-six to sixty hours), the vessel-wall undergoes such changes that, when the blood is again allowed to circulate, an exudation makes its appearance just as in inflammation. The alterations in the vessel which take place in inflammation cannot be histologically demonstrated. We infer them from the fact that the vessel-wall becomes more permeable. We must suppose that the ele- ments composing the vessel-wall are in some way loosened ; the cement- ing substance which unites the endothelial cells seems partially to give way. Arnold's researches make it likely that the cells transude chiefly at places where the intercellular cement is abundant. The slowing of the blood-current itself may probably be due to endothelial changes, in virtue of which the frictional adhesion between blood and vessel-wall is increased (Lister, Ryneck, Cohnheim). [It may be accepted as an established fact that in inflammation the vessel-wall is affected (Samuel, " Virch Arch.," vol. xliii., and Cohnheim, loc. cit.). But it is still questioned by some whether the affection is of the nature of a chemical alteration, or a mere widening of pre-existing intercellular apertures. Arnold, who has worked much at the subject, formerly thought that small openings (stigmata) normally existed be- tween the endothelial cells, and that these enlarged in inflammation into wider stomata. He based this theory mainly upon injection-experiments, which seemed to show that the vessel-wall was permeable, even to blood- cells. Cohnheim all along opposed the theory, and Arnold has now given it up. At the spots where stigmata were said to be we find nothing but little masses of cementing substance. Cohnheim argued against the ex- istence of openings, from the fact that the exudation has not the same composition as liquor sanguinis. The fact that inflammatory exudation is richer in albumen and in cells, and so coagulates more readily than the liquor which transudes in simple engorgement, speaks for a change in the permeability of the vessel-wall. This has indeed been demonstrated by injection-experiments (Winiwarter, "Wien. acad. Sitzungsber.," Iviii.; Arnold, loc. cit.). Cohnheim, like Hering (" Wien. acad. Sitzungsber.," Ivii.), regards the escape of the elements of the blood as due to a process of filtration. He thinks the altered quantity and quality of the transuda- tion (in inflammation as compared with health) are referable simply to an alteration of the vessel-wall, that is to say, to an alteration of the filter. INFLAMMATION AND INFLAMMATORY GROWTHS. 143 Thoma maintains (" Virch. Arch.," vol. Ixxiv.), on the strength of certain experiments, that the white blood-cells never escape from the vessels un- less they retain the power of independent movement. He would thus regard their migration as in some degree due to an active effort on their part. When the white blood-cells are deprived of the power of move- ment by irritating the mesentery with 1.5 per cent, salt-solution, the mi- gration at once ceases. On the causes of the slowing and stasis of the blood-current see Lis- ter, " Phil. Trans.," 1858 ; Ryneck, " Rollet's Untersuch. Graz," 1870; Cohnheim, Op. cit., 1873 ; Glax and Klemensiewicz, " Wien. acad. Sitz- ungsber.," Ixxxiv. The increased temperature of an inflamed surface is due merely to the increased circulation of blood through the part ; the loss of heat not keeping pace with the gain. Cohnheim found by experiment that, in the same time, nearly twice as much blood flowed through the inflamed paw of a dog as through the non-inflamed one. This is quite enough to account for the rise of temperature.] 98. The causes of the alteration in the vessels are thus the causes of the inflammation. In other words, the alteration in the vessels is the direct or indirect consequence of the injury which excited the inflamma- tion. Or still more accurately-any injurious agency which is capable of altering the blood-vessels in a particular way is capable of producing in- flammation. It is clear then that the number of agencies capable of exciting inflammation is indefinitely great ; they are beyond enumeration or separate discussion. All we can say is that mechanical, thermal, and chemical agencies (and especially the latter) may act so as to alter the vessels and produce inflammation. The exciting cause of inflammation may operate in one of three ways. It is in the first place conceivable that the injurious agent (noxa) may primarily attack the vessels. This will be the case when it is brought to them in the blood itself. The surrounding tissue suffers only by a secondary effect. In the next place, there are cases in which the excit- ing injury affects both tissue and vessels at the same time. In a third instance, the tissue alone is injured ; the alteration in the vessel-wall is secondary to alterations in the surrounding tissue. Of course these cases are not always completely independent. In the same case textural lesions and vascular lesions may intercombine in various ways at different times. To produce inflammation an injury must be of a certain severity, and yet must not be too severe. Thus a slight wound of the corneal epithe- lium does not excite inflammation ; the defect is simply filled up by re- generative proliferation. On the other hand, a powerful caustic applied to the skin produces at the cauterized spot not inflammation, but necro- sis. Inflammation is indeed excited ; but only in parts beyond the cauterized region. In these the caustic has not acted fully, so as to kill 144 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the vessels ; it has merely altered or damaged them by chemical action. This example shows that there are no noxse which can be described specifically as exciters of inflammation. Between the injury which is too slight to affect the vessels, and that which affects them too severely or kills them outright, there is an endless number of intermediate degrees. The repair of the damaged vessel-wall is brought about by the vis medicatrix of the blood itself. If, when the injurious influence has ceased, the blood brings to the injured vessel the materials required for restoring it to its normal state, a restitutio ad integrum is effected. The inflammatory disturbance of the circulation thereupon comes to an end, and with it the exudation ; and the process of healing is begun. 99. The textural changes. Inflammatory change in the vessels must of necessity be associated with tissue-change, antecedent, concomi- tant, or subsequent. An injury from without which excites Change in the vessel must always in the first instance affect a certain number of tissue-cells. By what is said in Arts. 78-80 we see that all such an injury can do is to set up disorganizing and degenerative changes in the cells. If the injury be slight, the cells may recover ; if it be graver, a certain number of them will perish. Multiplication is never induced by excitation of the cells from without. When the injurious agent affects the vessels primarily, being brought to them by the blood, there are two events possible. If the noxa be very powerful, it will attack (or even kill) not only the vessel-wall, but the surrounding tissue also. If it is of trifling intensity, and its operation is thus confined to the vessel-wall, the surrounding tissue escapes in the first instance. It will be affected secondarily only when the injury to the vessel-wall is great enough to lead to inflammatory disturbance of the circulation, and so to disordered nutrition of the tissue. Experiment and post-mortem observation have alike shown that in severe inflammation a certain number of cells invariably perish. The so-called "inflammatory stimulus" does not induce multiplication, but only degeneration and death, in the cells of the tissue. The slighter the inflammatory stimulus the less is the injury to the tissue. The degener- ative and destructive effects of the exciting injury are least in the mildest forms of inflammation. [Cohnheim's discovery of the migration of white blood-cells suggested a possible source of the extraneous cells found in all inflamed tissues, and in particular a possible source of pus. But the question has often been raised whether all these extraneous cells (round-cells or leucocytes) are derived from the blood. Before the discovery of migration, it was assumed that these leucocytes were the product of the multiplication of tissue cells, excited to proliferate by the "inflammatory stimulus." But it was quickly seen that there were well-founded objections to this hypothesis. Cohnheim himself (" Virch. Arch.," vol. xl.) had shown, and that before he made his discovery, that it was impossible to suppose that INFLAMMATION AND INFLAMMATORY GROWTHS. 145 all pus-corpuscles arose from fixed cells ; and that even the migratory- connective tissue-cells of Von Recklinghausen were inadequate to pro- duce the enormous multitude of cells found in pus. Numerous investi- gations made since then have shown that pus-corpuscles are derived solely from the blood, and that cells of the lymphoid type (such as pus- corpuscles) are never produced from fixed tissue-cells (Cohnheim, " Neue Unters. ub. d. Entztind.," Berlin, 1873, " Virch. Arch.," vol. Ixi. ; Key and Wallis, "Virch. Arch.," vol. Iv. ; Eberth, "Unters. a. d. path. Inst, in Zurich," parts 2 and 3). As has been stated in the text, the tissue- cells either show signs of degeneration or perish outright, and in this condition mingle with the exudations. This doctrine has not been without its opponents. Among the chief are Bottcher (" Virch. Arch.," vols. Iviii., Ixii.) and Stricker, with some of his pupils (" Studien aus d. Inst, filr exper. Path, in Wien," 1870 ; various essays in the "Wien. med. Jahrb.," 1871-1880; "Vorles. ub. allg. Path.," Vienna, 1877-1879 ; " Internat. Encyclop. of Surgery," vol. i.). Bottcher's objections have been completely answered by the pains- taking experiments of the observers above cited. Stricker's observations are admirably described by Burdon Sanderson in " Holmes's System of Surgery," vol. v. Recent researches have not tended to confirm the re- sults on which Stricker's objections are based. Experimental researches on the origin of pus-corpuscles have generally been made on the cornea ; as this has no blood-vessels it offers a favorable opportunity for discern- ing the parts played by the blood and by the tissue-cells respectively.] 100. The forms of necrosis and degeneration which may accompany inflammation are very various ; they vary with the nature of the exciting cause, and with the intensity of the inflammation ; with the character and extent of the vascular disturbance, and with the nature of the tissue. Any one of the forms of degeneration enumerated in Arts. 32-71 may occur. There is no rule determining in what cases any particular form shall appear. It deserves, however, to be specially mentioned, that a very common issue is the disintegration, solution, and liquefaction of the entire tissue-of its cells as well as its basis-substance. This is the case, for example, in all suppurations, to a greater or less extent. Another common occurrence is the coagulation of the exuded liquid, and also of the disorganized or necrosed tissue-cells. Fatty degeneration is not in- frequently a secondary result of the vascular disturbance. 101. Varieties of Inflammation. Inflammation is a process which may affect any tissue possessing vessels, or in connection with vessels. In other words, it may affect any tissue in the body, except a few epider- moid structures. Its seat may vary greatly. It may lie within the pa- renchyma of an organ, or be confined to its surface ; that is to say, we may have parenchymatous inflammation, or superficial inflammation. The former affects the interior parts of solid organs, like the glands, mus- cles, or brain. The latter form occurs on the exterior of the body, in mucous membranes, and in the lining membranes of the great serous cav- 10 146 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. ities. In the former the exuded liquid saturates the tissues, and is spoken of as an infiltration. In the latter it is deposited on the surface, and is spoken of as an effusion, or an exudation in a narrowed sense of the term. Parenchymatous inflammations are still further subdivided. Glands, muscles, and nerves possess a fibrous framework in addition to their specific elements. Inflammation of the former must be distinguished from that of the latter ; we have thus interstitial inflammation, as dis- tinguished from parenchymatous inflammation in a narrowed sense of the latter term. There is really no essential difference between the two. The only value of the distinction is-that it allows us to indicate briefly the seat of inflammation in certain organs, whose fibrous framework is well defined from the specific parenchyma. Thus interstitial inflammation of the liver implies that the chief inflammatory changes are to be found in the periportal fibrous tissue, the liver-cells being relatively less affected. If it is mainly the lobules which are affected, the inflammation is de- scribed as parenchymatous. Mistakes are often made by referring simple degenerative changes in the liver-cells to parenchymatous inflammation. In speaking of the parenchymatous inflammation of a particular or- gan, it is customary to make use of a term compounded of the Latin or Greek name of the organ and the affix -itis. Thus hepatitis, nephritis, encephalitis, oophoritis, refer respectively to the liver, kidney, brain, and ovary. In some cases old specific names are used instead, as pneumonia (for pulmonitis), an inflammation of the substance of the lung. Histologists often indicate that an organ has undergone inflammation by saying merely that it is infiltrated with small cells or leucocytes. This accumulation of cells is in reality the feature by which the fact of ante- cedent inflammation is most readily recognized. 102. The histological characters of inflammation depend on the one hand upon the nature of the exudation, on the other hand upon the changes in the tissue. Both factors have been utilized in classifying the forms of inflammation, according as one or the other happens to be the more prominent. With respect to varieties in the nature of the exudation, the fol- lowing types are distinguished. (1) Serous and fibrino-serous exudation. When the inflammatory alteration in the vessels is not very marked, the exuded fluid may be rela- tively poor in cells, and in its constitution may resemble the transudation from vessels that are merely engorged. It is, however, distinguishable from the latter by its greater percentage of albumen and of white blood- cells, and by its greater coagulability. Where it collects in quantity, therefore, it looks more or less turbid, and contains flakes and threads of coagulated fibrin. Collections of this fluid in serous cavities are described as fibrino-serous effusions. When it infiltrates the parenchyma of an in- flamed solid organ, it gives rise to inflammatory oedema. When it is effused on the surface of the skin or of a mucous membrane, it is spoken of as serous catarrh. INFLAMMATION AND INFLAMMATORY GROWTHS. 147 (2) Fibrinous or croupous exudation. When the exudation con- tains fibrinogenic and fibrinoplastic elements in abundance, it undergoes coagulation throughout. As explained in Art. 35, the fibrinogenic sub- stance is contained in the exuded liquid, the blood-cells yielding the fibrinoplastin. The presence of a certain percentage of leucocytes in the exudation favors coagulation. The term fibrinous exudation is especially applied to effusions into the various body-cavities. The coagulated masses form toughish, yellowish white, adherent films or coverings over the af- fected organs. When tissues are infiltrated, or mucous membranes cov- ered over, with the coagulated exudation, the term croupous is generally applied to it. The croupous false-membranes formed on mucous surfaces appear as yellowish white deposits, consisting chiefly of granular fibrinous trabe- STc. 23.-Section of a Croupous Membrane from the Trachea. + 250. a. false membrane ; b, surface layer of the mucous membrane infiltrated with leucocytes (d,); c, fibrin; d, pus-corpuscles. culse (Fig. 23, c) and filaments, interspersed with pus-corpuscles in vary- ing amount. In other cases, the false membrane is chiefly made up of hyaline flakes and lumps (Fig. 24, b). (3) Purulent or fibrino-purulent exudation. When the migration of white blood-cells from the vessels is very extensive, and coagulation does not immediately ensue, the exudation assumes a whitish milky or creamy appearance. It consists simply of a liquid plasma and small leu- cocytes containing from one to three nuclei, and is called " matter " or pus. It is commonly the consequence of bacterial infection. The bac- teria seem to act so as to hinder coagulation. When the purulent liquid contains in addition white flakes of fibrin infiltrated with pus-cells, the exudation is described as fibrino-purulent. It takes this form chiefly in inflammation of the serous membranes. When purulent infiltration leads to liquefaction and dissolution of the tissues, so that a pus-containing cavity is formed, we have what is called an abscess. If the loss of tis- sue is superficial, and a morbid surface is formed which secretes pus, we have an ulcer. Secretion of pus from the skin, mucous membrane, or synovial membrane, constitutes purulent catarrh. An infiltration, partly purulent and partly serous, is described as purulent cedema. (4) Hemorrhagic exudation. Blood may be mingled with serous, 148 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. fibrinous, or purulent exudations, and is readily distinguished by its col- oring them red. Such mixed exudations are called hemorrhagic. (5) Putrid exudation. When from the presence of septic bacteria the exudation undergoes putrefaction, it is described as foul, putrid, or sanious. 103. We may likewise distinguish certain types of inflammation, ac- cording to the way in which the inflamed tissue is affected. (1) Desquamative catarrh. In this form of inflammation, which affects the skin and mucous membranes, the epithelial cells are shed in large numbers and mingle with the secretion. It is also d-escribed as epithelial catarrh. Mucous catarrh is a variety of this distinguished by free mucus-secretion from the surface epithelium, or mucous glands. (2) Necrotic inflammation. This term is applied to cases in which an Fig. 24.-Section of Uvula from a Case of Diphtheria, x 100. (The epithelium has been shed; aniline- brown staining.) a, micrococci; b, sub-mucous tissue changed into amorphous flakes; c, infiltrated leuco- cytes ; d, fibrinous exudation; e, blood-vessels; /, lymphatic vessel containing cells and fibrin. inflamed tissue dies over an extent that is perceptible with the naked eye. The form of necrosis may vary; it may be simple necrosis, gan- grene, mummification, caseation, or coagulation (Arts. 32-42). A special interest attaches to inflammatory coagulative necrosis or diphtheritic inflammation (Art. 38). In this form, the tissue which has been killed by the injury causing inflammation, or by the inflamma- tion itself, coagulates into large flakes and reticulated masses. This happens, for example, in diphtheritic inflammation of the uvula, where the epithelium and infiltrated subepithelial tissue are transformed into a coarse mesh-work interspersed with amorphous lumps and flakes (Fig. 24, b). The granulating tissue of a wound may, in like manner, become ne- crosed, and solidify into diphtheritic denucleated flaky masses. Necrotic inflammation is of course always grave. It implies severe injury to the tissue, as well as serious alteration in the vessel-walls. CHAPTER XXII. LATER STAGES OF INFLAMMATION-RECOVERY-REGENERATION -GRANULATION-CICATRIZATION. 104. Inflammation ceases to advance so soon as the blood circulating through the vessels restores their walls to a healthy state. When this happens recovery at once begins. After a slight inflammation, i.e., one in which the vessel-wails are but slightly damaged, and the exudation trifling, the tissue affected may re- cover in a remarkably short time. So soon as the vessels perform their functions normally the exudation ceases to be formed ; what is already effused forthwith undergoes reabsorption by the lymphatics or by the blood-vessels themselves. Simple serous exudations are those most readily absorbed, but corpuscular elements in moderate amount present no great difficulty. If any of the constituent cells of the tissue have been injured in the course of the affection, they may now recover. Their normal nutrition becomes possible as the circulation re-adjusts it- self. In a short time nothing remains to show that inflammation has ex- isted. The affected part becomes perfectly normal again. If the inflammation has been more intense and the amount of exuda- tion greater, and if in addition tissue-elements have been actually de- stroyed over a small extent, the process of recovery is somewhat differ- ent. When the circulation becomes normal the exudation is reabsorbed as before. Liquid and cells are alike taken up by the lymphatics and blood-vessels. Even coagulated exudations are gradually removed after undergoing liquefaction. The necrosed tissues, like the more solid masses of exudation, are ultimately disintegrated and liquefied, and then removed by absorption. If they lie on the surface they may be directly cast off (Arts. 112-115). If the loss of tissue be not too great, and the remaining parts are healthy and vigorous, regeneration or repair is ef- fected by multiplication of the tissue-cells. Epithelium produces epi- thelium, muscle-cells form fresh contractile substance, periosteum gener- ates new bone, etc. (Arts. 84-89). By and by the lost tissue is replaced by new tissue after its kind. It may sometimes even happen that the amount of new tissue produced is in excess of what is needed, and hyper- plasia succeeds inflammation. This will happen when the excessive nu- trition of the tissue, which usually follows upon inflammation, is kept up for a considerable time. 150 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. The magnitude of the defect which can be filled up in this way, and the fitness of the new tissue to replace the old, are matters depending on the regenerative power of the affected structures. As we know, this differs greatly in different tissues (Arts. 84-89). The lining epithelia are able to cover over large denudations of surface, and, as in catarrhal des- quamation, may be reproduced again and again. But it would seem that brain-tissue has no power to form a single fresh ganglion-cell. For the efficient causes which call forth regenerative or hyperplastic proliferation, we refer the reader to Arts. 78-82. Here we have only to remind him once more that it is not the agency or noxa which excited the inflammation which now excites the cells to multiply, by some kind of direct stimulus. Multiplication is completely independent of the original cause of the inflammation. It is simply the result of changes in the vital conditions or environment of the cells ; and these changes are the result of the inflammatory process itself. M 105. If the inflammation continues for a time and is not too intense, and if the circulation is not too seriously interfered with, so that a good blood-supply is continuously kept up, we have all that is needed for the production of inflammatory tissue. The cells which build up the new tissue are the migrated white blood-cells or leucocytes ; the new tissue which they form is described as granulation-tissue and cicatricial tissue. The most important factor in this plastic process is the forma- tion of new blood-vessels. These alone make it possible to keep the young formative tissue supplied with adequate nutriment. The factors which cause the inflammatory process to take on a forma- tive or constructive character are not always the same. We must in general assume that some cause is acting which keeps up the morbid al- teration in the vessel-walls, and so gives the inflammation in some degree a chronic character. In open wounds the inflammation is kept up by contact with the air, with the floating matters suspended in it, with the dressings, with the secretions from the surface. This continues till the skin, growing over from the margins of the wound, at length protects the vascular tissue from further irritation. In subcutaneous necroses following on acute exudative inflammation, the dead tissues or dead exudations are enough to maintain a certain irritation in their neighborhood, especially as they undergo certain chemical changes be- fore they are finally absorbed. In other cases, the original cause of in- jury persists and continues to excite ever fresh inflammation ; or a new injury may affect a part in which inflammation is declining or over- past, and kindle it afresh. Which of all these possibilities applies to a given case is often hard to determine. Very frequently several such factors are in action, either at the same time, or at different stages of the process. Plastic inflammation is, moreover, always associated with some form of degeneration. In parenchymatous organs, for instance, the growth of new fibrous tissue involves the atrophy or destruction of the proper INFLAMMATION AND INFLAMMATORY GROWTHS. 151 and specific elements. Intrinsic sources of irritation of this kind are thus seldom wanting, and they maintain the inflammatory process, even when the original exciting cause has ceased to act. 106. The new tissue produced as a result of inflammation often fulfils the purpose of replacing tissue that has been lost. This application of the process is apparent in the healing of wounds. In an open skin- wound, for instance, there is formed first of all a delicate grayish-red vas- cular formative layer, the so-called granulating surface. This in a way unites the borders of the wound. After a time it becomes covered ©ver with skin, and is transformed into fibrous tissue. The breach is thus filled up, the separated parts united, and a scar is formed. The scar or cicatrix is thus the result of an inflammatory plastic process. Scar-tissue is formed in other organs in the same way, and with the same result of replacing a loss of substance. In many cases, however, the production of new tissue by inflamma- tion does not serve so useful a purpose. It often takes the form of a useless or injurious hyperplasia. This happens, for example, when after inflammation the corium of the skin thickens, or the papillae become en- larged ; or when the fibrous tissue of the kidney or the liver is morbidly increased, giving rise to disturbances in the nutrition of the organ. Even the formation of adhesions and adhesive membranes connecting the or- gans of the great serous cavities is often accompanied by impairment and hindrance of their functions. 107. As we have just stated (Art. 105), inflammatory tissues are de- veloped from extravasated leucocytes, in cases where the circulation has not been very seriously interfered with. This last ensures that the exuded corpuscles are speedily irrigated with a sufficient but not too abundant stream of plasma. These conditions are perfectly fulfilled in the aseptic healing of an ordinary wound. If an open wound be observed twenty-four hours after it is inflicted, the bottom and edges will be found to be intensely red and somewhat swollen. The elements of the tissue are still quite distinguishable, though the tissue seems turgid, and here and there small necrosed shreds are visible. On the second day, the tissues have a more gelatinous ap- pearance, the outlines of the tissue-elements (cells and fibres) are blurred, and the color is a grayish red. A reddish yellow liquid lies on the sur- face. After the second day little red nodules or granules begin to ap- pear over the entire wound. These increase rapidly in size and number, and become at length confluent. After two or three days there is thus formed a continuous red granular layer-the granulating surface. It is covered with a more or less abundant secretion, which changes to a gray- ish gelatinous film, and afterward becomes more yellowish and creamy in consistence. This film is composed of an albuminous coagulable exuda- tion and numerous leucocytes, some of them with one nucleus, but most of them with two or three small rounded ones. These are pus-corpus- cles. They are not capable of further development, but are rather to be 152 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. looked upon as cells in process of decay. The multiplication of the nu- clei is evidence, not of subdivision, but of disintegration. The whole of the new tissue formed is derived from this delicate red formative or embryonic tissue, the granulation-tissue. From this the cicatricial tissue is developed. [It seems beyond doubt that the multiple nuclei of pus-cells (Fig. 25, a^) are simply the result of disintegration. Nothing has been ob- served to indicate that the division of the nucleus is followed by a divi- sion of the cell, and nothing is known of their further development. Besides, it is noted that the combined size of the multiple nuclei is not greater than that of the single nucleus. This shows that the partial nuclei have not the power, like true daughter-nuclei, of growing by assimilation of substance from the protoplasm of the cell (Kuss, " De la vascularity et de 1'inflammation," Paris, 1846 ; Paget, " Surg. Path.," Leet. 10).] 108. The naked-eye appearances in the healing wound are referable, partly to the accumulation of white blood-cells, partly to dilatation and distention of the vessels, and partly to the formation of new vessels. This latter takes place by means of off-shoots from the capillaries, as de- scribed in Art. 86. No other mode of vascularization has been certainly made out. The development of granulations and cicatricial tissue takes place in the following way. The injury sets up inflammation, which leads to an infiltration of cells at the borders of the wound. Large numbers of migrated cells (with a certain quantity of fluid) are thus accumulated. Meanwhile, parts of the existing tissue disintegrate by softening and liquefaction. A soft text- ure is in this way produced-which is made up almost entirely of young round-cells, with very little intercellular substance. Some of these cells, chiefly those containing .several fragmentary nuclei (Fig. 25, aj, cease thereupon to live, and form true pus-corpuscles. They are either thrown off with the secretions from the wound, or are absorbed, or dissolved in situ and utilized to feed the more vigorous living cells. On the other hand, another set of (uninuclear) cells (a) begin to grow. Their proto- plasm increases in amount and becomes more markedly granular (Fig. 25, 5). At the same time the cloudy finely granular rounded nucleus becomes clearer, oval, and vesicular (5). The nuclear juice and nuclear substance become distinct, so that it becomes possible to discern clearly a nuclear membrane, nucleoli, and nuclear granules and filaments. This differentiation of the elements of the nucleus gives the cell an altogether different aspect and habit. It resembles an epithelial cell, or as it is phrased-it becomes epithelioid. The transformation of leucocytes into epithelioid cellsis accompanied by cohesion of the protoplasm of separate cells. A growing cell may INFLAMMATION AND INFLAMMATORY GROWTHS. 153 appropriate the substance of others which are decaying ; or two equal cells may coalesce to form a single one. The epithelioid cells are the formative cells of the granulation-tissue ; they alone have the power of producing new connective tissue. They are best described as fibroblasts. They are usually uninuclear, and their numbers increase partly by successive transformations of round- cells, partly by subdivision. Very probably the division of their nuclei is of the karyokinetic type. If the protoplasm does not subdivide for Fig. 25.-Grannlation-cells in various stages, x 500 (Picrocarmine staining.) a, uninuclear; a1; multi- nuclear migrated white blood-corpuscles : 6, various forms of uninuclear formative cells ; c,binuclear; c,. mul- tinuclear formative cell; d, formative cells developing into connective tissue ; e, developed connective tissue. some time after the nucleus has divided, binuclear (c) cells are formed ; and even in some instances large multinuclear cells, the so-called giant- cells (cj. In healthy granulations giant-cells are produced but sparingly. [Ziegler has endeavored to prove experimentally that the migrated white blood-cells are capable of further development, and are the primary source of cicatricial tissue (" Exper. Untersuch. Ub. d. Herkunft d. Tuber- kelelemente," Wurzburg, 1875, and "Untersuch. ub. path. Bindegewebs- und Gefassneubildung," Wurzburg, 1876). He made a small, disc-shaped chamber by fastening together two thin cover-glasses a slight distance apart. This was inserted under the skin of a dog and left for a certain length of time. When it was removed its contents could be examined microscopically. The thin interspace was found to be filled with cells, which either perished and broke up or underwent further development. In a single layer of cells obtained in this way, there were always some undergoing progressive change, and they could be observed with great ease. Thus not merely at the borders, but over the whole field, cells were 154 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. found in all stages of development from the lymphoid to the epithelioid and giant-cell type. The actual formation of tissue from them could be followed. When large cells are formed, a certain number of the round- cells in their neighborhood disappear. Jt is as if their protoplasm were appropriated by the larger growing cell. This is less surprising, as we know that migratory cells frequently pick up molecular matters (such as cinnabar) which they find in their way. The only difference is that the protoplasm is assimilated and utilized for growth ; the cinnabar of course is not. The various stages of nucleus-division cannot as yet be described in detail ; only some of them have been observed. So far as is known, they correspond with the scheme of Arts. 74 and 75. Now and then a radial arrangement of the granules of the protoplasm is observed near the poles of the nucleus. Ziegler's results have been called in question by various observers (Ewetzky, Weiss, Bbttcher, Baumgarten, and others). These observers maintain that the migrated cells have no power of further development, and attribute the formation of new tissue to the multiplication of the fixed tissue-cells, especially in the case of the epithelia. Their experi- mental methods have been so different from Ziegler's, and their criticisms rest so much more on their own special theories of inflammation than on the facts adduced, that it is difficult to find a common basis for the dis- cussion of them. Those who have used similar methods have in the main arrived at similar results. Senftleben (" Virch. Arch.," vols. Ixxii. and Ixxvii.) introduced fragments of dead lung, or artery-wall, into the peri- toneal cavity of an animal. Tillmanns (" Virch. Arch.," vol. Ixxviii.) used bits of hardened organs with artificial cavities in them. Hamilton (" Sponge-grafting," Edin. Med. Journal, 1881), introduced bits of sponge. All of these have found that the cells which migrate into the receptacles thus artificially provided undergo further development. Heidenhain had already discovered large cells in round bits of elder-pith, which he had inserted into the abdominal cavity of guinea-pigs (" Ueber d. Verfettung fremder Kbrper in der Bauchhbhle," Breslau, 1872). Schede ("Arch. f. klin. Chir.," xv.), Aufrecht ("Virch. Arch.," vol. xliv.), Bizzozero (" Annali universi di medicina," 1868), and others had already observed facts which were in favor of the notion that develop- ment does take place in migrated cells.] 109. The newly formed fibroblasts are rounded cells (Fig. 25, 6). They soon change their form, however, by sending out processes and be- coming elongated. In this way cells are produced which are club-shaped, spindle-shaped, or branched (6) ; and these cohere and coalesce in various ways. Meantime the larger formative cells are multiplied till at length they outnumber the small round-cells. Here and there they become tightly packed together. This is especially noticed in the deeper layers of the granulation-tissue. When their number has reached a certain INFLAMMATION AND INFLAMMATORY GROWTHS. 155 point, fibrous tissue begins to be produced by the formation of a fibril- lated intercellular substance. This latter arises in part directly from the cell-protoplasm, and in part from a homogeneous ground-substance de- rived from the fibroblasts. In the first case, from the ends and lateral borders of the formative cells (d) there grow out fine fibrillae, which unite with those of the neighboring cells. The direction and extent of the fibrous strands thus produced are independent of the original form and disposition of the formative cells. The run of the fibres is generally in the same direction for considerable lengths. When the fibrillae have reached a certain degree of definiteness and strength the process of fibrillation ceases, and the remaining cells with their nuclei remain as fixed connective tissue-cells (e). They lie along the surface of the fibrous bundles. The process is thus completed-granulation-tissue has become cicatricial tissue. The formation of new vessels starts as soon as the first formative cells are developed. It proceeds rapidly, and even in a day or two multitudes of vascular loops are already produced. They bring the granulations the nutriment they need, and supply cells to fill the vacan- cies occasioned by absorption of the first leucocytes. The only part taken by the epithelioid cells in vascularization is-that they serve to strengthen the thin-walled new capillaries, by disposing themselves along the outer surface of the vessels. It is possible that fibroblasts may now and then take part in the formation of new vessels. This they may do by attaching themselves to the budding off-shoots, and thus assuming the form of buds themselves. By excavation of their contents they are then converted into permeable channels. Giant-cells, when they are present, seem to play no special part in the transformation of the granulations. They form fibrous tissue in.the same manner as the other fibroblasts. [Ziegler has observed the process of scar-formation from granulation- tissue, both in ordinary granulations and by the cover-glass method. The latter yields preparations which are better than any sections, inasmuch as all the cells and cell-structures remain in situ; there is no possibility of disintegration or disturbance of the natural relations. Tillmann's (loc. cit.) observations agree with Ziegler's. The assertion is often made (Billroth's " Surgical Pathology," Rind- fleisch's " Pathological Histology ") that granulation-tissue passes into spindle-celled tissue. This is only partially the case. Spindle-cells are formed often enough, but the cells are just as often of many diverse shapes. The granulations, when they are first formed, are nourished by the plasma which escapes from the existing vessels. Thiersch has shown that the spaces in which this circulates among the granulations may be injected from the blood-vessels. This mode of nutrition is, however, in- adequate for the complete formation of the embryonic tissue ; new vessels are therefore required. 156 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. Ziegler (loc. cit.) and Brodowski (" Virch. Arch.," vol. Ixiii.) have de- scribed a special relation of the giant-cells to the process of vasculariza- tion, but this is no longer maintained.] 110. The constructive processes taking place in the wound are com- pleted when the cicatricial fibrous tissue is formed. The subsequent changes are limited to a certain amount of shrinking or contraction in the new tissue, and the suppression of some of the new blood-vessels. The scar, which from its vascularity is at first decidedly redder than its sur- roundings, begins to pale ; and at length becomes paler and whiter than its surroundings. A depression frequently results from the shrinking of the cicatricial tissue. The smaller the wound the smaller and less marked is the scar. This form of healing, in which the wound is closed by means of its own granulations, is called healing by second intention. Healing by first intention occurs when two wounded surfaces come into contact and grow together without the intervention of visible granulations. In principle the process is the same as in the first case. An inflammatory infiltration is produced, and in this new vessels and new fibrous tissue are developed. The difference is merely quantitative. In skin-wounds, for example, the exudation and granulations are so insignificant in amount that they are imperceptible ; they are very quickly bridged and covered over by regenerative multiplication of the epidermal cells. The chronic inflammatory processes leading to fibrous hyperplasia fol- low in general the same course as when new tissue is being formed. In different organs, however, there are special peculiarities to be noted. They will be treated of in considering the special pathology of the several organs. 111. While cicatricial tissue is forming in an organ by means of granulations, it usually happens that the fixed tissue-cells also begin to multiply by subdivision. The extent to which this multiplication goes on, and the share it contributes to the final result, are by no means constant. But they are by no means negligible, especially in long-con- tinued inflammations. Hence the different importance assigned to such cell-multiplication by different observers. Some ascribed all formation of new tissue to it, denying the existence of the inflammatory process above described. Others allow it small significance, or ignore it al- together. The truth is probably this-that, accompanying the inflam- matory constructive process, there is always some regenerative prolifer- ation in the tissue, and that this is in inverse relation to the severity of the inflammation. Epithelium is a tissue which cannot be reproduced by means of granulations ; it can be reproduced only by regenerative proliferation. Other specially differentiated tissues, such as muscles, nerves, bones, vessels, are in the same case. These, if replaced at all, must be replaced by regeneration starting in pre-existing homologous tissues. Cicatricial tissue pure and simple is therefore devoid of all such specialized structures, with the one exception of vessels. INFLAMMATION AND INFLAMMATORY GROWTHS. 157 If we were to define granulation-tissue according to its apparent purpose we might say that it is a structure fashioned out of the cellular material gathered by the blood from the system in general, and utilized to make good a defect which the fixed tissue-cells of the injured region are unable to repair. This final purpose, unfortunately for teleology, only appears in the process by which wounds are repaired. It is not apparent in the fibrous hyperplasias of glandular organs, or in the for- mation of adhesions and false membranes ; but the mechanism is the same. CHAPTER XXIII. IMPERFECT RE-ABSORPTION-FOREIGN SUBSTANCES. 112. The re-absorption of inflammatory exudations is not always so complete as we have hitherto assumed (Art. 104). Though it is true that in most cases even exudations containing numerous corpuscular ele- ments are sooner or later absorbed, still there are limitations to this; or it may be that circumstances arise which directly check or hinder the process. If re-absorption (or briefly resorption) does not ensue, further changes take place in the exudation, whether it be an effusion into a cavity or an infiltration of a tissue. The commonest result is condensa- Fig. 26.-Pus-cells becoming fatty and shrinking, x 400. a, pus-cell in solution of common salt; b, pus-cell treated with acetic acid ; 6,, so-called granulation-cdl; c. shrunken pus-cells; c,, shrunken and fatty pus-cell; d, pus-cells that have become fatty and broken up (Gluge's corpuscles). tion, depending on loss of water and caseation. In purulent effusions, for example, the pus-cells undergo fatty changes (Fig. 26, d, " Gluge's corpuscles "). They then shrink and break up, so that presently all that is left is a mass of small irregular lumps (c and c^, and granular detritus (da). The watery parts of the exudation being more or less absorbed, these products of disintegration form a creamy or cheesy pulp. Fibrin- ous effusions may also be transformed into a mass of cheesy detritus. These not infrequently become calcified as time goes on. Condensed effusions of this kind may long resist resorption. It often happens that they cannot be removed in this way at all. Infiltrated tis- sues which have necrosed may, in like manner, resist resorption, and so persist for an indefinite time. Dead bone and fascia especially, which are hard to liquefy or disintegrate, may long be retained. But softer tissues INFLAMMATION AND INFLAMMATORY GROWTHS. 159 may likewise become incapable of resorption, when necrosis has resulted in their caseation or mummification. 113. Tissues which have been killed by the original injury or by the subsequent inflammation, and inflammatory exudations, are no longer parts of the organism. They are foreign substances, and they act as such. In other words, they set up and maintain inflammation in their neighborhood. They act like foreign bodies thrust forcibly into the tis- sues from without. Necroses other than inflammatory, such as those re- sulting from ischeemia, and hemorrhagic effusions or extravasated blood which has become necrosed, all act in the same way as foreign substances. To the tissue affected by them it matters nothing whether they once be- longed to the organism or not. It is of more importance to consider the physico-chemical nature of the foreign substance. This it is which de- termines the intensity, the extent, the general character of the inflamma- tion induced. The great importance of the inflammations excited by such dead or foreign substances makes it absolutely essential to have a clear concep- tion of their nature. And we must in especial discover the characteris- tics of the inflammation set up when the foreign substances are of cor- puscular size. Stated generally, we may put it-that in such a case we have in addition to the ordinary phenomena of inflammation other pro- cesses whose object is the removal of the foreign substance. The pecu- liarities of special cases depend on the physico-chemical nature of the substance. Foreign substances may be divided into two groups :-those which have but a slight effect or none in altering the surrounding tissue, and those which act destructively and excite violent inflammation. Among the first group are some substances easily absorbed, and others which are absorbed with difficulty. 114. The easily absorbed substances include liquids and small solid matters which have no intense chemical action on the surrounding tissue. Of this latter kind are, for example, cinnabar, which is rubbed into the skin in tattooing ; the dust of coal, lime, or iron, which is inhaled and passes from the alveoli into the lung-tissue ; and lastly, fatty and disin- tegrated exudations, softened and disintegrated tissues, and such like.. The effects produced in the organism by small corpuscular bodies of the above kinds are not serious. Perceptible inflammatory changes are brought about only when large quantities of them are present together; their effects are thus integrated as it were. Most of the pulverulent or corpuscular matters referred to are removed from the tissue containing them by resorption. If they lie within a liquid exudation (as do fatty pus-cells or free oil-globules) they may be taken up along with it into the lymphatics, and so carried off. A large number of them would still, however, remain, if another means were not at hand for disposing of them. The additional resource is brought into play by the mild inflammation which the foreign substance excites. The agents 160 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. are the white blood-cells which thereupon migrate from the blood-vessels. These migratory cells appropriate the foreign substances lying in the tissue (Fig. 27, h, Ax, h^, As). They let their protoplasm flow round them, and so take them up into their interior. By frequent repetition of this process granule-carrying cells are produced. According to their con- tents, these have been variously described as fat-granule carriers (AJ, blood-cell carriers (A3), pigment-granule cells (Fig. 28, c), dust-cells, cin- nabar-carrying spherules, etc. In cerebral degenerations, we constantly find cells containing granules and minute drops (Fig. 27, hlf ; these Fl&. 27.-Section through a Degenerating Patch from the Brain, y 200. (Osmium preparation.) a, blood-vessel filled with blood ; b, tunica media; c, adventitia with its lymph-sheath ; d. unaltered neuroglia- cells; e, fatty neuroglia-cells; /, binuclear neuroglia-cells; g, sclerosed tissue; h. round cells; A,, round- cells containing single oil-globules; fat granule carriers; A3, pigment-granule cells, some containing blood-cells. are migratory cells, which have taken up some of the products of disinte- gration of the brain-substance. The carrier-cells ultimately reach the lymphatics. Thus in the brain they accumulate in the lymph-spaces surrounding the adventitia of the arteries (Fig. 27, c). Hence they are carried on by the lymph-current, and at length reach the lymphatic glands. Here they are retained for a time, and ultimately filtered away-at least in part. In Fig. 28 is represented a lymphatic gland infiltrated with pigment-carrying cells ; these were de- rived from an extensive hemorrhage which had undergone resorption. The pigment-carriers for the most part remain within the lymph-sinuses ; only a few have penetrated the follicles. The greater portion of the for- eign substance absorbed usually remains in the lymphatic gland; but it INFLAMMATION AND INFLAMMATORY GROWTHS. 161 may happen that a part filters through it and reaches the next gland, or ultimately the blood-vessels. A considerable quantity of corpuscular for- eign matter can in this way be removed. Often, however, the absorption is inadequate, and a portion of the substance remains in loco. Foreign substances may be deposited along the walls of the lympha- tics as well as in the glands. The granules inclosed in the carrier-cells are set free as the cells decay. Hence it often happens that lymphatics, which have conveyed away quantities of pigmented substance, show traces of pigmentation all along their course. This happens likewise in the corresponding glands. The deposits may even excite the respective tissues to inflammatory hyperplasia. - Fig. 28.-Section of a Lymphatic Gland whose Sinuses and Alveoli contain Pigment-granule Cells, x 80. (Carmine staining.) a, follicle; &, trabeculse ; c, pigment-granule cells. The above process is, of course, only carried out in its entirety when the foreign substances are insoluble and indestructible. Soluble and de- structible matters like chalk, fat, myeline, are sooner or later dissolved or attacked ; the agency of the cells, of oxygen, or of non-organized fer- ments completes their destruction. [References :-Virchow's " Cellular Pathology ; " Ponfick, " Virch. Arch.," vol. xlviii.; Rindfleisch, " Exper. ub. d. Histol. des Blutes," 1863 ; Orth, "Virch. Arch.," vol. Ivi.; Bizzozero, "Med. Jahrb.," 1872.] 115. The process of resorption and the associated inflammation are somewhat different in character when the foreign substance forms a com- pact mass, offering more or less resistance to removal. Such are, for ex- ample, ligatures, drainage-tubes, ivory pegs, leaden pellets, necrosed bone, compact hemorrhagic patches, haematomata and infarcts, thrombi, coagu- lated or condensed exudations, necrotic cheesy masses, etc. All of these excite in the surrounding tissue a certain amount of in- flammation, though its intensity is very various. If the foreign body is quite insoluble in the juices, as glass is, and if the introduction of it is unaccompanied by any injury to the tissues among which it lies (e.g., in 11 162 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the abdominal cavity,) then the effect may be almost nothing. Bodies which are soluble, and undergo chemical changes in the tissues, usually irritate them much more, and the inflammatory processes excited are gen- erally intense. This is also true of bodies (like bullets) which produce laceration as they penetrate the tissue. The first stage is the formation of a zone of inflammatory infiltration around the foreign body. This is followed by the development of gran- ulation-tissue, and at length of fibrous tissue. If the foreign body is not meanwhile absorbed, it thus becomes encapsuled. Only insoluble and compact bodies can remain quite unaltered, for resorption is as it were attempted, even though it be in vain. Bodies which are at all assailable are sure sooner or later to undergo changes. These ensue as follows : the migratory leucocytes, transformed into uninuclear or multinuclear formative cells, attach themselves to the surface of the object. If this be made up of smaller parts, or if particles of necrosed tissue be mingled with it (such as decomposed blood in hemorrhagic patches), these are taken up by the cells and carried off in the manner set forth in Art. 114. If the body be compact and not to be broken up, the cells cling to its surface. If there be accessible cavities or clefts in it, they penetrate into these. If the cells be insufficiently nourished, they become fatty and die. If new vessels are formed to supply them, they develop as granula- tions. Very often indeed multinuclear or giant-cells are found in such circumstances. A dead piece of bone inserted under the skin of an animal, and examined a few weeks after, will be found interpenetrated with vas- cular granulations, and the trabecuLe will be beset in many places with giant-cells. The whole process is very similar to that of physiological bone-resorption. By means of the clinging cells blood-clots, necrotic patches, inserted pieces of dead liver or lung, ligatures, etc., are absorbed amid the granulations. They are partly softened and dissolved, partly broken up and carried away. This process is peculiarly modified when the foreign substance is firmly connected with the surrounding tissue ; when it is in fact a necrosed frag- ment of the tissue itself, such as bone or kidney. In this case the first step is the separation of the living tissue from the dead. At the common boundary of the two an inflammatory zone is formed, which by the soft- ening and resorption of the border-tissue leads to the loosening of dead from living. This zone is called the zone of demarcation; the loos- ened piece is a sequestrum. The sequestrum is by and by broken up and absorbed. If it lies on the surface it is thrown off as a slough; it leaves an ulcer behind it. A further modification ensues when the foreign substance simply lies on the surface of an organ. This occurs, for example, in the fibrinous effusions which form on the surface of the pleura. The deposit is in this case invaded by granulations and cicatricial tissue from one side only. If it lies between two separate organs or lobes it may be invaded from both sides. INFLAMMATION AND INFLAMMATORY GROWTHS. 163 [Langhans (" Virch. Arch.," vol. xlix.) was the first to describe minute- ly the processes by which the larger foreign bodies are absorbed. He pursued the subject experimentally by producing extravasations of blood in various animals. He thus discovered the giant-cells. Heidenhain (" In. Diss.," Breslau, 1872) also found them in pieces of elder-pith, which he had inserted in the abdominal cavity of animals. Ziegler always met with them on the surface of his cover-glasses (Art. 108). By introducing bits of boiled bone into the abdomen of auimals, he found that granulations always penetrated to the interior, and that large osteoclasts or resorp- tion-cells (with one or many nuclei) were developed in contact with the bone. Senftleben (" Virch. Arch.," vol. Ixxvii.) and Tillmanns (" Virch. Arch.," vol. Ixxviii.) have gone further into the matter, and find that hardened aseptic animal tissues, such as bits of liver, kidney, or lung, are partly absorbed and partly adhere and heal in. Fresh tissues are absorbed faster than hardened tissues. Hegar (" Klin. Vortrage," No. 109) and Rosenberger (" Langenbeck's Arch.," xxv.) have- shown that absorption is most speedy in the case of tissues taken quite fresh from a living organ, and introduced into the body. The inflammatory re- action is very slight and ends with the process of resorption. The re- sorption of bone has excited special attention. Kblliker ("Die normale Resorption des Knochengewebes," Leipzig, 1873) and Wegner ("Virch. Arch.," vol. Ivi.) have studied it minutely. They as well as others have made out this process to be something quite peculiar. Ziegler ("Virch. Arch.," vol. Ixxiii.) has sought to do away with the attempted isolation of the process, and to put bone-resorption on a level with other resorptions. He thinks it possible to view all processes of resorption from the same stand-point. In every case the process is carried out with the purpose of removing from the organism a substance which is foreign and useless to it. Giant-cells are very usually formed in such circumstances, and it is possible that they take up the soluble parts of a tissue when it under- goes liquefaction. But resorption is not confined to their agency ; it goes on where they are absent. It remains a remarkable fact that they should so frequently be found on the surface of solid objects. It is perhaps conceivable that the contact of the cell with a foreign body hinders in some way the process of cell-division, without affecting the subdivision of the nucleus. It has long been known that foreign bodies may " heal into " a tissue. Details of the histological process will be found in the memoirs quoted above. Hallwachs has lately published some observations on the subject ("Langenbeck's Arch.," xxiv.).] 116. Many foreign substances, and especially certain altered organic products, have a far more baneful effect on the surrounding tissues than any we have yet considered. Such, in a high degree, is dead tissue which from contamination with septic matters has passed into a state of putrid decomposition. 164 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. In the course of this decomposition various chemical compounds are formed which act harmfully on the tissue (Art. 42), and set up in it pro- gressive destructive changes, and violent hemorrhagic or purulent inflammation. Under the action of the pus-cells, which form in great quantity, and of the septic ferments, the necrosed tissue becomes dis- solved. If it is connected with living tissue, a suppurative zone of demarcation is formed and sets it free ; the result is a cavity filled with pus-an abscess. The process often continues, the infiltration and dissolution of tissue go on, and the abscess grows larger and larger. If decomposing matter from the abscess reach the blood-vessels or lymphatics, and is so conveyed to other regions, it may lead to putrid decomposition and purulent inflammation at the spots where it lodges. In this way metastatic abscesses are formed. If the inflamed region be near a free surface and at length breaks through it, we have a suppurating ulcer formed. Should death not result from this destructive suppuration or purulent necrosis, the injury done may be repaired by the formation of granulation- tissue at the boundary of the living tissue and the dead. In the course of time the pus secreted may be absorbed, or solidified and encapsuled. CHAPTER XXIV. THE INFECTIVE GRANULOMATA. General Characters. 117. The granulative formations we are about to discuss are all distin- guished by similar characters. Their development usually stops short at the fibroblast stage, and having reached it (or even before that) the con- structive process gives place to retrogressive changes. Cicatricial de- velopment being arrested, the granulation-tissue persists for a time un- modified, and often develops to a considerable amount. For this reason Virchow described the formations as granulative growths or granulo- mata. All these growths have furthermore the clinical character of infec- tiveness. Hence they have been termed infective growths by Klebs and Cohnheim, and specific inflammations by Rindfleisch. - Their infective character may be recognized by various signs. Thus they are all locally invasive, i.e., the granulation-tissue spreads cen- trifugally from a centre into the surrounding structures. At the same time the central (or oldest) part of the new formation usually dies and disintegrates. In many cases the lymphatic system becomes affected, so that secondary granulative foci are formed in it. From the lymphatics the process is at times transferred to the blood ; or it may invade the blood-vessels directly. The final result is the spread of the disorder to various organs, or throughout the system. In most of the granulomatous disorders we may have not merely a diffu- sion of the disease throughout the individual organism, but also a transfer- ence of it from one individual to another ; the affection is inoculable. If one person be inoculated with the inflammatory products derived from another, he acquires a disease whose course is exactly similar to that of the original one, and which yields identical inflammatory products. This latter character of infectiveness is that by which it is most readily recognized. To this group of infective granulomata belong the neoplastic forma- tions found in tuberculosis, syphilis, leprosy, lupus, glanders, and acti- nomycosis. All these affections are due to the invasion of the body by a virus or poison derived from the outer world, or from the body of another individual. This virus may probably be produced by vegetable parasites. In leprosy (Armauer Hansen, Neisser), tuberculosis (Koch), 166 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. and syphilis (Klebs) bacteria have been found, and in actinomycosis a special fungus. These are declared to be the originating causes of tht respective diseases. Our ideas as to the nature and character of these affections are as yet mainly based upon their clinical course ; but we have also derived something from inoculation-experiments. Tuberculosis and syphilis are thus known to be communicable from one person to another ; tuberculosis is also communicable from man to lower animals. [It was Virchow who invented the term " granulative growth " or " granuloma " for these formations, which he was the first to define ac- curately (" Die krankhaften Geschwiilste," ii.). He set it down as char- acteristic of them-that they usually fail to develop beyond the stage of granulation-tissue ; that this is unstable in character ; and that the regular issue is in ulceration. He laid stress on their near alliance to the products of inflammatory processes. Klebs (" Prager Vierteljahrs- schr." vol. cxxvi.) called such growths "infective growths or tumors," and the name has been adopted by Cohnheim. Neither description is exactly adequate. Virchow's takes no account of their infective char- acter ; Klebs's bears no reference to their structure. As it is by no means certain that there are no other new formations of infective origin, some apter designation seems called for. Even Rindfleisch's term " speci- fic inflammation " is too indefinite, for it might perfectly well apply to a number of other processes, such as those of pyaemia, erysipelas, variola, etc. In this book the term " infective granuloma " will be used ; this serves to keep in view both the structure and the clinical character of the morbid formations in question.] Tubercle and Tuberculosis. 118. The structure characteristic of tuberculosis is the tubercle, or tuberculous nodule. The notion of tuberculosis is thus primarily an anatomical one-tuberculosis is a tubercular (i.e., nodular) disease. Of course it does not follow conversely-that every nodular growth found in the organism implies tuberculosis ; the special nodule of tuber- culosis, the tubercle par excellence, is a structure of definite and special constitution. Virchow ("Die krankhaften Geschwulste," ii., 636) de- scribes a freshly formed tubercle as a small gray translucent nodule, not exceeding a millet-seed in size, mainly composed of cells, and developed from connective tissue. The cellular elements (he adds) are essentially similar to those of lymphatic glands ; they are round cells of various sizes, some of them like white blood-cells, some larger, some smaller. Their nuclei are homogeneous and bright, small and spherical or large and oval, vesicular, and transparent ; they contain nucleolar corpuscles. The larger cells often contain two nuclei, and frequently more, to the number of twelve or over. Between the cells are found fibrous filaments arranged in a network and sometimes vessels also. The latter are never INFLAMMATION AND INFLAMMATORY GROWTHS. 167 new-formed ; they existed before the tubercle was developed, and lie within the tubercle only because the tubercle has grown around them. The nodules occur either singly or in numbers ; or they may be grouped in confluent masses. In the latter case, the internodular tissue does not remain unchanged ; it seems made up of imperfect granulation-tissue, or inflammatory fibrous hyperplasia takes place. The appearance is then rather that of a mass of compact uniformly diseased tissue, than of nor- mal tissue containing nodular deposits. When the nodule becomes older, the centre of it is invariably found to be caseated. It is then yellowish-white and opaque. Under the microscope it appears as a granular friable mass, while the periphery still shows its cellular constitution. The aggregations of cells may stretch out in various directions through the tissue, as if the nodule threw out pseudopodia. The nodular groups undergo caseation like the single nodules. The internodular granulation-tissue also becomes cheesy, so that at length large and continuous caseous patches are formed. It is much rarer to find the nodules undergoing fibrous transformation. Caseation is characteristic of the later stages of the tuberculous nodule. [The term tubercle (tuberculum) was formerly applied to all varieties of nodular growth. Baillie (1794) and Bayle (1810) were the first to direct attention to the gray miliary nodules which we now call tubercles. Bayle however applied the term to other growths in the lung. Laennec applied it mainly to the cheesy masses found in phthisical lungs. Larger caseous foci and caseous lobular infiltrations were also described as tuber- culous. The caseous nodes and masses were simply " tubercles," the diffused infiltration was " tuberculous infiltration," the gray nodules (or true granulative tubercles) were " miliary tubercles." Cheesy change was thus made the main characteristic of tuberculosis ; caseation was spoken of as " tuberculization." In opposition to this view, Vir- chow maintained that caseous masses might arise in many different ways, and hence had very various significance in different cases. He laid it down that the anatomical basis of tuberculosis is the cellular tubercle (Virchow, loc. cit. ' Waldenburg, "Die Tuberculose," Berlin, 1869 ; Grancher, " L'Union med.," 1881).] 119. We may define a tubercle, then, as a non-vascular cellular nodule, which does not grow beyond a certain size, and at a certain stage of its development becomes caseous. This definition includes all that w'e can say, in general terms, of tubercle from the histological point of view. The histological researches of the last fifteen years (by Langhans, Schiippel, Koster, Rindfleisch, Cohnheim, Ziegler, Klein, Sanderson, and others) have added only this-that the tubercle possesses in many cases a special structure, and that certain cell-forms frequently occur in it and give it a characteristic appearance. The central part of the tubercle 168 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. usually contains giant-cells (Fig. 29, «). These possess numerous nuclei, which are not uncommonly arranged round the periphery, or gathered together at one pole of the cell. The uninuclear cells are partly lymphoid, partly larger and like swollen epithelial or endothelial cells- these are called epithelioid (Fig. 29, Giant-cells and epithelioid cells are marked by their coarsely granular protoplasm, and large vesi- cular oval nuclei with clear nuclear juice and nucleoli. The round or lymphoid cells (c) are finely granular, with a small round nucleus in which the nuclear juice and nuclear substance are not clearly distin- guished. Fig. 29.-Tubercle from a Fungating Granuloma in Bone, x 250. (Aniline-brown staining.) a, giant- cell ; &, epithelioid cells; c. lymphoid cells. These cells lie in a stroma which in many cases exhibits a reticular arrangement. 120. The epitheloid cells and giant-cells have been thought by some to be characteristic of tuberculosis. Many writers have thus come to speak of specific tubercle-cells, and have based the diagnosis of tubercu- losis merely on the presence of these larger varieties of cells. This is certainly unjustifiable. Such cells, indeed, are common enough in tuber- culous affections, but they are by no means exclusively confined to them. All inflammatory tissue-formation is preceded by a stage in which large cells are developed. It is very easy to generate experimentally in such formations all the various elements found in tubercle, and especially the giant-cells. The constituent cells of tubercle are precisely equivalent to the corresponding cells of granulation-tissue. All the evidence points to the conclusion that tubercles arise in the same way as granulations. The chief materials are derived from the migrated white blood-cells ; and the endothelial cells and fixed connective-tissue cells supply only a minor INFLAMMATION AND INFLAMMATORY GROWTHS. 169 part. So far as the cell-forms are concerned, the only difference between tubercle and granulation is-that in tubercle the larger cells are often found in relatively greater numbers. The characteristic features of tubercle, therefore, do not lie in the forms of its cellular elements. As has been already said, the character- istic features are these : that the cells form a definite nodule, which does not exceed a certain size, contains no new-formed vessels, and in conse- quence at a certain stage of its development ceases to progress ; that the nodule thereupon undergoes retrogressive changes, and becomes fatty, necrotic, and caseous. If this proposition be duly considered, it will be seen that the diag- nosis of tubercle cannot be made to depend on anatomical structure and constitution alone. A cellular nodule made up of round-cells only, with- out a single giant-cell, or a nodule whose general texture is fibrous, may perfectly well be characterized as a tubercle, if its life-history corresponds with what we have set down. As an actual fact, in perfectly typical cases of tuberculosis we may find such nodules close by others that con- tain giant-cells. We may explain the occurrence of the former, by sup- posing in the one case that the aggregated round-cells have prematurely ceased to develop or have not yet had time to reach their full develop- ment ; in the other case the fibroblastic stage (that of epithelioid cells and giant-cells) has been exceptionally transcended, and that of fibrous- tissue formation has been reached. The physiological analogue of the last is of course the transformation of granulations into cicatricial tissue. [According to the recent investigations of Koch (Art. 127), the defi- nition of tubercle just given must be amended. By tubercle we are, it seems, in future to understand-a cellular nodule containing within it the specific tuberculous virus, the Bacillus tuberculosis of Koch. The general doctrine of tuberculosis must be altered in many points in consequence of Koch's discovery. The text has been allowed to re- main as representing the hitherto accepted doctrine, and as containing what is probably the truth, though not the whole truth. Langhans was the first to examine carefully the giant-cells (" Virch. Arch.," vol. xlii.) and to describe their forms. Schiippel (" Untersuch. iib. d. Lymphdrusentuberculose," Tubingen, 1871), maintained that they were always present in tuberculosis, and based the diagnosis of the affec- tion upon them. Koster (" Virch. Arch.," vol. xlviii.), Buhl (" Die Lungenentziindung," Munich, 1872), and Rindfleisch (" Pathological Histology," i., 136, and " Ziemssen's Cyclopaedia," vol. v.) have also in- sisted on their importance in diagnosis. The latter has even declared that any large-celled infiltration of a tissue is to be regarded as tubercu- lous or scrofulous in character. In opposition to this view Hering (" Stud, uber Tuberculose," Berlin, 1873), has disputed the specific sig- nificance of giant-cells and epithelioid cells, and has demonstrated that they are often absent in undoubted tubercles. The second constituent 170 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. of the tubercle, the fibrous reticulum, has been investigated by Schuppel {loc. cit.), Wagner ("Das tuberkelahnliche Lymphadenom," Leipzig, 1871), Klein (" Report of Med. Officer of Privy Council," 1874). Cornil and Ranvier ("Man. of Path. Histology," vol. i., 1882), maintain that the reticulum is produced post mortem by the action of hardening re- agents on the intercellular substance. For further references to the his- tory of the question the student may consult Treves (" Scrofula and Tubercle," London, 1882), Hamilton {Practitioner, 1879-1881), Klein {Practitioner, 1881), Burdon Sanderson {Practitioner, 1882), Gee (Arti- cle "Tuberculosis:" " Quain's Diet, of Medicine," 1882). Ziegler (" Ueber die Herkunft des Tuberkelelemente," Wurzburg, 1875, and " Ueber path. Bindegewebsneubildung," 1876) has sought to show that neither giant-cells nor epithelioid cells are exclusively confined to tubercle, but are to be found in all granulations. Between the latter and tubercle the only difference is-that in healthy granulations the multi- nuclear cells occur but sparingly, while in tubercle they are in great num- bers and highly developed. In tubercle the formative material is abun- dantly provided and fibroblasts produced, but they are not utilized for further development into fibrous tissue. The giant-cells of granulation-tissue are to be distinguished from those which arise from epithelial cells. When tubercles form in epithelial ducts, such as those of the liver or testis, the affected epithelial cells seem to coalesce and form structures much resembling the giant-cells of granula- tions (cf. Klein, " Lymphatic System," part ii., London, 1875). They have properly nothing to do with the formation of the granulomatous tubercle. They are accidental consequences of the locality in which the tubercle is developed. To draw conclusions from them (as do Gaule, " Virch. Arch.," vol. xlix., and Liibimow, " Virch. Arch.," vol. Ixxv.) with regard to the genesis of all tuberculous giant-cells is not permissible.] 121. Diffusion of tubercle. When a tuberculous organ is examined we do not usually find the tubercles in their earlier stages ; they have already undergone certain advanced changes. Parenchymatous organs contain caseous nodulated patches or foci, which are either firm and com- pact in texture, or are already softened and broken down toward the centre. In surface-tissues, ulcerations are produced by this softening process, and their edges and base are caseous. The caseated tissue passes at its boundaries into a zone of gray or grayish-red translucent tissue, re- minding one exactly of granulation-tissue. This gray or grayish-red tis- sue is found in other parts of the affected organ in the form of larger or smaller patches ; these often quite visibly contain small gray or yellowish white and opaque nodules. Lastly, the affected organ also contains small gray nodules lying in apparently unaltered tissue ; and sometimes surrounded by a hypenemic zone, sometimes not. The gray or grayish-red translucent tissue, whether it surrounds the INFLAMMATION AND INFLAMMATORY GROWTHS. 171 caseous focus, or forms the base of an ulcer (Fig. 31, h and h^, or occurs in isolated patches, is nothing else but tissue infiltrated with cells ; it is granulation-tissue. The gray and the yellow nodules are fresh or " crude " tubercles generally containing giant-cells (Fig. 30,/"), and old already caseated tubercles (Fig. 31, respectively. The gray and yellow iso- lated or aggregated nodules in the neighborhood of the larger patches are of the same character (Fig. 30, and Fig. 31, i and From these observations we may gather-that tubercles sometimes Fig. 30-Fungating Granuloma with Tubercles from the Calcaneum. x 60. (Heematoxylin staining.} a, medullary tissue containing fat; 6, blood-vessels; c, bone trabeculae ; d, osteoclasts (Art. 115); e, gran- ulation-tissue ; f, tubercles in the granulation-tissue, some containing giant-cells; g, isolated tubercle. occur aggregated or grouped within a tissue which is already infiltrated with cells ; and that the affection spreads by the formation of fresh no- dules in the neighborhood of the old. In other cases granulation-tissue and fibrous tissue may develop between and around the aggregated tu- bercles. The process may thus begin, with an eruption of tubercles, or with a more diffused inflammatory infiltration. These propositions prac- tically include all that is important concerning the diffusion of tubercle in the tissues. [It is not usually difficult to recognize tubercles in the substance of tuberculous granulation-tissue. The giant-cells and epithelioid cells seen in microscopical sections do not take color nearly so well as the small round-cells which form the main component of the tissue. Three zones are usually distinguishable in a tubercle. In the centre lies the core of aggregated giant-cells of a dark or dull color. Then comes the zone of faintly stained epithelioid cells, and finally at the periphery the zone of deeply stained round-cells ; these last are usually deeper in tint than the granulation-cells around them. When the middle of the tubercle has 172 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. already become caseous, giant-cells are generally to be made out here and there over it. It is not always correct to say that tuberculous patches take their rise from single nodules. The formation of nodules may be preceded by a diffused infiltration, or even the development of granulation-tissue ; the nodules only making their appearance as secondary growths.] 122. The eruption of fresh tubercles in the neighborhood of an exist- ing tuberculous focus is usually followed sooner or later by the appear- ance of nodules in the lymphatic system. The nearest lymphatics are, of course, the first to be affected ; they receive their lymph from the re- gion primarily affected. Thus in tuberculous ulceration of the mucous Fig. 31.-Subepithelial Tuberculous Granulations and Discrete Tubercles in the Wall of the Large Intes- tine. x 30. (Bismark-brown staining.) a. mucosa ; b, submucosa; c, muscularis interna ; d. muscularis externa; e, serosa; f, solitary gland; g, mucosa infiltrated with cells; h, tuberculous ulcer ; focus of softening or tuberculous abscess; i, " crude " or fresh tubercle; ilt caseous tubercle. and submucous coats of the intestine, first the lymphatics of the muscu- lar coats (Fig. 31, c, d} are infected, and then those of the serous coat. In this way strings of tubercles may be formed along the course of the vessels. From the nearer lymphatics the eruption may pass in succession to others, and at length approach the thoracic duct. More frequently the affection is not uniformly diffused in this way, but attacks certain parts of the lymphatic system rather than others, especially those through which the lymph is as it were filtered, namely the lymphatic glands. It is in the glands that the tuberculous eruption is most intense. Generally the process makes a kind of halt at these gland-stations ; but it sooner or later finds opportunity to spread onward, and at length reaches the main trunks and the thoracic duct itself. INFLAMMATION AND INFLAMMATORY GROWTHS. 173 Wherever the tuberculous process has become established, it is dis- tinguished by the development of tubercles, and this in the lymphatic vessels as well as the glands (Fig. 32). A more or less intense inflammation of the surrounding tissue is always associated with the tubercular eruption ; it is manifested by hy- peraemia with infiltration and swelling. If the process last for a certain time, it not infrequently happens that young connective tissue is devel- oped at the seat of the eruption. The usual fate of the tuberculous growth is caseous necrosis and disintegration. It rarely issues in the formation of fibrous tissue, and still more rarely in complete resorption of the tubercle. Fig. 32.-Tuberculosis of a Lymphatic Gland, x 150. (Haematoxylin staining.) a, large-celled tuber- cle with giant-cell (c); an tubercle with central caseation and giant-cells (c.); d, epithelioid cells lying outside the tubercles in the adenoid reticulum (&) of the gland ; e, lymphoid cells. 123. The virus which engenders tubercle may be carried out of the lymphatic system into the blood, either from a tuberculous focus in a gland or a tuberculous ulcer in the thoracic duct. It may thus be con- veyed to distant organs. This will also happen when the virus passes directly from a tuberculous focus into an artery or vein. The result is an eruption of new tubercles either local or general. When the infection of the blood results in a general eruption of tuber- cles throughout all the organs or in most of them, the affection is called acute miliary tuberculosis. The various organs are beset more or less densely with minute (miliary) gray or translucent nodules, or here and there with yellowish-white opaque nodules with cheesy centres. This is the case whether the affection extend to several organs or to one, or even to a single arterial territory within an organ. All these nodules are made up of cells. In their earliest stages they 174 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. are nothing but little heaps of small round-cells (Fig. 33, unquestion- ably derived from the blood. Many foci maintain this character until they are mature ; all the cells do is to multiply. In other cases giant- cells and epithelioid cells (Fig. 32, a) are developed. In these cases, as in the others, the nodule ultimately becomes caseous. Very seldom does fibrous transformation or resorption occur. Diffused and wide-spread inflammatory disturbance of the circulation is very often associated with the eruption of the nodules. This is espe- cially the case in the pia mater, the serous membranes, and in the lungs, where the process is often accompanied by copious and diffuse exuda- Fig. 33.-Miliary Tuberculosis of the Liver. (Carmine staining.) a, mature tubercle in the portal sheath ; b, tubercle beginning to develop in a liver-cell. tion. In the liver, kidney, thyroid gland, etc., on the other hand, the changes elsewhere than in the immediate neighborhood of the nodules are usually but slight. [Ziegler has investigated the development of miliary tubercles occur- ring in very diverse structures, and maintains that their basis is always a collection of white blood-cells which have migrated from the veins and capillaries. These indeed often form the entire mass of the tubercle. In other cases the endothelia contribute something. When the nodule has reached a certain size it becomes difficult to make out certainly the behavior of the fixed cells of the tissues. He has not been able to con- firm the often-made assertion that miliary tubercle is specially apt to de- velop round the smaller arteries. The direct penetration of the tuberculous virus into the blood-vessels may be the result of tuberculous change in their walls. If a consider- able number of sections of phthisical lung be examined, there will here and there be found vessels whose walls are the seat of tubercles. If these penetrate the intima, they may then break into the blood-channel INFLAMMATION AND INFLAMMATORY GROWTHS. 175 directly. Weigert has shown that large venous trunks may be invaded in this way. There are two reasons for the fact that all organs are not simultane- ously and equally attacked when the blood is infected with the tubercu- lous virus. One is that the virus, though it is circulating in the blood, may not reach all the organs alike. The other is that all the organs are not equally predisposed to infection. The skin, for instance, seems to enjoy almost perfect immunity. General miliary tuberculosis is not an inevitable result of tuberculosis occurring in an organ. The rule rather is that the tuberculous process does not extend beyond the boundaries of the organ primarily affected, and the lymphatic glands pertaining to it. What most commonly leads to general infection of the blood is the disintegration of caseous tubercu- lous glands.] 124. Tubercle may be disseminated in other ways, and independently of the lymphatics and blood-vessels. Consider, for example, the mode in which it spreads on the surface of mucous membranes. It is easy to verify that solitary nodules, as well as tuberculous patches and ulcers of larger size developed in mucous membrane, do not long remain isolated, but soon give rise to new foci. These are situated not merely in the immediate neighborhood of the first, but often at a considerable distance from them. They may even appear unconnected with the first lesions ; while it is certain that they are not, at least in every case, propagated through the lymphatics. In pulmonary tuberculosis, for instance, which has already passed into the ulcerative stage, it is not at all uncommon for the mucous membrane of the air-tubes to become affected. This is especially apt to occur in the larynx, epiglottis, and at times in the pharynx ; and the affection often extends to the lower segments of the large and small intestines. When the kidneys become tuberculous, and contain caseous ulcerations, the ureters, bladder, seminal vesicles, and prostate may become consecutively diseased. In other cases the process commences in the latter organs and extends upward. From such instances it becomes plain that the infective virus may actually be transported along the surface of the mucous membrane. It attacks the spots at which it is allowed to linger, and penetrates the mu- cous tissue. It there sets up the specific inflammation manifested by the development of nodules, which disintegrate and produce ulcerations. Tubercle is in like manner disseminated on the surface of the serous membranes lining the great body-cavities. In their case it is obvious that the transport of the virus is favored by the normal movements and displacements of the contained organs. [It must be remembered, in connection with this question, that' all mucous membranes are not equally susceptible with regard to the tuber- culous virus. The mucous membrane of the mouth, pharynx, and oeso- 176 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. phagus is far less susceptible than that of the larynx and trachea. The stomach, duodenum, and bile-ducts, as also the urethra, are very rarely attacked. This is explicable now that we know that the virus is a special micro-organism (Art. 127) ; for the secretions of the stomach, duodenum, and common bile-duct are prejudicial to the development of bacteria. The oesophagus and urethra have this advantage-that they are continu- ally being swept clean, as it were. In the small and in the large intestine, where the process of absorption goes on most actively, the ingesta and with them any tuberculous sputa which may happen to have been swal- lowed, may lie a long time in contact with the mucous membrane. In the neighborhood of the larynx, the bronchial secretion continually ac- cumulates before it is coughed out, and the virus has thus abundant opportunity of attacking its mucous membrane. The bladder, in like manner, contains the accumulating secretion of the kidneys, while the urethra is only '£ flushed" with it from time to time. In addition to these factors, however, we must not leave out of account the possibility of special predisposition in the various structures and tissues.] 125. The clinical significance of tubercle. The processes just described (Arts. 118-124) are comprehended under the term tuberculosis. Tuberculosis, so defined, is distinguished by two chief characters. The one is anatomical, namely, the development of specific nodules ; the other is clinical, namely, the consecutive invasion of one or more parts of an organ or of the entire system. As a disease, tuberculosis is distinguished by its progressively destruc- tive tendency. It not only destroys gradually the organ first attacked, but it seizes by various routes upon other organs, or spreads throughout the organism. In addition to this clinical characteristic of progressive invasion, we have the anatomical characteristic-the tubercle. Tuberculosis is anato- mically an inflammatory process; but its course does not correspond with that of other inflammations. It is sharply distinguished from them by the development of nodules both in its original seat and in the parts that are secondarily attacked; and these nodules have a definite type and structure-they are cellular and non-vascular. There is still another characteristic, but we owe our knowledge of it not so much to observation at the bedside or at the post-mortem table, as to direct experiment. Villemin and Klebs were the first to show- what many investigators (such as Waldenburg, Cohnheim, Orth, Bollin- ger, Simon, Wilson Fox, Klein, and Burdon Sanderson) have since veri- fied-that tuberculosis is transmissible to animals. In other words, when animals are inoculated with matter from fresh or caseous tuberculous foci, they are forthwith attacked by a disease which, judging from its clinical course and anatomical products, is identical with human tuberculosis. This character determines the genus of tuberculosis in the classifica- tion of human diseases. It is an infective disease. INFLAMMATION AND INFLAMMATORY GROWTHS. 177 [The proposition that tuberculosis is anatomically an inflammatory process is disputed by many pathologists. There has always been a strong inclination to reckon tubercle among the true tumor-formations, like cancer. Such a view will hardly be maintained now. The genesis of tubercle, its cellular constitution, its whole life-history, are all in favor of its kindred with the inflammatory new-formations; they offer no fair grounds for comparing it with the tumors. We may add that the possi- bility of generating tubercles by inoculation with caseous or necrotic tu- berculous matter is a strong argument for regarding tubercle not as a tumor but as a product of inflammation. The fact of the transmissibility of tuberculosis to animals is now placed beyond doubt. It is true that the experiment does not always succeed; for though some animals are very susceptible, such as rabbits, guinea-pigs, and ruminants generally, others, like dogs, enjoy a certain degree of immunity. This only proves, not that tuberculosis is not infec- tive, but that the tuberculous virus is not a universal poison, capable of attacking each and every organism. This is likewise the explanation of the fact that physicians have observed comparatively few cases of quite indubitable transmission of the disease from man to man. Among human beings there are predispositions ; tuberculosis does not attack all with equal readiness. Nor must we forget, in criticising the clinical data, that it is scarcely possible to discern the exact time at which tuberculosis sets in. The clinical manifestations may not appear till long after the first infec- tion, when it is impossible to make out anything that throws light on the origin of the disease (Budd, Lancet, 2, 1867 ; Weber, "Clin. Soc. Trans.," 1874; Rindfleisch, "Virch. Arch.," vol. Ixxxv.; Burney Yeo, " Contagiousness of Pulm. Consumption," London, 1882). A short but very comprehensive summary of the evidence for the transmissibility of tuberculosis from man to man, and from man to lower animals, is given by Klein ^Practitioner, August, 1881). The student who desires to know the " state of the case " for the specific nature of tuberculosis immediately before Koch's discovery cannot do better than to consult this article. Inoculation experiments have been made in various ways. The tu- berculous matter has been inserted under the skin, into the peritoneal cavity, into the eye, and into the joints ; it has been mixed with the food; it has been pulverized and conveyed to the lungs with the respired air. References:-Villemin, "Gaz. hebd.," 50, 1865; "Comp. Rend.," 61, 1866; " fitudes sur la tuberculose," 1868 ; Lebert, "Bullet, de l'acad.," xxxii. ; "Gaz. med. de Paris," 25-29, 1867 ; Lebert and Wyss, " Virch. Arch.," vols. xl. and xli.; Roustan, " L'inoculabilite de la Phthi- sic," Paris, 1867 ; Feltz, "Gaz. med. de Strasbourg," 1867 ; Wilson Fox, "The artificial production of Tubercle," London, 1868 ; Chauveau, "Gaz. med. de Lyon," 1868; Langhans, "Die Uebertr. der Tuberculose auf Kaninchen," 1868 ; Waldenburg, "Die Tuberculose," Berlin, 1869 ; Vir- 12 178 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. chow and Hirsch, " Virch. Jahresber.," 1868-1870 (containing full and very useful references to previous research) ; " Trans. Path. Soc.," 1873 (an instructive discussion of current views) ; Klebs, "Virch. Arch.," vols. xliv., xlix.; "Arch. f. exp. Path.," i.; " Naturforscher-versammlung in Munchen," 1877 ; Cohnheim and Fraenkel, "Virch. Arch.," vol. xlv.; " Die Tuberculose vom Standpunkte der Infectionslehre," Leipzig, 1880 ; Klein, " Lymphatic System," ii., London, 1875 ; Tappeiner, Lippi, Schweninger, " Naturf.-versamm.," 1877 ; Tappeiner, "Virch. Arch.," vol. Ixxiv.; Orth, " Virch. Arch.," vol. Ixxvi.; Bollinger, " Arch. f. exp. Path.," i.; H. Martin, " Recherches sur le tubercule," Paris, 1879; " Arch, de Physiologic," 1881 ; " Revue de med.," April, 1882 ; Sanderson, " Re- port to Med. Off. of Privy Council," 1868-69 (republished in Practitioner, September to December, 1882 ; a critical summary of preceding researches is given in the latter of these reports); Kiener and others, " L'Union med.," 1881.] 126. Two important questions remain unanswered. Tuberculosis is an infective disease ; and it bears the anatomical character of a destruc- tive nodular inflammation. It is important for diagnostic purposes to know something more. Does the tuberculous inflammatory process mani- fest itself by the formation of nodules only ? Conversely, are all varie- ties of cellular nodules, exhibiting the general structure of tubercles, to be regarded as evidence of tuberculosis ? The second question is-What is the nature of the tuberculous virus ? In answer to the former ques- tion, clinical observation and experiments on animals have shown that all nodular eruptions are not tuberculous. Thus when small irritating for- eign bodies are introduced into the body of an animal, it sometimes hap- pens that a nodular affection is produced which anatomically simulates tuberculosis. Yet these nodules have in reality no kindred with true tubercles. The exciting cause is essentially different (Art. 127) from that which engenders true tuberculosis ; while neither the life-history of the nodules, nor the course of the process as a whole, corresponds with what is observed in human tuberculosis. Moreover, there occur in man certain nodular inflammations whose clinical course is radically different from that of tuberculosis, though the nodules in some degree resemble tubercles. The best known instance is lupus of the skin (Art. 132). In this affection perfectly typical tubercles are frequently formed; but they never induce tuberculosis in other or- gans, or general tuberculosis. In the peritoneum, again, there are now and then found tuberculoid nodules ; but they have probably nothing whatever to do with tuberculosis as a disease. While the domain of tubercular eruptions is on one hand somewhat wider than that of tuberculosis, on the other hand the domain of tuber- culosis goes beyond that of tubercular eruptions. In other words, there may be tuberculosis without isolated tubercles. It not infrequently hap- pens that in the course of tuberculous disease inflammatory patches are INFLAMMATION AND INFLAMMATORY GROWTHS. 179 formed, consisting of diffuse continuous granulations in which no tuber- cles can be detected. These patches must nevertheless be acknowledged to be tuberculous ; the clinical course of the process, and the life-history of the new inflammatory tissue, indicate this ; while tubercles may actu- ally be developed in later stages of the same affection. In such cases it may be hard to determine whether the process is really tuberculous ; especially in organs like the lungs, where the usual inflammatory changes are at all times apt to make the recognition of tubercle a difficult matter. Experimental inoculation, or the detection of the specific virus (Art. 127), can alone settle the question. As regards the latter test we may expect that the near future will bring us much additional information. It is fortunate that these ambiguous cases are not very numerous. Although, therefore, the anatomical notion of tubercle and the clinical notion of tuberculosis do not precisely correspond throughout their full extension, they do correspond in the vast majority of cases. It is a rule almost without exception, that tuberculosis is distinguished microscopically and on the post-mortem table by the presence of tubercles. [Much confusion has arisen in the discussions on tuberculosis from the assumption that the production of a nodular or tubercular eruption in an animal is necessarily the same as the production of tuberculosis. The result of the assumption has been that observers have fancied they have induced tuberculosis in animals by the introduction of all sorts of foreign bodies. The diagnosis is not to be based on the presence of nodules simply ; the life-history of the nodules and the general course of the whole process are also of essential importance (H. Martin, " Arch, de Phys.," 1881).] 127. We are now able to give a definite answer to the second ques- tion raised in the last article-What is the nature of the tuberculous virus ? At the meeting of the Berlin Physiological Society held on March 24, 1882, Dr. R. Koch communicated some result of his researches on tuberculosis, which constituted a distinct advance in our knowledge of its etiology. He announced that the tuberculous virus is a special bacillus (Bacillus tuberculosis, Art. 206). Its length is about a third of the diameter of a red blood-cell, and its breadth one-fifth to one-sixth of its length. In- dividual bacilli contain clear bright spores. The bacilli are chiefly found in fresh tubercles, more sparingly in older ones. Some of them lie within the cells and especially within the giant-cells, others lie outside. They are generally single and scattered ; at times they are found in prettily grouped clusters. By treatment with methylene-blue and vesuvin, they take up a different tint from that of the surrounding tissues. The tis- sues stained in the first instance with methylene-blue have their color discharged by vesuvin, while the tubercle-bacilli retain it. 180 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [Ehrlich, Gibbes, and others {Brit. Med. Journ., October 14, 1882) have devised simpler and speedier methods than Koch's for staining, and so detecting the bacilli. These methods are readily applicable to the clinical examination of phthisical sputa.] Koch has shown that the bacilli may be cultivated in the serum of ox-blood. The bacilli so bred may then be introduced into the bodies of various animals, such as rabbits, rats, and dogs, and tuberculosis is there- upon induced ; in other words, they are attacked by a disease character- ized by a progressive formation of cellular nodules. The nodules always contain the characteristic bacilli. In guinea-pigs the first appearance of disease is manifested ten days after inoculation. It may therefore be accepted as an established fact that tuberculosis is an infective disease, induced by the presence of a specific bacillus. In the light of this knowledge, the various theories which have been advanced with regard to the causation of tuberculosis become in some respects irrelevant. It will be matter for further experimental investiga- tion to determine the vital properties of the tubercle-bacillus. Among other points, it will have to be settled whether the bacillus can develop only within the bodies of men and other mammals, or whether it may not pass through some stage of its existence outside the body ; in other words, whether the disease is strictly contagious, i.e., transmissible di- rectly from one subject to another ; or whether it is due to something of the nature of a miasma-a poison which may develop outside the body. According to Koch, the bacillus can only be bred between the tempera- tures of 30° C. and 41° C. (8G° F.-105.8° F.). If this be so, it is hard to see how it can multiply outside the body. With regard to the trans- mission of tuberculosis from animals to man, it is to be noted that Koch has found the specific bacillus in the nodular growths which occur in the " pearly disease " of cattle (Perlsucht, or bovine tuberculosis). Clinical experience would seem to indicate that the tubercle-bacillus is no ordinary bacterium, such as may enter and affect any organism without distinction. It would seem rather as if infection occurred only where a definite predisposition exists, or where a considerable quantity of the virus is introduced. This predisposition may be local as well as general. The local predisposition may perhaps depend mainly on ante- cedent inflammatory change. A general predisposition is attributed to scrofulous subjects especially. These are persons whose tissues ex- hibit a certain frailty or susceptibility to injury, that makes them partic- ularly liable to chronic inflammatory disorders. It is, however, not at all uncommon for the term " scrofulous " to be applied to individuals actu- ally affected with tuberculosis, as well as to those who are only predis- posed to it. We may imagine the course of the infection to be this : The bacilli settle in a tissue accessible from without, pass thence into the deeper structures, and ultimately into the blood ; or, without any primary local INFLAMMATION AND INFLAMMATORY GROWTHS. 181 settlement, they may be taken up by the circulating juices directly, and carried to various parts ; wherever they settle they begin to develop, and so set up inflammation and the formation of cellular nodules. [Koch has found the bacillus not only in general miliary tuberculosis but in caseous pneumonia, caseous bronchitis, intestinal and glandular tuberculosis, 11 pearly disease," spontaneous and inoculated tuberculosis in various animals, and in the so-called scrofulous hyperplasia of lympha- tic glands. All these affections are thus to be included under the head of tuberculosis ; they are all the result of the same bacterial infection. Tuberculosis, from this point of view, is an infective disease not always manifested by the formation of tubercles. It may even appear as a purely local affection, and yet be unaccompanied by tubercles. If is of special interest to note that Koch has detected the bacillus in the sputa of phthisical patients. As the bacillus produces spores within the body, it is very likely that the virus exists and diffuses itself outside the body mainly in the form of spores. Koch finds that the bacilli grow very slowly, and after inoculation proceed to develop and multiply only when they reach a spot where they are not subject to jnuch mechanical disturbance or displacement. From this we may understand how it happens that many persons, though again and again exposed to the invasion of tubercle-bacilli, yet remain unin- fected. It is, moreover, conceivable that individuals in whose tissues inflammatory changes have already occurred are those who are most disposed to tuberculous infection. At the time when Koch was bringing his researches to an end, Baumgarten (£< Centralblatt f. d. med. Wiss.," 15, 1881) succeeded in detecting bacilli in tubercle by treating microscopic sections with dilute solution of caustic potash. He did not, however, go on to cultivate and inoculate the bacilli. Aufrecht had already described bacilli which he had found in tubercle (" Path. Mitth.," Magdeburg, 1881) ; but his de- monstration was likewise defective. He did not show that the bacilli were peculiar and specific as regards tuberculosis. It has been a much-debated question whether or not human tubercu- losis is identical with the bovine " pearly disease." Anatomically the pearly disease is a progressively advancing; affection in which nodes and nodules are formed. These may be single or agglomerated into masses as big as a potato. They are chiefly found in the serous membranes, as also in the lymphatic glands, lungs, and liver. In the serous membranes, the nodular masses are often pedunculated and pendulous. Caseation is not very common ; calcification much more so. The nodules are es- sentially cellular in structure, often contain giant-cells (Virchow, "Virch. Arch.," vol. xiv.), look very like tubercles, and may lie together in great numbers in the midst of a cellular stroma. A. C. Gerlach (" Jahresb. d. k. Thierarzneischule in Hannover," 1869) fed and inoculated rabbits and goats with matter from such nodules, and 182 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. on the strength of his experiments maintains that the pearly disease is transmissible to other animals and is identical with human tuberculosis. Schuppel ("Virch. Arch.," vol. Ivi.) and Creighton (" Bovine Tubercu- losis in Man," London, 1881), from microscopic comparison of tubercles and the pearly nodules, declare that they are identical. Orth (" Virch. Arch.," vol. Ixxvi.) arrived at the same conviction through experiments in which the animal was fed with the infective matter ; as did also Bollinger and Klebs ("Arch. f. exp. Path.," i.), Chauveau ("Jahrb. der. ges. Med.," 1872), and Baumgarten (" Berl. klin. Woch.,"49, 1880). On the other hand, Colin (" Compt. Rend., 1876), Gunther, Harms, and Muller (" Jahrb. der ges. Med.," 1873-74) obtained only negative results. Virchow ("Berl. klin. Woch.," 1880, and "Virch. Arch.," vol. Ixxxiii.) also made experiments by the method of feeding, but his results were ambiguous. He thinks that, so far as experiments have hitherto gone, the transmissibility of the pearly disease to other animals (by feeding them with diseased milk or meat) is not yet certainly established. Koch's observation of the specific bacillus in the pearly nodules seems to remove all doubt of their identity with tubercles. How far the bovine disease may be transmitted to man is not yet made out. The transmis- sion is at any rate possible, and that by various channels.] Syphilis. 128. Syphilis is an infective disease, originating in a fixed conta- gium. It starts at a wounded or abraded spot, gives rise there to certain local tissue-changes, and thence spreads through the entire system. The poison of syphilis occurs in the human organism only ; it is nowhere reproduced but within the human organism ; and it is conveyed to other individuals only by direct transference. When transplanted into a new organism, it excites inflammatory processes of the most diverse intensity and extent-from simple localized and transitory hypersemia to the formation of enormous exudations, or granulomatous growths, or exten- sive fibrous hyperplasias. If a child be procreated while the infection lasts, the disease may be transmitted to it from the mother's side as well as from the father's. The primary inflammatory tfocus is formed at the seat of infection as an indurated chancre or " hard sore." It is an ulcer with an hardened bacon-like or gristly base and margin. It generally begins as an excoria- tion, i.e., a slight and superficial loss of substance, and over this a vesicle or pustule is formed. In other cases it is developed from a node formed (for example) in the scar of a former ulcer ; this then breaks, giving rise to the characteristic ulcer with its hardened gristly base. In other cases again the ulcer is first formed, and the induration follows later on. The node or induration which forms the primary lesion of syphilis appears under the microscope at first as a dense infiltration of the con- nective-tissue with small cells (Fig. 34, a). The process may not advance INFLAMMATION AND INFLAMMATORY GROWTHS. 183 beyond this ; but in many cases the infiltrating cells proceed to develop further. From the small round-cells larger formative cells (Fig. 34, 5), and not infrequently giant-cells (c), are formed. The development does not advance beyond this point; the greater part of the affected tissue breaks down and ulcerates, or is reabsorbed. Some part of the cells go to form a cicatrix. [Nothing certain is known concerning the nature of the syphilitic virus. Klebs (" Arch. f. exp. Path.," x.) regards the disease as a para- sitic bacterial affection. Our histological knowledge of syphilitic growths Fig. 34.-Section of a Syphilitic Hard Sore, x 350. {Alum-carminepreparation.) a, infiltration with round-cells ; 1, large uninuclear; c, multinuclear, formative cells. is mainly due to Virchow (" Krank. Geschwiilste," ii.), E. Wagner (" Arch. d. Heilk.," iv., 1803), Auspitz and Unna (" Vierteljahrsschr. f. Derm, und Syph.," iv., 1877). See also Baumler, " Ziemssen's Cyclo- paedia," vol. iii. ; Van Oordt, " Des tumeurs gommeuses," In. Diss., Paris, 1859 ; Cornil and Ranvier, "Man. of Path. Hist.," vol. i.] 129. After a certain time the "initial sclerosis" or hard sore is fol- lowed by inflammations of the lymphatic glands, skin, and mucous mem- brane. These are the "secondary symptoms." Still later appear syphilitic inflammations of the viscera and bones. These are the "ter- tiary symptoms." The various inflammations are for the most part similar to other, non-syphilitic, inflammations. Certain special granulo- matous formations are also developed which are called syphilomata (Wagner) or gummata, and condylomata. The syphilitic condyloma (condyloma latum or mucous patch) is a raised level patch on the skin or mucous membrane, due to inflamma- tory change in the epidermis and corium, or in the epithelium. The upper layers of the corium, and especially the papillae, swell up greatly owing to infiltrations of cells and liquid exudations. The cutis appears as a loose sodden gelatinous tissue infiltrated with cells (Fig. 35, i and A'). There is no true granulation-tissue as a rule, for no organization of the cellular material takes place, and no new vessels are formed. In condy- lomata of the mucous membranes, the tissue may take on something of 184 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the look of granulations owing to abundant cell-production. The epi- the liumis usually swollen (Fig. 35, e, f, g) and infiltrated with cellular and liquid exudations. The syphilitic gumma in its earlier stages is histologically very similar to the condyloma. The gumma is a circumscribed patch of mor- bid tissue, not unlike granulation-tissue. It occurs chiefly in the perios- teum, muscles, brain-substance, and membranes, as well as in the paren- chymatous organs of the abdomen, such as the liver, spleen, and testis. Fig. 35.-Condyloma Latum Ani, or "Mucous Patch." x 100. (Aniline-brown staining.) a, horny layer ; 6, rete Malpighii; c, corium ; d, loosened horny layer infiltrated with leucocytes: e. rete Malpighii swollen and (/) infiltrated with cells ; ff, degenerate epithelial cells containing leucocytes : A, granular coagula; i, papilla swollen and infiltrated with cells and exuded liquid ; k, corium infiltrated with cells, exuded liquid, and coagula; Z, lymphatic distended with coagula; m, sweat-gland. The relative proportion of cells in the gumma varies with its site. Varieties which are poor in cells, such as are found at times in bone, are soft and gummy in texture. On section they have a gelatinous look, the liquid constituents exceeding the cellular in quantity. The older surrounding tissue undergoes in part a mucoid change. Varieties rich in cells, met with chiefly in the pia mater and arachnoid, and the spleen, form nodes or patches which are translucent, gray or whitish, or grayish- red in color, and rounded (spleen) or irregular (brain-membranes) in shape. They have in fact the exact appearance of granulations. In the affected organs or tissues there are usually found, in addition to the gummata, more diffused and extensive inflammatory changes. INFLAMMATION AND INFLAMMATORY GROWTHS. 185 130. These syphilitic granulomatous growths are generally of a very perishable or unstable nature. Frequently there is no proper granulation- tissue developed ; that is to say, no vessels are formed and no further development of the extravasated leucocytes takes place. The leucocytes usually perish by fatty degeneration. Small infiltrated patches may of- ten disappear by reabsorption. In other cases, as in the bones, suppur- ation or fatty necrosis and ulceration is the issue. In larger patches abounding in cells, caseous nodes are not infrequently formed ; they may be either rounded and spherical or irregular in shape. If the caseous process is still in a comparatively early stage, these patches are found sur- rounded by highly cellular granulations. After a time these latter pass into dense fibrous tissue (Fig. 36), and contract into a narrow zone sur- rounding the caseous patch. Lastly, this zone may be further trans- formed into connective tissue of a more ordinary type. Caseous nodes, thus imbedded in an irregular puckered capsule of scar-tissue, are found most commonly in the liver and testis. It is these scar-surrounded caseous nodes which are chiefly referred to when gummatous nodes are spoken of. They have of course ceased Fig. 36.-Gumma of the Liver undergoing Caseation. + 25. a, gumma enclosed in an irregular cap- sule of scar-tissue; b, artery with thickened wall; c, obliterated portal vein. to be strictly gummatous, for they contain merely the caseous detritus of the original cellular gumma. The caseous change often involves not merely the cellular new-formation, but also the normal tissue of the af- fected organ. The node comes thus to contain more than the necrotic remains of the true gumma ; it includes all or most of the proper or spe- cific tissue affected and destroyed by the original infiltration. This common issue of syphilitic inflammation in disintegration and necrosis seems to depend chiefly on the nature of the virus which pro- duces the disease. It is not, however, impossible that another factor may lie in the aptness of the vessels and especially the arteries to be attacked by the specific inflammation. Wherever granulations are formed or hy- perplasia set up in consequence of syphilitic inflammation, the vessel- walls and chiefly the intima are observed to thicken. The lumen is thus narrowed, and often entirely occluded (Fig. 36, b and e, and Art. 297). 186 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [On syphilitic disease of the arteries see Greenfield, etc., " Trans. Path. Soc.," vol. xxviii.; Heubner, " Die luetische Erkrankung der Gehirnarterien," Leipzig, 1874; Lancereaux, "Gaz. des Hop.," 21, 1876.] Leprosy. 131. Leprosy, lepra or elephantiasis graicorum, is a disease distin- guished anatomically by the formation of nodes and tubers in the tissues. These, when cutaneous, are usually seated on the surfaces exposed to the air-the face, hands, and feet. They may at times occur elsewhere. The subcutaneous tissues, nerves, mucous membranes, and viscera may also be affected. The nodes may reach the size of a walnut. When a node is about to form in the skin, there appears first a red spot, which becomes bluish and then brown ; the underlying tissue be- comes meanwhile thickened and indurated. The swelling then increases, and the patch becomes gradually transformed to a firm red protuberance, which later on becomes softer and paler. The basis of the node is made up of cellular granulation-tissue, lying immediately beneath the epidermis. It is spread in a uniform layer, or sends down cellular processes into the deeper structures. In color it is grayish-white and somewhat translucent. The cells are of various sizes according to their stage of development. When the nodes break down, leprous ulcers are formed, though these are more commonly the result of external injury. Fatty metamorphosis of the cells and resolution of the tumor thereby are not unknown, but the process is very slow. The nodes of the mucous membrane are more apt to ulcerate than those of the skin ; this occurs, for example, inside the nose, and in the conjunctiva, mouth, and larynx. Leprous growths in the nerve-sheaths may lead to disturbance of the nerve-functions ; we may thus have local amyotrophy and anaesthesia, as in Lepra anaesthetica. Visceral leprosy is rare. Armauer Hansen and Neisser have discovered that leprosy depends on the presence of a specific bacillus (Bacillus leprae) in the affected tis- sue. The bacillus is found in all leprous foci (Neisser), generally en- closed in the larger cells. The hereditariness of leprosy has not been proved. It is but slightly contagious ; yet in certain regions it is en- demic. It is nowadays rare in Europe ; Norway and Sweden, Finland, and the Baltic provinces of Russia, are the regions where it is most prev- alent. It occurs (but more rarely) in special districts of Greece and Italy. It is prevalent in Central and South America, and in Southern Africa and Asia. [Virchow's " Onkologie " (vol. ii.) contains a full account of leprosy, from which the above details are chiefly drawn. Thoma (" Virch. Arch.," vol. Ivii.) gives a description of the histological characters of the disease INFLAMMATION AND INFLAMMATORY GROWTHS. 187 agreeing in essence with Virchow's. Neisser's discovery of the Bacillus leprae was announced in the " Breslau, arzt. Zeitschrift," 20 and 21, 1879 ; Armauer Hansen's in "Virch. Arch.," vol. Ixxix. See also Neisser, " Virch. Arch.," vol. Ixxxiv. The bacilli have been found in the nodes of the skin, oral epithelium, and larynx-as well as in diseased foci in the nerves, cartilages, testes, lymphatic glands, liver, and spleen. Neisser has inoculated rabbits and dogs with leprous matter, and so produced inflammatory nodes corresponding with those of human leprosy. He supposes that the bacilli enter the system as spores, and develop wher- ever they find a suitable nidus, especially in the lymphatic glands. Thence they invade the entire body. Kdbner (" Virch. Arch.," vol. Ixxxviii.) found the bacilli in the blood. His attempts to transmit the disease to monkeys did not succeed. He is thus inclined to question Neisser's demonstration of its transmissibility. In Lepra anaesthetica the skin is usually smooth and shining. This form has therefore been distinguished as L. Icevis or glabra. White or brown stains appear on the skin at times, probably at the site of a former infiltration. This variety is described as Lepra maculosa ; the patches as morplweae nigres or albas (not to be confounded with the skin disease Morphoea).] Lupus. 132. Lupus (or 11 noli me tangere ") is an affection of the skin and contiguous mucous membranes. The surface becomes red, and this is fol- Fig. 37.-Section of Skin through a Lupus-patch, a, normal epidermis; b, normal corium with sweat gland (i); c, focus of lupus-tissue; cl, vascular nodule surrounded by diffuse cellular infiltration; e, non- vascular nodule; f, strings of cells; g, lupous ulcer ; h, proliferating epithelium. lowed by the formation of large or small nodules (Fig. 37, c?) with more diffused swellings. Granulation-tissue is formed in the corium and sub- cutaneous connective tissue. The granulations are generally vascular, the cells small, spherical, and 188 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. lymphoid ; but at times numerous epithelioid cells and giant-cells may also be found. In the latter case, nodules may also develop having the exact appearance of tubercles. Surrounding the true granulomatous focus there are found nests and strings of cells following the course of the lymphatics (Fig. 37, e, f). When the subepithelial granulations have reached a certain degree of development, they begin to break down and ulcerate (Fig. 37, gY It seldom happens that ulceration is averted by reabsorption or cicatrization. The exciting cause of lupus is unknown. The general course of the process, and especially its progressive character, seem to indicate that it is due to some virus capable of reproduction. [Schuller (" Centralb. f. Chir.," 49, 1881) has found certain micrococci in lupus-tissue, which he holds to be the cause of the affection. His ob- servations are not, however, enough to establish the fact with certainty.] Glanders. 133. Glanders (or Equinia) is a contagious disease of the horse, communicable to man by direct transmission. Glanders and farcy are manifestations of one and the same infective disease ; the first affects chiefly the nasal mucous membranes, the second the skin. The initial lesion in the horse is usually situated in the nasal mucous membrane. The submaxillary gland is then affected ; and then, by meta- stasis, various other organs. The first effect of the infection is to give rise either to wide-spread cellular infiltration of the mucous membrane, or to subepithelial nodules from the size of a millet-seed to that of a pea, and not unlike those of lupus. In chronic farcy larger nodes and nod- ules form in the skin, and sometimes link themselves into vermiform cords (" corded veins "). The epithelial nodules are very unstable in structure. The cellular elements of which they are built up maintain throughout the characters of lymphoid cells or pus-corpuscles. Owing to fatty change, disintegra- tion, softening, or suppuration in the nodules, ulcerations are soon formed which have a yellowish infiltrated base. These grow by progressive nodular (or simply diffused) infiltration of their borders, followed by gradual disintegration. In this way contiguous ulcers may become con- fluent. In horses that have died of glanders, the mucous membrane of the nasal septum is beset with large irregular excavated ulcers with eroded edges and grayish or yellowish bases. In addition to these, there are other minute lenticular ulcerations, and gray or yellow nodular patches on the point of breaking down. The whole process is near akin to that of suppurative inflammation. The ulcers may heal up by the for- mation of irregular puckered cicatrices. The cervical glands are always inflamed and swollen. Among the viscera the lungs are the most liable to be affected. They contain either INFLAMMATION AND INFLAMMATORY GROWTHS. 189 nodes with caseous detritus in the centre and a grayish cellular per- iphery ; or on the other hand lobular pneumonic patches of a light gray or blood-stained color, or opaque and yellow from fatty and caseous change. At times the alimentary mucous membrane contains nodes of various sizes, composed either of light gray cellular tissue, or of opaque yellowish-white caseous or suppurative matters. In farcy, which is usu- ally chronic, the nodes ("buttons" or "buds") formed in the skin and muscles are made up of small-celled granulation-tissue, which later on undergoes retrogressive change, and becomes caseous or breaks down. In man, as in the horse, infection with glanders-poison is followed by the formation of nodes and nodules, especially in the nasal cavities and frontal sinuses, and in the larynx and trachea. At the same time vesicu- lar and pustular eruptions appear on the skin, followed by phlegmonous ab- scesses in the skin and muscles. The viscera are also affected in like manner. The development of the granulation-tissue is generally very imperfect ; the inflammation tends rather to take on a suppurative char- acter. In chronic farcy large nodes (" farcy buds ") are formed in the skin and muscles. When these break down they give rise to indolent and obstinate ulcerations. [For a fuller description of equine glanders and farcy see Youatt, "On the Horse," London, 1859 ; Fleming, "Man. of Veterin. Sanitary Science," vol. i., London, 1875 ; on the human affection see Poland, " Holmes's System of Surgery," vol. i. , The nature of the glanders-poison is unknown. See Villemin (" Etudes sur la tuberculose," Paris, 1868), Bollinger (" Ziemssen's Cyclopaedia," vol. iii.), and Piltz (" Die Seuchen und Herdekrankheiten," Stuttgart, 1882).] Actinomycosis. 134. Actinomycosis is a progressive inflammatory affection, set up by a certain fungus, the Actinomyces. It results in the formation of granulations and fibrous tissue, and in suppuration. It attacks human beings, cattle, and swine, and may be communicated to cattle by inocu- lation. The disorder was first recognized and described in man by Israel (1877), and in cattle by Bollinger (1877). The parasite which causes the disorder is a peculiar fungus. It first appears as a tufted rosette of radiating pyriform or club-shaped struc- tures ; these are either simple or divided by dissepiments, and are of con- siderable bulk. They are possibly the conidia (Art. 213). The fungus on reaching its full development appears as a peculiar gland-like body, with the outward form of a mulberry. It is produced by the aggregation of the club-shaped conidia ; these spring in all directions from the fila- ments of a matted tuft which we may provisionally call the mycelium. 190 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. and are thus crowded into a compact mass. The true botanical position of the fungus is as yet undetermined. When the actinomyces settles in a tissue, it at once sets up inflamma- tion in its neighborhood. While the spore is developing its mycelium and its bunch ("gland" or "core") of conidia, a nodular inflammatory focus is formed around it, which in its structure exactly resembles a tuberculous nodule. Recent nodules consist chiefly of round-cells ; in less recent ones the zone in contact with the fungus-core contains epithe- lioid cells and giant-cells. The core is yellowish in tint, and in later stages of the process it often becomes calcified. When the nodules increase greatly in number and become confluent, the internodular inflammation also extending, large areas of inflamma- tory swelling are formed. In many cases, and especially in cattle, scar- like bands of fibrous tissue may be formed in the spaces between the nodules. The nodules themselves usually break down and suppurate. If the tendency to further development be strong enough, we may have, in- stead of suppuration, large nodular patches of new tissue formed. These may grow for weeks or months and finally become as large as the fist, or larger. The tumor is made up partly of coarse fibrous tissue, partly of granulations, with the intermediate stages. It always contains small pus-cavities and other excavations, in which the fungus-cores are found as small white or yellow greasy-like1 masses lying among the purulent detritus. If on the other hand the tendency to disintegration and suppuration prove the stronger, we have formed large sacculated cavities with branch- ing intercommunicating fistulae. The walls of these are lined with gran- ulations and hyperplastic fibrous tissue, containing here and there colo- nies of the fungus. 135. In the case of cattle the disorder attacks chiefly the lower jaw ; then the upper jaw, tongue, pharynx, larynx, oesophagus, stomach, and intestinal wall. The skin, the lungs, and the subcutaneous and inter- muscular connective tissue are also liable to invasion. In these sites it generally gives rise to nodular tumors of various sizes, such as we have described. Till the true nature of the disease was made out, these were described by a multitude of names, such as osteo-sarcoma, bone-canker, bone-tubercle, fibro-plastic degeneration, woody-tongue, lingual tuber- culosis, lymphoma, fibroma, spina ventosa, etc. In the cases observed in the human subject the disease has chiefly attacked the soft parts of the neck, the thorax near the spine, the mediastinal tissue, and the lungs. In one case the infective matter had entered the blood, and gave rise to metastatic foci in the viscera (Ponfick). The inflammatory growths seldom reach any great size in man ; they are apt rather to break down early. In the cases referred to, cavities and fistulae were formed, some of them subcutaneous and some extending deeper. Among their purulent contents were found the fungus-cores. Where the process invaded the bone, it led to destructive caries ; this INFLAMMATION AND INFLAMMATORY GROWTHS. 191 was notably the case with regard to the vertebrae. In all the affected regions the destruction of tissue was very considerable. As regards the genesis of the disease, it seems very probable that the mouth is the starting-point of the infection. Israel, Johne, and Ponfick affirm that in healthy individuals the specific fungus is now and then found lying in the follicular crypts of the tonsils. It has also been dis- covered in concretions from the lacrimal duct, and in hollow teeth. The observations of the above authors, with those of Bollinger, make it prob- able that infection often follows upon wounds of the oral cavity {e.g., those left after the extraction of teeth). Israel believes that the spores or fungi may be inhaled, and so give rise to the disease in the lungs. Clinically speaking, the disease is chiefly marked by its chronic course and local malignancy. Metastasis is not common. [Israel's researches were published in "Virch. Arch.," vols. Ixxvi., Ixxviii.; Bollinger's in the " Centralb. f. med. Wiss.," 27, 1877. Since then the affection has more than once been observed in man. Johne and Ponfick have been the chief writers on the human affection. Johne de- monstrated the inoculability of the disease in animals (" Deutsch. Zeitsch. f. Thiermed.," vii., 1881). Ponfick has quite recently published a mono- graph (" Die Actinomycose des Menschen," Berlin, 1882), in which the published observations on the disease are brought together; light is thrown on its etiology by new observations and experiments ; and the significance of the various morbid processes is explained. Gannet gives a useful summary in Boston Med. and Surg. Journal, August 31, 1882. Pflug lately described a case of actinomycosis in a cow, which took the form of miliary nodules disseminated through the lungs (" Cent. f. med. Wiss.," 14, 1882); Sink {ibid., 46, 1882) gives another case, in which the nodular affection was confined to a part of one lung.] SECTION VI. TUMORS. CHAPTER XXV. GENERAL CONSIDERATIONS. 136. In Arts. 79-92, under the heading of Hyperplasia and Regenera- tion, we discussed a series of progressive or formative disturbances of nutrition. Some of these were the result of normal development carried to an excessive degree. Others seemed due to the resumption or inten- sification of processes of growth which had been interrupted or enfeebled. These processes led to the formation of new tissue, which either re- sembled exactly the matrix-tissue from which it arose, or at least was composed of the same elements. Another mode of tissue-formation was discussed in the last section, under Inflammation. This process, as we saw, gave rise only to a single form of new tissue ; it resulted in the development of granulations and fibrous tissue from them. , The mode of tissue-formation which leads to the development of a tumor, neoplasm, or new growth in the restricted sense of the term, is not comparable either with hyperplastic proliferation or with inflamma- tion. It differs from the former in this, that the new tissue is not simi- lar to the matrix-tissue, but specifically different from it. A true tumor or neoplasm proper is always composed of tissue differing in type from that out of which it grows. It is distinguished from inflammatory tissue by the great variety of forms it may assume, and by the mode of its genesis. The diversity existing between the neoplasm and the matrix is mani- fested in two ways. First, the new-formed tissue appears as a more or less sharply bounded and defined mass. Secondly, its texture and struct- ure differ from those of its matrix, and generally to such an extent that the difference is recognizable with the unaided eye ; it is of course still more plainly marked under the microscope. These two marks are gener- ally enough to determine the diagnosis of tumor, though not invariably. In a whole series of new-formations, it is difficult or even impossible to distinguish anatomically between hyperplastic or inflammatory tissue and true neoplasm. The distinction must in such cases be based on the life- history of the tissue in question. It should be noted-by way of distinction between inflammatory tis- sue and a neoplasm-that the latter does not originate in extravasated 196 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. blood-cells, so far at least as its essential elements are concerned. As distinguished from hyperplasia, the genesis of a neoplasm is not depend- ent on exaggerated function or increased activity in the affected organ ; moreover it does not retrogress, but continues to grow on without reach- ing any particular or typical termination. [The term tumor, or neoplasm, has been very differently interpreted by different writers. Virchow, for example, includes all hyperplasias and inflammatory or granulomatous formations among the tumors ; while Cohnheim definitely excludes them. Others take up a middle position. This difference of view is closely connected with the different theories held concerning the etiology of tumors (Arts. 177-181). We think with Cohnheim that it is better to narrow the meaning of the term tu- mor so as to exclude hyperplasias and the infective granulomatous growths. References: Virchow ("Die krankhaften Geschwiilste ") ; Lucke (" Handb. d. Chir. v. Pitha u. Billroth," vol. ii.) ; R. Meier (" Lehrb. d. allg. Path.," 1871); Cohnheim ("Allg. Path."); Paget ("Surgical Path.").] 137. Tumors have been distinguished by various names according to their external form. Nodular tumors are made up of circumscribed nodes or nodules, single or grouped. Nodules of the size of a millet- seed are called miliary ; smaller ones submiliary. If the neoplasm is im- perfectly marked off from its matrix, and extends into it by continuous or disconnected outgrowths, it is called infiltrating. The terms nodular and infiltrating are not, however, antithetical. A tumor may have nodes and nodules, and yet infiltrate the tissue in which it lies. This latter depends on the mode of growth. If the tumor increase interstitially (" central " or "expansive" growth), it merely compresses and thrusts away the surrounding tissue, but does not infiltrate it. If it grows at the periphery by including ever fresh portions of the matrix-tissue ( "ap- positional " or " eccentric " growth), it will give rise to the appearance of infiltration. A tumor seated on any of the surfaces of the body, and protruding so as to form a segment of a spheroid, is said to be tuberous. If the base be smaller than the body of the tumor, it is fungous. If stalked, it is polypous or pedunculated. If it consist of several small and close- set protuberances, like the papillae of the skin, rising from a common stalk or base, the tumor is called warty, verrucose, papillomatous, or briefly a papilloma. If the papillae are very long and branched, it is described as a dendritic or ramifying growth. 138. The texture and structure of tumors are very various. A large group consists of tissues resembling some of the adult or embryonic con- nective tissues ; they are thus made up solely of mesoblastic elements. Such are distinguished as histioid tumors, or more simply as connec- TUMORS. 197 tive-tissue tumors. Some of them are firm and of the texture of fibrous tissue, cartilage, or bone. Others are soft and contain adipose tissue, mucous tissue, or embryonic or indifferent tissue. Very soft varieties, resembling brain on section and yielding a white creamy juice on being scraped, are described as encephaloid or medullary. Not uncommonly a tumor may have a different texture in different parts of it ; it is then spoken of as a mixed tumor. It arises when two distinct tissue-forms are simultaneously developed, or when a single tissue has undergone partial transformation into another. A second group of tumors are more complex in structure. They con- sist not only of mesoblastic elements, but of epiblastic and hypoblastic elements in addition ; in other words they contain elements derived from epithelial cells. They are therefore described as epithelial tumors, in contradistinction to the connective-tissue group. Inasmuch as they ex- hibit a certain similarity of structure with various organs of the body, they have also been called organoid tumors. Their structure may often be recognized with the naked eye. On section the general appearance is that of a dense basis-substance, built up of reticulated bands and trabe- culae, and containing within its meshes a substance of different color and softer consistence. The latter often takes the form of a milky or creamy juice. Medullary forms are also met with in this group. [A tumor resembling its matrix-tissue in texture Virchow calls homceoplastic ; one which differs widely is heteroplastic. The latter term implies that in normal circumstances tissue like that of the tumor never occurs at all at the spot in question ; or at any rate not at the par- ticular stage of development reached at the time in question. A tumor may thus be heteroplastic as regards its site (heterotopic), or as regards its date (heterochronic). By excluding the mere hyperplasias from the category of tumors, we are bound in strictness to regard all tumors as heteroplastic ; they never are of exactly the same structure as the matrix-tissue. A division of tumors into homologous and heterologous growths has been proposed. Homologous growths are such as resemble some normal tissue of the body ; heterologous growths such as resemble no mature normal tissue. Unless a homologous growth is heterotopic it is not distinguishable from a hyperplasia. A growth which is strictly heterologous must be heteroplastic.] 139. Every tumor is developed from pre-existing tissue-cells by pro- liferation ; in some tumors new blood-vessels are also formed. The pro- cesses of cell-division and of vascularization are identical with those de- scribed in Arts. 74 and 86. Nuclear subdivision is indirect ; new vessels are formed by off-shoots from existing ones. Tumors usually develop from small beginnings. It is rarely that their site of origin extends over an entire organ. From this it follows that they do not usually lead to an enlargement of the organ as a whole, but 198 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. rather tend to form definite nocles or protuberances. Some grow with great rapidity ; others slowly and intermittently. There is no limit to their growth ; they often reach enormous dimensions. They may cease to grow at all for years together, and then suddenly begin again. Neoplastic or tumor-tissue is very liable to retrogressive changes ; this is especially true of quickly growing cellular tumors. All the retro- gressive changes which affect normal tissues are observed in tumors- fatty degeneration, mucoid degeneration, necrosis, caseation, disintegra- tion, softening, liquefaction, gangrene, infarction, calcification, pigment- ation (as in melanoma), etc. Inflammations are also very common in tumors. Any of these processes may lead to partial destruction of a tumor. Cavities or ulcers are often formed in consequence of softening, and the new tissue may thus be disintegrated and destroyed-slowly or rapidly as the case may be. It is unfortunate that this process does not usually bring about the removal and eradication of the tumor, especially in the so-called malignant forms. The centre may break down, but the peri- phery continues steadily to advance. It may even happen that the peri- pheral advance is accelerated by the inflammatory disintegration of the central parts. [It is highly probable that, during the development of a neoplasm, the walls of the blood-vessels are somehow damaged or impaired. In support of this it may be mentioned that in the neighborhood of tumors we always find aggregations of small extravasated leucocytes. The manner in which this impairment of the vessel-walls is brought about remains unknown.] 140. Most tumors are solitary. In other words, there is originally but a single primary tumor. It is less frequent to find two tumors grow- ing in an organ simultaneously, or in quick succession. In the latter case we must suppose that appropriate conditions arise at the same time at the different sites. Now and again it happens that several tumors, all of different structure, appear simultaneously in the same person. From such multiple primary neoplasms we must of course distinguish what are called metastatic formations. Metastasis in this case implies a secondary neoplastic eruption, resulting from the transmission of ele- ments of the original or parent tumor to a remote part of the body, and the development of a daughter-tumor from these germinal elements. The germ or other virus given off by the parent tumor is conveyed to other regions through the lymphatics, or through the blood-vessels. Ac- cording to the channel of transport, we find metastatic affections in the lymphatic vessels and glands which receive the infected lymph ; or in remote organs irrigated by the infected blood, either directly or after passing through the heart. Thus in cancerous disease of the intestine we find secondary nodules developed in the liver, through the medium of TUMORS. 199 the portal system ; from the liver some germs may even find their way into the lungs. The germinal elements usually reach the blood by the direct penetration of the tumor-tissue into the lumen of a blood- vessel. The development of the daughter-tumor starts unquestionably from these transported germs. This is probable d priori from the fact that the metastatic or secondary tumor has always the same structure as the primary. The germs are, furthermore, essentially composed of cells in a condition of vital activity. The share taken by the matrix-tissue in which the germs are deposited is not always the same. In all cases it must furnish the necessary nutriment and blood-vessels, for without these no new growth is possible. But it very often furnishes other elements, and especially connective tissue. Proliferation is set up around the transplanted germs, and tissue is thereby formed ; while migratory leu- cocytes generally contribute something to the whole. The secondary tumors developed may vary greatly in number. They are usually marked off definitely from the surrounding tissue ; it is very uncommon for metastases of the kind to take the form of diffuse infiltration. This hap- pens (if at all) in the case of bone, which may be transformed into tumor- tissue by secondary change affecting almost the entire skeleton. Metastases are not invariably produced by all tumors ; many of these never extend beyond the limits of their primary seat. The clinical char- acter of benignancy or innocency is generally correlated with this prop- erty of tumors ; malignancy is a character of the metastatic varieties. Other marks of malignancy are the tendency to infiltrate and so destroy the surrounding tissue, and the tendency to recur after apparent extir- pation. [Malignancy, or the tendency of a tumor to invade the neighboring tissue and to produce metastatic tumors, is usually regarded as an inher- ent property of the tumor. Cohnheim has recently expressed a different opinion (" Allg. Path.," i.). He tries to explain malignancy by assum- ing that the physiological resistances to invasion are somehow dimin- ished. Germs transplanted into fresh tissue are sure, he thinks, to perish in consequence of the normal chemical or metabolic changes which go on in the tissue. They can only develop when these metabolic changes cease to be normal. His main ground for this view is derived from an experiment made by himself and Maas (" Virch. Arch.," vol. Ixx.). They introduced pieces of living periosteum into the pulmonary vessels, and found that they grew for a time, but were ultimately absorbed and disap- peared. The diminished resisting power of the tissues may be either congenital or acquired. The latter is especially the case in advanced age. Ziegler is unable fully to agree with this view. Though the condition of the tissue has undoubtedly a great influence on the development of a germ transplanted into it, yet this alone cannot determine the malignity 200 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. of the parent tumor. It surely depends on the structure and texture of the tumor whether its germs can be carried off at all and transported by the stream of lymph or blood. And the faculty of developing in proper circumstances must be inherent in the germs themselves. Zahn (" Sur le sort des tissus emplant&s dans 1'organisme," Geneva, 1878) found that foetal tissues continued to grow for a time when introduced into the body of an animal. Leopold has quite recently confirmed this observa- tion (" Virch. Arch.," vol. Ixxxv.). Pieces of living tissue, taken from embryo rabbits and transplanted into other rabbits, are in part absorbed, and in part continue to grow. The latter is especially true of embryonic cartilage.] 141. The formation of a tumor is always more or less fraught with injury to the affected organ, and in many cases to the entire system. The least harmful tumors are those which grow slowly and by expansion, so that they merely compress the surrounding tissue. If this is expansi- ble or yielding, like the skin, the resulting changes may be trifling. But it is not rare for the compressed tissue to become atrophied or absorbed. If the neoplasm be an infiltrating one, the surrounding tissue suffers much more seriously. It either perishes outright, or begins to prolife- rate and so contributes materials to the general growth. This is espe- cially the fate of tissues which have specific functions ; the specific ele- ments die, while the fibrous or connective framework persists and becomes hyperplastic. A tumor requires to be fed if it is to grow ; hence the organ in which it is placed and the system generally are deprived of a certain proportion of nutriment to supply the tumor. If growth is slow the deprivation is unimportant, but it may become grave in the case of rapidly increasing tumors. The seat of the tumor is of serious import. It need hardly be said, for instance, that a tumor growing in the brain or spinal cord has an alto- gether different significance, so far as life is concerned, from that of one developed in the skin. So also a tumor in the oesophagus obstructing the passage of food, or one in the stomach interfering with digestion, will lead to more serious results than one, say, in the bone of the finger. In the one case the function of an essential organ is impaired by the presence of the tumor, in the other the effects are merely local. Metastatic or secondary formations have always an unfavorable signi- ficance. As the neoplastic foci become more numerous, so also do the organs exposed to the risk of injury by pressure, invasion, or abstraction of nutriment. Disintegrative changes and ulcerations connected with tumors are specially destructive. There is nearly always an active secretion and loss of substance from the surface of such ulcers, and the body is re- duced by the constant drain. Moreover, it is not uncommon for putre- factive changes to be set up in the products of disintegration, and then TUMORS. 201 the risk of blood-poisoning by absorption of septic matters becomes con- siderable. Tumors may thus impair the function of essential organs, or give rise to a serious drain of matter from the body, or bring about a kind of blood-poisoning through the absorption of deleterious products of decay; in any or all of these ways the general nutrition may be profoundly dis- turbed, and the patient fall into grave ill-health. This is spoken of as the cachexia of tumor. It may become so profound that the patient dies of exhaustion. CHAPTER XXVI. TUMORS DEVELOPED IN MESOBLASTIC TISSUES-CONNECTIVE- TISSUE TUMORS. a. Fibroma. 142. A fibroma is a tumor made up of fibrous tissue. It usually takes the form of a sharply defined node or lump, and occupies a part only of the organ in which it is seated. More rarely the organ (as e.g., the ovary) becomes transformed throughout into a fibrous mass. Fibro- mata occurring on epithelial or mucous surfaces often take a papilloma- tous form. The fibroma is of very varying consistence, according to the texture of its component tissue. It is often very firm and tough, grating under the knife, and having a glistening gristly look on section (desmoid fibroma). In other instances it may be soft and flabby, with a grayish translucent section. Other specimens will be found in which the scat- tered fibrous bands are dense and white and glistening, but the general structure is loose and incompact ; so that the tumor, as a whole, is ren- dered limp and flabby. All varieties of intermediate forms occur be- tween the firm and the soft, and even within the same tumor different parts may be of different consistence. The firm varieties are seen under the microscope to be made up chiefly of large coarse fibrous bundles, in- terspersed more or less thickly w'ith cells whose protoplasm is scanty. The softer fibromata, with their translucent grayish section, are usu- ally richer in cells. By teasing out a fragment it is easy to isolate num- bers of slender spindle-shaped or caudate cells. The intervening sub- stance is more scanty, the fibrils less coarse and gathered into smaller bundles. Stained sections of such fibromata appear as if they were full of nuclei (Fig. 38). In loose-textured fibromata a clear juice is contained between the fibrous bundles, which are crossed and plaited and interwoven in all direc- tions. The fibroma is developed from proliferous connective-tissue cells. Accordingly spots are often to be found in it where cells are more abun- dant than in the tumor generally ; in such spots we find not only the slender spindle-shaped kind, but also round and oval cells, and even stel- late cells. The transformation of the proliferated cellular tissue into TUMORS. 203 fibrous tissue is effected by the same steps as in fibrous hyperplasia (Art. 85). Fibromata may occur in very various tissues ; in any structure indeed which contains any form of connective tissue. Thus they are found in the skin, nerves, ovary, periosteum, fasciae, uterus, and less often in the mamma, alimentary canal, etc. Their appearance is always manifestly different from that of the matrix in which they are seated (Fig. 38). Fibromata do not give rise to metastatic or secondary tumors, though they are often enough multiple, especially in the skin, nerves, and uterus. Within the same tumor we may often make out several centres of growth ; the fibroma is, in fact, composed of several nodes separated by ordinary fibrous tissue. Such tumors can only do injury in virtue of their size or of their site. Fig. 3S.-Fibroma Molluscum of the Skin, x 25. (Injected preparation stained with haematoxylin.) a, fibroma ; b, papilla thinned out by distention. Now and then fibromata undergo degenerative changes. They may become fatty, or may soften and break down, so that cavities form within them. They may give way at the surface, and so ulcerate ; sometimes they become partially calcified, as in the case of uterine " fibroids." They may be highly vascular, or the reverse (Fig. 38). In rare cases the blood- vessels become wide and dilated, so that the tissue is pierced with capa- cious channels and cavities containing blood. In other instances the lymphatics are similarly dilated. [It is not always easy to distinguish between true fibroma and fibrous hyperplasia. In general the fibroma is characterized by the difference between its texture and that of the surrounding tissue, from which, more- over, it is for the most part sharply defined. These characters are usually wanting in hyperplasias, such, for instance, as those consequent on chronic inflammation. Now and then, however, we meet with inflammatory hyper- plasias which are circumscribed-such as venereal warts in the skin, and the nodes developed in the lungs around inhaled dust-particles. As in the last instance, their texture may be different from that of the ma- trix. It is the life-history and mode of genesis to which we must appeal 204 A TEXT-BOOK OE PATHOLOGICAL ANATOMY. in such cases. Inflammatory hyperplasias, being mere products of in- flammation, cannot properly be reckoned among the true tumors.] b. Myxoma. 143. When the ground-substance of a fibroma swells up by the im- bibition of fluid, it becomes gradually more and more translucent and may even become transparent. The tumor at length resembles a mass of jelly. A swollen fibrous tumor of this kind is best described as an oede- matous fibroma. The texture of many oedematous fibromata much re- sembles that of the umbilical cord in nearly mature foetuses ; where the cells and fibrils are more or less thrust asunder and interpenetrated by a transparent juice (Wharton's jelly). Fig. 39.-Cells from a Periosteal Myxoma of the Thigh, x 400. (Gold staining.) Adipose tissue, whether neoplastic (Art. 144) or normal, may simi- larly become transformed into a gelatinous mass. The fat disappears from the cells, and a dense saline liquid collects between them. They ultimately assume a ramified or stellate form. No sharp line can be drawn between jelly-like oedematous fibromata and lipomata, and true myxoma. Many writers do not hesitate to in- clude the former class among the myxomata. It is perhaps more correct to reserve the name for tumors in which we have not only a swollen and semi-liquid condition of the interfibrillar substance (a substance normally containing mucin), but also an actual solution of the fibrillae and replace- ment of them by dense saline juice. Such a tissue is highly translucent, almost transparent, in fact. The cells it contains are generally much ramified, though some remain rounded (Fig. 39). They here and there TUMORS. 205 undergo mucoid degeneration and so perish. Pure mucous tissue, such as we have just described, is never uniformly present throughout the tumor ; there is no such thing as a perfectly pure myxoma. The bulk of the tumor is generally made up of oedematous connective tissue ; some parts of it may even be coarsely fibrous. It is thus best described as myxofibroma or myxolipoma, as the case may be. Myxomata are most commonly found in the fibrous tissue of the peri- osteum, skin, fasciae, and muscular septa, as also in the subcutaneous and subserous fat, and in the marrow of bone. They are innocent and rarely give rise to metastases. On the other hand, they may grow to an inordi- nate size, and may also be multiple. [Koster (" Sitzungsb. d. niederrhein. Ges. f. Natur- und Heilk.," Jan- uary T7,1881) and his pupil Rumler (" In. Diss. Bonn") have investigated the relation between myxoma and cedematous fibroma. Koster regards swollen and saturated connective tissue as identical with mucous tissue. Myxomata arise merely from the swelling up (by imbibition) of the ground-substance of the various connective tissues.] c. Lipoma. 144. Lipomata are tumors composed of adipose tissue. They form soft or firm lobular masses, often of considerable size. Their structure is very much like that of the subcutaneous panniculus adiposus ; it is made ,up of a series of fatty lobules bound together by fibrous septa of varying thickness. The lobules of the tumor are, however, rather larger than the normal ones. If, as is not uncommon, we have mucous tissue associated with the adipose, the tumor is described as a lipomyxoma; if it contains abun- dant fibrous tissue it is a lipofibroma. Lipomata generally arise from normal adipose tissue, though they may also be developed in connective tissues which normally contain no fat, such as the submucous coat of the intestine, and the dura mater. The larger lipomata not infrequently undergo either calcification, necrosis, gangrene, or putrid decomposition. They do not form metastases, though they are often multiple. The fat they contain is never completely ab- sorbed, even when the patient becomes utterly emaciated. d. Glioma. 145. Gliomata are tumors which develop from the neuroglia-cells of the central nervous system, and when mature are largely made up of neuroglia-cells. They are formed in the brain, and more rarely in the spinal cord. They appear as tumors which are imperfectly marked off from the healthy brain- or cord-substance ; the margin of the tumor grad- ually merges into the healthy tissue. They have thus the look rather of 206 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. localized swellings than of tumors ; but the difference in tint, and the blurring of the normal distinctions between the various elements of the brain-substance, serve to make good the diagnosis. Their appearance varies. Some are light gray and translucent like the cortical substance, and fairly firm in consistence. Others are whiter, coarser, and firmer. Others again are grayish red or even dark red, in which case they are traversed by large and numerous blood-vessels. Vas- cular gliomata often enclose hemorrhagic patches. They are subject to fatty degeneration, caseation, softening, and disintegration. A section of a mature glioma exhibits under the microscope a kind of felted texture, made up of excessively fine lustrous filaments (Fig. 40, J3) interspersed with a multitude of slightly oval nuclei. The nuclei are surrounded by a scanty hardly visible protoplasm. If, however, the prep- Fig. 40.-Glioma from the Brain, x 350. A, cells isolated by teasing and stained with carmine. B, section of the same tumor hardened in Muller's fluid, mounted in Canada balsam, and stained with aniline brown. aration be examined when quite fresh, or after treatment with Muller's fluid, it is readily seen that the nuclei belong to cells which are furnished with numerous delicate ramifying processes going off in various directions (Fig. 40, A). These cells are very similar to neuroglia-cells, though they are often decidedly larger and coarser. Some of them may contain two, three, or more nuclei. Researches on the development of glioma have shown that the neu- roglia-cells are the parent cells to the tumor. The ganglion-cells take no part in the proliferous process. The proportion of cells in the tumor varies greatly ; sometimes the cells form the bulk of it, and sometimes the fibrous framework. The vessels are often highly developed, and may be sacculated or generally dilated. Glioma is usually solitary, and as regards metastasis is innocent; it is only locally malignant. TUMORS. 207 Certain cellular tumors of the retina have been described as glioma- tous ; their elements resemble the cells of the granular layer. As they grow they invade on the one hand the orbital cavity behind the eyeball, or on the other hand break through the cornea and sclerotic, passing- forward. They recur after apparent extirpation, and give rise to metastases. The cells in which they are made up are partly round and simple, and partly ramified. It seems questionable whether we are justified in calling these tumors gliomata. We are inclined to maintain that they are really sarcomata. [Glioma was first defined and named by Virchow (" Die k. Ge- schwiilste," ii., ch. 18). Klebs has recently propounded the theory ("Bei- trage zur Geschwulstehre," i., 1879) that the ganglion-cells play an active part in the formation of gliomata. Ziegler and Christoph examined a large number of gliomata, both fresh and hardened, but failed altogether to find evidence for this view. The nuclei of the ganglion-cells seemed never to subdivide. In the instances where this at first sight appeared to occur, closer investigation showed that the suspected ganglion-cell had merely incorporated a neuroglia-cell.] e. Chondroma. 146. Chondromata (or enchondromata) are tumors which consist essentially of cartilage. The slight amount of fibrous tissue usually present in a chondroma is of altogether minor importance. It either serves to cover the surface of the tumor, or penetrates the interior, carrying the nutrient blood-vessels. Cartilaginous tumors are chiefly developed in regions which normally contain cartilage ; that is to say, in the osseous system or in the cartila- ginous parts of the respiratory system. They may occur, however, in tissues which are normally devoid of cartilage, such as the testis and parotid gland, and more rarely in other organs. They are of very various size ; the smaller ones are generally globular, the larger are lobed or nodular. The several lobes are in the latter case separated by fibrous tissue. They are often multiple, especially in the skeletal structures of the hands and feet. The tumor-tissue has usually the structure of hyaline cartilage, though sometimes yellow cartilage or fibro-cartilage largely replaces it. Even in hyaline chondromata, however, there are always patches in which the matrix-substance is beset with fibres. At the periphery the cartilage passes gradually into fibrous tissue, which forms a sort of perichondrium. The hyaline matrix often has a dusty or ground-glass appearance. The number, size, shape, and grouping of the cartilage-cells vary much in different cases, and even within the same tumor. Many tumors abound in cells, in others they are sparse ; in some the cells are large, in others small. They may be surrounded by capsules, or they may be 208 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. naked ; and crowded in groups within single capsules, or more uniformly scattered. Every variety of normal cartilage may occur also in chon- dromata. The form of the cells varies accordingly ; they are usually spherical, but fusiform and stellate cells are not uncommon, especially in the neighborhood of the fibrous septa which divide or surround the lobules of the tumor. So far as the development of the tissue is con- cerned, all that was said in Art. 87 applies also here. The matrix is de- rived either from pre-existing cartilage, or from marrow, periosteum, bone, or other connective tissue. Cartilaginous tumors which originate in cartilage have been called ecchondroses (cf. exostoses). Chondromatous tissue is very apt to undergo retrogressive change. Some of the cells generally contain oil-globules. In large tumors the matrix-substance frequently undergoes mucoid softening and liquefaction, at points scattered here and there through it. This results in the forma- tion of mucous tissue (Arts. 90-92) ; or in complete liquefaction of the matrix and destruction of the cells, and so in the formation of cysts con- taining liquid. In other cases the cartilage becomes calcified, or true bone is developed (Art. 165). Sarcomatous tissue may be produced when the cartilage-cells multiply rapidly. Chondromata are generally speaking innocent, though metastases are occasionally met with. [In reference to cartilaginous growths, we must be careful to dis- tinguish hyperplasia from true neoplasm. We must not set down all cartilaginous formations as chondromata, even when they are extensive. We often find considerable cartilaginous growths in connection with bones (especially at the articular ends), which are quite certainly to be regarded as hyperplastic. It is the general course of the process which must decide in each case. The more completely a growth differs from its matrix, and develops as an independent tissue, the more certain we are that it is a real tumor. Virchow (" Monatsber. d. Acad. d. Wiss.," Berlin, 1875) has made it probable that many osseous enchondromata originate in remnants of cartilage which have abnormally remained unossified. Such quiescent islands of cartilage certainly exist and are not at all uncommon ; it may well happen that they suddenly resume the habit of growth and begin to proliferate. Virchow suggests (by way of accounting for parotid en- chondromata) that outlying bits of foetal cartilage may lodge in the rudimental parotid gland, which properly belong to the rudimental pinna of the ear. See Paget, " Surg. Path.," Leet. 26 ; " Medico-Chir. Trans.," 1855 ; Ranvier, "Bull. Soc. Anat.," 1865 ; Virchow and Hirsch, "Virch. Jahresber.," 1869. | f Osteoma. 147. The osteomata are tumors composed of osseous tissue. Their usual seat is in connection with the bones, though they may occur elsewhere. TUMORS. 209 Osseous formations connected with the bones have received different names according to their site and disposition. Hyperostosis is dif- fused and extensive overgrowth in a bone. When the new-formed tissue is seated upon a definite spot in the old bone it is described as an osteophyte; or, if it be larger and more like a tumor, as an exostosis. Circumscribed bony growths in the interior of bones are called enosto- ses. Bony growths which are not rigidly connected with the bone are divided into-mobile periosteal exostoses, which are seated on the peri- osteum though separate from the bone ; parosteal osteomata placed near to the bone, but not connected with it ; independent osteomata remote from the bone and seated in tendon or muscle ; and finally, the strictly heteroplastic osteomata, which may be seated in the lungs, brain- membranes, diaphragm, skin (rarely), parotid gland, etc. Excrescences also occur in connection with the teeth. If they consist of cement or crusta petrosa, they are called dental osteomata ; if they consist of dentine they are odontomata. The latter originate in a hyper- plasia of the pulp during the development of the tooth. The texture of an osseous tumor may resemble that of ivory, as in eburnated osteoma ; or it may be soft and spongy, as in spongy or can- cellous osteoma ; the former varieties are built up of dense and compact tissue with narrow nutrient canals, and similar to the cortical layer of the long bones. The latter are built of thin and delicate trabecuhe en- closing large medullary spaces ; they are allied in texture to cancellous bone. The surface is sometimes uniform and smooth, so that the entire tumor is conical, spherical, or pyriform ; sometimes it is irregular, rough, or tuberculated, without any definite figure. Ivory-like tumors are gen- erally of the first kind ; they occur most commonly as exostoses of the skull. Spongy exostoses are of the second kind, as are also the inde- pendent and heteroplastic osteomata. The development of the osseous tissue in tumors follows the course described in Art. 88. It is effected partly by the agency of osteoblasts, partly by metaplasia of the existing tissue. The ground-substance is chiefly derived from the connective tissue of the periosteum and of the structures in which the tumor is bedded ; as well as from cartilage and bone-marrow. WThen cartilage is first produced by periosteal prolifera- tion, and then transformed into bone, the growth is described as a car- tilaginous exostosis. When bone is directly produced, by suppression of the cartilaginous sta^e, we have a fibrous exostosis. Many abnormal bony growths are not, strictly speaking, tumors, but rather hyperplasias resulting from excessive growth or inflammation. This is true not only of most hyperostoses, osteophytes, and exostoses, but also of some parostoses and independent osteomata. Of this nature are the bony growths produced in the adductors of the thigh by con- stant riding, and in the deltoid by the shouldering of the rifle in manual- exercise. In what way fibrous tissues which never produce bone nor- 14 210 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. mally are excited to produce it by long-continued irritation, is not easy to determine. We only know that the occurrence is not by any means impossible. The diagnosis between true and false osteoma is not always easy. If the new growth is unaccompanied by signs of irritation or of inflammatory change in its neighborhood, it is probably a true osteoma. [References:-Muller, " Zeitsch. f. wiss. Zool.," ix. ; Paget, " Surg. Path.," Leet. 27 ; Virchow, * Die k. Geschwiilste."] g. Angioma. 148. Angiomata are tumors principally made up of blood-vessels. Some of these blood-vessels may be new-formed, others are pre-existing vessels more or less altered. The alteration is chiefly in the direction of dilatation, or thickening of the walls. Angiomata are not sharply marked off from the surrounding tissue. According to our definition of tumor, which makes the formation of new tissue an essential feature, we should exclude from the angiomata all vascular tumors which are pro- duced merely by the dilatation or overgrowth of pre-existing vessels. General usage has, however, sanctioned a certain relaxation of this strict rule, inasmuch as simple vascular dilatations extending over a definite region, and so giving rise to a definite tumor-like swelling, are universally described as angiomata. According to its structure the an- gioma is spoken of as simple or cavernous. Racemose aneurisms, and racemose varices, have also been included among vascular tumors ; and a fifth variety is furnished by lymphatic angioma or lymphangioma. 149. Simple angioma (telangiectasis or simple erectile tumor) is a structure made up of some normal basis-tissue, containing an abnormal number of distended and altered veins and capillaries. Such formations are most frequently met with in the skin ; they are usually congenital, and after birth merely increase in size. They are de- scribed as vascular naevi, and chiefly occur at places where foetal clefts have become closed (fissural angiomata). They can hardly be spoken of as tumors, for they do not raise the skin. A simple naevus merely looks like a level patch of a different tissue substituted for the normal skin. The color is either bright red (n. flammeus, strawberry mark), or livid (n. vinosus, port-wine mark). It is not usually marked off very sharply from the normal tissue. Small circumscribed red specks are often found round the edges and in the neighborhood of the chief patch. The red color is due to the wide and distended blood-vessels, which are seated in the corium or subcutaneous fat. In the latter site they are often beset with minute sacculations. It is rare for such naevoid angiomata to be found elsewhere than in the skin ; but they occur now and then in glands like the mamma, in bone, and in the brain. They occur also, and more frequently, in the interior of morbid growths, such as gliomata and sar- comata. TUMORS. 211 When the vascular changes are more closely examined, by isolating the vessels or by making sections of the tumor, it is seen that they de- pend essentially on localized dilatations of new-formed or pre-existing capillaries (Fig. 41). The dilatations are fusiform, cylindrical, saccu- lated, or spherical ; and these varieties of form are combined in all pos- sible ways. In naevi the dilatations are even more exaggerated than those in the figure. They form wide cavities connected together by normal or but slightly dilated capillaries. The walls of the capillaries are not percep- tibly thicker than the normal ; they have thus the appearance of being rather thin than otherwise. Fig. 41.-Dilated Capillaries from a Simple Angioma of the Brain, x 200. (Isolated by removal of the basis-tissue.) Another form of simple angioma, best described as the hypertrophic form, is made up of dilated capillaries whose walls are very considerably thickened. The dilatations are not usually so extreme as in the former varieties, but the number of vessels is so vast that on section they seem everywhere contiguous, the basis-tissue being as it were thrust out of sight (Fig. 42). The capillary-walls are abnormally thickened and beset with nuclei, resembling somewhat the walls of the arterioles. When the blood is abstracted and the lumen of the vessels diminished as much as possible, so that the nuclei are set radially, the section looks very like one through the glomerulus of a sweat-gland. This resemblance is further increased by the fact that the tumor is made up of a number of lobules or nodules 212 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. separated by fibrous tissue, each composed of a convoluted knot of hyper- trophied vessels. Moreover, as these angiomata occur in the skin, and chiefly in the deeper parts of the cutis and subcutaneous connective tis- sue, it sometimes happens that the section includes actual sudoriferous tubules (Fig. 42). A third form of simple angioma is the venous or varicose tumor ; it likewise occurs chiefly in the skin and subcutaneous tissues. In the forms already described the smaller veins are often dilated, but this fea- ture is not marked in comparison with the capillary changes. In the venous angiomata the dilatation is almost entirely confined to the smaller veins, the anastomosing capillaries remaining almost unchanged. The venous dilatations or varices are cylindrical, ampullate, or saccular, with distinct and somewhat thickened walls. Haemorrhoids or piles are of this nature ; they are tumors formed in the mucous membrane of the rectum Fig. 42.-Section of a Simple Hypertrophic Angioma of the Skin, x 200. The duct of a sweat-gland has been cut across at the middle of the section. near the anus, and consist mainly of hyperplastic submucous tissue, and of blood-containing saccules, derived from the small veins by morbid dila- tation. {References :-Rokitansky, "Lehrb. d. path. Anat.," 1855 ; Virchow, "Die krankhaften Geschwulste ;" Billroth, "Arch. f. Chir.," xi.; Lucke, " Chirurgie v. Pitha u. Billroth," ii.; Monod, " fitude sur l'angiome sim- ple," Paris, 1873 ; Paget, " Surg. Path.," Lecture 28 (containing further references).] 150. The cavernous angioma is distinguished from the simple an- gioma by the fact that the tubular form of the vessels is more or less lost. In its fully developed form, the tumor is made up of a series of wide variously shaped cavities, separated from each other merely by fibrous septa (Fig. 43). In section these cavities appear as sinuses of various size, separated by a trabecular network of nucleated fibrous or spindle-celled tissue. The separation is not complete, as the spaces com- TUMORS. 213 municate with each other. The mass resembles greatly the corpus ca- vernosum of the penis, and is sometimes described as composed of " erec- tile " tissue. The walls of the cavities are lined with endothelium. These tumors are commonly seated in the skin, and may be congenital (Fig. 43). In other cases they are developed from simple angiomata by FlG. 43.-Congenital Cavernous Angioma of the Skin, x 20. (Haematoxylin staining.) a, epidermis; b, corium; c, cavernous blood-spaces. continued dilatation of the already dilated vessels. In the skin they form livid, raised, and sometimes uneven patches (noevus prominent). Among the viscera the liver is by far the commonest seat. Here they take the form of dark brown patches, not raised above the surface, and not compressing the liver-tissue, which, indeed, they simply replace. They are never congenital, but are developed in advanced age when the liver is tending toward atrophy. It is easy to make out in favorable specimens that the cavities have arisen from the varicose dilatation of individual capillaries within the lobules, the liver-cells disappearing simultaneously (Fig. 44). At first there is no proliferation from the ves- sel-walls. Then several capillaries coalesce by disappearance of the septa, and so form larger cavities. When the cavernous metamorphosis reaches the border of a lobule, the periportal fibrous tissue forms a cap- Fig. 44.-Section from the advancing Border of a very small Cavernous Angioma of the Liver, x 150. sule round the transformed vascular mass, which at first has no definite boundary. At this stage proliferation of the tissue not infrequently sets in (cf. Rindfleisch, " Path. Hist.," vol. i., p. 163). Angiomata are found, though very rarely, in the kidney, spleen, ute- rus, intestine, bladder, muscles, bones, etc. 214 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [The above account of the development of cavernous tumors in the liver is considerably at variance with that given by Virchow (" Die k. Geschwiilste," iii.). Virchow supposes that the first step is not a dilata- tion of the vessels, but the formation of new granulation-tissue. In this the vessels and vascular sinuses are formed. Ziegler is unable to find any traces of such a mode of genesis. He examined a liver which con- tained a multitude of angiomata varying from a scarcely perceptible speck to a tumor the size of a walnut. All stages of development were represented, from the dilatation of a single capillary up to the cavernous metamorphosis of an entire lobule. Yet, in no instance was there any sign of proliferation at starting ; atrophy and dilatation only were ob- served. Payne describes a remarkable case of a similar kind in the "Trans. Path. Soc.," 18G9. The term angioma nowadays embraces formations which are geneti- cally very diverse. Some angiomata are congenital, and are therefore conditioned by some disturbance of development. Others arise from new-formed vessels. Others, again, are the result of a kind of degenera- tive change ; vascular dilatation following an abnormal relaxation of the vessel-wall, or on atrophy of the intervascular parenchyma. Formations of this kind, produced merely by dilatation and cavernous degeneration, should be excluded from the category of true tumors.] 151. Aneurism by anastomosis (anastomotic or racemose aneu- rism) is not properly a neoplasm ; it is rather a morbid change affecting a vascular territory. The arteries of the territory become dilated and convoluted, while the intervening tissue atrophies. The pulsating growth feels to the finger like a knot of writhing worms. Many of these growths originate in congenital faults, especially those which occur in the scalp, and lead at times to erosion of the bone. Others are acquired, and follow upon mechanical injuries. The dilated arteries generally have thickened walls. The racemose or anastomotic varix is analogous to the racemose aneurism. It is a common affection of the veins in the leg, the labia pudendi, and the spermatic cord (varicocele). Further details concerning aneurism and varix will be found in the Special Pathological Anatomy, under Vascular Affections. 152. Lymphatic angioma (or lymphangioma) is, in relation to the lymphatic system, what angioma (as hitherto considered) is to the haemic system. The essential character of the growth is dilatation of the lym- phatic vessels, associated at times with hypertrophy of the vessel-wall and atrophy of the intervening tissue. We may distinguish the various forms into simple lymphangioma or lymphatic telangiectasis, and cavern- ous lymphangioma ; together with a third form, the cystoid lymphangi- oma. As in the foregoing cases, the magnitude and arrangement of the dilatations may vary greatly. In the extreme stages actual cysts may be formed. The cavities contain lymph, which is generally clear and limpid, though it is sometimes milky. TUMORS. 215 The growth may be congenital or acquired. Congenital lymphatic dilatations take various forms according to their seat, which may be the tongue (macroglossia), lips (macrocheilia), skin (lymphatic naevus), labia, etc. Lymphangiectasis of the skin is not rare as an acquired affection ; it chiefly occurs in the thigh and thorax. Sometimes it gives rise to considerable tumors, which fluctuate on palpation. The section repre- sented in Fig. 45 was taken from a tumor as large as the fist, which had formed in the subcutaneous fat of the thigh. The dilated and sacculated lymphatics have their walls more or less thickened, and they are gener- ally embedded in the adipose tissue. Fig. 45.-Subcutaneous Cavernous Lymphangioma, x 20 (Section mounted in Canada balsam, and stained with alum-carmine.) a, dilated lymphatics ; ft, connective tissue; c, adipose tissue; d, larger blood- vessels; e, groups o£ small cells or leucocytes. If the more superficial cavities of a cutaneous lymphangioma should rupture, a grave lymphorrhcea may ensue. The affection is often com- plicated with fibrous hyperplasia of the skin (as in elephantiasis lym- phangiectodes) or of other organs. [References :-Maier, " Lehrb. d. allg. path. Anat. ; " Virchow, op. cit.; Arnstein, "Virch. Arch.," vol. liv. ; Anger, "Tumeurs ^rectiles lymphatiques," In. Diss. Paris, 1867 ; Gjorgewic, "Arch. f. klin. Chir.," xii.; Reichel, "Virch. Arch.," vol. xlvi.; Wegner, " Langenbeck's Arch, f. klin. Chir.," xx.; Pinner, " Centralb. f. Chir.," 12,1880; Pospelow, " Vierteljahrs. f. Derm. u. Syph.," 1879; Hebra and Kaposi, "Diseases of the Skin" (Syd. Soc.), vol. iii.; Nieden, "Virch. Arch.," vol. xc.] h. Myoma. 153. Myoma is a tumor consisting essentially of new-formed muscu- lar fibres. It occurs only in certain parts of the body. If the fibres are 216 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. non-striated the tumor is described as a leiomyoma, if striated as a rhab- domyoma. Leiomyoma (or levicellular myoma) is of frequent occurrence in the uterus, less frequent in the muscular coats of the intestine. It takes the form of a spherical nodulated growth, not unlike a fibroma. The smooth muscular fibres form bundles (Fig. 46), which are plaited and in- terwoven. They are usually surrounded by abundant fibrous tissue, which binds the fibres and the bundles together. If the fibrous tissue form a considerable part of the bulk, the tumor is described as a fibro- myoma. Most of the uterine " fibroid " tumors are of this nature. The fibrous bands are white and lustrous, the muscular elements are pink, or reddish gray, or white. It is often by no means easy to distinguish the muscular elements from the purely fibrous. To make an exact deter- mination, it is advisable to isolate the muscle-cells by teasing while the preparation is fresh. The isolation is easier if small fragments of the Fig. 46.-Section through a Leiomyoma (from Peris). The nuclei are shown partly lengthwise, partly cut across. tumor have been steeped for twenty-four hours in a 20 per cent, solution of nitric acid, or for twenty to thirty minutes in a 34 per cent, solution of caustic potass. The nuclei of the muscle-cells are then easily recog- nized. Under the microscope the muscle-fibres are distinguished by their rod-like nuclei (Fig. 46) and by the regular structure of the tissue they form. In cross-section the muscle-spindle is seen as a small polygonal area enclosing the rounded section of the nucleus. Leiomyomata are in- variably innocent ; though they may cause danger by their tendency to bleed. They are liable to fatty change and to softening, which may lead to their disintegration or putrefaction, or to cystic excavations. Calcifi- cation is not infrequent. [On the nature of so-called uterine " fibroids " see Bristowe, "Trans. Path. Soc.," 1853 ; Oldham, "Guy's Hosp. Rep." (2d series), vols. ii., viii.; Williams, Lancet, 1, 1880 ; Courty, "Dis. of Uterus," London, 1882 (contains full references).] TUMORS. 217 Rhabdomyomata are very rare. They are hardly ever made up entirely of striated muscular fibres. In cellular sarcomatous tumors, chiefly of the kidney and testis, spindle-cells with more or less perfect striation are found associated with smooth muscle-fibres (myosarco- mata). It is probable that such tumors (which are found only in chil- dren, and are of great size) are due to fcetal deposits of muscular ele- ments in the rudimental kidney and testis. [References to the literature of rhabdomyoma are given by Huber and Bostrom ("Arch. f. klin. Med.," xxiii.). The name is due to Zenker ; Virchow uses the term striocellular myoma. See also Eberth, " Virch. Arch.," vol. Iv.; Cohnheim, "Virch. Arch.," vol. Ixv.; Marchand, " Virch. Arch.," vol. Ixxiii. ; Kocher and Langhans, " Deut. Arch. f. Chir.," ix.; Brodowski, " Virch. Arch.," vol. Ixvii.] i. Neuroma. 154. Neuroma is a term which in strictness should be applied only to tumors composed essentially of new-formed nerve-fibres. What we are accustomed to describe as neuroma is a growth occurring indeed in a nerve, but due to multiplication of the cells of its neurilemma and peri- neurium, not to the formation of new nerve-fibres. It is generally a fusiform, oval, or cylindrical outgrowth, whose axis may coincide with that of the nerve, or deviate laterally. Such tumors are very often mul- tiple, and may affect either single nerve-territories or the entire system. Neuromatous nodes may also occur in the central nervous organs ; they may be as large as a hen's egg, or (rarely) larger. If the nodular changes affect an entire nerve-territory, a network of coarse bands and nodes may be formed. This form has received the name of plexiform neuroma (Verneuil). Sometimes painful nodular growths form at the ends of di- vided nerves, as in amputation-stumps. They are spoken of as amputa- tional neuromata. Almost all of these varieties are false neuromata ; they are really fibromata and myxomata of the connective tissue of the nerve, unasso- ciated with any multiplication of its nerve-fibres. The latter, indeed, are compressed and atrophied. This is true of the multiple varieties as well as of the amputational neuromata. The latter are in most cases due to inflammatory fibrous hyperplasia. It is asserted, however, that, in some neuromatous tumors, a true new- formation of nerve-tissue may occur. Amputational. neuromata have furnished examples of this, as well as the tumors of various sizes which develop in the continuity of a nerve without any discoverable cause. These, then, would be instances of true neuroma. Nerve-fibres are said to multiply by subdivision and by offshoots. According as the new-formed fibres are medullated or not, we have the varieties myeline neuroma and amyeline neuroma. Neuromata are en- 218 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. tirely innocent ; they never give rise to metastases. It has been shown that the multiple false neuromata are apt to be inherited, or at least to depend on some congenital fault. (See Special Pathological Anatomy of the Nerves.) [References :-Virchow, op. cit. and " Gesammelte Abhand.; " Smith, "On Neuroma Peris, " Handb. d. allg. Path. Verneuil, "Arch. gen. de med.," vol. xviii. (5th series) ; Czerny, "Arch. f. klin. Chir.," xvii.; Soyka, " Prager Vierteljahrs.," 35, 1877 ; Peris, " Arch. f. Ophthalm.," xix.; P. Bruns, " Virch. Arch.," vol. 1.; von Recklinghausen, " Ueber d. multiplen Fibrome d. Haut," Berlin, 1882.] j. Lymphoma and Lymphosarcoma. 155. Lymphoma is a comprehensive term, and includes formations which are not strictly tumors, but rather hyperplasias of the tissue proper to lymphatic glands-lymphadenoid (or briefly adenoid) tissue, as it is called. Lymphoma, as a neoplasm, would imply the development and deposit of new lymphadenoid tissue, in the form of a tumor, within a lymphatic gland, a follicle, or some other structure of the connective-tis- sue group. In what is usually called lymphoma this does not happen. What does happen is-that the tissue of the lymphatic gland or follicle increases in size because the lymphoid cells it contains are multiplied, while the reticular tissue undergoes hyperplasia. The process is often inflammatory in character, and should then be classed with the inflamma- tions ; in other cases the lymphoid hyperplasia seems to begin idiopathi- cally, i.e., without any cause hitherto discovered. It may often be doubtful whether the increased growth of a lymphatic gland should bo regarded as neoplastic or as hyperplastic. Many cases o£ lymphoma, es- pecially the leukeemic kinds, seem referable to hyperplasia. The lym- phatic glands, lymphadenoid structures of the intestine, and lymphoid follicles of the spleen, all maintain their structure as they grow in size, or alter but slightly. Moreover, the functions of the glands seem to be more actively performed. This does not seem to indicate that they are invaded by anything of the nature of a neoplasm. In addition to the hyperplastic lymphomata, there is a true or hetero- plastic tumor whose structure agrees with that of lymphadenoid tissue. As the term lymphoma has been perverted to describe the hyperplastic formations, we may do well to distinguish the genuine tumor as lym- phadenoma or lymphosarcoma. This latter title corresponds with the fact-that the tumor agrees in its characters with the sarcomata. It will therefore be treated in connection with them (Art. 158). [The relations of lymphoma and lymphadenoma to Hodgkin's disease and to leukaemia are discussed in the Special Pathological Anatomy. Recent researches have shown that lymphadenoid tissue is, in normal TUMORS. 219 conditions, widely distributed throughout the body. The overgrowth of some such normal deposit may simulate a heteroplastic formation.] k. Sarcoma. 15G. The sarcomata are tumors constructed on the type of the con- nective tissues, in which, however, the cellular constituents predominate over the intercellular substance. In this respect they resemble the im- mature connective tissues ; so that the comparison of sarcoma to embry- onic formative tissue is perfectly apt. Sarcoma originates invariably in a structure belonging to the connec- tive-tissue group ; i.e., in formed or unformed fibrous tissue, in cartila- ginous, bony, mucous, lymphoid, neurogliar, or adipose tissue. The transformation of these into tumor-tissue is effected by the growth and multiplication of the constituent cells. Fig. 47.-Section through the Advancing Margin of a small Sarcomatous Nodule from the Mamma, x 300. a. fibrous tissue; b, cells of the sarcomatous tissue; c, smaller cells; d, cells with hypertrophied nuclei; e, multinuclear cells. In favorable circumstances it is possible to follow up this mode of genesis histologically. At the advancing margin of a growing tumor we may find all kinds of transitional cell-forms, from the small cells of the normal connective tissue to the large cells of the tumor. Fig. 47 repre- sents the advancing margin of a small sarcomatous nodule from the mamma, and in it the various stages of development can be made out. Enlarged and swollen cells (c) lie beside the small cells of the fibrous tis- sue (er) ; others with enormous nuclei (d), or with several (e), are also noticeable. At the same time the number of the cells is vastly increased. In bone and cartilage it is possible to demonstrate the subdivision and multiplication of the fixed cells even more clearly than in connective tissue. The multiplication sometimes occurs in the substance of non- vascular cartilage or bone away from the medullary spaces, and thus the part played by the individual cells within their cavities is very readily followed (Ziegler, " Virch. Arch.," vol. Ixxiii.). In connective tissue it is less easy to exclude the possibility of cell-infiltration from neighboring parts. Virchow has thus shown that sarcoma-cells may arise by prolifer- 220 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. ous multiplication from connective-tissue cells of perfectly normal as- pect. This is the process in a large number of cases ; but it may vary to this extent-that the development begins in tissue which is already mor- bidly altered. Thus new-formed cartilage may pass into sarcoma by over-intense proliferous growth of the cartilage-cells, and disappearance of the matrix-substance. It is of great interest to note that cells, which form part of what we might call congenital heteroplastic foci, may often serve as the starting- point of a sarcoma. Congenital warts and pigment-spots are specially remarkable for this. The transformation into sarcomatous tissue is ef- fected by the growth and multiplication of the nests of cells that are always found in such spots. Summing up what we know of the development of sarcoma we may say-that sarcomatous tissue may arise either from connective tissues •which up to then seem normal, or from tissues that are to be regarded as already morbid. [References on the genesis of Sarcoma:-Virchowr, "Die kr. Ge- schwiilste," ii. ; R. Maier, "Allg. path. Anat.;" Peris, "Allg. path. Anat. Bizzozero, " Med. Jahrb.," iv., 1878 ; Billroth, "Arch. f. klin. Chir.," xi. ; Steudener, "Virch, Arch.," vol. lix. ; Sokolow, "Virch. Arch.," vol. Ivii. ; Cornil and Ranvier, "Man. Path. Hist.," vol. i.j 157. The form and mode of growth of the cells varies much in differ- ent varieties of sarcoma. The intercellular substance is sometimes scanty, soft, and stringy ; in other cases its texture approaches that of the mature normal tissue. The various varieties are distinguished ac- cording to the constitution of the ground-substance as well as of the cells, but chiefly of the cells. That constituent is taken as characteristic, which prevails in the tumor in question. Seeing that a sarcoma is con- tinually in process of growth, it always contains some parts which are as yet immature, and merely represent an earlier stage of development of the tumor. Jn settling the classification of the tumor such parts are not taken into account. The texture of the sarcoma, as made out by the unaided eye, varies much in the different forms. In its mature condition it is generally more or less sharply marked off from its surroundings. It may occur in any locality where connective tissues are found, but the frequency of its occurrence is different in different tissues. Thus it is much commoner in the skin, fasciae, intermuscular fibrous tissue, bone, periosteum, lymphatic glands, brain, and ovary-than in the liver, lungs, intestine, or uterus. The amount of intercellular substance present chiefly determines the consistence and the tint. Forms which are soft, marrowy, and white or grayish-white on section, are rich in cells and poor in intercellular sub- stance. Firm and coarse-grained forms are poorer in cells and abound more in fibrous intercellular tissue. The latter kinds pass without any TUMORS. 221 break into the fibromata. Intermediate forms are described as fibrosar- comata. The cut surface of a sarcomatous tumor has a uniform look throughout ; unless, indeed, it has undergone retrogressive changes, or the amount of blood in it varies from part to part. It looks evenly smooth, in medullary tumors milk-white, in firmer kinds clear grayish- white and translucent, or grayish-red or brown. The hard forms are white or yellowish-white, and lustrous on section. The blood-vessels are variously developed ; now and then they are exceptionally wide and numerous, or even irregularly dilated, as in tel- angiectatic sarcoma. Lymphatics have not been shown to exist in sar- comata. Retrogressive changes are apt to happen, such as fatty change, mucoid change, liquefaction, caseation, disintegration, hemorrhage, putre- faction, ulceration, etc. 158. Round-celled sarcoma. The small-round-celled sarcomata are very soft rapidly growing tumors. They chiefly occur in the connective tissues of the locomotive and skeletal system ; as also in the skin, testis, "Fig. 48.-Section through the Margin of a Sarcoma affecting the Intermuscular Connective Tissue, x 300. (Carmine staining.) a, normal muscle-fibre; a„ atrophied muscle-fibres; b, round-cells intruded between the muscle-fibres; c, fully developed tumor-tissue ; d, round-cells resembling white blood-corpuscles. ovary, and lymphatic glands. They are usually milky white on section, and not infrequently contain softened or cheesy patches. A milky juice can be got by scraping the cut surface. Their structure is very simple ; it consists almost entirely of round-cells and vessels (Fig. 48). The former are small and fragile, have but little protoplasm, and enclose a rounded or slightly oval vesicular nucleus (Fig. 48, c). This nucleus seems more highly developed than it is in ordinary lymphoid cells. The intercellular substance is scanty, and fibro-granular in texture. The vessels appear as thin-walled channels between the groups of cells. In the case of an invaded muscle, such as that in the figure (Fig. 48), the tumor seems to consist of an aggregation of round-cells (Fig. 48, b, c) seated in the intermuscular connective tissue. Lymphoid elements are not infrequently found mingled with the tumor-cells ; their nuclei (Fig. 222 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. 48, cl) are easily distinguished by the fact that they take a deeper stain- ing than the other elements. A second variety of small-round-celled sarcoma is the so-called lymphosarcoma. It is a sarcoma whose structure somewhat resembles that of a lymphatic gland. There is a kind of reticular stroma (Fig. 49, a), made up in part of anastomosing ramifying cells (Fig. 49, 6) ; and this contains a multitude of round-cells in its meshes. If a small piece of the tumor be first shaken up in a test-tube with some liquid, so that the cells drop away, the structure can then be easily made out under the microscope. The tumor has the same general appearance as the commoner small- round-celled variety. Both forms are highly malignant, partly because of their rapid growth, partly from their tendency to give rise to second- ary growths, which may affect the entire body. Fig. 49.-Section of Lymphosarcoma from the Nasal Mucous Membrane. «, reticulum (the a to the left points to a blood-vessel with subdividing cells) ; b, cells of the reticulum ; c, round-cells. Lymphosarcoma most commonly originates in lymphatic glands, and in the lymphadenoid tissue of the mucous membranes. It may, however, arise elsewhere. When it attacks a lymphatic gland, it may be distin- guished from mere hyperplastic lymphoma by its rapid growth, and by its tendency to overpass the limits of the gland, and to form metastases. 159. Large-round-celled sarcomata are made up of cells considerably larger than those of the varieties just described. They occur in the same localities. They are not quite so soft in texture. Their cells are often uniformly large, and have an abundant protoplasm and large oval vesicu- lar nuclei (Fig. 50). Many of the cells are binuclear, a few are multinu- clear. The intercellular substance is arranged in a kind of network, in- terspersed with fusiform and ramified cells. Together they form an alveolar reticulum in whose spaces lie the large epithelium-like round- cells. On account of these characters Billroth has described the tumor as a " large-celled alveolar round-celled sarcoma." The vessels have usu- ally very thin walls. TUMORS. 223 In the other varieties of large-round-celled sarcoma, the cells are very unequal in size. Fig. 51 represents a section of a mammary sarcoma in which the cells are for the most part round ; but their sizes vary greatly, and there is a partial admixture of elongated cells, as well as of multinuclear giant-cells (e). If this last be taken as characteristic, the tumor may be called a giant-celled or myeloid sarcoma (Art. 160). The large-round-celled sarcomata are generally less malignant than the small-celled kinds ; but they likewise may form metastases. The patient from whom the tumor represented in Fig. 50 was taken died from metastatic growths. Fig. 50. Fig. 51. Fig. 50.-Section from a Fungating Large-round-celled Sarcoma, x 400. (From the skin of the leg; carmine staining.) Fig. 51.-Section of a Sarcoma of the Mamma containing variously formed Cells. x 300. (Bismark- b'rown staining.) «, fibrous tissue; b, cells of the sarcomatous tissue ; c, smaller cells; d, cells with hyper- trophied nuclei; e, multinuclear cells. 160. Spindle-celled sarcoma (including forms with ramified multi- form cells, and fibrosarcoma). Sarcomata consisting of spindle-shaped or ramified cells are among the most common of all tumors. They are usually much firmer in texture than the round-celled forms. On section they look grayish or yellowish-white, and translucent ; if the vessels are full of blood they may accidentally be tinged with red. They are, gener- ally speaking, much less malignant than the round-celled sarcomata, but this depends somewhat on where they are seated. Sarcomata in which spindle-cells predominate are called briefly spin- dle-celled sarcomata ; they are divided into large-celled and small-celled varieties. The cells may be more or less isolated by teasing out frag- ments of the tumor-tissue, and in this way very long spindle-cells may occasionally be found (Fig. 52). They lie side by side in the tumor, and group themselves into bundles. In a section these bundles may be seen cut through lengthwise, crosswise, or slantwise ; which shows that they run in diverse directions through the growth. The grouping of the spindles into definite bundles is often very strik- ing ; but sometimes there is no such grouping, the spindles all lying par- allel to the same direction throughout a considerable area. Sometimes 224 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. also the arrangement of the spindles seems to depend on the direction of the vessels, the bundles forming a kind of sheathing to each vessel. The intercellular substance may be very scanty, or altogether imper- ceptible in a section. In other cases it is abundant, and shows a kind of fibrillated structure. The cells are then poorer in protoplasm ; so much so, in fact, that there is often none to be seen around the nucleus, and the cell-processes seem to start from the nucleus itself (" nuclear fibres "). Such tumors are firm and coarse-grained, and approach the fibromata in texture. They are called fibrosarcomata. Fig. 52. Fig. 53. Fig. 52.-Spindle Cells from a Large-spindle-celled Sarcoma of the Cheek, x 400. (Teased preparation.) Fig. 53.-Section from a Giant-celied Sarcoma originating in the Medulla of the Tibia ("Myelogenic" Sarcoma), x 400. (HEematoxylin staining.) Sarcomata whose cells are of several diverse forms are equally com- mon. Their cells are spindle-shaped, pyramidal, prismatic, stellate, or altogether irregular (Fig. 53). Each cell seems in fact to take the form of the space which is left to it to fill. Sarcomata of this kind, as also the spindie-celled kind, usually contain a larger or smaller number of giant-cells (Fig. 53). These tumors are perhaps more properly described as giant-celled or myeloid sarcomata than those referred to in Art. 159. They chiefly affect the osseous system. The vessels of a sarcoma have generally walls which are quite distin- guishable. In some cases, however, they have the appearance of canals excavated in the substance of the tumor, the tumor-cells themselves bounding the lumen of the vessel. Here it would seem as if the tumor had in part arisen from multiplication of the cells in the original vessel- wall. TUMORS. 225 161. Sarcomata of peculiar types. Sarcomata do not usually exhibit any special structure, or any resemblance to a glandular type. The cellular elements, even when they seem to resemble epithelial cells are dispersed uniformly throughout the intercellular substance, as in the connective tissues. There are, however, exceptions to this in special cases. There are sarcomata which have a structure resembling that of gland-tissue, or of epithelial new growths. This appearance of structure is due in part to the epithelial look of the cells, but chiefly to their aggre- gated arrangement in groups separated by fibrous septa. Such tumors are described as alveolar sarcomata. Fig. 54 represents a section from an alveolar sarcoma of the skin. Fig. 54.-Section from a Melanotic Alveolar Sarcoma of the Skin, x 300. (Haematoxylin staining,) o, uninuclear; «„ multinuclear epithelial-like tumor-cells: b, pigment-cells; e, stroma enclosing blood-ves- sels and pigment. The cells a exactly resemble epithelial cells ; they are grouped into masses, and sharply distinguished from the fibrous framework (e) in which they are embedded. This latter contains the blood-vessels, or rather the framework is chiefly made up of a network of blood-vessels ; but no vessels enter the cell-groups. This is another point of structure in common with the epithelial growths. Tumors of this kind occur chiefly in the skin, but they are also met with in the bones, lymphatic glands, and pia mater. In the case of the skin they originate in warts and pigment-spots, which generally contain such groups or nests of cells (Arts. 156 and 398). The way in which the alveolar structure is developed can often be clearly made out, especially in tumors of the central nervous system. The normal intervascular tissue is transformed into masses of sarcoma- cells, while septa are formed between the cell-masses by the fibrous tis- sues lying along the course of the vessels. In other cases it looks as if 15 226 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. a plexus of pre-existing or new-formed vessels took on, as it were, an in- vestment of cells, and this grew thicker and thicker, till at length the intervascular spaces were entirely filled up. Accordingly we find this form of growth described as plexiform angiosarcoma. It has also been described, and not infrequently, as endothelioma. On this view the cell-nests arise by proliferation from endothelial cells. This certainly happens when masses of cells are formed from the endothelial covering of the subarachnoid meshwork and pia mater ; the masses afterward group themselves into " nests." Sometimes the proliferous endothelial cells of the pia mater are aggregated into small spherical nodules of a peculiar lustrous appearance. The tumor into which the membrane is transformed then contains small shining pearly bodies, made up of lam- inated layers of squamous or tabular cells. Such tumors have been called cholesteatomata, or pearly tumors. [The expression " plexiform angiosarcoma " is due to Waldeyer ("Virch. Arch.," vol. lv.). The vessels of the brain, lymphatic glands, serous membranes, and testis possess what is called a perithelium ; that is, the adventitia is invested with endothelial cells. Proliferation begins in the cells of this perithelium, and the vessel is thus invested with a stratified covering. See Kolaczek, "Deutsche Zeitsch. f. Chir.," ix. ; Maurer, "Virch. Arch.," vol. Ixxvii. ; Neumann, "Arch. d. Heilk.," 1872 ; Klebs, " Prager Vierteljahrsschr.," 1876. [It is still a matter of dispute whether the cholesteatomata are really endotheliomata of the pia mater (Eppinger, " Prager Vierteljahrsschr.," 1875). They may possibly belong rather to the dermoid tumors (Art. 1 78). Similar growths are met with in the middle ear (Wendt, "Arch. d. Heilk.," 14, 1873 ; Lucse, "Arch. f. Ohrenheilk." (New Series), 1, 1874.) Some regard them as tumors, others (with Wendt) as inflammatory products.] 162. Sarcomata which contain deposits of pigment are described as melanosarcomata (Fig. 54). The pigment is black or brown, and lies partly in the tumor-cells, partly in the fibrous matrix and vessel-walls. It occurs chiefly in the form of amorphous granules ; but there are generally a number of diffusely stained cells as well. Melanosarcomata are malignant. When the pigmentation is not extreme the tumor has on section a brownish-gray look, or it may only show patches of brown or black. In more marked cases the section is uniformly black. Very often the secondary growths are more intensely pigmented than the primary tumor, and this is also the case in growths that have recurred after re- section. Tumors of this kind develop in tissues like the eye and pia mater, which normally contain pigment-cells, or in pigmented pathological formations. The black pigment-spots (melanomata) of the skin are of this latter class ; it has already been mentioned that they contain peculiar clusters or nests of cells (Fig. 54). TUMORS. 227 We do not know in what way the pigment is formed (Art. 67). It is not to be confounded with the brown pigment derived from extravasated blood. Patches stained with this blood-pigment are sometimes found here and there in a sarcomatous growtlq but the true melanotic pigment is something quite distinct. Psammomata, like melanosarcomata, are growths which arise in certain definite tissues, and but rarely anywhere else. They are sarcomatous, fibrous, or myxomatous tumors originating in the brain and its membranes, more particularly in the choroid plexus and pineal gland, and containing a multitude of chalky concretions. These have the same structure as the grains of the normal brain-sand (acervulus cerebri). They are made up of concentric calcareous strata, and form spherical or dendritic aggregations. They may be so abundant as to give the tumor a stony feel. [We may here just mention the variety of sarcoma called chloroma. It is a cellular tumor, whose section has a light green or dirty brownish- green tint. The color soon fades on exposure to the air. Nothing is known of the nature of the coloring-matter. Chloromata occur chieflv in the periosteum of the skull. See Huber, "Arch. d. Ileilk.," 1878.] 163. Some very peculiar forms of tumor are produced when sar- comatous tissue undergoes partial hyaline or mucoid degeneration ; or when sarcomatous and myxomatous for- rpations combine. They are generally in- cluded under the term cylindroma, though this may also be applied to tumors of an- other species in which epithelial cells are in- volved (Art. 173, Fig. 72). The ordinary soft cellular sarcomata have now and then a more translucent ap- pearance than usual, and yield on section a turbid slimy juice. These have already begun to undergo mucoid change, as may be recognized by the swollen appearance of the cells, and the formation of drops of liquid within them. When the tissue has been hardened the change is not so easily made out. The cells then seem shrunken (Fig. 55, 5), and separated from the stroma (a) by a clear zone. Sometimes a few distended and transparent nuclei are observed, their protoplasm having become mucoid and so vanished. This mucoid change may at times extend throughout the entire sub- stance of the tumor ; or it may be confined to scattered patches, sepa- rated by unchanged cells. Isolated hyaline spherules are occasionally Fig. 55.-Sarcoma Myxomatodes. x 400. (Hsematoxylin staining.) a,stroma; b, sar- coma-cells separated from the stroma by a clear zone (in part due to hardening in chromic acid and alcohol); c, swollen nu- cleus which has lost its protoplasm. 228 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. noticed among the cells. Such partially degenerate sarcomata we may describe as myxomatodes. The tumors in which sarcomatous and mucous tissue are found combined have on section either a hyaline or an opaque dirty white ap- pearance. The mucous tissue is partly composed of a network of ramified and anastomosing cells (Fig. 56, a), in addition to a mucoid basis-substance. Within this tissue lie also branching clumps and strings (b) made up of closely compacted cells. These strings are very irregular in form and anastomose in all directions ; they give the tumor a very peculiar texture. Its general structure justifies the name of myxosar- coma, which has been applied to it. It forms, as has been said, a sub- division of the class of cylindromata. It is not clear, from a histological Fig. 56.-Section of Myxosarcoma (Cylindroma), x 250. (Carmine staining.) «, mucous tissue; ft, strings and clumps of ceils ; c, fibrous tissue. point of view, in what way the clumps and strings of cells are formed. They seem to have no relation to the ramifications of the vessels, for these are seen to be unchanged, and run through parts where the fibrous tissue has undergone no degeneration. A third variety of cylindromatous tumor, also somewhat translucent and in part gelatinous, is characterized by the hyaline degeneration which affects the walls of its vessels and the tissue around them. If one of these vessels be isolated, it is seen to be invested with a more or less abundant deposit of hyaline substance (Fig. 57, a). To this sheath are attached similar hyaline appendages not traversed by vessels. Outside the hyaline sheaths, alternating with them in fact, are nests and strings of cells which here and there seem fastened or anchored to the hyaline masses (Fig. 57, 6). The strings of cells have much the same look as those shown in Fig. 56, and we infer that the tumor in question is allied to the myxosarcomata just described. The homogeneous appendages are TUMORS. 229 the result of hyaline degeneration of the vessel-walls, or of the neighbor- ing tumor-cells ; and this hyaline degeneration is either identical or con- nected with mucoid degeneration. The fact that actual mucous tissue (like that in Fig. 50) is occasionally found mingled with the hyaline masses tells in favor of this view. This form of cylindroma may therefore be regarded as a peculiar vari- ety of myxosarcoma, in which the mucoid change is chiefly confined to the vessels, and in which the formation of new vessels is an essential feature. To emphasize the important part played by the vessels in this neoplasm, we might call it angiosarcoma myxomatodes. Tig. 57.-Bloodvessels with Hyaline Sheath and Appendages from a Cylindroma, x 200. (From Sattler's •" Cylindrome," 1874.) a, small vessel; b, patch of epithelial-like cells on one of the hyaline appendages. Such growths have been found principally in the lachrymal glands, salivary glands, and in the brain. They occur, however, elsewhere, as in the lip, placenta, adipose tissue, etc. [Cylindroma is a term due to Billroth ("Untersuch. uber die Entwick. d. Blutgefasse," 1856). Such tumors, characterized by gelatinous masses and reticula, have since then been very variously interpreted. Koster de- scribed them as cancroids (" Virch. Arch.," vol. xl.); Sattler ("Ueb. d. sogen. Cylindrome," Berlin, 1874) as alveolar sarcomata, in which the cell-masses derived by proliferation from the adventitia had been trans- formed into hyaline cylinders; Ewetzky (" Virch. Arch.," vol. Ixix.) as plexiform angiosarcomata with hyaline degeneration of the fibrous stroma, or of the adventitia of the vessels. R. Maier ("Virch. Arch.," vol. xiv., and " Lehrb. d. allg. path. Anat.") found cylindromata in the placenta and dura mater ; he regarded the presence of an abundance of hyaline mu- cous tissue persisting for a long period unchanged as characteristic of the tumor. This tissue may develop out of cells or out of intercellular sub- stance, fibrous tissue, cartilage, or tunica adventitia. 230 A TEXT-BOOK OE PATHOLOGICAL ANATOMY. Various tumors have been described as cylindromata which certainly do not all belong to the same species. A number of them belong to the sarcomata. Within this group we may, as we have said, distinguish two main forms : first, the combined sarcoma and myxoma, and secondly, the sarcoma with hyaline or mucoid degeneration extending to the cells, but chiefly affecting the sheaths of the vessels. Between these two, however, many transitional forms are found.] I. Mixed Tumors of the Connective-tissue Group. 164. We have already referred to various tumors in which combina- tions of different tissues present themselves. In one sense, no tumor can be said to consist of a single kind of tissue only. In a new growth of any size we must always have new vessels, for instance. And tumors whose characteristic element is not fibrous tissue-such as chondromata, osteomata, sarcomata, myomata, and myxomata-always contain a very considerable quantity of fibrous tissue as an accessory. We do not speak of such cases as examples of mixed tumors, because the accessory tissue is, as it ■were, put out of sight by the characteristic element ; it is entirely subordinate. But if the second tissue comes into the foreground and affects the texture of the growth in a perceptible way, we must indicate this in our terminology. This is done by applying to the name of one neoplastic tissue the name of the other as a qualify- ing term ; or by simply combining the two names into a compound word. Thus, as in gliomata and fibromata, the blood-vessels may be remarkable by their abundance, size, and dilatations ; we then speak of the growth as a glioma (or fibroma) telangiectodes or cavernosum. A morbid com- bination of adipose tissue with mucous tissue is called lipoma myxoma- todes or lipomyxoma ; a combination of cartilage and sarcoma-chondro- sarcoma ; and so on. It is not rare for three or more kinds of neoplastic tissue to be found within the same tumor. A growth which starts in fascia or intermuscular fibrous tissue may consist, for example, of fibrous, sarcomatous, mucous, and adipose tissue ; there may even be vascular changes here and there which give it a telangiectatic character. Such a combination is not very surprising. The neoplastic proliferation may it- self result in the development of several diverse tissues-or, what is more common, the tissues of the connective group become transformed the one into the other. We showed, for example, in Arts. 90-92, that cartilage readily passes into mucous tissue, which is also frequently produced from fibrous or adipose tissues. Sarcomatous tissue may easily be the result of proliferation of the cartilage of a chondroma, or the fibrous tissue of a fibroma ; and conversely, sarcomatous tissue may equally well be trans- formed partially into osseous tissue. Tumors originating in bone are very apt to show a tendency to bone-formation. There are two forms -peCBsially in which this often occurs-namely, osteoid chondroma, a com- TUMORS. 231 bination of cartilage and bony tissue ; and osteosarcoma, a combination of sarcoma and bony tissue. 165. Osteoid chondroma (or osteochondroma) chiefly affects the larger long bones. If no sarcomatous proliferation has modified it, it usually forms a hard tumor seated on the bone or embracing it. It often reaches an enormous size ; and cannot be cut with the knife, unless a patch of unaltered cartilage be hit upon. When sawn through, the cut surface has the look of dense, white, continuous bone ; on closer examination this is seen to be interspersed with streaks and islands of more translucent cartilage. Fig. 58 shows well the general texture of the growth and its Fig. 58.-Section from an Osteoid Chondroma of the Humerus. (Magnified by means of a simple lens; double-staining with haematoxylin and carmine.) a, cortical layer; b, medullary spaces or cancelli; c, perios- teal growth ; d, normal Haversian canals ; e, Haversian canals distended with cartilage, which at/contains a core of new bone; g. cartilage developed from periosteum, which at h. contains bony trabeculae; i, cartilage developed from medullary tissue, which at k contains bony trabeculae; I, original trabeculae; m, remnants of medullary tissue. matrix, and its relation to the bone. The section represented is taken from a tumor of the humerus. The tumor was very firm and bony, and surrounded the bone so as to double its diameter. It was found on di- viding the bone longitudinally that the medullary spaces were filled with firm tumor-tissue of the same structure as the periosteal growth. The original bone was only recognizable in the region of its cortical layer. Fig. 58 represents a section taken at right angles to the axis of the bone, and including the periosteal growth, the cortical layer, and a part of the altered cancellous tissue. We find instead of periosteum a mass of cartilaginous tissue {g} in- 232 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. terspersed thickly with bony trabeculae (A). These run generally at right angles to the surface of the original bone, but anastomose freely. Small lacunae and canals are seen throughout the cartilage ; they contain a few blood-vessels and a small amount of fibrous tissue. The corti- cal layer (a) is still distinguished by the concentric stratification of the lamellae. Many of its Haversian canals are dilated and filled up (except fora small lumen in which the blood-vessel runs) with masses of cartilage. These masses sometimes contain trabecular cores of new-formed bone (/'). Instead of the marrow, which should fill the interior of the bone we find vascularized cartilage, also containing numbers of trabeculae. The genesis and primary seat of the growth may thus be made out at once from this preparation. Cartilaginous proliferation has been set up in the periosteum and in the medullary tissue, and the product has subsequently been partially transformed into bone. Osteosarcoma has an exactly analogous appearance. The difference is merely that sarcomatous tissue fills the spaces between the trabeculm instead of cartilage. The trabeculae are at the same time more delicate and less numerous. The seat of the tumor (as is the case too with os- teoid chondroma) is often confined to the periosteum. The bone is then more or less eroded. [References :-Muller, " Muller's Arch.," 1843 ; Virchow, " Die kr. Geschwiilste," i.; Rindfleisch, " Path. Hist.," ii.; Wilks and Moxon, "Path. Anat.," London, 1875 ; Paget, " Surg. Path.," Lecture 33. A summary of cases and some beautiful drawings of sarcomatous tumors connected with bone will be found in Butlin's " Sarcoma and Carci- noma," London, 1882.] CHAPTER XXVII. EPITHELIAL TUMORS. 166. The tumors we have hitherto treated of have been developed out of tissues belonging to the connective-tissue group; in other words, out of tissues derived from the mesoblast. The tumors we have now to deal with contain in addition epithelial elements, that is to say, structures derived from the epiblast and hypoblast. These epithelial elements are in fact the structures which give its special character to the class. The tumors of the class are therefore very fitly comprehended under the one title of epithelial neoplasms. All of them consist of epithelial cells on the one hand, and of vascular connective tissue on the other. The latter tissue goes to form the framework or stroma in which the epithelial ele- ments are embedded. The type or plan of their construction is that of the simple gland, and they maintain the resemblance throughout many of the phases of their development. They thus call to mind in many ways the various glands of the body ; though the degree of resemblance differs much in the different forms. Some of them are built exactly on the plan of some particular gland ; the new-formed tissue corresponds to a definite glandular type. Tumors of this kind we call adenomata. Another group never reach this perfection of structure. They ex- hibit as it were only the first stage of the gland-making process. Epithe- lium and fibrous tissue interpenetrate each other in an inchoate way. nihe process is never carried higher, but the crude formation is repeated and reproduced indefinitely. By multiplication of the epithelial cells we have produced nests and clusters and strings of cells, and these are em- bedded in connective tissue whose elements are likewise multiplying. The result is a neoplasm consisting of a fibrous network or framework, in the meshes of which are lodged a multitude of variously shaped epithelial cells. But there is no orderly arrangement of these epithelial cells. In the adenomata they tend to clothe the walls of the alveoli in a regular way, leaving open a central lumen as in the acinus of a gland. In the tumors now considered these cells remain in compact irregular masses. Epithelial tumors of this kind, in which the glandular type is most im- perfectly followed, are described as carcinomata or true cancers. Adenoma and carcinoma are generally malignant. They tend to in- 234 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. vade the surrounding tissues ; and, by the channels of the lymph or of the blood, are apt to affect distant regions and produce metastases. But the degree of malignancy varies greatly ; it depends not only on the histological structure of the growth, but, to an even greater extent, on its locality. [The definition we have given of adenoma and carcinoma is based partly on their histology, partly on their mode of genesis. From the morbid anatomist's point of view this is the only correct mode of defini- tion. Tumors containing none but mesoblastic cells may and do corre- spond in their general structure with others, in which undoubted epi- thelial cells form the characteristic element ; and for this reason a merely anatomical method of diagnosis would be insufficient. If carcinoma be defined as an alveolar tumor composed of a fibrous network containing nested cells, it is impossible to separate between carcinoma and alveolar sarcoma. It is owing to this purely anatomical mode of definition that we have had controversies as to whether carcinoma really depends upon epithelial proliferation, and whether cancers may not have their origin in fibrous structures. Such controversies become irrelevant if we base the distinction on histogenetic grounds. A tumor is to be called car- cinomatous only when the epithelial elements take an active part (as above described) in its formation. A connective-tissue tumor which has ostensibly the same structure, but whose mode of genesis is entirely dif- ferent, is to be distinguished as an alveolar sarcoma.] a. Adenoma. 1G7. Adenoma is a tumor constructed after the type of a secreting gland. The definition might at first sight tempt us to term every glan- dular enlargement, in which the elements are abnormally multiplied, an adenoma. This would, however, be incorrect. Adenoma is a true neo- plasm, characterized physiologically by its impotence to produce the nor- mal gland-secretion, and anatomically by its want of relation to the tissue in which it is seated. A gland enlarged by overgrowth, or overwork, or chronic inflammation, cannot be described as an adenoma. It is a hyper- plasia ; and if it be the true gland-tissue and not merely the fibrous framework which is excessively developed, the physiological activity of the gland is thereupon increased. We must regard in the same way the tumor-like growths which occa- sionally develop in mucous membranes, chiefly as a result of chronic in- flammation. They are mere localized proliferations, rising above the general surface as nodular, polypous, or papillary outgrowths. The fibrous tissue is the first to increase, and this leads to some increase of the epithelium, chiefly because the local submucous swelling involves an increase of the mucous surface. If any glands are present (as in the in- testine or uterus), they also undergo change. If their ducts become TUMORS. 235 blocked, they may become distended with secretion, and form larger or smaller cysts. Other glands may enlarge by increase of their stroma ; and lastly, there may be in some an active growth and increase of the specific gland-tissue. It is easy to demonstrate that such new-formations of fibrous and glandular tissue do take place. The most suitable objects for examina- tion are perhaps the papillary or villous growths which form on the inner sur- face of glands undergoing cystic de- generation (Fig. 59, c). These are sometimes so abundant that the cyst seems quite filled up with the new tissue. Such an overgrowth of the mucous membrane, in which the local glands are simultaneously enlarged, is best de- scribed as a glandular hyperplasia. 168. True adenoma is generally dis- tinguishable from glandular hyper- plasia by obvious characteristics. Its consistence, color, and structure all mark it off plainly from the surround- ing tissue. Adenomata are usually knot-like growths arising within the substance of glands, or in glandular epithelial or epidermic tissues. In the first case it is generally a part only of the gland that is transformed into tumor-tissue. In the mucous membranes and skin the tumor is likewise circumscribed. When an entire organ like the ovary is included in the growth, it is easy to make out by the alteration in the structure that it is an adenoma, and not the result of simple hypertrophy. Adenomata are often pale, soft, and marrowy ; in other cases they are dense and coarse. Microscopic examination will obviate any doubt, which mere inspec- tion may leave, as to the nature of a questionable adenoma. The struct- ure of the neoplasm is always different from that of the affected tissue. It always corresponds with the type of some normal tissue ; but this is not the type of the matrix in which it lies. Adenoma of the intestine may be made up of ramified and convoluted tubules-not of Lieberkiihn- ian crypts. Adenoma of the liver may be made up of tubular glands in- stead of lobules. Adenoma of the mamma is at once distinguished from the normal gland-tissue by the mode in which the epithelial cells are repro- duced and arranged, and by the structure of the neoplastic acini. The difference between normal and neoplastic gland-tissue is perhaps most marked of all in the case of the ovary. Ovarian adenoma is apt to grow to an enormous size, and very often imperils the life of the patient afflicted with it. It usually takes the form of a multilocular cystoma, or cystadenoma, as it is called, and is made up of a multitude of small and large cysts. These contain a ropy, clear or turbid, and variously Fig. 59.-Papillary Growths inside a Cyst, x 300. (From a gastric polypus : haematoxylin staining.) a, gland tubules with cylindrical epi- thelium ; b. stroma infiltrated with cells; c, pa- pillary growths into a cyst, covered with mucoid epithelium. 236 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. tinted liquid. Their inner surface resembles that of smooth mu'cous membrane. The walls are chiefly of a fibrous texture ; but here and there occur masses of tissue with a soft marrow-like section, and white or pink in color, which resemble parenchymatous gland-substance. These masses exemplify the early stages of the tumor's development ; they con- sist of a fibro-cellular stroma, containing glandular tubules lined with tall cylindrical epithelium (Fig. 60). Some of the tubules are dilated. This dilatation is the first step toward the formation of a cyst ; it is the re- sult of an accumulation of secretion. When small cysts are thus formed, the fibrous tissue round them often proceeds to grow into the cavity in the form of papillary protuberances (Fig. 60). These papillary growths, which often develop in vast numbers, give to this variety its specific name of papilliferous cystadenoma. Fig. 60.-Section from a Papilliferous Cystadenoma, x 40. (Hematoxylin staining.) 169. All adenomata have not the same grave significance, whether we regard the affected organ or the system generally. Ovarian adenoma destroys the organ and jeopardizes life by its size ; but it forms no me- tastases and does not invade neighboring structures. Adenoma of a sweat-gland or sebaceous gland remains as a local tumor, never reaching any great size. But the case is different with the adenomata of the ali- mentary canal, namely those of the stomach, large or small intestine, and rectum. Each of these tends to invade and destroy the surrounding parts, and to form metastases. They are as malignant as the malignant carcinomata. In order to indicate this fact in their distinctive name, they have been called destructive adenomata, or adenocarcinomata. Their malignancy is manifested even in their local behavior. Fig. 61 represents a section through the advancing margin of a small destructive adenoma of the stomach ; it is remarkable for the great size of its glan- dular tubules and of the epithelial cells which line them. The figure (Fig. 61) shows that the neoplastic tubules are first devel- TUMORS. 237 oped in the mucosa, the normal constituents of the mucous membrane simultaneously disappearing. Starting thence the neoplasm invades the submucosa (Z>). It intrudes itself along the intermuscular septa between the muscle-bundles of the muscularis (c) ; and finally extends along the serous layer ('/). Here and there through the fibrous tissue may be seen heaps of small cells ; this indicates that proliferation is going On in this tissue likewise. Fig. 61.-Section through the Advancing Margin of a Destructive Adenoma of the Stomach, x 25. (Haematoxylin staining.) a, mucosa ; 6, submucosa ; c, muscularis ; nt, serosa; e. neoplasm which, starting from the mucosa, has invaded the other layers. Small-celled infiltration here and there accompanies the formation of the neoplastic tubules. This invasion of the neighboring tissues is the first step toward the formation of metastases. Clearly the lymph-spaces of the tissue are cer- tain to be encountered by the advancing growth, and when this happens the path of infective transport stands open. Destructive adenoma is a soft marrowy tumor, taking the form either of a papillary or fungous outgrowth, or more commonly of a level and ex- tensive thickening of the mucous membrane. The new tissue frequently breaks down and ulcerates. The ulcers have a soft infiltrated base and raised rampart-like edges, or the surrounding tissue is beset with nodular growths. b. Carcinoma. 170. If we define carcinoma as a growth characterized by epithelial multiplication (Art. 166), and not agreeing with any normal glandular type, we must at the same time lay stress on the fact that this epithelial 238 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. multiplication is no merely accessory or subordinate feature. It is the essential and distinguishing character of the neoplasm. Simple non-typical multiplications of epithelium are by no means uncommon ; but they are not necessarily to be interpreted as carcinoma- tous. Subepidermic granulomatous tumors of the skin (Art. 132, Fig. 37) will often exhibit in their superficial layers clusters and rolls and strings of epithelial cells altogether diverse from any normal mode of grouping ; and the same may be observed in skin-wounds which are in process of re- pair by epidermic growth and multiplication. So, too, in glands altered by inflammation, and in fibrous tumors occurring in glands, the glandular epithelium may begin to multiply and lead to the formation of epithelial Fig. 62.-Section from a Cutaneous Cancer or Epithelioma, x 20. (Aniline-brown staining.) a, epi- dermis ; b, corium; c, subcutaneous areolar tissue; d, sebaceous gland: e, hair-follicle ; f. cancerous in- growths from the epidermis; g, deep-set cancerous cell-groups; h, proliferating fibrous tissue; i (above), cell-nest or epidermic globe; i (below), sweat-gland. masses that are altogether non-typical or atypical in appearance. For- mations of this kind are not to be classed with the carcinomata. They lack the power of growing indefinitely and of infiltrating the surrounding tissues. They are incapable of raising themselves to the rank of the independent tumor, that is nourished like a parasite at the expense of the organism, and invades the tissues to their destruction. They can only extend where a free surface is open to them, due either to antece- dent inflammation or to the formation of a true tumor. In wounds or subepithelial granulations these proliferous growths have no more signi- ficance than the covering of an abraded surface with new epithelium. The epithelium forms only in places where the underlying tissue is so arranged as to leave free surfaces or open. fissures, and the process amounts, in a word, merely to the " skinning-over " of internal surfaces. The mode in which true carcinoma develops and extends is quite dif• TUMORS. 239 ferent. The epithelial new-formation is not limited to free or bared sur- faces ; it actively invades the contiguous connective tissues. Thus we may have a cutaneous cancer or epithelioma, which consists essentially of cellular prolongations of the interpapillary promontories of the Mal- pighian layer, penetrating and ramifying in the fibrous tissue of the corium (Fig. 62, f). These prolongations go on growing and multiply- ing, and ultimately infiltrate the corium over a more or less extensive area, taking the form of detached strings and nests of cells (^). In this case, then, we may regard the carcinoma as an epithelial infiltration of the corium starting in the superficial epidermis. The share taken by the corium itself is not always the same. At first we are generally unable to detect in it any histological change whatsoever. The fibrous stroma in which the epithelial cells are lodged is furnished by the unaltered corium alone. In other cases, and in later stages (Fig. 62, A), a percep- tible amount of cell-multiplication, and occasionally of vascularization, takes place. It almost looks as if the fibrous tissue were endeavoring, by compensatory growth on its own part, to counteract the invasion of its borders by the epithelium. In tumors formed in the way we have described, the intruded masses of epithelial cells are spoken of as cancerous cell-nests, and the sepa- rate cells as cancer-cells. The fibrous framework in which they lie, made up partly of pre-existing and partly of new-formed fibrous tissue, is called the cancerous stroma. 171. The development of cancer in glands is essentially similar to that which starts in squamous epithelium or epidermis. Thus in the glands of the uterus we have cancer commencing with active growth and multiplication of the cylindrical epithelial cells. The single layer of cylindrical cells is transformed into a series of stratified or disorderly masses of epithelium (Fig. 63) piled upon each other. The size of the gland (J) is thus considerably increased, and soon its typical structure is overlaid and lost by the substitution of great cell-masses and cancerous cell-nests or loculi. The cells retain their cylindrical form only at the borders of these groups. This represents the first stage. In the second, the surrounding tissue is invaded and infiltrated by cancerous cell-nests. A section from the advancing margin of a mammary cancer (Fig. 64) shows at one view the various steps of the process ; a low magnification is all that is necessary. The first stages in the formation of the mammary cancer are essentially the same as those observed in uterine cancer, though the peculiarities of the matrix bring about certain minor variations. The primary aberration is an excessive multiplication of the glandular epithe- lium. This is followed by general epithelial infiltration. The small and scattered acini of the mamma are replaced by cancerous cell-nests of various form and size (e), embedded in a scanty stroma. Starting from these as primary foci, the infiltration of the connective tissues ex- tends far and wide beyond the region of the gland-tissue itself. The fibrous bundles are thrust asunder by the multiplying cells, which link 240 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. themselves into fusiform or rounded masses, or into long ramifying strings and bands. Spreading upward these invade the corium ; single cell- nests may even be found immediately underlying the epidermis (^). Within the substance of the nipple (a), also, we may discover numerous cancerous patches (A) in the fibrous tissue between the galactophorous ducts (<7). In the figure we note that the only uninvaded part of the gland is near its edge. Even here, however, the groups of round-cells scattered through the connective tissue (k) show that the structures are not altogether in their normal condition. Fig. 63.-Section from a Cancer of the Uterine Glands, x 250. (Haematoxylin staining.) a, stroma; b, cancerous ingrowths or loculi; c, isolated cancer-cells. To sum up all that we learn from this preparation concerning the ex- tension of the cancer we may say-that the process consists in infiltra- tion of the connective tissue with epithelial cell-nests ; that this is ac- companied or succeeded by inflammatory or proliferous changes in the connective tissue ; and that these ultimately result in fibrous hyperplasia. [We are chiefly indebted to Thiersch (" Der Epithelialkrebs," 1865) and Waldeyer ("Virch. Arch.," vols. 41, 55) for the discovery that a hrge class of tumors (other than the adenomata) existed, in which epithe- lium formed an essential constituent. Thiersch demonstrated that can- cer-cells are derived from epithelium, drawing his arguments principally from cases of cutaneous cancer or epithelioma. Waldeyer extended his TUMORS. 241 researches to organs of every kind. Many subsequent observations have proved-that a considerable number of tumors which were believed by Virchow and others to originate as connective-tissue growths do really originate in epithelial growth and multiplication. The class of con- nective-tissue tumors has thus been greatly diminished. The great ma- jority of the alveolar tumors included by Virchow under the general term carcinomata must now be ranked as epithelial tumors. See Bill- roth's " Surg. Pathology," third edition ; Lucke, in " Billroth u. v. Pithas Handbuch," vol. ii.; Schrbn, " Contrib. alia anat. della cute umana," 1865 ; and, for criticism of the " epithelial theory " of carcinoma, Paget's Fig. 64.-Section through a Mammary Cancer. (Magnified by means of a simple lens.) a, nipple; b, mammary tissue; c, skin; d, galactophorous ducts; e, cancer-tissue replacing the gland-tissue; /, fat- lobules, normal or undergoing cancerous change; g, cancerous skin ; h, cancerous cell-nests in the nipple ; i, normal acini; k, infiltration of fibrous tissue with round-cells. " Surg. Path.," Leet. 35. Koster's attempt (" Die Entwickelung der Car- cinome," 1869) to disprove the participation of the epithelium in a large class of alveolar tumors, and to derive the cell-nests from the proliferous endothelium of the lymphatics, has not proved successful. This being the case, it will be best in future to designate the various tumors not according to their structure merely, but also with respect to their genesis. Carcinoma will then imply not only an alveolar structure, but an epithelial origin also. The mode of genesis is the distinctive and definitive character ; the alveolar structure is merely a result of contin- gent or non-essential factors.] 172. From the description we have given, it will be manifest that the 16 242 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. so-called cancer-cells are nothing other than proliferous epithelial cells ; and we may therefore expect them to exhibit epithelial characteristics. Accordingly we find that they preserve throughout the traces of their descent. They are comparatively large, and have large vesicular nuclei containing nucleolar corpuscles ; and they have certain habits of group- ing peculiar to the parent structures. Cutaneous cancers (epitheliomata) contain cells exactly like those of the Malpighian layer, and they may undergo cornifying processes analogous to those which are normal in the case of the epidermis. Cancers starting in the intestinal mucous mem- brane are provided with cylindrical epithelium. But this maintenance of the ancestral cell-type has its limits. When strings or wedges of epithelial cells penetrate the fibrous tis- sues, it invariably happens that the tightly packed elements affect each other mutually, and chiefly as regards their form (Fig. 65). We may see how this occurs by considering a sec- tion of one of these conical epithelial wedges-which from their appearance have been called " bird's-nest bod- ies" (concentric or epidermic globes). When the cells are isolated it is found that there are scarcely two alike in shape. This multiformity of the cells of cancer has long been a familiar fact; it has even been exalted into a characteristic feature. It obtains in squamous epithelioma and in cylindrical carcinoma, starting in the cylin- drical epithelium of intestine or gland. The original type is only in a few cases preserved pure and unmodified. At the same time we must not look upon this multiformity as any- thing peculiar to cancer. Multiform cells may occur in other tumors-in the sarcomata, for instance. All we can say is-that in virtue of the peculiar mode of cell-multiplication in the carcinomata, multiform cells are especially apt to be produced in them. What is true of their alveo- lar structure is also true here. In consequence of their mode of develop- ment we always find that cancers are alveolar ; but other tumors whose genesis is entirely different may nevertheless exhibit the same structure. 173. Varieties of carcinoma have been distinguished according to their site and place of origin, the form and texture of the cells, the ar- rangement of the cells, and the mode of epithelial infiltration dependent thereon, and finally the abundance and texture of the fibrous stroma. Many of these distinctions have now ceased to have any real significance. The title given to certain cancers of the skin or mucous membrane- namely, epithelioma or epithelial cancer-is now useful only as indicat- ing conveniently their seat and histological structure. Formerly the title implied a contradistinction between cancer of the epithelia and can- Fig. 65.-Bird's-nest Body or " Concentric Globe " from an Epithelioma, x 250. TUMORS. 243 cer of the connective tissues. Other terms, like medullary, simple, or scirrhous, applied to various structural varieties of cancer chiefly origin- ating in the glands, have also only a limited application ; inasmuch as an individual cancer may not have exactly the same structure throughout all its parts, or in all its successive stages. Generally speaking, the form of the cancer depends on the structure of the matrix in which it is seated. A certain group of forms are found to recur perpetually in each particular organ. It would seem most nat- ural d priori to divide the carcinomata into two groups-those, namely, which start in investing or surface epithelium, and those which start in glandular epithelium. Such a division might be preferable from a theo- retical point of view ; but it is not always practicable, as it demands rather minute histological investigation. An epithelioma starting in a sebaceous gland has generally the very same appearance as one starting in a hair-follicle or in the epidermis. In cancer of the intestine, it would often be a matter of very great difficulty to decide whether the disease started in the simple lining epithelium, or in that of the crypts of Lieb- erkuhn. For this reason it is advisable to classify the carcinomata under a few main types, distinguished by sufficiently well-marked anatomical differences. The following are the most important. (1) Squamous epithelial cancer. The chief representative of this class is epithelioma or cutaneous cancroid (Fig. 62). This gives rise to warty and nodular tumors, or to diffuse thickenings of the skin. It is characterized by the occurrence in it of large epithelial nests, made up qf large multiform squamous cells. Ulcers are very often formed by the breaking down of the new tissue. If the section of an epithelioma be scraped, a gritty mass is obtained consisting mainly of nests and single cells. The nests often take the form of globes, in which the cells are arranged concentrically like the coats of an onion (Fig. 62, i). These at times become horny, forming what are called epithelial pearls. Epitheliomata in which these pearls are a distinct feature have been called horny or corneous cancroids. The tumor-cells of epithelioma are descendants of the superficial epidermis, and also of the epithelia of the hair-follicles and sebaceous glands. Squamous epithelial cancers occur in all the mucous membranes covered with squamous epithelium-in the mouth, pharynx, oesophagus, bladder, vagina, etc. (2) Cylindrical epithelial cancer. This has its seat in mucous membrane, chiefly that of the intestine, but also in that of the uterus. It forms soft nodulated tumors which start in the columnar epithelium of the glands. In consequence of active multiplication among the epithelial cells the glands become distended into more or less globular nests (Fig. 66). By mutual compression the cells assume very various forms, retaining their columnar character only at the periphery. Sometimes an unoccupied space or lumen remains at the centre. The cell-nests having thus the 244 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. appearance of gigantic gland-acini, the tumor has also been described as adenocarcinoma ; we reserve this term for the destructive adenoma de- scribed in Art. 169. Glandular cancer of a like kind, with a coarse alveolar stroma, occurs in glands like the kidney and mamma, as well as in mucous membrane. In them it likewise starts in overgrowth and multiplication of the glandular epithelium. The difference between this variety and the last consists simply in the absence of tall columnar epithelial cells among the other constituents. This is due to the fact that the epithelium in which the growth originates is spheroidal rather than columnar. Fig. 66.-Glandular Cancer of the Uterus, x 250. (Haematoxylin staining.) a, stroma ; 6, cancerous nests or loculi; c, isolated cancer-cells. (3) Simple carcinoma is a term often applied to a variety usually originating in glands, and forming rather firm nodulated tumors. In section these have generally a light grayish translucent look. The stroma and the cell-nests are often sharply distinguished from each other by the difference of their color ; especially when the cells have already under- gone partial fatty change, and so look white or yellowish-white and opaque. By scraping the section we can often obtain a fairly abundant milky juice. The tumor has a somewhat coarse fibrous framework (Fig. 67, a), containing alveoli of various sizes and shapes filled with masses of epithelial cells. It particularly affects the mamma, and occurs also in the stomach, pancreas, and kidneys. TUMORS. 245 (4) Medullary (or encephaloid) cancer. When the cells are very abundant and the stroma delicate and scanty, the consistence of the tu- mor may become remarkably soft and semifluid. Such forms occur chiefly in mucous membrane, but also in the ovary, kidney, testis, etc. They are described as medullary or encephaloid cancers. They resemble very much the softer adenomata and sarcomata. An abundant milky cancer-juice may be expressed from the cut surface ; it contains numerous cells and free nuclei, with fatty detritus and free oil-globules. (5) Scirrhus, or scirrhous cancer. In this the cell-groups are small and scanty and the stroma coarse and dense. The tumor feels firm or even hard, and looks very much like a dense fibroma. PlG. 67.-Section from a Simple Carcinoma of the Mamma, x 200. (Haematoxylin staining.) a, stroma; ft, nests or loculi; c, single cancer-cells; d, blood-vessel; e, fibrous stroma infiltrated with small cells. There is no sharp line to be drawn between scirrhus and simple can- cer. Within one and the same growth we may find a part having the text- ure of scirrhus, and another resembling simple cancer (Fig. 68). The question is merely whether the stroma or the cellular elements predomi- nate. The characteristic hardness of scirrhus is found at spots where the fibrous stroma is not so much alveolated as interspersed with small fusi- form cell-nests (Fig. 68, <7, A). The cancer-cells often perish by fatty degeneration, and are then ab- sorbed. The coarse fibrous stroma is left, looking like a deposit of firm scar-tissue. Cancers which have become hard and fibrous in this way are found not only in the mamma but also in the stomach, testis, ovary, and kidney. (6) Colloid (otherwise gelatinous or alveolar) cancer occurs as a def- inite tumor or a diffuse infiltration. It is most frequently found in the alimentary tract and in the mamma, more rarely in the ovary or other or- 246 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. gan. It is characterized by the translucency of its substance. The stroma seems to contain masses of jelly rather than the usual more or less opaque cell-nests. The transparent glassy look may be apparent even on Fig. 68.-Simple Cancer of the Mamma (Scirrhous in parts). (Magnified by means of a simple lens; same as Fig. 64.) a, nipple; b, mammary tissue ; c, skin ; d, galactophorous ducts ; e, cancer-tissue replac- ing the glandMissue; /, fat-lobules, normal or undergoing cancerous change ; g, cancerous skin; A, cancer- ous infiltration of the nipple; i, normal acini; k, infiltration of fibrous tissue with round-cells. the outside of the tumor. This is true, for instance, in the case of col- loid cancer of the mucous membrane, which usually forms semitranspar- ent papillary or fungous excrescences. In the mamma the colloid char- Fig. 69.-Colloid Cancer of the Mamma, x 250. (Haematoxylin staining.) a, stroma ; ft, cancerous cell- nests ; c, empty alveoli; d, cells containing globules of colloid substance. acter becomes apparent only on cutting through the tumor. It often happens that the whole tumor is not alike, some parts being translucent, others grayish or reddish like the more ordinary forms. TUMORS. 247 The colloid or gelatinous texture of the tumor is due to mucoid or colloid change affecting the cancer-cells (Fig. 69). It begins with the formation of clear globules in their interior (c?). The cells then perish, and the globules coalesce with each other and with larger gelatinous lumps already formed. In this way a large homogeneous colloid mass is ulti- mately built up. It is not uncommon for all the cells over a wide area to perish in this manner, so that the stroma is the only formed constituent remaining. In other spots, cell-groups may still be found encircled by colloid masses (Fig. 69, b) ; in others again there is no colloid substance at all. (7) Carcinoma myxomatodes. A cancerous tumor may likewise assume a gelatinous texture in consequence of mucoid change affecting the stromq, (Fig. 70). With this metaplasia of the fibrous tissue there Fig. 70.-Carcinoma Myxomatodes of the Stomach, x 250. (Hiematoxylin staining.) a, cancerous lo- culi ; b, fibrous stroma ; c, mucoid stroma ; cl, mucoid cancer-cells. may also be associated a mucoid degeneration of the cancer-cells (Fig. 70, d) ; and this may increase considerably the transparent and gelatinous appearance of the growth. The connective tissue-cells of the stroma may also perish, so that we are often unable to find any traces of cell-structure over wide areas. The favorite seats of this variety are the same as those of colloid cancer. (8) Cylindroma carcinomatodes is a very rare variety of cancer, characterized by the formation of homogeneous spherules within the cell- nests (Fig. 71). These spherules, which are possibly to be regarded as masses of col- loid substance, press asunder the other cells of the group (Fig. 71, b). If a considerable number of spherules form within the same loculus, the cells may be compressed into slender trabecube (c), and so come to form a kind of anastomosing network. This variety has been described as a cylindroma (Ziegler has only once met with it, and then in the lachrymal 248 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. gland). To distinguish it from the sarcomatous kind (Art. 163), it has been called carcinomatodes. (9) Giant-celled (or myeloid) cancer is a form in which some of the cancer-cells attain an inordinate size. All parts of the cell-protoplasm, nucleus, and nucleolar corpuscles-contribute to this enlargement. They become at the same time remarkably transparent, and the general aspect is much as if the cell had imbibed a great quantity of water, and had in consequence swollen out enormously. Fig. 71.-Section from a Cylindroma Carcinomatodes. x 150. (Carmine staining.) a, unaltered locu- lus or cell-nest; b, cell-nests with a few hyaline spherules; c, cell-nests reduced to a honeycombed reticulum by the formation of numerous hyaline spherules. (10) Melanocarcinoma is a sufficiently distinct variety to deserve mention. It gives rise to gray, brown, or black tumors. The pigment is contained partly in the cancer-cells, partly in the stroma. It is seldom met with ; being much rarer than melanotic sarcoma. [References:-Waldeyer, "Virch. Arch.," vol. Iv. ; Rindfleisch, " Path. Histology," vol. i. ; Lucke, Art. " Geschwtilste " in " Hand. d. Chirurgie v. Pitha u. Billroth," ii. ; Peris, " Allg. Path.," 1877 ; Paget, " Surg. Path.," Lectures 30 to 35 ; Lebert, "Des maladies cancereuses," Paris, 1851.] 174. The extension of a cancerous growth is not at an end when the organ originally attacked is infiltrated throughout. Cancer pays small heed to the boundaries between the various tissues. Sooner or later (latest of all in encapsuled organs like the kidney), the cancerous process invades the neighboring tissues. Some of these, chiefly the spe- cific tissues like glandular epithelium, muscle, bone, etc., disappear before the advancing growth. Fibrous tissue, on the other hand, is usually ex- cited to proliferation, and new tissue and blood-vessels may thus be formed and converted into cancer stroma. Now and then other prolifer- ations are set up in the neighborhood of the tumor, and in this way, for example, new bony growths may be formed. TUMORS. 249 In addition to this peculiar power of invasion, cancer has also in a high degree the power of originating metastases or secondary growths. The germs which give rise to these metastases are the can- cerous epithelial cells, which are carried off to remote places by the blood or lymph. The first development of the secondary nodules starts in these, when they have found a suitable nidus. An epithelial germ may reach the liver, for instance, and become wedged in one of the terminal radicles of the vena portm. If it finds adequate nutriment there, it begins to grow. It subdivides and multiplies, and thus a cell-nest is presently formed (Fig. 72) which distends the capillary vessel, and by compression causes the liver-cells to dwindle and atrophy. By the aid of the fibrous elements of the vessels, which proceed to multiply, and so furnish a fibrous stroma and accessory vessels, a secondary nodule is at'length Fig. 72.-Section passing through a Cancerous Embolus of a Hepatic Capillary, x 300. (From a case of primary adenocarcinoma of the stomach; haematoxylin staining.) The cancer germs have just begun to develop into a, secondary nodule. Fig. 73.-Metastatic Development of Cancer in a Hepatic Capillary, x 250. (The primary focus was in the pancreas; fibrous tissue as well as cell-nests have been formed within the capillary.) Fig. 72. Fig. 73. evolved, whose structure resembles in all points the structure of the parent nodule. The hepatic lobules are either pushed aside and com- pressed, or they are interpenetrated by strings of cancer-cells starting from the nodule. This is the result of the mode of growth of the nodule. It grows chiefly at its periphery, and extends along the open capillary channels (Fig. 73). In this way the capillaries themselves are one after another replaced by cancer-tissue. As this latter extends, the liver-cells gradually disappear. The epithelial elements of the secondary nodules are to be regarded as, without exception, the progeny of the original cancer-cells trans- planted from the parent growth. The fibrous tissue in which they are embedded is furnished by the connective-tissue elements of the blood- vessels. 250 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [The origin of the cancer-cells in secondary nodules has been the sub- ject of as much discussion as the genesis of the primary growth. Even now a certain amount of disagreement exists on the question. Rind- fleisch, Klebs, Gussenbauer, Weil, and others, maintain that the connec- tive-tissue cells, and especially the endothelia of the blood-vessels and lymphatics, take an active share in forming the cancer-cells of the me- tastatic growths. Gussenbauer (" Langenbeck's Arch. f. Chir.," xiv.) and Weil (" Wien. med. Jahrb.," 1873) go so far as to say that even striated and non-striated muscle-fibres may be stirred up (in £ manner infected) so as to produce cancer-cells. Simon, Creighton, Moxon, and others in this country, have put forward like theories ; they are accus- tomed to speak of a " spermatic " influence exerted by the transported germs upon the tissue-elements of their new seat (" Trans. Path. Soc.," 1874). Ziegler is unable to find any satisfactory evidence for such a view. He made numerous investigations bearing on the question, and under his guidance Fronista examined a multitude of secondary growths in various organs ; but no certain grounds for the theory were ever dis- covered. Active changes in the fixed cells were often very beautifully shown ; but wherever it was possible to trace the fate of these cells it was found that they merely went to form the type of tissue which they would reproduce in normal circumstances. The osteoblasts of the peri- osteum and marrow form bone or fibrous tissue ; endothelial cells like- wise produce only connective tissue. It is not, however, to be inferred that these investigations absolutely and certainly exclude the possibility of a cancerous transformation of the products of connective-tissue pro- liferation. When a tissue has undergone extensive proliferous changes, nothing certain can be made out from it regarding the origin or the fate of individual cells. The cancerous embolus acts like a foreign body. Round it are set up inflammatory infiltration of leucocytes on the one hand, and multiplication of the fixed cells on the other. Both processes result in fibrous hyperplasia, which in many cases goes to form a new stroma for the growing nodule. The same processes are thus repeated here as occur in the fibrous structures of the primary focus. It is there- fore well to hold by the doctrine of Remak and Goodsir-at least until it is certainly disproved-that as the descendants of the different em- bryonic layers are never transformed into each other in normal circum- stances, so also under pathological conditions no such metaplasia can occur. Even the transformation of one epithelial formation into another suggested by some (Rindfleisch, " Path. Histology," Art. 531 ; Peris, " Virch. Arch.," vol. Ivi., etc.) has not been established. When carcino- mata of the liver are examined the liver-cells are seen to dwindle and perish, but not to change to cancer-cells. Even in cases where mammary cancer penetrates the corium and reaches the epithelial layers of the skin, it is always possible to distinguish clearly between the cancer-cells and the true cutaneous epithelium.] TUMORS. 251 175. Carcinoma is very prone to undergo retrogressive change. In the juice scraped from the cut surface of a cancer we may nearly always find cells which are fatty or disintegrating. This is especially the case in soft quickly growing tumors. If the fatty change is extensive the af- fected spots look white and opaque, and by and by break down into a creamy pulp. The disintegrated cells may also become condensed into cheesy masses. More commonly, however, we find that a part of the cells become absorbed. In tumors lying beneath the surface of an organ or raised above its general level, a central depression or dimple may thus be formed. The tumor is then said to be umbilicated. In cancers with a dense stroma, in which the disappearance of the cells is accompanied by hyperplasia of the fibrous elements, we may find the original growth replaced by a dense coarse deposit of fibrous tissue containing few, if any, cancerous cell-nests. This transformation is specially frequent in the case of mammary and gastric scirrhus. Mucoid degeneration has already been discussed (Art. 173). Amy- loid degeneration of the stroma has frequently been observed. The necrotic disintegration of cancerous growths, and the consequent formation of cancerous ulcers, deserve special mention. Tumors of great size may in this way be wholly destroyed. In intestinal cancer, for example, it is no rare thing to find after a certain time nothing but an ulceration, replacing the original tumor, and bearing hardly any re- semblance to it. If the ulcerative process is not far advanced, the re- mains of the tumor may be recognized as nodules or papillary excres- cences rising from the base or border of the ulcer. In later stages the base may be smooth and clean, consisting simply of firm fibrous tissue ; while the edges rise like ramparts, or are beset with papillary or nodular growths. Now and then these may disappear in like manner, and the ulcer appears as a non-cancerous sore with an indurated base. Even on section it may not always be possible with the unaided eye to decide whether the tissue still contains cell-nests or not. We must in such cases have recourse to the microscope. Cutaneous or epitheliomatous cancers, like those of mucous mem- brane, may also ulcerate ; and so, too, may cancers of the mamma or other subcutaneous glands. The surface of these breaks down, and great putrid or fetid ulcers are the result. The seat of an ulcer is always the seat of a more or less intense in- flammatory infiltration. Sometimes this results in vigorous granulative proliferation, the granulations rising above the surface as fungous ex- crescences. They are distinguished from ordinary granulations by the cell-nests they contain. From this granulation-tissue ordinary cicatricial tissue may be elaborated. A sort of local healing and recovery may thus result-from the destruction of the tumor, and the formation of granula- tive and cicatricial tissue. The growth may seem to have altogether disappeared. But this healing is only local and relative, and it does not last. Microscopic examination shows that the cancerous invasion of the 252 A TEXT-BOOK OE PATHOLOGICAL ANATOMY. deeper structures still persists. The formation of secondary growths, even after the surface ulceration is scarred over, testifies to the fact that the malignancy of the process is not removed with the removal of the primary growth. 176. Adenoma and carcinoma may be combined with other neoplastic formations ; that is to say, the stroma may be composed of other than fibrous tissue. In the first place, it must be remembered-that as cancer invades successive tissues, the most various structures may in turn be utilized to form its stroma. Thus when a uterine cancer reaches the muscular coats of the organ, we find that the stroma of the tumor con- tains smooth muscular fibres. When secondary nodules form in the liver, we often see liver-cells, atrophied no doubt but still recognizable, in the trabeculae of the stroma. The new-formed tissues which actually originate in the stroma are to be distinguished from such pre-existing formations. In the former case we may find that not only fibrous tissue but even cartilage or sarcomatous tissue has been developed. Such neo- plasms are described as complex or mixed tumors. They are most common in the testis and parotid gland. They resemble the simple car- cinomata in their general relations. CHAPTER XXVIII. ETIOLOGY OF TUMORS. 177. Our knowledge of the etiology of tumors is still very defective. What we have to say on the subject is, generally speaking, largely hypo- thetical. We might at first be inclined to regard a tumor as the result of a local overgrowth of tissue, and to look for the conditions of its develop- ment among those which determine ordinary hyperplasia. But facts soon appear wThich tend to show that the processes are not parallel. There is, first, the histological diversity of the tumor (Art. 136) from the matrix in which it grows. Secondly, there is the associated impairment or extinc- tion of the physiological function of the matrix-tissue. These facts do not suggest a mere over-active growth in situ. The anatomical facts are thus against our regarding tumors as localized hyperplasias. It follows that we cannot expect to discover the efficient causes of tumor-growth among the factors which give rise to such hyperplasias. Nor can we fairly compare the tumors with the inflammatory new- formations. Tumors may indeed contain foci which are infiltrated with leucocytes. But these are of secondary significance. The entire process of neoplastic histogenesis shows that it is something quite different from the formative processes which originate in inflammation. We thus ex- clude at once the possibility of attributing the growth of a tumor to a traumatic lesion, at least in any immediate or direct way. Clinical ex- perience bears this out ; for, if now and then we have tumors developed in a substratum of tissue which has been injured and has undergone in- flammatory change, it is on the whole a rare occurrence, and does not prove that such injury would of itself suffice to set up tumor-formation in previously healthy tissue. This being the case, we are perforce constrained to admit that other factors must be sought, if we are to explain the genesis of tumors. If we did not know that tumors may develop at the most various periods of life-nay, that many forms are wont to appear only in ad- vanced age, it might perhaps suggest itself to look for their etiological factors in the embryo-to regard them, in fact, as local malformations. But the peculiar modes of occurrence referred to, and the observation that tumors originate in tissues which before looked perfectly normal, 254 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. would scarcely make us regard such an embryonic theory as very proba- ble beforehand. Cohnheim has very recently propounded an embryonic hypothesis of another kind. We are not to refer the actual development of the tumor itself to the embryonic period, but are to attribute its appearance in later life to the persistence of germinal embryonic tissues in the other- wise mature organism (Cohnheim, " Allg. Path.," i.). A tumor takes its rise in what we might call a belated rudiment-a focus of formative em- bryonic tissue, which has not been utilized in elaborating the normal tis- sue of the part-and so has lingered on unchanged. Cohnheim therefore defines a tumor as-an atypical new-formation starting in a latent embry- onic rudiment. The tumor-germs, consisting as they do of embryonic cells, may be very small and so elude observation. It is even conceiva- ble, he thinks, that the germinal cells may be quite unrecognizable among the ordinary physiological elements of the part. They may linger on for a long time inactive. It is only when they are favored by the external conditions-such as the supply of nutriment, and their relation to the surrounding tissues-that they begin to multiply and to form a tumor. In this way it becomes possible that a traumatic lesion may set up the active change. In most cases, however, the a»wakening impulse is beyond our power to discover. We cannot deny that Cohnheim's hypothesis would explain satisfac- torily many of the peculiarities of tumors. Those growths, for example, whose structure reminds us so strongly of earlier developmental stages of particular tissues, would be acquitted of their (at present) unaccountable heterology. It also tells in favor of the theory-that a class of tumors does actually exist, of which we can say with certainty that they date their origin from the embryonic stage. At the same time we may well question whether our knowledge of the subject justifies us in attributing an embryonic origin to all tumors, or whether we should accept the theory only with considerable limitations. [Cohnheim bases his view mainly on the arguments-that many tu- mors have been shown to be hereditary ; that many exist at birth, or at least develop in infancy ; that they show a preference for sites where in earlier developmental stages some complication of structure occurred, e.g., for the places where diverse epithelial formations pass one into the other (lips, anus, stomach, cervix uteri), or for parts where the entire process of development is highly complex (genital apparatus). Finally, he holds that the atypical structure of tumors generally is in favor of his account of them. It must be granted that these arguments speak strongly for the hypo- thesis. They at least make it highly probable for certain classes of tu- mors. But they do not suffice to prove its applicability to all. The view that tumors arise in consequence of injury, especially of frequently repeated irritation, is very widely accepted (Virchow " Die TUMORS. 255 krankhaften Geschwiilste ;" Krbnlein, "Lang. Arch. f. klin. Chir.," xxi.; Kocher, Art. " Krankheiten des Hodens," " Handb. d. spec. Chir. v. Pitha u. Billroth;" Bbgehold, "Virch. Arch.," vol. Ixxxviii.). Cohnheim has justly objected to this view-that the number of cases of tumors in which antecedent injury has been demonstrated does not reach more than four- teen per cent, of the whole number, and is by some given as seven per cent. (Boll, "Das Princip des Wachsthums," Berlin, 1876 ; S. Wolff, " Zur Entstehung von Geschwiilsten nach traum. Einwirk.," In. Diss., Berlin, 1874 ; Von Winiwarter, " Beitrage z. Statistik d. Carcinome," Stuttgart, 1878). From this we may infer that an injury may perhaps give rise to a tumor ; but that neither injury nor inflammation is at all a necessary antecedent.] 178. We are acquainted with a considerable number of forms of con- genital tumor whose origin can be referred with more or less certainty to the embryonic period. Of these it is, however, to be remarked-that their structure and composition are only in part analogous to those of the post-embryonic growths hitherto discussed. Many of them possess a structure entirely peculiar to themselves, so that they cannot be classed with any of the preceding tumors. They are therefore regarded by all authorities as special and peculiar formations, and are distinguished as teratomata. Teratomata, or teratoid tumors (Art. 13), are congenital growths, which are remarkable for the heterogeneity of their constituent elements. They may be large even at birth, or they may grow from small begin- riings to a large size after birth. They may contain fibrous tissue, carti- lage, bone, muscle, skin, hair, nerves, gland-tissue, and simple cellular or embryonic tissue. At times they may have the look of complex histioid tumors ; but the combinations they present are usually much more vari- ous and heterogeneous than in any ordinary histioid growth. We even meet in them with structures which recall the appearance of some normal organ-the differences lying chiefly in the rudimentary nature of the out- ward shape or configuration, and the abnormal site. Sometimes the vari- ous tissues are grouped into something like orderly disposition, giving one the impression of a more or less organized foetus. Teratomata, when externally visible, are usually placed at parts of the trunk corresponding to those at which double monstrosities cohere. These are chiefly the lower end of the spine, the head, and the neck. Internal teratomata are usually connected with the genital apparatus. Such teratomata are some of them true double monstrosities. One foetus has been surrounded and enclosed by another, and so has become stunted and ill-developed (Art. 13). The remainder are due to some mis- development of the tissues within a single foetus. Dermoid cysts form a special class of teratomata. They are cysts whose inner surface has the same structure as the normal skin ; but they occur in places where no skin is ever found normally. Their commonest 256 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. seat is in the generative organs, especially in the ovary. More rarely they are found in other parts, such as the peritoneum, neck, and around the orbit. The smallest examples form little cysts which, as in the ovary, are distinguishable from their contents. The contents are usually greasy, semi-solid, yellowish-white, and interspersed with hairs. The wall is thicker, firmer, and whiter, than that of the Graafian follicles. Under the microscope it is seen to be composed of a corium and epidermis ; it may even contain hair-follicles and sebaceous glands, or more rarely, sweat-glands. Now and then an adipose layer, like the subcutaneous fat, is found beneath the corium. In rare cases, flat or irregular frag- ments of bone or cartilage, and even teeth, are found beneath the cuta- neous layer. The teeth may also be found free within the cyst. Very rarely the cyst-wall contains muscular or nervous tissue. The larger dermoids, i.e., those reaching from the size of a walnut to that of the fist, are sharply marked off from the surrounding tissues by a fibrous capsule. They enclose large quantities of oily or greasy detritus, interspersed with fair or reddish hairs. Dermoids are found in young individuals as well as old. Some are found even in the new-born. They grow very slowly. Judging by the special character of their lining membrane, these formations would seem to be derived from the same rudimentary elements as the external skin. They are probably due to aberrant germinal cutaneous cells from the epi- blast, which have somehow wandered to an abnormal site, and there have at a later stage begun to develop after their kind. [References on the subject of teratomata and dermoid cysts :-Art. 13 ; Kohlrausch, " Muller's Arch.," 1843 ; Lebert, " Gaz. med. de Paris," 1852 ; Remak, " Deutsche Klinik," 16, 1856 ; Heschl, " Prager Vier- telj.," 1860 ; Lucke, " Handb. d. Chir. v. Pitha u. Billroth," ii.; Haffter, " Arch. d. Heilk.," xvi., 1875 ; Panum, " Virch. Arch.," vol. Ixxii.; Klebs, "Handb. d. path. Anat.;" Danzel and Martini, "Arch. f. klin. Chir.," xvii.; Waldeyer, "Arch. f. Gynak.," i.; Wilson Fox, Journal of Anat- omy, 1865 ; Gordon, " Med.-Chir. Trans.," xiii.; Paget, " Surg. Path.," Lecture 23.] 179. Besides the teratomata there are other tumors more nearly- allied in structure to the ordinary forms, which are either congenital or appear so soon after birth that their origin may, with more or less cer- tainty, be referred to the embryonic period. The best-known examples are the congenital angiomata and pigment-spots (beauty-spots, moles) in the skin. The former have already been discussed (Arts. 148- 150). Of the latter we have merely to say, that they appear as brown or black slightly raised patches in the skin, and are composed of tissue ex- actly resembling alveolar sarcoma (Fig. 54) covered over with epidermis. We may likewise mention in this connection-certain cutaneous fibro- mata ; enchondromata of the skull, spinal column, and fingers ; myxo- TUMORS. 257 mata of the jaws ; renal adenomata and cancers ; and cystic adenomata seated on the sacrum and communicating with the central canal of the spinal cord. The number of really congenital tumors observed is by no means great. Cases of tumors appearing in the earlier years of infancy and referable to embryonic conditions are more numerous. Of this kind are the sarcomata of infancy ; especially the form of myosarcoma of the kid- ney referred to in Art. 153. It is not impossible that some of the ova- rian adenomata may date back to the embryonic period. If we consider carefully the scanty details we possess of congenital tumors, taken in conjunction with the familiar facts of post-embryonic tumor-formation, we must admit that the support which Cohnheim's theory derives from this side of the subject is not very great. It must not, however, be forgotten that this theory requires the exist- ence, not of congenital tumors, but only of congenital rudiments of tumors. As to these latter our knowledge is unfortunately very small. It is almost entirely confined to the pigmentary and vascular naevi we have mentioned. They may be regarded, and with equal justice, either as germinal rudiments of tumors, or as developed growths. The former view is justified by the fact that in later life it is not uncommon for these structures to develop into true malignant tumors. Tumor-germs in bone were discovered some years ago by Virchow (" Berlin, acad. Monatsbericht," 1875). He showed that islands of car- tilage, which remain untransformed in the general ossifying process, may in later life become the starting-points for the formation of chondromata. Nothing certain is known of embryonic epithelial germs, such as may subsequently develop into tumors. Their existence may be surmised in the case of early epithelial tumors of the ovary, kidney, or intestine ; but it has not been demonstrated. The frequently observed accessory glands occurring in connection with the pancreas, mamma, thyroid, etc., are not to be regarded as mere germinal rudiments, inasmuch as they contain fully developed gland-tissue. From what we have said, then, it will be seen that the histological evidence for the existence of embryonic germinal tissue in the fully de- veloped organism is very slender. [Ziegler describes a tumor of some interest which he found in the small intestine, seated in the submucosa ; it was as large as a pea, and was made up of minute cysts. It should probably be regarded as a local misformation, rather than a deposit of germinal tissue. Its cysts con- tained papillary excrescences covered with columnar epithelium ; and small gland-tubules were found in the cyst-walls. It is conceivable that, from a misformation of this kind, a true tumor might at some time or other begin to develop. * References on congenital tumors : - Virchow, " Die krankheit. Ge- schwtilste Duzan, "Du cancer chez les enfants," Paris, 1876 ; Ahlfeld, 17 258 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. " Arch. f. Gynak.," xvi. ; Rohrer, " Das primare Nierencarcinom," Zu- rich, 1874 ; Maas, "Berl. klin. Woch.," xlvii., 1880 ; C. Vogt, " Ueber angeb. Lipome," In. Diss., Berlin, 1876 ; Chiari, " Jahrb. d. Kinderheilk.," xiv. ; Weigert, "Virch. Arch.," vol. Ixvii. (renal adenoma). Many authorities are of opinion that Cohnheim's theory is strongly borne out by the experiments of Zahn (" Sur le sort des tissus emplantes dans 1'organisme," International Medical Congress, Geneva, 1873), and Leopold (" Virch. Arch.," vol. Ixxxv.). They took bits of cartilage from a living foetal rabbit, and transplanted them into the peritoneal cavity and anterior chamber of the eye of an adult rabbit. The cartilage con- tinued to grow, while pieces of cartilage taken from animals after birth were merely absorbed. This scarcely seems sufficient ground for Cohn- heim's generalization. The faculty of growing after transplantation is not manifested by all foetal tissues ; many or most of them are dissolved and absorbed by the disintegrating action of the fixed and migratory cells of the new matrix (Leopold, " Arch. f. Gynak.," xviii.). These experiments only show that foetal cartilage has the power of persisting, and even of growing for a time, in spite of defective nutrition, and the absorbent action of the cells of the other tissues.] 180. The inadequacy of the evidence for the existence of germinal embryonic rudiments in the adult tissues makes it appear a somewhat bold step to ascribe an embryonic origin to all tumors whatsoever. The observed and recorded cases do not justify us in saying more than that some tumors arise in rudimental structures, which were histologically dis- tinguishable from the normal tissues before the tumor began to grow. And even in saying so much we must not interpret the term embryonic too literally. Embryonic formations are such as possess a structure re- sembling that of undeveloped tissue-an indefinite structure preceding the definitive or specialized structure. Tissues that are merely misde- veloped, pieces of tissue (such as epithelium or gland-tissue) displaced from their proper seat and transplanted elsewhere, as in the case of ac- cessory glands and dermoid cysts, are not what we understand by embry- onic tissues. The class of tumors referable to embryonic rudiments will be some- what enlarged, if we enlarge the signification of the term embryonic so as to include under it all tissues in process of active and energetic growth. So long as an organ continues to grow, so long are multitudes of new cells formed in it. These formative cells may be called embryonic, inas- much as they continue to multiply actively, and so are nearer akin to the cells of the embryo than to those of mature tissue. Tn this way osteo- blasts and osteoclasts and the ^proliferating cartilage of growing bone, the cells of the enlarging uterus in pregnancy, the tissue of the mamma preparing for lactation, all might be described as embryonic. If the hy- pothesis be thus extended, a whole series of tumors will certainly be com- TUMORS. 259 prehended under it. When, for instance, a tumor develops in the mamma or uterus in connection with parturition, or a sarcoma or enchondroma forms in bone, periosteum, or marrow during ossification, it is not diffi- cult to believe that the same cells which are building up the normal tis- sue may also give rise to the tumor. But if we extend the meaning of the term embryonic so as to include all this, where are we to stop ? Growth, i.e., restoration and replacement of what is being used up, continues throughout life. Surface epithelium is cast off and is regenerated ; glandular epithelium is used up and re- placed ; even bone, though it seems so stationary, is exposed to changes at all stages of life-it is being resorbed by the osteoclasts and built up again by the osteoblasts. If all post-embryonic processes of growth are to be styled embryonic, we cannot refuse to give the same title to all the processes of new cell- formation that occur during life. If this be granted, embryonic tissue becomes exactly the same as that which Virchow called proliferous tissue, i.e., tissue capable of proliferation. We gain nothing by the mere sub- stitution of one name for another ; in the present case we lose some- thing, for we are no longer able to distinguish in expression between embryonic and post-embryonic formation. For this reason it is better to confine the term embryonic to tissues which actually originate in the em- bryonic period. [The fact that we really know nothing of the persistence of true em- bryonic tissue-or, in other words, that it has not been histologically de- monstrated-is acknowledged by Cohnheim. He seeks to explain, the fact by supposing that the embryonic foci are very small and hard to distinguish ; or even that the germinal cells may be mingled with the normal elements and so not distinguishable at all. It is not easy to im- agine how embryonic cellular germs can possibly remain unchanged in the midst of mature tissue. Cohnheim and Mass (" Virch. Arch.," vol. Ixx.) have shown that living tissue, such as periosteum, when introduced into another tissue like the lung, may continue to grow for a time ; but afterward it is absorbed and destroyed by the tissue in which it lies. An embryonic germ seems to have but three courses open to it. It may remain embryonic ; in this case it is as it were alien to the tissue in which it lies, and will be absorbed like an organic foreign substance. It may assimilate itself physiologically as well as anatomically with the surround- ing tissue, taking part in its physiological function and working with it ; in this case it loses its embryonic character. Or thirdly, it may develop into an independent formation, interpolated as it were into the general system ; in this case it forms what we call a congenital tumor (nmvus, adenoma, sarcoma). Hasse has attempted to give Cohnheim's hypothesis a morphological basis (" Die Beziehungen der Morphologie zur Heilkunde," Leipzig, 1880). The morphologist distinguishes two kinds of substances within 260 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the organism : one kind undergoes a series of transformations, the other provides for the formation of new tissue. The latter he describes as " embryonic substance." It is represented by cells which have undergone little or no transformation, and are the more apt to multiply the less their original character and structure has been modified-the nearer they stand to the formative cells of the embryo. From these cells only can new tissue be formed. Tumors are especially likely to be developed at spots where these "embryonic cells" are abundant and unmodified. Hasse's distinction between proliferous and non-proliferous tissue-ele- ments is perfectly just (Arts. 84-89) ; and any one may if he chooses call the former embryonic (as do French writers especially). In this case, however, the antithesis, on which Cohnheim lays so much stress, between the cells of the embryo and the proliferous elements of the organism after birth, simply ceases to exist.] 181. It is plain, from the above, that we do not think the hypothesis tenable which refers all tumors whatsoever to pre-existing embryonic germs. Anatomical investigation forces us rather to the conclusion that tumors may arise in tissues that are in very different states-embryonic, growing, mature, or retrogressive. What is then the efficient cause of the formation of a tumor ? It is as yet impossible to give any precise answer to this question. It is highly probable that the causation of the various classes of tumors is not subject to one law only, but to several. The entire behavior, anatomical and biological, of tumors justifies us in regarding them as formations more or less emancipated from the matrix-tissue. It is true they draw their nutriment from the organism, and cannot continue to grow without its support. In other respects, however, they behave like independent growths isolated from the rest of the organism. It is in this independence or quasi-isolation that the eti- ological difficulty really lies. How does the neoplasm thus assume prop- erties distinct from those of its surroundings ? We believe that the phe- nomenon is ultimately due to some change affecting individual elements of a tissue, whereby they are rendered dissimilar to their neighbors. The change is manifested especially in this-that the normal checks to the indefinite growth of the proliferous cells (Arts. 78-83) are inoperative or inadequate ; either because the formative and productive energy is in- creased, or because the restraining influence of the surrounding structures is diminished, or from both causes together. In the case of tumors appearing in the organism during the stage of development, it is most natural to suppose that the originating cause lies in an increased local growth due to intrinsic conditions ; or, it may be, in a disturbance and diversion of the developmental process from its normal course. What the ultimate factors determining these deviations may be we know as little as we do the causes of gigantic overgrowth or local dwarfing of a limb or organ. When the anatomical and physiologi- TUMORS. 261 cal relations of the affected tissue are altered to a certain extent by this local change, it would seem as if the tissue had no longer the power to maintain the normal direction in which its development should proceed. The altered relations (such as misplacement, etc.) seem to involve the withdrawal of the limiting and directing influence exerted on the grow- ing tissue by its environing structures. The result is the development of a tissue of abnormal type, a local misformation in the histological as well as the anatomical sense. The tumors whose genesis is probably of this kind are chiefly the connective-tissue growths of childhood. Among epi- thelial tumors we may also perhaps include the few observed cases of renal and intestinal cancer, and of ovarian adenoma, in infants. It is thus not impossible that tumors of the developmental period may arise from causes similar to those which give rise to local malformations in the stricter sense of the term. Arrest of the process by which osteo- blastic cells are transformed into bone might thus, for example, give rise to an abnormal formation of tissue such as cartilage, in other words, to enchondroma ; or, by encouraging an over-abundant cellular growth, to sarcoma. Tumors arising in a mature tissue are to be explained only by suppos- ing some antecedent alteration over a more or less extensive region of the tissue. This alteration must be of such a kind as to favor the emancipa- tion of the subsequent neoplasm from its matrix-tissue, without at the same time diminishing the neoplasm's own productive power. This last, indeed, must rather be increased. In this way we may perhaps explain the operation of a traumatic lesion in inducing the growth of a tumor. In special circumstances it is conceivable that such a lesion may fulfil both the essential conditions we have named. In the case of the connective-tissue growths of later life, it would seem as if increased cell-activity were always a necessary condition for their development. This must presumably always be a condition of tumor-formation in tissues whose cells are replaced but slowly or not at all. The primary impulse which excites the cells to active growth may be derived from some change either in the cells themselves, or in the intercellular basis-substance. With regard to epithelial tumors, anatomical investigation shows that increased cell-production is not an indispensable prerequisite. In the carcinomata of later life, for instance, it would appear that the origin of the neoplastic growth is to be looked for, not so much in any in- creased activity on the part of the cells, as in a change of mutual relation between the several constituents of the tissue. Thiersch has pointed out-that in old age this latter effect may be due to certain re- trogressive changes which then make their appearance. In the corium, for instance, such changes lead to a loosening of its texture, and so modify the relations of the epithelial cells to the fibrous tissue. This modification may make itself felt in one of two directions. In the first place, the epithelium, always in process of decay and replacement, may 262 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. in the course of its physiological growth and multiplication penetrate to regions which are normally devoid of epithelium. Loosening and dis- placement affecting the fibrous basis of an organ may give rise to some- thing like fissures or spaces with free surfaces, and into these the contiguous epithelium may readily penetrate and grow. The first sprout- ings or outgrowths of glandular or lining epithelium may conceivably take place in this manner. We might fairly expect that the fibrous structures would, as it were, rise up against the intruder, and attempt to eliminate it as a foreign substance. This may well happen in many cases, and then the further advance of the process will be checked. In other cases it does not happen, probably because the invaded tissue is no longer in its normal or healthy state. We have, indeed, evidence of vascular alteration, infiltration of leucocytes, and even of new-formation of vessels and fibrous tissue ; but this, the normal eliminating process, is feeble and sluggish, and is inadequate to deal with the intrusive epithe- lium. The vascular changes and the increased afflux of nutriment tend rather to react favorably upon the epithelium, and to foster its reproduc- tion. It becomes gradually more and more active-and so the foundation of a carcinoma is laid. It seems not improbable that the process of neoplastic development does in fact occasionally pursue this general course. In other instances, it may well be that the fibrous basis-substance has a certain intrinsic predisposition favoring the formation of cancer, while the primary im- pulse which brings this into play is afforded only by some increase of formative activity on the part of the epithelial cells. [The instructive discussion on the nature of cancer reported in the "Trans. Path. Soc.," 1874, should be consulted in this connection. For an exposition of the constitutional theory, which makes cancer a specific blood disease, see Paget, " Surg. Path.," Lectures 34, 35. See also Paget and Moore, " Holmes's Syst. of Surg.," vol. i.; Wilks, " Guy's Hosp. Rep.," 1872.] SECTION VII. PARASITES. CHAPTER XXIX. GENERAL CONSIDERATIONS. 182. A parasite is a living organism inhabiting another living or- ganism, and deriving its nutriment either from the tissues or from the food-supply of its host. The parasites inhabiting man are some of them animal, and some of them vegetable. If they inhabit the superficial parts of the skin or mucous membrane they are called ectozoa (or epizoa), if animal, and epiphytes, if vegetable ; if they inhabit the deeper struct- ures they are entozoa and entophytes, respectively. The parasitic animals occurring in man belong to the classes of Arthropoda, Scolecida (embracing the Platyelminthes and Nematoidea), and Protozoa. The vegetable parasites are all of them Fungi, and belong to the subdivisions Schizomycetes (bacteria), Blastomycetes (yeasts), and Hyphomycetes (moulds). The various parasites are of very various importance. Many of them produce no perceptible injury to the tissue in which they lie. Others produce very serious local changes, but have no power to extend their in- fluence to remote tissues. Others invade the system, so to speak, and migrating in various directions produce multiple local affections. Many are conveyed throughout the body by the blood or lymph, in which case serious general affections and frequently death itself are the result. The great majority of parasites, and especially the vegetable parasites, in- crease and multiply within the body, often to an enormous extent. Others, chiefly the animal forms, pass only a part of their existence within the body. The local changes they produce are generally confined to the mechanical compression and destruction of tissue, and to the set- ting up of inflammation. They affect the system as a whole by abstract- ing nutriment and oxygen from it, and by giving rise to multitudes of centres of disturbance ; while many of them generate actual poisons. The Schizomycetes or Bacteria play the most important part of all. It is they of all the parasites that have most power of exciting general or sys- temic affections. The Blastomycetes and Hyphomycetes, fungi akin to the yeast-fungus and mould-fungus respectively, exert a merely local in- fluence. The animal parasites become dangerous in virtue of their size or multitude, or by penetrating into vital organs. 266 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [Parasitism is an extremely common mode of life throughout the or- ganized world. Innumerable plants and animals are parasitic either for a season or for the whole course of their life. Accordingly there are few living organisms that are not inhabited by parasites. A plant or animal which merely inhabits the body of an organism is not necessarily a para- site. The term is only applicable to organisms nourished at the expense of their host.] CHAPTER XXX. THE SCHIZOMYCETES OB BACTEBIA. Morphology, Development, and Classification. 183. The Schizomycetes or Schistomycetes, frequently included under the general term Bacteria, belong to the Protophytes-the smallest and simplest of all plants. Many of them are so small that they approach the limit of visibility, even when the highest powers of the microscope are used. When they occur in animal tissues they are to be distinguished only with great difficulty, and by special methods. Special reagents or staining processes must be employed ; sometimes certainty is only reached by experimental cultivation of the products of disintegration of the tissue in question. That they do occur in animal tissues is now established be- yond all doubt. Their growth and multiplication have been experimen- tally demonstrated. The Bacteria are all of them unicellular organisms devoid of chloro- phyll ; they are often, however, aggregated into larger or smaller colonies. Cohn has classified them according to their form into Spherobacteria (globular cells), Microbacteria (minute rod-like cells, Bacteria proper), Desmobacteria (larger rod-like or filiform cells, Filobacteria), and Spi- robacteria (twisted or spiral cells). Movements are noticed in the three latter forms ; their protoplasm is therefore contractile. Neither potash, ammonia, nor dilute acids destroy them, so it is probable that they pos- sess a bounding membrane. Bacteria grow longitudinally ; new cells are formed by transverse subdivision. These remain in connection with each other, or become detached. Von Nencki's researches (" Journ. f. prakt. Chem.," 1879, " Beitrage zur Biologie der Spaltpilze," 1880) go to show that the Bacteria are com- posed of a peculiar albuminoid body which he has called mycoprotein. They contain only the minutest quantities of bodies resembling cellulose. [The above classification of the Bacteria is taken from Cohn (" Bei- trage zur Blologie der Pflanzen," vol. i.; Quarterly Journal of Microsco- pic Science, 77, 79, 1873), and his work has been mainly followed in the next four paragraphs. He makes the following remarks on the general question of classification :-" I have come to the conclusion that the Bac- 268 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. teria are as capable of exact specific classification as other plants. They lie at the limit of microscopic visibility. In the minuter forms it is there- fore impossible to make out either structure or organization. The size and shape of the cells, and the mode in which they are combined into colonies, are then the only differential; of these, however, it is not always easy to say whether they indicate original specific distinctions, or whether they depend on external conditions and lie within the limits of variability of one and the same species. Size is the easiest feature on which dis- tinctions may be based, though even this is by no means easy to deter- mine in the minuter forms. Differences in the mode of reproduction are only discoverable in the higher forms, such as the Bacilli. The genera of Bacteria have not the same significance as those of the higher plants. They are based chiefly on the characters of the vegetative cell-forms, not on the reproductive features. Every form distinguished by prominent or obvious characters is provisionally furnished with a generic name ; smaller deviations serve to designate the species. It is thus not at all impossible that some of such species and genera may really represent different developmental stages of one and the same fungus." Since this utterance of Cohn's a great number of researches have been made into the growth and multiplication of the Bacteria. Koch especially has de- voted himself to the subject (" Mittheil. a. d. kaiserl. Gesundheitsamte," Berlin, 1881). After long-continued experiments on cultivation, in which bacteria were bred in nutritive gelatine ("the dry process") he has reached the conclusion-that each species of bacteria possesses character- istic and easily recognizable peculiarities in respect of structure, form, size, and mode of growth of its colonies on the gelatine. The Schizomycetes have been very variously named by different au- thors. Pasteur speaks of them as vegetaux cryptogames ou micro- scopiques, animalcules, champignons, infusoires, torulac'ees, bacteries, vibrioniens, monades, mycoderma. In Germany the terms Monaden, Vibrionen, Mikrozyma and (by Klebs) Mikrospora and Monadine have been used. Billroth introduced the term Coccobacteria. In England we have corresponding terms, with others like monads, zymes, microzymes (Sanderson), microphytes, etc.] 184. The Spherobacteria are the smallest of all bacteria. Under the microscope they appear as bright round or ovoid spherules of scarcely measurable size. Two genera are distinguished : Micrococcus (Fig. 74, 1) and Sarcina (Fig. 74,15). The spherules known as micrococci exhibit no perceptible organiza- tion, but it is highly probable that they are differentiated into cell-mem- brane and cell-contents. They are found in liquids and in tissues, either isolated or arranged like strings of beads or "chaplets " (Fig. 74, 1Z>), or grouped in colonies (zoogloea, Fig. 74, 2). On examination it is found that in these colonies or zoogloea the separate spherules are united by a gelatinous intercellular substance. Cohn affirms that this is nothing but PARASITES. 269 the swollen and thickened cell-membrane. Von Nencki affirms that it consists of mycoprotein. With regard to their growth and increase, it is made out that the in- dividual cells first elongate and then subdivide transversely. If the sub- divided cells remain conjoined the result is a diplococcus (Billroth). If the process of subdivision goes on, the new cells remaining attached and in line, chains or chaplets are produced. If large numbers of spherules remain after subdivision within the swollen and continually enlarging membrane, the result is a mass of zooglcea. The genus Micrococcus includes several species. These are distin- guished partly by their morphological and partly by their physiological characters. In the first place the micrococci are of various sizes. When cultivated on a proper soil they form colonies of various types. Many of them as they multiply produce yellow, red, blue, green, or brown coloring matters. Lastly, the effects produced in the soil or liquid in which they grow are various ; nor do they all flourish on the same kind of nutriment. It is still doubtful whether the micrococci are motile. The oscillatory movements observed in them are probably to be regarded as Brownian or pedetic movements. Klebs believes that the zooglcea are contractile. The genus Sarcina is very clearly marked. The globular cells divide crosswise, and the daughter-cells usually remain combined in tetrads (Fig. 74, 15). Various species have been distinguished according to the size of the cells. [Billroth and Klebs assert that Micrococci may grow into rodlets or bacilli. It is not to be denied that some bacterial spherules become trans- formed into rods (Art. 185), but Cohn is probably right in maintaining that Micrococcus is a definite genus of constant form. Ziegler has culti- vated Micrococcus luteus, a bacterium which develops on boiled eggs exposed to the air and forms yellow zoogloea ; and though the experi- ments were carefully made to that end, he could never obtain bacilli, but always micrococci. Experiments on parasitic micrococci seem equally to indicate that there is a genus of bacteria which forms globular cells only. It is not yet certain whether or not the micrococci produce spores. Koch thinks it unlikely. See also Ewart, "Proc. Roy. Soc.," xxvii.] 185. The Microbacteria are classed together as a single genus Bacterium. The principal species are Bacterium termo (Fig. 74, 3) and Bacterium lineola (Fig 74, 5). The first appears in the form of minute cylindrical rods, 0.5 to 1.5 micromm. in length, and appearing bright or dark according to the mode of illumination. Sometimes they remain at rest, sometimes move about more or less actively. From their manner of subdivision they are often found coupled in pairs ; they do not usually form chains or chaplets ; but are often grouped as zooglcea (Fig. 74, 4), which are remarkable for the great abundance of the gelatinous inter- cellular substance. B. termo is very generally found in putrefying mat- 270 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. ters. B. lineola resembles B. termo, but it is larger in every way. It is found in water, in infusions, on potatoes, etc. The cells, which are from 3.8 to 5 micromm. in length, contain a clear bright substance inter- spersed with fine granules. In other respects the bacterium resembles B. termo ; it swims about actively, moving forward and backward in curves, rotating or oscillating. At times it remains motionless. It forms continuous pellicles on the surface of liquids containing it. When micrococci or microbacteria have exhausted the nutriment con- tained in the liquid in which they live, they fall to the bottom as a pow- dery precipitate. Fig. 74.-Various Forms ot Bacteria, x 500 (in*ach case). 1, Micrococcus septicus: a, separate, 6, in chaplets ; 2, Micrococcus diphtheriticus, forming a zoogloea-mass; 3, Bacterium termo ; 4, Zoogloea of B. termo ; 5. Bacterium lineola ; 6, Bacillus subtilis; 7, Bacillus anthracis, with red blood-cells; 8, Flagellate bacillus from the mouth; 9, Bacillus leprce (Armauer Hansen); 10, Bacillus with terminal and medial spores, from a putrefying liquid ; 11, Bacillus malarice (Klebs), with spores ; 12, Vibrio serpens (Cohn) ; 13, Spirochaeta Obermeyeri ("spirillum" of relapsing fever) ; 14, Spirillum volutans (Cohn) ; 15, Sarcina ventriculi. [As has been indicated in Art. 184, Billroth, Hallier, and Klebs main- tain that the microbacteria represent merely a developmental stage in the life-history of the micrococci. Billroth (" Unters. uber Coccobacteria sep- tica," Berlin, 1874) believes that all bacteria belong to a single species of plants, the members of which are composed partly of round and partly of rod-like segments varying greatly in size. The round segments are the cocci, the rod-like segments bacteria. Each form may pass into the other on occasion ; though they so far breed truly that for some generations cocci produce only cocci, and bacteria only bacteria. According to size we may distinguish them as micrococci, mesococci, and megacocci, and microbacteria, 'mesobacteria, and megabacteria. Megacocci may break up into micrococci. The plant which passes through all these stages Billroth calls Coccobacterium septicum. In the process of multiplication it develops a gelatinous envelope or gliacoccus. When this occurs at the surface of a liquid so that a pellicle is formed, he calls it petalococcus or petalobacterium. Masses of cocci enclosed in a cylindrical sheath of gliacoccus are called ascococci (Van Tieghem, " Bull. Soc. Botanique," PARASITES. 271 1880). Coupled spherules are diplococci; chains or chaplets of spherules, streptococci ; and, in like manner, he describes diplobacteria, and strep- tobacteria. Ray Lankester ( Quarterly Journal of Micros. Sci., 1873) also inferred from certain experiments of his that Cohn's forms are not really distinct. Haberkorn (" Bot. Centralb.," 10, 1882) maintains that Cohn's four divisions merely represent diverse species of a single genus. Bill- roth's view of the specific unity of all the bacterial forms has been dis- credited by later researches (cf Tiegel, " Virch. Arch.," vol. lx.; Lister, " Trans. Roy. Soc. Edin.," 1875). Klebs (" Arch. f. exp. Path.," iv.) divides the globular and rod-like bacteria into Microsporina and Monadina. He defines the Microspo- rina as small micrococci which in the resting state form well-defined and compacted balls ; the several spherules being regularly deposited in layers and surrounded by only a small quantity of gelatinous matter. The peripheral spherules grow into minute motile bacteria, which tend to move away from the mass, and thus further the diffusion of the organ- isms through the nutrient liquid. The highest stage of their develop- ment is reached in the formation of a matted tuft of unbranched fila- ments. The monadina form loose balls, from which motile monads or vibrios break away. These grow into rodlets which are relatively short and broad ; and these again subdivide ; they probably increase also by conjugation. They then pass into a resting state, and lie quietly along- side each other. Lastly they break up into spherules ; it is rare for them to form tufts or clusters. They require oxygen, and thrive better on al- bumen than on gelatine. It is not yet certainly known whether Bacterium termo produces spores or not. It has been described as possessing flagella by Dallinger and Drysdale (Month. Mic. Journ., xiv.), and by Koch (" Beitrage zur Biol.," 1877).] 186. The Desmobacteria (or Filobacteria) are cylindrical rodlets of varying length ; some of them are thick, and some slender and delicate. Cohn describes a straight form which he calls Bacillus, and a wavy or curved form which he calls Vibrio. Bacillus increases by transverse subdivision, and frequently forms a long string (Fig. 74, 6), commonly re- ferred to as a leptothrix (Hallier). It is not always easy to make out that the string is made up of distinct rodlets. In other cases bacilli form swarms. Many bacilli pass through both a resting state and a swarming state. Many are provided with a flagellum or cilium, which acts as an organ of locomotion (Fig. 74, 8). The best representatives of this genus at present known are B. subtilis (Fig. 74, 6), B. anthracis (Fig. 74, 7), B. tuberculosis (Fig. 80), and B. leprce (Fig. 74, 9). The various specific forms are distinguished by their general size, and by the relation of their length to their breadth. Some of them are cut off square at the ends, others are rounded off or pointed. Even more marked differences than these become apparent when the various forms are cultivated in nutrient 272 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. liquids. " Cultures " of this kind have been made by Cohn, Koch, Klebs, Brefeld, Prazmowski, Lister, Naegeli, Buchner, Klein, and many others, and we have thus come to know something of the life-history of many of the varieties. Cohn bred the JB. subtilis in hay infusions ; Koch the 7?. anthracis found in the blood and tissues of animals suffering from splenic fever ; and also the JB. tuberculosis (Art. 206). The life-histories of the different species differ in many details ; but they usually agree in their main features. Features which thus con- stantly recur are-the longitudinal growth of the rodlets, their transverse subdivision and abstriction, and the formation of spores or gonidia. The life-history of JB. anthracis is briefly as follows. Fig. 75.-Development of Bacillus Anthracis. x 400. (From Koch.) a, bacilli from the blood; dead bacilli; &, bacilli cultivated for three hours; c, for ten hours; d, for twenty-four hours; spores are forming and the filaments are breaking up; e, germination of spores. If the anthrax-bacillus be observed under proper conditions, it is found in a short time to grow lengthwise to a very considerable size (Fig. 75, b}. Within twenty-four hours a string or filament is formed (Fig. 75, c), which may be ten or twenty times as long as the original rodlet. In ten or fifteen hours more the clear contents of the filament become granular. Then appear at regular distances small darker bodies, which grow in a few hours into larger highly refracting spores (Fig. 75, d). The filaments afterward break up, and the spores are set free. In favor- able circumstances these spores may germinate and develop into bacilli exactly like those originally taken from the blood. According to Koch, each spore consists of a bright body surrounded by an envelope of clear protoplasm. As the spore germinates the latter grows into a rodlet (Fig. 75, e). The researches of Klein, Brefeld, Praz- mowski, Ewart, and others do not corroborate this account. They make out that the spore consists of protoplasm enclosed in a membrane. The rudimentary bacillus is developed not from the peripheral layer of the spore, but from its protoplasmic centre. In addition to this mode of increase by spore-formation observed in cultivated bacilli, the rodlets multiply by transverse subdivision. This is especially the case in the blood of living animals. PARASITES. 273 As we have said, all bacilli have the power of forming spores. It is not, however, essential to the process that long filaments should be formed. Many bacilli produce spores without having undergone any marked increase in their length. The number of spores in each rodlet varies from one to three. They may occupy either a terminal or a medial position (Fig. 74, 10 and 11). Anthrax-bacilli cultivated on gelatine are never motile (Koch) ; they always form flakes or tufts made up of long, wavy, tress-like or twined filaments. The bacilli of hay-infusion grow out into long filaments in very young colonies only. When they become more mature and cause the gelatine to liquefy, they are seen in active movement at the centre of the colony, while round its periphery they stand in regular array all perpendicular to the surface and penetrating the firmer gelatine. The colony then looks as if it were surrounded by an aureole of rays. Other bacilli form colonies looking like tufted roots of trees ; others again spread out in one plane and form mosaic designs. [Cohn's and Koch's researches are published in the " Beitrage zur Biologie d. Pflanzen," vol. ii., and " Mittheil. a. d. kais. Gesundheit- samte," Berlin, 1881 ; Brefeld's are in the " Botan. Zeitung," 1878, and in "Botan. Unters. fiber Schimmelpilze," 1881; Klein's, Sanderson's, and Ewart's, in the Quart. Journ. of Micros. Science, 1878. Prazmow- ski asserts (" Unters. uber d. Entwick. einiger Bacterien," Leipzig, 1880) that the germination of the spores of B. subtilis follows a different course to that of B. anthracis. The mature spore is oval, highly refracting, sharply defined, and surrounded by a transparent zone. On germination the spore becomes pale, and loses its lustre and its sharp contour. At each pole a kind of shading appears, the spore meanwhile beginning to move in a tremulous manner. After a time the contents escape laterally in the form of a minute cylindrical shoot, which grows into a rodlet ; and this latter then proceeds to subdivide. Prazmowski has also made out the life-history of the so-called Clos- tridium butyricum (Pasteur's vibrion butyrique, Van Tieghem's Bacil- lus amylobacter}. It forms rodlets 9-10 micromm. long, which are seen alternately at rest and in moving swarms. Before fructification they in- crease in thickness and become more fusiform or pear-shaped. On ger- mination the spore swells and begins to jerk about. The membrane at one end is absorbed, the germinal cylinder escapes, and as it grows pro- ceeds to subdivide as before. Kern describes a bacillus under the name of .Dispora Caucasica ("Biolog. Centralb.," 5, vol. ii.), much resembling B. anthracis ; it is, however, distinguished from the latter by its always exhibiting terminal spores at each end of the rodlets. When cultivated in milk this bacillus sets up a peculiar fermentation, which produces an agreeable drink much used in the Caucasus. Brefeld distinguishes an external spore-membrane or exosporium 18 274 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. which is thrown off in germination, and an internal or endosporium which becomes the envelope of the germinal cylinder. With regard to the term leptothrix^ it is to be noted that all filaments or strings so named do not necessarily represent developmental stages of a bacillus. The filaments formed by algre, for example, are also spoken of as leptotrichcs.\ 187. The Spirobacteria are divided into two genera-Spirochaeta (Fig. 74, 13) with long, flexible, close-wound spirals ; and Spirillum (Fig. 74, 14) with short, stiff, open spirals. For the pathologist, Spirochaeta Obermeyeri (13) and Spirochaeta denticola are the most important spe- cies of the first genus. The former (often referred to simply as "spiril- lum ") is constantly found in the blood of patients suffering from relaps- ing fever, during the paroxysms. The latter is found in the mouth and nose of persons who may be quite healthy or suffering from nasal catarrh. The length of the former is twice or thrice the diameter of a red blood- cell. It moves with extraordinary agility through the blood, and is there- fore hard to see unless it be somehow fastened down or restrained. No structure has been made out in it. No details are known of the life-history of Spirochaeta. It plainly increases very rapidly within the body. It probably produces resting- spores. The largest of all bacteria, Spirillum volutans, belongs to the Spirilla (Fig. 74, 14). Apart from its size it is distinguished by its granular pro- toplasm and its pair of flagella. It sometimes moves about actively, sometimes lies quiescent. It is occasionally found in drinking-water. Two smaller forms, Spirillum tenue and Spirillum undula, also belong to this genus (Art. 207). Biology of the Bacteria. 188. Conditions of life. All bacteria require to be supplied with certain definite nutritive substances if they are to develop normally. The requisite substances are partly inorganic, and partly organic (carbohy- drates and albuminoids). The inorganic components are derived from salts containing sulphur, phosphorus, magnesium, and potassium. The requisite carbon and nitrogen are mainly derived from animal and vege- table matters. But bacteria have also the power of assimilating nitrogen from ammonia, urea, or even nitre, provided only the other mineral substances needed are also present, and in addition some appro- priate organic carbon-compound, such as sugar. These nutritive substances must be presented to the bacteria as- sociated with a certain amount of water. None of the bacteria can develop without water, though many of them may be without it for a time and still continue to live. This is especially the case with bacterial spores. If the water contains no proper nutriment, or if the nutriment PARASITES. 275 is already used up, the bacteria cease to develop, and after a time die outright. But here, as when water is lacking altogether, it is possible for the bacteria to maintain life for a time. The spores are still more tenacious of life, and can hold out almost indefinitely. Free oxygen is absolutely necessary to the development of many of the bacteria ; others can do without it if they are otherwise favorably placed, and in circum- stances where they can set up fermentation. The former kind, e.g., Bacillus anthracis and B. malarice (Klebs), have been called by Pasteur aerobious fungi. The latter, of which Bacterium termo and Clostridium butyricum are the best-known examples, are anaerobious. Pure oxygen is said to kill bacteria outright. [Niigeli gives minuter details of the conditions of life of the various bacteria (" Die niederen Pilze," Munich, 1877, and " Untersuch. uber die nied. Pilze," 1882). Pasteur, Joubert, and Chamberland have papers in the " Gaz. med. de Paris," 1876, on the relations of bacteria to oxygen. Prazmowski asserts that, so far as concerns Clostridium, oxygen is not merely unnecessary but positively harmful. B. anthracis, on the other hand, dies if deprived of oxygen, breaking up into rounded fragments. Pasteur again affirms that the bacillus which gives rise to the " Pasteur- ian " septicaemia in rabbits, dies if exposed to the air. According to Koch (" Mittheil. a. d. k. Gesundheitsamte," Berlin, 1881), the anthrax-bacillus perishes if it is allowed to become dry ; while the spores may be preserved for years in the dry state. They may even be kept moist for a time with- out losing their power to germinate or to produce the specific infection.] 189. The temperature of the nutrient medium has great influence upon the development of bacteria. If the temperature be lowered, the effect is generally to slow and to weaken the vital processes, and ulti- mately to put an end to them altogether. As the temperature is raised, on the other hand, these processes become more and more active until a certain maximum is reached ; carried beyond this point they rapidly and suddenly cease, in most instances not to revive again. The maximum temperature which can be borne by fungi varies in the different species ; a few are capable of growth at 70° to 74° C. (Van Tieghem). The de- velopment of all kinds is stayed at a temperature of 5° C. They become stiff and immobile, but are not absolutely killed even by very extreme degrees of cold. The rigor frigoris sets in at different temperatures in different species ; in the case of B. termo at 5° C., of B. anthracis at 15° C. For B. anthracis the temperature most favorable to development is 30°-40° C.; at 42° C. development ceases. B. termo develops best between 30° C. and 35° C. All bacteria and all bacterial germs are killed by boiling-hot water or steam, after exposure for a certain time. The spores are much more resistant than the bacteria. In dry air both may endure much higher temperatures. Spores, for instance, are not destroyed at a temperature 276 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. of 140° C. until after three hours' exposure. B. termo perishes at G5° 0., if the temperature be kept up for a considerable time. [Researches on the effect of temperature on the bacteria and their spores have been made chiefly by Eidam (" Cohn's Beitrage z. Biologie d. Pflanzen," vol. ii.), Koch, Wolffhiigel, Gaffky, and LbfHer ("Mitth. a. d. k. Gesundheitsamte," Berlin, 1881), Van Tieghem ("Bull. Soc. Bot.," 1881). The following are the chief results arrived at. Bacterium termo passes into rigor frigoris at 5°, into rigor caloris at 40°. At 45° the ordinary putrid decomposition of albuminoids ceases to go on (Eidam). Bacillus anthracis multiplies the more slowly as the temperature is lower, within certain limits. Between 30° and 40° growth and spore- formation are completed in twenty-four hours ; at 25° this time is in- creased to thirty-five or forty hours. At 23° the spore-formation occupies forty-eight or fifty hours ; at 20° seventy-two hours ; at 18° it takes five days, at 16° seven days. Below 15° growth and spore-formation cease (Koch). Spores are still formed at a temperature of 42°. See also San- derson and Ewart, Quarterly Journal Mic. Sci., 1878. Bacteria without spores, when exposed to hot air, cannot endure a temperature much over 100° for so long as an hour and a half. The spores of bacilli are only destroyed after three hours' exposure to a temperature of 140°. In the case of objects exposed to heat with a view to disinfection, it is noteworthy that the temperature penetrates very slowly. Objects of moderate size, such as bundles of clothing, pillows, etc., are not completely disinfected even when exposed for three or four hours to a temperature of 140° (Wolffhiigel). Anthrax-bacilli perish when exposed to boiling water for two hours ; when exposed to steam in a closed space ten minutes suffices. On the other hand, the peculiar bacillus found in garden-soil is not destroyed by this exposure. Super- heated steam at 105° kills all bacterial germs. A jet of steam is more powerful than steam in a closed chamber. It will kill all kinds of germs in ten to fifteen minutes, and it readily penetrates the articles to be dis- infected (Koch, Gaffky, Lbffler). When using boiling water for disin- fecting purposes, care must be taken that the heat is kept up long enough, i.e., until all the parts are warmed up to 100°. The effect of temperature in modifying the virulence of pathogenous bacteria will be referred to later on.] 190. Another factor of importance in regard to bacterial development is the presence of foreign or non-nutritive substances in the nutrient liquid. Many substances (like corrosive sublimate, bromine, iodine, and some acids) have a very powerful effect even in small quantity. They put an end to growth and fermentive action, or kill the organisms out- right. Other substances have no injurious effect unless present in con- siderable quantity. PARASITES. 277 The fermentive action of the fungi leads to the formation in the nutrient liquid of substances which, when they reach a certain degree of concentration, may ultimately put a stop to the growth and multiplica- tion of the fungi themselves. In alcoholic or lactic fermentation, for instance, the gradually accumulating alcohol or lactic acid ultimately brings the fermentive process to a standstill. If nutritive matters be present in excess (or if, in other words, the supply of water be inadequate), the growth and multiplication of the fungi ceases in like manner. This is the reason why conserves of fruit made with sugar do not ferment, why condensed milk does not turn sour, and why dried or salted meat does not putrefy. By withdrawing water, or by adding substances which dissolve in the organic liquids, we are able to increase the proportion of solids to liquids in organic substances such as provisions, and so preserve them from decomposition by fungi. The quantity of water necessary for the development of fungi like bacteria and the yeast-plant is greater than in the case of the mould- fungi. Horwath's and Reinke's researches (" Pfliiger's Arch.," xvii., xxiii.) show that constant agitation of the liquid hinders the development of bacteria, and may even check their multiplication altogether. A further factor of importance in bacterial development is the pres- ence of lower orders of fungi in the nutrient liquid. As higher plants often encroach on and interfere with each other, so it is possible for bac- teria, yeast-plants, and moulds to interfere and compete with each other for nutriment (Nageli). A bacterium, which is thriving and multiply- ing in a given liquid, may be checked and ultimately killed merely by in- troducing another fungus which is still more at home in the liquid. Thus, if we introduce into a nutrient liquid containing sugar the germs of a number of fungi of different classes, the bacteria alone will multiply and set up lactic fermentation. If a half per cent, of tartaric acid be now added, the yeast-fungi alone will proceed to multiply, and alcoholic fermentation will begin. Add now from four to five per cent, of tartaric acid, and mouldy growths appear. The tartaric acid does not kill the other fungi ; it merely favors one more than the others. Thus it is that in grape-must it is only the yeast-fungi which flourish, though other germs are certainly present. Only when the sugar is all used up have the bacteria a chance to multiply, and then they set up acetous fermen- tation. Mould-fungi may then develop in the presence of the vinegar, and they consume the acetic acid. Lastly, when this is done, the bac- teria reappear and set up putrefaction. Even among the Bacteria themselves a like mutual interference and struggle for existence is observed. Micrococci may be thrust aside by microbacteria. Bacilli may be killed by Bacterium ter mo, when the supply of oxygen is insufficient for both. It is also a point of importance, when there are various kinds of fungus-germs present, to know which kind is most abundant. If the 278 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. soil be equally well adapted for two or more forms, the form represented by the majority of germs will have the advantage. [Koch and Wolffhiigel have made very careful investigations into the action of various substances on the life and multiplication of bacteria. (" Mittheilungen, etc.," 1881). The subject has also been treated by Buchholtz (" Arch. f. exp. Path.," iv.), Schotte and Gartner ("Deutsche Viertelj. f. off. Gesund.," xii., 1880), Nageli (" Die niederen Pilze," Munich, 1877 and 1882), Roberts ("Phil. Trans.," 1874), Hamlet (Journ. Chem. Soc., 1881), and many others. The following results of investi- gation are worthy of note. Corrosive sublimate has the most powerful effect on bacteria : an aqueous solution of 1:20,000 kills the spores of bacilli in ten minutes. A solution of 1: 5,000 is thus a certain disinfectant, even when the time of exposure is very short. Mercuric sulphate is somewhat less active. Koch finds that an aqueous sublimate-solution of 1:300,000 puts a stop to the germination of bacterial spores. Sulphurous acid does not take a high place as a disinfectant. Bac- teria clinging to dry objects are killed by twenty to thirty minutes' ex- posure to an atmosphere containing 1 vol. per cent, of sulphurous acid. Spores of B. subtilis and B. anthracis are still capable of development after ninety-six hours' exposure to an atmosphere containing 5 to 6 vols. per cent, of sulphurous acid. Even when moist they are very hard to kill with it. It is thus an altogether untrustworthy disinfectant, and all the more because it has little power of penetrating compact masses or bundles (Wolffhiigel, Buchholtz, Schotte and Gartner, Koch, Buchner). Carbolic acid in five per. cent, solution will kill the spores of the anthrax-bacillus in twenty-four hours. A three per cent, solution will not do so in the same time. The bacilli, however, are killed in a few minutes even by a one per cent, solution. A solution of 1:400 checks the development of bacterial spores. Vapor of carbolic acid at ordinary temperatures is without effect ; at 55° C. it kills spores in two or three hours (Koch, loc. cit.; De la Croix, "Arch. f. exp. Path.," xiii.). Chlo- ride of zinc in five per cent, solution has no effect on anthrax-spores- even when they have lain in it for a month (Koch). Iodine, bromine, and chlorine are far more active than sulphurous acid. Bacilli cease to grow in presence of iodine in the proportion of 1:5,000, and of bromine of 1:1,500. Steam from bromine-water kills spores in twenty-four hours, from chlorine-water in two days. lodine- water and chlorine-water kill spores in one day, a five per cent, solution of chloride of lime in ten days. Benzoic acid, sodium benzoate, potas- sium chlorate, and quinine have little effect on spores. The following substances, even in dilute solution, have a restraining influence on bac- terial development: allylic alcohol ; oils of mustard, peppermint, turpen- tine, and cloves; thymol ; chromic, picric, hydrochloric, and salicylic acids ; quinine. The effect is perceptible in solutions of 1:300,000 for PARASITES. 279 oil of peppermint, of 1:800 for quinine, of 1:75,000 for oil of turpen- tine. All disinfecting agents should be used in aqueous solution. In alco- hol or oil they are either inactive or enfeebled. Bacillus-spores still retain their power to germinate after lying for months in absolute alco- hol. In water and in glycerine they may lie for weeks undestroyed. Bacteria become less able to resist heat in presence of small quantities of acid. They are made more resistant by alkalies. For the effect of light on their development see Engelmann, " Rev. internat. Sci. biol.," 1882.] 191. Influence on the nutrient liquid. In the first place the bac- teria, as they grow and multiply, withdraw from the nutrient liquid the elements they require for building up their cells. These elements are chiefly nitrogen, carbon, hydrogen, and oxygen, as also the mineral con- stituents mentioned in Art. 188. In the next place they set up marked chemical changes in the nutrient liquid. It is bacteria which superinduce putrid decomposition in albuminoid bodies ; they transform sugar into lactic acid (as in soured milk) ; lactic acid into butyric acid (as when sourkrout ferments, or butter becomes rancid) ; sugar into a gum-like slime (as in "slimy" or "long" wine); and alcohol into acetic acid. Large quantities of material may in this way be very rapidly transformed. When albuminoids undergo putrid decomposition, we have formed peptones and similar bodies ; a certain putrid principle or poison (Panum), and bodies resembling ferments ; sepsin (Bergmann and Schmiedeberg) ; nitrogenous bases, like leucin and tyrosin ; amines like methylamine, ethylamine, propylamine ; fatty acids, like formic acid, acetic acid, propi- onic acid, butyric acid, valerianic acid, palmitic and stearic acids, lactic acid succinic acid, etc. ; aromatic matters, indol, phenol, cressol, pyro- catechin, hydroquinone, hydroparacuminic acid, and paroxyphenylacetic acid (von Nencki, Salkowski, Brieger) ; and lastly, sulphuretted hydro- gen, ammonia, carbonic anhydride, and water. These products are the result partly of hydration, partly of reduction, and partly of oxidation. The immediate cause of the process is unknown. Nageli (" Die niederen Pilze," 1877), Pasteur, Lister, and others, regard the decompo- sition as the direct result of the vegetation of the bacteria. Decomposi- tion and fungus are inseparable ; the one ceases when the other is removed. Processes of this nature, set up by bacteria, are best distin- guished as fermentations. Considered with respect to their property of setting up fermentation, bacteria are often described as " formed " or " organized " ferments. Bacteria have also the power of setting free certain substances which have a decomposing action like themselves, but are capable of separation from them, and are known as "unorganized" ferments. Such unorganized ferments can, for instance, change lactose into fermentable sugar, transform starch and cellulose into grape sugar, and render soluble coagulated albumen and other insoluble albuminoids. In consequence of such changes milk may undergo alcoholic fermenta- 280 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. tion, wood may become soft and rotten, damp bread turn sour, and in- soluble albuminous matters be transformed into a putrid ammoniacal slime. Under the influence of bacteria are also developed certain bitter, acrid, and nauseous products, of whose composition nothing is known (as when milk turns bitter). Now and again coloring matters are produced by them, red, yellow, green, blue, and violet. So bread may become covered with a blood-red film of Micrococcus prodigiosus (" bleeding " bread). Bandages and pus in wounds become blue from the presence of Micro- coccus cyaneus. Boiled eggs exposed to moist air are often quickly covered over with a yellow film of Micrococcus luteus. [The hypotheses proposed to explain fermentation, especially the alcoholic fermentation, have been very various. Some of them attempt to connect the process intimately with the vital activity of the cells which give rise to it ; others seek to separate them. Liebig describes the pro- cess as a molecular motion transmitted by matter (the unformed ferment) already in a state of chemical motion (i.e., in the act of decomposing) to other matters composed of elements in loose combination. Hoppe-Seyler and Traube (" Pfliiger's Arch.," xii., 1875, and " Physiologische Chemie ") imagine that the cells secrete certain unformed ferments, which produce decomposition by mere contact (or catalytically), without themselves taking part in the chemical changes they set up. Pasteur (" Annal. de Chimie et de Phys.," 58, 64; " Comptes Ren- dus," 45,46,47, 56, 80; "Studies on Fermentation," London, 1879; Duclaux's "Ferments et Maladies," Paris, 1882) regards fermentation as immediately dependent on the activity of the living cells. Fermenta- tion begins only when the supply of free oxygen to the cells is restricted. They then begin to abstract oxygen from the compounds contained in the nutrient liquid, and so disturb their molecular equilibrium. Nageli's physical (or molecular) theory (" Abhand. d. bayr. Akad. math, physic. Cl.," xiii., p. 76, 1879) supposes that the natural motions of the molecules and atoms of the various constituents of the living cell- protoplasm are transmitted mechanically to the fermenting matter. The protoplasmic constituents remain chemically unchanged, but the mole- cular equilibrium of the fermenting matter is disturbed, and disintegra- tion results. Nageli's theory emphasizes strongly the dependence of the fermentive process on the life of the cells, and is thus in harmony with our general view that all vital processes are ultimately cellular. The power of exciting fermentive decomposition in nutrient liquids is very probably possessed not merely by bacteria and yeast-cells, but also by the cells of higher organisms, as of man. Voit ("Physiologic des Stoffwechsels," Leipzig, 1881) refers the disintegration of the soluble albumen circulating through the system to fermentive action of the tissue- cells. Pasteur has shown that in proper conditions fruits and leaves may exhibit fermentive properties. PARASITES. 281 The chemical changes occurring in the putrid decomposition of the albuminoids have been studied by Nencki, Salkowski, Brieger, and Hil- ler. See Hiller, "Die Lehre von der Faulniss," Berlin, 1879 ; Nencki, " Zersetzung der Gelatine und des Eiweisses bei der Faulniss mit Pan- creas," Berne, 1874, and articles in the " Journ. fur prakt. Chemie," " Journ. fiir physiol. Chemie," and " Bericht. d. deutsch. chemisch. Gesell.," 1876-82 ; Salkowski, articles in the " Bericht. d. d. chem. Ges.," and " Zeitsch. f. physiol. Chem.," of the last year or two ; Brieger, " Zeitsch. f. physiol. Chem.," ii., iii., iv., and " Zeitsch. f. klin. Med.," iii.; Gautier and ^tard, " Comptes Rendus," 1882. The quantity of oxygen present has an important influence on the products formed in bacterial decomposition. Pasteur asserts that fungi which grow in presence of oxygen set up chiefly oxidative changes. Those which can multiply in the absence of oxygen give rise to non-oxi- dative decompositions. Hoppe-Seyler (" Ueb. d. Einfluss des Sauer- stoffes auf Gahrungen," Strasburg, 1881) supports this view by his ob- servation that when oxygen is abundantly supplied to the yeast-plant the disintegration of sugar into alcohol and carbonic anhydride is retard- ed, and volatile acid bodies are produced in abundance. If bacteria in an albuminous liquid be well supplied with oxygen, products like indol, hydroparacuminic acid, and sulphuretted hydrogen (which are largely formed when oxygen is wanting), entirely disappear. The oxygen oxi- dizes them as they are produced ; the primary products of the fermenta- tion at once undergo further change. On pigment-producing bacteria see Cohn and Schroeter, " Beitrage z. Biol. d. Pflanzen," vol. i.] 192. Fermentation and putrefaction can only take place in the pres- ence of the corresponding fungi, and the amount of decomposition pro- duced depends on the quantity of fungi present. It does not, however, follow that each kind of decomposition is due to a single specific fungus, nor that one fungus may not give rise to more than one kind of decom- position. We cannot as yet define with certainty the kinds of decompo- sition which correspond to each species of fungus. We know, however, that ordinary putrid decomposition occurs under the action of Bacterium termo ; while Cohn asserts that micrococci do not give rise to putrid change, but to changes of another kind. The butyric fermentation is said to be chiefly due to the presence of Clostridium butyricum. An- thrax-bacilli generate ammonia in the nutrient liquid. In most putrefy- ing substances we find bacteria of several species. Nageli affirms that it is possible by cultivation so to alter the prop- erties of a bacterium that it no longer has the power to produce the changes originally associated with it ; while it assumes the power of calling forth fermentations of a different kind. Thus the bacterium which produces the lactic acid fermentation may, he says, be cultivated in saccharated extract of meat in such a way that at first it produces in 282 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. milk an ammoniacal decomposition only ; and it does not resume its power of generating lactic acid until after several generations. If this be so we may perhaps infer that within certain limits the physiological properties of a bacterium may be transmuted ; or at least that, by change of condition, one or other of several potential functions may be called into activity. The facts have not, however, been sufficiently confirmed. [We have said that fermentation and putrefaction are always due to fungi ; but we do not thereby deny that other kinds of decomposition may affect organic substances in which fungi play no part. Such changes do in fact occur. They usually take the form of slow oxidation or combustion, in which carbonic anhydride, water, and (in nitrogenous substances) ammonia, are formed. Such slow changes are set up w'hen organic matters are in contact with water and atmospheric air. They also, of course, occur in the living organism. In dead organic matters the process corresponds in part to what is called "dry rotting" or " mouldering." Brieger ("Zeitsch. f. klin. Med.," iii.) thinks that the various aromatic products of the putrefaction of albumen are equally well obtained whether it is set up by the addition of sewer-mud or of pancreas. The essential factors are the duration of the putrefactive process, the tem- perature, and the amount of oxygen present. The albuminoids undergo the same changes in the intestine as they do in artificial putrefaction brought about outside the body. The same series of changes are also set up in putrid pleurisy and bronchitis, and in pulmonary gangrene.] 193. Bacteria without and within the body. If the facts already cited be duly considered, it will appear very probable d priori that the diffusion of the bacteria is enormously wide. Matters on which they can grow and thrive are found almost everywhere. We might especially expect to find them wherever dead organic substances occur, either in solution or at least associated with a certain amount of water. This expectation is fully confirmed by experience. Bacteria are found in all waters, whether flowing or stagnant, in all liquids that can ferment or putrefy, and in all vegetable and animal tissues that are sufficiently moist. Koch's researches have shown that the surface soil or mould is extra- ordinarily rich in bacterial germs. It is surprising to learn that these are chiefly the germs of bacilli ; but micrococci are also found. In soils soaked with midden-runnings the micrococci are more numerous than the bacilli. If the soil become very dry, the micrococci disappear while the bacilli persist. This is due to the fact that the resting-spores of bacilli are very tenacious of life. The micro-organisms present diminish rapidly as we go deeper. At the depth of a metre they seem entirely absent. Spring-water coming from a depth contains hardly any. But we have by no means exhausted the field of their distribution. When liquids containing fungi are violently shaken or broken into spray, PARASITES. 283 the fungi pass into the air. This happens also when such a liquid dries up, or when a solid nutritive substance is broken up or disintegrates. If in the latter cases no substances are present which agglutinate the bac- teria into a compact mass, they may pass into the air in immense num- bers. Owing to their extreme smallness and lightness (Nageli estimates the weight of small moist bacteria at one ten-thousand-millionth (10-10) of a milligramme) they are carried about by the faintest breath of air. In this way they must of course very often reach and rest on bodies which can offer them no nutriment. But they must also often fall on a fit soil, and then proceed to grow and multiply afresh. Circumstances in gen- eral are in fact so favorable to the bacteria, that we find them or their germs almost everywhere ; but chiefly where the presence of organic matters, moisture, and warmth go to favor their multiplication. [Nageli (" Die niederen Pilze," Munich, 1877) asserts that fungi can only pass into the air when their nutrient liquids dry up. Soyka (" Miinch. acad. Sitzungsber., math.-phys. CL," 1871) has shown that bac- teria may be swept out of liquids that contain them by gentle air-cur- rents. Buchner (" Ueb. d. Beding. d. Ueberganges von Pilzen in d. Luft u. tlb. d. Einathmung derselben, Zur Aetiol. d. Infectionskrankh.," Mu- nich, 1881) disputes Soyka's conclusions. He maintains that even strong currents of air are insufficient to sweep bacteria from a liquid ; and that even in the case of dried-up masses containing fungi, the fungi are not set free unless the surface is actually broken. Ziegler agrees rather with Btichner's view. Nageli further thinks that very slight upward air-currents are enough to prevent floating bacteria from settling down. The condensed watery vapor that surrounds them tends to maintain their buoyancy. Friction also retards their fall. See Soyka, "Ueb. Canalgase als Verbreiter epi- dem. Krankh.," and "Ueb. Richtung und Starke d. Luftzuges in Sielen, Deutsche Viertelj. f. bffent. Gesundh.," xiv., 1882 ; and "Ueb. d. Natur und d. Verbreitung d. Infectionserreger, Zur Aetiol. d. Infectionskrankh.," Munich, 1881 ; Nageli, "Untersuch. tlb. nied. Pilze.," Munich, 1882. Wernich (" Cohn's Beit. z. Biol. d. Pflanzen," iii.) has shown that air- currents may sweep off bacteria from moist fungus-masses adhering to the surface of solid bodies. Researches on the bacteria and bacterial germs found in the air have been published by Cohn (loc. cit.), Miquel (" Des bacteries atmosph^riques," " Gaz. med. de Paris," 30, 1880), Wernich (" Virch. Arch.," vol. Ixxix.), Tyndall ("Floating-matter of the Air," London, 1881); Cunningham ("Microscopic Exam, of Air," Calcutta, 1874) gives an excellent summary of previous observations. On bacteria and their germs in the soil, see Koch (loc. cit.), and Ceci ("Arch. f. exp. Path.," xv.).] 194. Consideration of the wide-spread occurrence of the bacteria and their peculiar vital properties will already have raised the question 284 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. whether these micro-organisms may not have the power of exciting more or less grave disturbances in the human system, provided they obtain an entrance into it. We have seen that almost all fluids contain bacteria or their germs, unless they are actually poisonous or are " sterilized " by appropriate means, such as by boiling. Micro-organisms are also fre- quently found in solid organic matters. In view of this it would seem that we cannot avoid swallowing numbers of bacteria with our food. Moreover, we frequently eat articles which are in a state of partial pu- tridity or fermentation (such as cheese and milk) ; in this state they of course contain numerous bacteria. The alimentary tract must thus be reached by enormous multitudes of bacteria, together with the products of decomposition which they set up. This is, however, by no means the only way in which we come into in- timate relation with these organisms. The air always contains a greater or lesser number of them. In breathing we draw them into the lungs, and they settle in the bronchi or alveoli. Lastly, all parts exposed to the air come into contact with bacteria, the unwounded skin as well as the wounded or abraded skin. What becomes of all these organisms ? The greater number un- doubtedly pass out of the body again. It is hardly possible that any can penetrate into the deeper tissues through the uninjured skin. Those which settle on the mucous membranes are certainly for the most part not absorbed, but are thrown off after a longer or shorter time. This is, however, not always the case. Experience shows that, in special circum- stances, bacterial invasion of the system may actually start from the mu- cous membrane. What is the exception in the case of mucous membranes is the rule in the case of matters inhaled into the lungs. Experiment shows that fine corpuscular or particulate matters are very quickly taken up by the lymphatic capillaries of the lungs, and are so carried into the lymphatic glands, or it may be into the blood. Wounded surfaces are in like man- ner quick to absorb such corpuscular bodies. Resuming what we have said, we may put it generally that bacteria of various forms may reach, not only the surfaces of the body which are directly accessible from without, but also at times the deeper structures, if circumstances favor their penetration. [The question whether bacteria occur in the healthy body seems easily answered from such general considerations, though it is one which has been much disputed. Bacteria are perpetually entering the body with the food we eat and the air we breathe. They must, therefore, be at times found in the tissues, especially in places where access is direct. The fact that they are not easy to demonstrate is readily explained. It must be only a small number that can multiply in the tissues they have penetrated; the majority must quickly perish. See Nencki, "Journ. f. prakt. Chemie," 1879 ; Weissgerber and Peris, "Arch. f. exp. Path.," vi.; PARASITES. 285 Rosenbach, "Deutsche Zeitsch. f. Chir.," xiii.; Leube, "Zeitsch. f. klin. Med.," iii.; Sternberg, "Stud. Biol. Lab.," Baltimore, 1881; Lister, " Trans. Roy. Soc. Edin.," 1875. Leube, Lister, Roberts, and others have been unable to find living bacteria in healthy urine. This would indi- cate that the greater part of the bacteria which penetrate into the body are destroyed.] 195. If the bacteria were inert corpuscular elements, incapable of multiplication, we should have little more to say concerning their signifi- cance to the human organism. We should merely have to point out that they are in part taken into the body at certain points, are carried about hither or thither within it, are deposited here or there as innocuous substances, and sooner or later are destroyed or cast out again through the liver, kidney, or other secreting organ. As a fact this is what really happens with regard to some of the bacteria. Even when they pass through the bronchial glands from the lungs into the blood, they have no more significance than any other like minute foreign matters, such as occasionally circulate in the blood without causing disturbance. These are simply deposited and destroyed, or excreted. Thus the Micrococcus luteus may be introduced in considerable quantity beneath the skin of a rabbit, without inducing any serious affection either of the tissue or of the system generally. The bacteria which are thus innocuous may easily be indicated from previous considerations. They are such as cannot find within the human body the conditions favorable to their development. , This is unfortunately not the case with all bacteria. There are some which find their appropriate soil in the perfectly healthy organism, and in it they grow and multiply. Others are unable to settle in a perfectly healthy body ; they can only develop when the physico-chemical consti- tution of the tissues is morbidly altered so as to correspond with their re- quirements. The forms of bacteria that have the power of gravely affecting the system, whether it be healthy or diseased, are described as pathogenous bacteria. [It is manifest from the above that the determination of the vital properties and conditions of the different bacteria is a matter of the greatest importance. This knowledge would enable us to combat earlier the development of bacterial disease, and the injury it produces. It would further give us the necessary hints for preventing its invasion ; for we should know where to seek the bacteria and how to destroy them or render them harmless. Our knowledge in this respect is unfortu- nately still defective. There are but few species of bacteria whose life- history we know with any exactness of detail.] 196. The factors which determine the invasion and the course of de- velopment of bacteria within the human body are two. On the one 286 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. hand, the bacteria must be endowed with certain vital properties of a special kind ; on the other hand, there must be a predisposition on the part of the system. Our present knowledge does not yet allow us to specify accurately the properties which an infective bacterium must possess. We can only say in general-that it must find within the body and in proper combination^ all the conditions necessary for its growth and multiplication. Thus the temperature of the body must be such as favors its development ; it must be able to abstract fit nutriment from the tissues in which it settles ; it must nowhere encounter substances which check or injure it. Investigations into the bacterial affections have shown that very slight chemical changes in the constitution of a tissue are often enough to determine whether a given bacterium can develop in the tissue or not. Tn other words, the significance of this factor of predisposition is greater than it may have appeared at first sight. Now and then, of course, the predisposition is due to very obvious alterations in the tissues. For in- stance, we find that many cases of bacterial invasion depend on the for- mation of a local necrosis or wound, in which the fungus can settle and develop. In other cases some grave disturbance of the circulation may lead to a failure of resistance on the part of the tissue. These instances are, however, matched by others in which the anatomical basis of the pre- disposition is beyond our power to discover. We know, for example, absolutely no reason why-of two individuals exposed to the infection of measles, scarlatina, small-pox, typhus, or tuberculosis-the one should be taken with the disease and the other left. The factors which decide the matter in such cases are plainly such as at present escape our notice, either from their apparent slightness, or because they are not such as our tests can discover. Yet they doubtless consist in very real and very spe- cial differences in the condition of the tissues. Many of the bacteria can only come to development within the human body on rare occasions, as their usual habitat is without it. Others only meet with fit conditions for their existence and growth within the body, and do not multiply at all without it. [The respective parts played by the inherent properties of the bacte- rium and the predisposition of the tissues to invasion have been illus- trated by many observations both clinical and experimental. If a mass of bacteria of different forms be introduced into an animal's body, some of the forms develop and lead to certain tissue-changes, others perish in- ert. If a similar mass be injected into an animal of a different kind, the bacteria which develop are not the same as in the first instance. Koch (" Aetiologie der Wundinfectionskrankheiten," Leipzig, 1878, " Trau- matic Infective Diseases," London, 1880) has shown that there is a fungus which brings certain death to one species of mouse, while it is entirely inactive when introduced into another species of mouse. Mice are highly susceptible to the infection of anthrax ; rats enjoy an almost per- PARASITES. 287 feet immunity. The poison of " rabbit-septicaemia " kills rabbits and mice with unfailing certainty ; guinea-pigs and rats are unaffected by it ; sparrows and pigeons again are highly susceptible. The spirillum of human relapsing fever will develop only in monkeys among the lower ani- mals. Animals of the same species, but differing in age, have different degrees of susceptibility. Young dogs are easily infected with anthrax, old ones are not (Koch). We cannot at all tell on what circumstances immunity of this kind can possibly rest. Similar examples are easily ob- tained (Arts. 204, 206). The majority of the infective disorders are in fact limited each to a few species of animals or to a single one. Differences also exist in respect of the diffusion of the bacteria through the body. The fungus, which in one kind of animal brings about a fatal general disease, may in others produce a merely local and non-fatal dis- turbance. Even the point of entrance of the bacteria into the body has its importance. A rabbit inoculated with bacteria in the back of the neck may die, while inoculation of the ear is followed by a simple local affection. Rossbach has quite recently announced (" Centralb. f. med. Wiss.," 5, 1882) that injection of papayotin into the vessels is followed by a rapid development of micrococci in the blood, so that in two hours the blood in the heart is found to be swarming with them. If this observation be confirmed, it would seem to show that the composition of the blood is so altered by the unorganized vegetable ferment that germs can proceed to develop in it which before were unable to do so. In other words, that the action of a chemical substance has called forth a special predisposi- tion. Rosenberger (" Centralb. f. med. Wiss.," 4 and 41, 1882) observed a like result after the injection of sterilized septic blood. The animals died of septicaemia, bacteria being developed. If the injected liquid were really sterilized, we can only interpret the observation as showing that the septic matter so altered the blood and liquids of the animals as to make them predisposed for the development of micro-organisms. The experiments do not, however, seem quite free from objection. In 1869 Semner communicated similar results, which he obtained with the use of sepsin prepared from yeast (" Viertelj. f. wiss. Veterin.," xxxii.). Boser maintains that the most essential condition for the settlement of bacteria in the body is their adaptation to the quantum of mineral salts present in the blood and tissues. This can hardly be a sufficient condition.] 197. The healthy organism is always beset with a multitude of non- pathogenous bacteria. They occupy the natural cavities accessible from without, and especially the alimentary canal. They feed on the substances lying in their neighborhood, whether brought into the body or secreted by the tissues. In so doing they set up chemical changes in these substances. 288 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. While the organs are acting normally, these fungi work no mischief to the tissues in which they lie, or to the system generally. The products of decomposition set up by such non-specific micro-organisms are either harmless, or are conveyed out of the body before they begin to be active. Settlements of this kind may, however, become of importance if the bacteria proceed to develop to any unusual extent. This happens when the contents of the natural cavities in question remain unchanged for any great length of time, or when (as in catarrh) the normal secretion under- goes some alteration. The products of bacterial fermentation may then accumulate to an excessive amount, and products may also be formed which do not normally occur. Thus, when the contents of the stomach are not passed on, and become as it were stagnant, an abnormally acid fermentation may be set up. If the chyme is retained over-long in the small intestine, the aromatic products of albuminoid putrefaction will gather in excessive quantity. So, too, we may have decomposition in the stag- nating secretions of the bronchi, prepuce, etc. All these changes react harmfully on the tissues and may set up inflammation, not unfrequently ending in suppuration and necrosis. Moreover, the system in general may suffer by absorption into the blood of the soluble products of de- composition. The latter contingency is not to be lightly regarded. Though we may partake with impunity of many fermenting or decaying substances as food, we must not think that all the products generated by the non-patho- genous fungi are equally harmless. Highly poisonous substances are formed in many of the bacterial decompositions. One of the most speedily fatal of diseases, septicaemia, is due to poisoning of the system with the products of bacterial putrefaction, or sepsis. Cadaveric poison, the poison of decaying fish, sausage, cheese, mussels, etc., are very probably the chemical products of special forms of putrefaction. We un- fortunately know but little, in some cases we know nothing, of the substances which have this poisonous character. Bergmann and Schmiede- berg have, it is true, prepared their so-called " sepsin," and Panum his "putrid poison," from decaying substances ; but we do not know the composition of these bodies, and they are certainly not the only poisons of the kind. Putrid or septic poison may be absorbed by wounds as well as by mu- cous surfaces. Septicaemia, which has just been cited as an instance of septic poisoning, is generally due to wound-infection. It is due to the absorption of products of bacterial decomposition formed in a wound con- taminated by bacteria (Art. 204). This is especially apt to happen when necrosed tissue exists in the wound, for this affords the bacteria a suit- able soil for their development. [The poisonous action of putrid matters is fully discussed by Hiller in " Die Lehre von der Faulniss," Berlin, 1879. He gives full references to the literature of the subject. Hiller lays special stress on the fact that PARASITES. 289 in the septic process it is not simply the bacteria themselves that do mischief, it is the products of their action which act so as profoundly to alter or even to destroy outright the tissues exposed to them. If the in- fection become generalized, it is almost always due to intoxication of the system with unorganized chemical substances. Panum's paper just alluded to is in "Virch. Arch.," vol. lx.; Berg- mann's is a work called " Das putride Gift und die putride Intoxication," Dorpat, 1866. Wolff (" Virch. Arch.," vol. Ixxxi.) has lately taken up the question. On the absorption of putrid matters by the alimentary canal, see Salkowski, " Centralb. f. med. Wiss.," 46, 1876, and " Berichte d. chem. Gesells.," x., 1877 ; Nencki and Brieger, ibid.; Brieger, "Zeitsch. f. phys. Chem.," ii., "Zeitsch. f. klin. Med.," iii.; Bollinger, " Ueber Fleischvergiftung, intestinale Sepsis, und Abdominal-typhus, Zur. Aetiol. d. Infection," Munich, 1881. It is possible that harmless colonies of bacteria may become danger- ous if they are removed from their normal seat to other regions. Thus the saliva, when it contains bacteria, may excite violent inflammation if it reaches the bronchi or alveoli of the lungs.] 198. Pathogenous "bacteria have the power of settling, not merely in the ingesta and secretions or in dead tissue, but also in living tissue. This happens chiefly in the mucous membranes and in the lungs. The uninjured skin is protected against invasion by the horny epidermis. Many of the bacteria can settle in perfectly healthy mucous mem- branes. In the case of others we must imagine that they do not find a proper soil for their development, unless the mucous membrane is injured or altered. Of course, injury or alteration of this kind may serve to make the outer skin, or any other accessible tissue, the starting-point of a bac- terial invasion (wound-infection). All that is necessary is that a bacte- rium should reach a spot that affords the conditions for its development. If this occur, it multiplies and forms colonies or swarms. These may, ac- cording to the species of the fungus and the nature of its soil, remain in aggregation forming heaps or masses, or may spread through the tissues. Such a settlement is never without effect on the affected tissues. The bacteria may force their way into the substance of the constituent ele- ments, and especially into the tissue-cells, which are sometimes found to be crammed with bacteria. The effect of the invasion is not always at once apparent, even under the microscope. The cells attacked by the fungi often appear quite unin- jured ; in other instances they are seen to be altered. The epithelial cells swell up (Fig. 76, c) and liquefy, or degenerate into flaky homoge- neous lumps, or turbid denucleated masses. Often they break down into granular detritus. The nucleus is broken up, or swells and disappears (Fig. 76, c). The fibrous elements of the connective tissue degenerate like the epithelial cells. The ground-substance alters at the same time. It becomes turbid, loses its structure, and ultimately dissolves. 19 290 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. In general terms we may say-that local settlements of bacteria will sooner or later bring about degeneration and necrosis of the affected tis- sue. When this may occur, and how widely it may spread, are circum- stances depending on the nature of the bacteria and of the tissue. The processes we have considered are not without their influence on the circulation. The direct action of the bacteria, and the influence of the chemical changes they set up, tell at length on the vessel-walls within the affected region. The result is to disturb the circulation in various ways, chiefly in the way of inflammatory exudation and hemorrhage. In some instances the circulation is stopped altogether, and the preservation of the affected tissue is then impossible. Fig. 76.-Section containing Colonies of Micrococci from the Vocal Cord of a Child. X 200. a, epithe- lium ; b, connective tissue of the mucous membrane: c, swollen degenerated and denucleated epithelial cells ; d, layer of micrococci; e, inflammatory small-celled infiltration of the degenerated epithelium and of the fibrous structures. The inflammatory process set up by bacterial action (Fig. 76, e) may be of very different intensity and extent in different cases. It may be slight and transient, or it may be severe and issue in suppuration and necrosis. Not unfrequently a more or less perfect granulation-tissue is formed as a result of the inflammation, as in tuberculosis. The extrava- sated cells often take up the bacteria into their substance. 199. The inflammation excited by the presence of bacteria often re- sults in a great aggregation of living cells in the tissue affected. These may so act as to repel the continued advance of the fungi, which straight- way perish, and the affection issues in healing and cicatrization. The fixed tissue-cells of the region may likewise act so as to check the devel- opment of the bacteria, and may further suffice to make up any loss of tissue by their regenerative activity. If this does not happen the bacte- rial invasion continues to advance. The bacteria spread first into the surrounding tissues, passing along the natural lines of division. Then they break into the lymphatics, and PARASITES. 291 often into the blood-vessels also. If they can live in lymph or blood they go on multiplying ; if not they perish. Many bacteria, like the micrococcus of erysipelas, flourish best in the lymphatics. Others, like the anthrax-bacillus, are more at home in the blood. The extent to which the bacteria can spread within the lymphatic system is subject to no general rule. Many of them make a halt at the first gland they come to. Others pass beyond, and finally reach the blood-vessels by way of the thoracic duct. Their path is generally marked by degenerative and necrotic changes, and by the inflammatory reaction they excite. The degree and amount of these changes are de- termined partly by the nature of the bacteria, partly by their number. They reach the blood either through the lymphatics or directly. In the latter case the walls of the veins in the invaded region are penetrated by the fungi, or they pass into the veins from the capillaries. Once in the current they are carried on by it to remote parts. Many of them Fig. 77. Fig. 78. Fig. 77.-Micrococcus Septicus in Hepatic Capillaries; Necrosis of the Liver-cells, x 350. Fig. 78.-Bacillus Anthracis; Liver-cells unaffected, x 350. perish in the blood, others again increase and multiply. Of the last some (anthrax-bacillus) thrive best in blood that is flowing; others (tu- bercle-bacillus, pyaemic micrococcus) prefer blood that is at rest, that is to say, they only grow when they have come to a standstill in some ve- nule or capillary. It depends on the properties of the fungus, which of these events takes place ; just as do the changes it calls forth in the course of its multiplication. The tissue-changes are the slightest in the case of bacteria which cir- culate and multiply in the blood (Fig. 78). Bacteria which settle in the smaller vessels give rise, on the other hand, to degenerations, necroses (Fig. 77 and Fig. 79, e), inflammations (Fig. 79, d, e), and hemorrhages. The spot where a lodgement takes place is mostly matter of chance ; but it is to be noted that a bacterium may not be able to settle in every spot indifferently. One part of the vascular system may be more favora- ble to it than another. Many bacteria remain and multiply within the vessels. Others escape from them, and when the surrounding tissue is suitable they may multiply in it, and set up changes resembling those produced at the point ofc first invasion (as in tuberculosis). 292 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. [References : Frisch, "Exp. Studieniiber d. Verbreitung der Faulniss- organismen in d. Geweben," Erlangen, 1874 ; Koch, "Traumatic Infec- tive Diseases " (Syd. Soc.), London, 1880 ; Peris, "Lehrb. d. allg. Path.," ii. We should mention, with regard to the spread of bacterial infection within the system that the mode of invasion and the number of the fungi present are points of importance. If mice or guinea-pigs be inoculated Fig. TO.-Hepatic Abscess; first stage, x 40. (Bismarck-brown staining.) a, normal lobules; b, necrosed lobules; c, capillaries filled with micrococci; d, small celled infiltration of the periportal tissue; e, aggrega- tion of small round-cells in a vein, into which opens an intra-lobular venule crammed with micrococci. beneath the skin with a few oedema-bacilli, the resulting affection is merely local. If the bacilli be numerous the animals die of a general dis- order. The bacilli of anthrax and those of "rabbit-septicaemia" may be injected in small quantity into the ear of a rabbit without causing its death. In the quantity ordinarily used in inoculative experiments they are always fatal.] 200. The facts just given (Arts. 198, 199) regarding the spread of Bacterial infection within the system are derived from observations on PARASITES. 293 pyaemia, erysipelas, anthrax, and tuberculosis. The greater number of the diseases now referred by many to the action of bacteria (such as ty- phoid, relapsing fever, diphtheria, the exanthemata, croupous pneumonia, acute atrophy of the liver, cholera, etc.) are as yet too little known to en- able us to give the corresponding details for them. We do not exactly know how the poison finds entrance, where it is multiplied, and in what manner it spreads. We only know that in these affections we find at certain times in the blood or tissues definite bacterial forms ; and we be- lieve that they are the exciting cause of the disease. If this belief be correct, we must admit that many kinds of bacteria have the power to penetrate into the blood and other juices without leaving any traces at the point of entrance. This supposition is confirmed by the fact that in anthrax we are often unable to detect the point of entrance of the bacilli. In the case of these diseases we must likewise assume, as in the case of the others, that the bacteria find access through the mucous membranes or lungs, or through open wounds if any exist. Once the bacteria have entered the body they multiply in the blood or in some tissue, spread through the system, and call forth the special changes characterizing the several diseases. It is worthy of remark that each poison has a corre- sponding special group of tissues, in which its mischievous effects are in- variably and especially apparent. The anatomical changes produced in these diseases, as in the others, are of the nature partly of degeneration and necrosis, partly of inflammation or hemorrhage. Proliferous changes in the tissues may also ensue as secondary to the former. । 201. We are not yet in a position to formulate a theory of bacterial action that will apply to all cases. The researches of the last year or two have, however, enabled us to form some picture at least of the way in which bacteria affect the several tissues and the system in general. The pathogenous bacteria are parasites which draw their nourishment from man's body. They withdraw this nourishment only from the tis- sues among which they are growing and multiplying. The effect of this withdrawal is in general not very grave. It can only become dangerous to life when the bacteria multiply within the circulating blood and with- draw from it the indispensable oxygen it contains. The withdrawal of nutriment is not, however, the only result ; it is seldom even the most important. Investigations show that the vital activity of the bacteria of necessity sets up extensive chemical change in their own nutrient ma- terials. These changes are partly due to their direct action (Art. 191), partly to the action of the unorganized ferments which they form. Lastly, in the course of these changes, matters are produced which act as poisons upon the system. This effect of the bacteria on their nutrient fluids, and the production of poisonous matters, have much more to do with the genesis of the symptoms in most of the microparasitic affections than has the mere withdrawal of nutriment. The influence of such factors is manifested in disturbances of the functional, formative, and nutritive activities of the organism. These 294 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. activities are the expression of the cell-life of the tissues ; hence the statement that bacteria disturb the vital actions of the tissue-cells. In Art. 81 we compared the life-history of the tissue-cells with that of the bacteria. We may not inopportunely refer to the comparison once more in this place. The nutritive activity of the tissue-cells is not confined to the replacement of used material by the absorption and assimilation of new material. Like the bacteria, the tissue-cells act catalytically on their surroundings, partly by fermentive action (Art. 191), partly by the for- mation of unorganized ferments. Many cells have in addition the power of setting up synthetic processes. When bacteria proceed to multiply within a tissue, a double influence is brought to bear on the common nutrient medium ; the bacteria enter into conflict with the tissue-cells. We do not, of course, know in what exact way this conflict is carried on. But we may believe that the bac- teria do not communicate to the organic compounds contained in the juices the same kinds of chemical motion as the tissue-cells. They will not, therefore, give rise to the same chemical changes as the latter. More or less serious disturbance of the normal metabolism of the tissues must ensue. This is the first effect, but not the only one. Different kinds of fer- mentation cannot go on in presence of each other for any length of time. One is more and more repressed, and at length suppressed, as the other advances. This cannot, of course, happen without simultaneous inj'ury to the corresponding ferment. Thus the prolonged presence of bacteria re- sults in the suppression not alone of the nutritive activity, but also of the other functions of the tissue-cells ; and at length their life itself is enfeebled or extinguished. The products of the decomposition set up by the bacteria, the unor- ganized ferments and other poisons, also give rise to changes in the tissue-cells. It is possible that in many cases they only tend to modify the nutritive activity, i.e., the metabolism of the cells ; but the other functions are doubtless often affected likewise. These modifications of the normal cell-life in their totality are manifested as disturbances of the functions of the organism, and we speak of them as symptoms of disease. The mode in which the several symptoms are produced we cannot here stop to discuss. All we need say is that a disturbance of cellular activity is always at the bottom of a morbid symptom ; mere alteration in an organic fluid is not enough to give rise to symptoms. Thus the origin of fever cannot be explained otherwise than by assuming the exist- ence of some cellular disturbance. The chief factor in producing the elevation of temperature may be a change in the fermentive action of the cells, or it may be a disturbance of the functions of the central nervous system. That is a question which is open to discussion ; but it does not touch the question of the cellular nature of the febrile process. Inflammation itself is only to be explained by cellular change. In bacterial affections, inflammation appears as a specially beneficent pro- PARASITES. 295 cess. By it a number of living cells are thrown out at the seat of danger, and they are the readiest instruments for checking the harmful influence of the fungi. The issue of a bacterial affection is either the death of the patient, or the death and elimination of the bacteria. In the former case the bac- teria interfere with the functions of cells so numerous or so essential to life, that life becomes impossible. In the latter case the tissue-cells gain the upper hand in the struggle for nourishment and existence, and the bacteria are at length deprived of the conditions essential to their con- tinued life. Observations on the infective diseases of man, and on experimentally produced bacterial diseases in animals, have shown that a disease of the kind successfully withstood leaves the tissues in a peculiarly unsuscepti- ble condition. This condition may endure for months or years, and it insures an immunity almost or quite complete against a fresh invasion of the same or kindred bacteria. We do not know whether this singular effect is due to a modification in the chemical constitution of the tissues, or to a change in the vital activity of the cells. [References : Voit, "Physiologic des Stoffwechsels," Leipzig, 1881 ; Nageli, " Die niederen Pilze," Munich, 1877, and 1882 ; Buchner, " Die Nageli'sche Theorie der Infectionskrankheiten,'' Leipzig, 1878 ; Klebs, Article " Ansteckende Krankheiten," " Realencyclopadie der gesammten Heilkunde von Eulenburg," and " Cellular-pathologie und Infections- krankheiten," "Tageblatt der Naturforscherversammlung in Kassel," 1878 ; Virchow, " Krankheitswesen und Krankheitsursachen," " Virch. Arch.," vol. Ixxix. ; Hiller, " Die Lehre von der Faulniss," Berlin, 1879 ; Wernich, " Die Entwickelung der organisirten Krankheitsgifte," Berlin, 1880 ; Koch, " Untersuchungen uber Wundinfectionskrankheiten," Leip- zig, 1878, "Traumatic Infective Diseases," London, 1880 ; Wolff, "Zur Bacterienlehre bei accidentellen Wundkrankheiten," "Virch. Arch.," vol. Ixxxi. ; Toussaint, " Comptes Rendus," nos. 2 and 5, vol. xci. ; Chau- veau, ibid., no. 16; Duclaux, "Ferments et Maladies," Paris, 1882 ; Brieger, " Einige Beziehungen der Fiiulnissproducte zu Krankheiten," "Zeitsch. f. klin. Med.," iii. ; Buchner, "Ueber d. Wirkung d. Spalt- pilze im lebend. Kbrper," " Zur Aetiol. d. Infectionskr.," Munich, 1881 ; Cheyne, " Antiseptic Surgery," London, 1882 ; Discussion, " Trans. International Med. Congr.," vol. i., 1881. Of late years many experimenters have sought to furnish an experi- mental basis for the doctrine that individuals who have passed through an infective disorder are "protected " against the same or a kindred dis- order (as in the case of vaccinia and variola). They have attempted to make out that this holds for bacterial disease artificially communicated to animals. Pasteur was the first to make communications on this head (" Gaz. med. de Paris," no. 18, 1880). Toussaint refers the so-called fowl-cholera 296 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. to the action of a certain micrococcus. Fowls die when inoculated with the bacteria cultivated in chicken-broth. If the poison be attenuated by- letting it stay in the culture-liquid exposed to the air for eight or ten months, it is no longer fatal on inoculation ; but the fowls become by one or more inoculations "protected" against the unattenuated poison. Pasteur further discovered that the activity of the anthrax-bacillus may be diminished by cultivation at a temperature of 42° to 43° C. Animals inoculated with the cultivated bacillus do not die, but are as it were " vaccinated " against the unmitigated poison. After repeated inocula- tions sheep become at last quite unaffected by inoculation with the un- altered bacillus. Bouley communicated to the Paris Academy a research of Toussaint's, in which he found that the anthrax-poison can be mitigated by warming infected blood to 55° C. for ten minutes with the addition of one per cent, of carbolic acid. Young dogs, sheep, horses, and rabbits may be protected by inoculation with this blood. Colin (Paris Academy, March 1, 1881) has disputed the force of these experiments, as it is known that some individual animals are specially "refractory" with respect to the anthrax-poison, without any protective inoculation. The Royal Hun- garian Ministry of Agriculture instituted at Buda-Pesth an extensive series of experiments, superintended by one of Pasteur's assistants, and the results obtained confirmed on the whole what Pasteur had announced (Roszahegyi, "Biolog. Centralb.," 5, 1882, and Practitioner, February and March, 1882). Similar successful experiments were made in Berlin in April, 1882 (" Gaz. med.," July, 1882). Oemler ("Arch. f. wiss. und pract. Thierheilk.," 1876-81) made similar inoculation-experiments with- out reaching any positive results. Chauveau likewise experimented on sheep, but was not able to draw any certain inferences ; he thinks, how- ever, that an imperfect protection may be obtained by repeated inocula- tion. Lbffler ("Mitth. a. d. k. Gesundheitsamte," Berlin, 1881) experi- mented on mice, rats, guinea-pigs, and rabbits, but was not able to verify Pasteur's and Toussaint's statements. He did not succeed either in at- tenuating the poison or in effectively "vaccinating" the animals. He therefore disputes the force of their experiments, thinking that they must have lighted on sheep already immune against the poison. The ex- periments on fowl-cholera he thinks trustworthy. It was he who showed that when a mouse has lived through one attack of specific septicaemia it is protected against a further attack. This specific septicaemia of the mouse is caused by a delicate bacillus, which can be " purely " cultivated in nutritive gelatine, weakly alkalized with sodium phosphate and impregnated with one per cent, of peptone. The bacillus will infallibly kill a rabbit injected with it in from forty to seventy-two hours. If it be introduced into the tip of the ear it merely produces a plastic inflammation of the skin, and the animal does not die. Rabbits so inoculated are then protected for three or four weeks against any further inoculation with the same bacillus. PARASITES. 297 There are, therefore, some bacterial diseases in which one attack pro- tects against a subsequent one, as in the case of small-pox, measles, and scarlatina. But this does not hold true of all bacterial diseases. Koch and Carter found that a monkey inoculated with the spirilla of relapsing fever gained no immunity against a second inoculation. Semmer (" Cen- tralb. f. med. Wiss.," 48, 1880, and " Virch. Arch.," vol. Ixxxiii.) asserts that rabbits may be protected against septicaemia by vaccination with bacteria heated to 55° C. for fifteen minutes ; Lbffler repeated the ex- periments and obtained opposite results. Experiments with the Bacillus cedematis (Art. 206) were likewise negative. Bergmann has recently (" Chirurgencongress," 1882) made out that in all infective disease, and in all intoxication with unorganized ferments, the white blood-cells become dissolved in the blood. This produces greater viscidity and coagulability of the plasma. He refers to this cause the local congestions in the capillaries of the lungs and intestine, and the ecchymoses of the serous membranes observed in the affections named.] 202. The infective diseases form a group distinguished by their markedly specific character and their special mode of origin. The specific character is manifested in this-that the disease runs a similar course in each individual attacked, conditioned solely by the nature of the morbific virus. As to the genesis of the disease, it is always referable to the passage into the organism of a poison from without. The infective diseases have been divided into miasmatic, contagious, and miasmo-contagious. In miasmatic disease the morbific virus is con- fined to certain localities, and develops outside the human body. When it passes into the body it sets up an affection which is not transmissible to other individuals. The malarious or intermittent fevers are classed as miasmatic. In contagious disease the seat of the virus is in the affected organ- ism. From this it is transmissible to others, either through the air directly, or by means of bodies acting as carriers (fomites}, or by actual contact. Instances of contagious disease are scarlatina, small-pox, measles, vaccinia, typhus, diphtheria, glanders, syphilis, etc. In miasmo-contagious disease the actual virus is derived from without, but the germs from which the virus develops must be furnished by a previous case of the disease. Of this kind are cholera, dysentery, yellow fever, and typhoid. In the case of the last it is probable, or at least possible, that the virus may be also derived from previously unin- fected localities ; in other words, that it may originate as a pure miasm. 203. Some of these diseases, especially the epidemic pestilences or plagues, have from ancient times been suspected to be due to organized poisons. The suspicion has now and again been re-expressed ; but it is only within the last twenty years that, in a few instances at least, the fact has been demonstrated. 298 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. The strongest point of evidence in favor of the organic nature of the poisons that produce the infective diseases is their power of unlimited re- production and multiplication. Thus, starting with the lymph from a single vaccine vesicle, we can vaccinate on indefinitely, continually gener- ating new vaccine matter. Infection transmitted through the medium of the air (which certainly takes place), is scarcely to be explained if it be not that the air has had corpuscular particles suspended in it. Chemi- cally active gases would very quickly become diffused through the atmos- phere, and at short distances would become attenuated beyond the power of doing mischief. The small quantity of infective matter required to set up the corre- sponding disease is another point in the evidence. The extraordinary potency of the matter can only be explained by the theory that the virus is reproduced and multiplied within the organism. The researches of the last ten years have shown (as we have said in Arts. 198-201) that there are bacterial fungi which are able, by virtue of their specific properties, to affect the animal body and generate disease in it. On the other hand, we find such fungi in the blood and tissues of persons affected with infective disease. We must admit beforehand that the available observations on this head have not the extent or exactness which we could desire. Only in the case of a few diseases is the bacte- rial nature of the virus demonstrated by indefeasible histological and ex- perimental investigation. In others the presence of bacteria has been demonstrated in single cases, but their causal relation to the disease has not been proved. In many others, neither the one point nor the other has hitherto been made out. As the question at present stands, then, we can only say-that among the infective diseases there are cer- tainly some which are due to the invasion of a microphyte, and that it is highly probable the others have a like origin. If the microparasitic theory be correct, we must admit that some of the pathogenous bacteria are accustomed to develop and multiply with- out the body, while others only do so within it. The former kind we may describe as ectogenous, the latter as endogenous. The distinc- tion must not, however, be over much insisted on. Sometimes the ecto- genous bacteria proceed to multiply within the body, while the endoge- nous bacteria may meet with the necessary conditions for their growth (warmth and nutriment) outside it. [The fact that bacteria have not been found in most of the infective diseases, at least in number sufficient to account at all for the phenomena, is no proof that the affections are non-bacterial. It must not be forgot- ten that the demonstration of bacteria is often a very difficult matter, and the material obtained from the post-mortem table is by no means well- fitted for this purpose. The patients examined generally live on to a comparatively advanced stage of the disease. We know indeed in the case of many bacterial affections that, by the time the tissue-changes oc- PARASITES. 299 casioned by the invasion are complete, all trace of bacteria has long dis- appeared.] 204. The micrococci are among the most important of the pathoge- nous bacteria. They are the fungi most frequently found in connection with infective disease. In the first place they occur in various wound- affections, such as pyaemia, and erysipelas simple or phlegmonous ; and that not merely in the wound itself, but in its neighborhood, and even in distant organs. In this last case they are diffused through the lymphatics and blood-vessels. They also occur in internal suppurations like metritis, puerperal peritonitis, infective osteomyelitis and periostitis, and in stru- mous inflammations, meningitis, cerebral abscess, etc. Among infective diseases of another kind we have to mention diph- theria, small-pox, measles, vaccinia, scarlatina, endocarditis, pyelitis, hremophilia neonatorum, acute atrophy of the liver, croupous pneumonia, gonorrhoea, etc. In all of these micrococci have been seen scattered through the tissues, partly as masses of zoogloea, partly as chains or chaplets. It would seem as if in some diseases zoogloea, in others chap- lets or swarms, were chiefly formed. The spherules are of various sizes ; but this character of size is not enough to enable us to distinguish be- tween specific forms. We have as yet but few results of culture-experi- ments on these bodies, so that their life-history is little known. The micrococci are therefore distinguished merely by the disease to which they are related, and so we speak of Micrococcus septicus, erysipelatis, variolas, diphtheriticus, etc. The part played by these micrococci (which are not found in every case) is by no means certainly determined. Of some we can only say that they are frequently or always found in connection with the corre- sponding disease (small-pox, scarlatina, measles, haemophilia neonatorum). Of others (as in wound-infections) we know, by experimental investiga- tions, that they are only able to attack the tissues when they find in the system poisonous products of tissue-necrosis, or of fermentive decompo- sition set up by bacteria like themselves. Of many (such as those found in simple and phlegmonous erysipelas) we have every ground for believ- ing that they can develop in the system without any special auxiliary conditions (other than slight traumatic injury). (We shall here consider briefly the evidence for the bacterial nature of some of the infective diseases. (1) Purulent Inflammations ; Cellulitis ; Purulent Catarrh. There can be no doubt that micrococci are the exciting causes in many inflammatory processes associated with the formation of pus. This is true not only of purulent affections of the skin and mucous mem- branes, but also of suppurations in the deeper structures of the body. 300 A TEXT BOOK OF PATHOLOGICAL ANATOMY. Many of these affections start in wounds, but in others it is impossible to make out any surface-injury, and we are constrained to admit that the micrococci have penetrated into the deeper tissues without entering through a wound. Purulent catarrh of the mucous membranes, when due to fungi at all, is generally excited by micrococci from without ; but these may sometimes come from deeper organs already affected, as when the urinary tract is infected from the kidney. This also holds for phleg- monous or parenchymatous inflammations of the subcutaneous and sub- mucous structures (cellulitis), associated with purulent, serous, or fibrin- ous exudations. In the case of deep-seated organs, the micrococci must be conveyed by the lymphatics or blood-vessels. If by the blood-vessels, the affection should perhaps be described as pysemic. When the micrococci lie in the blood-vessels, they generally form col- onies. In liquid exudations within the body-cavities they are found sin- gle or in chains ; in solid structures they form swarms. In all places they occur both free and enclosed in cells. It is a question whether in all the affections just cited the micrococ- cus met with is of the same species. Comparative examinations show that in the different cases the spherules vary in size. Ziegler found that the largest of all occurred in a case of spontaneous cellulitis of the face and neck, in which suppurating and hemorrhagic patches were found in the lungs. References: Klebs, " Ilandb. d. path. Anat.," i. (pyelitis), " Bei- trage zur path. Anat. d. Schusswunden," Leipzig, 1872, and " Arbeiten a. d. path. Inst.," Berne, 1872 (pyaemia) ; von Recklinghausen, "Verh. d. Wiirzburger physic. GeselL," 1871 (pyaemic foci) ; Rindfleisch, " Lehrb. d. path. Gewebelehre," first edition (pyaemia) ; Birch-Hirschfeld, "Unters. ub. Pyamie," Leipzig, 1873 ; Koch, " Wundinfectionskrankheiten," Leipzig, 1878, " Traumatic Inf. Diseases " (Sydenham Soc.), 1880 ; Wolff, " Virch. Arch.," vol. Ixxxi.; Lucke, "Deutsche Zeitsch. f. Chir.," iv.; Braidwood and Vacher, Brit. Med. 1, 1882, with a very full summary of the contributions to this subject ; Kocher, " Arch. f. klin. Chir.," xxiii. (osteomyelitis, infective periostitis, strumous inflammation) ; Greenfield, etc., " Trans. Path. Soc.," 1879 ; Haab, " Corresp. f. schweiz. Aerzte," 1881 (blennorrhoea, gonorrhoica neonatorum, gonorrhoea) ; Neis- ser, " Centralb. f. med. Wiss.," 28, 1879 (gonorrhoea) ; Cheyne, Brit. Med. Journ., 1880 (gonorrhoea) ; Peris, "Lehrb. d. allg. Path.," ii.; Ogs- ton, Brit. Med. Journ., 1, 1881 ; and under Art. 199. (2) Erysipelas. Ziegler has satisfied himself by his own researches that erysipelas is due to a micrococcus. It spreads chiefly by way of the lymphatics, which are sometimes seen to be crammed full of aggregated masses of spherules. Thence it penetrates into the tissues and forms chains or swarms. It excites inflammation and leads to tissue-necrosis. It can be PARASITES. 301 transmitted to the rabbit, and spreads in it also by way of the lympha- tics. The animal usually dies. References : Nepveu, " Gaz. med. de Paris," 1872 ; Lukkomsky, "Virch. Arch.," vol. lx.; Orth, " Arch. f. exp. Path.," i.; Klebs, "Arch, f. exp. Path.," iv.; Tillmanns, "Arch. f. klin. Chir.," xxiii.; Fehleisen, "Deutsche Zeitsch. f. Chir.," xvi.; Koch, "Traum. Inf. Diseases," 1880. (3) Septicaemia. This is a term which includes various rapid and fatal affections of the blood. Septicaemia in the human subject implies blood-poisoning with various chemical products of septic decomposition. It is a septic intoxi- cation, but actual bacteria are not found in the blood. It is not progres- sive, and not infective in the strict sense of the word (Burdon Sanderson, Brit. Med. Journ., 1, 1877). But the term is also applied by some to certain specific and infective affections of animals, in which bacteria grow and multiply in the blood itself. Davaine's septicaemia is an infective disease of rabbits, produced by subcutaneous injection of septic matters (such as putrefying blood). It is characterized by a definite incubation-period, and a rapid course ; it is transmissible to other animals of the same species. The blood is found to contain numerous oval bacteria. Pasteur's septicaemia has been called by Koch malignant oedema ("Acad, de med.," February 1 and 8, 1881). It is produced in rabbits by ipserting garden-mould under the skin of the abdomen. Death ensues in twenty-four to forty-eight hours. The blood itself seems to contain no organisms ; but subcutaneous oedema results, and in the oedematous tissues a delicate motile bacillus is found. Gaffky has cultivated the ba- cillus on slices of potato. Mouse-septicaemia (Koch) is a blood-affection generated in mice by in- oculation with a certain delicate bacillus. The injection of human saliva produces in rabbits a form of septicaemia not, as it seems, identical with that of Davaine (Raynaud, Pasteur). Gaffky produced still another form of septicaemia in rabbits by injecting river-water (from the river Panke). The bacteria which developed and multiplied in the blood re- sembled B. termo (Art. 205). References : Davaine, " Acad, de med.," September 17, 1872 ; Coze and Feltz, "Rech. exp. sur la presence des infusoires dans les maladies infect.," Strasburg, 1866 ; Semmer, "Virch. Arch.," vol. Ixxxiii.; Koch, " Wundinfectionskr.," Leipzig, 1878, "Traum. Inf. Dis." (Sydenham Society, 1880) ; Gaffky, " Mitth. a. d. k. Gesundheitsamte," Berlin, 1881 ; Raynaud, "Acad, de med.," February 8, 1881; Ewart, "Proc. Roy. Soc.," xxxii.; Tizzoni, " Arch, per le scienze," 1880-81 ; Sternberg, " Rep. of Nat. Board of Health (U. S.)," 1881 ; Braidwood and Vacher, Brit. Med. Journ., 1, 1882 (a full list of contributions to the subject of pyaemia and septicaemia is given). 302 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. (4) Diphtheria. This is a specific infective disease. The anatomical changes are usu- ally first discerned in the pharynx and in the neighboring mucous mem- branes. They take the form of catarrhal, croupous, and diphtheritic inflammations (Arts. 423-426). They are probably caused by a micro- coccus which settles in the tissues of the parts named (rarely elsewhere- as in the eye, or in wounds), and thence spreads through the system. This view is chiefly supported by the fact-that in and upon the affected mucous membranes we find micrococci scattered or aggregated as zoo- gloea, which do not occur under normal conditions. Occasionally it is possible to demonstrate the presence of micrococci in the swollen cervical glands, or even in deeper organs. If these micrococci be experimentally introduced into animals, they produce a disease resembling diphtheria. The micrococci multiply mainly within the body, but they may also find a suitable soil for growth outside it. The theory of the genesis of diphtheria is still defective, in spite of the many investigations that have been made. Even what we have stated above regarding it is by no means beyond question. References : Hitter and Tommasi, " Centralb. f. med. Wiss.," 12 and 34, 1868 ; Oertel, "Arch. f. klin. Med.," viii., "Ziemssen's Cyclopaedia," vol. ii., " Die Aetiol. d. Diphtheric, Zur Aetiol. d. Infectionskr.," Munich, 1881; Trendelenburg, "Arch. f. klin. Chir.," x.; Klebs, "Arch. f. exp. Path.," iv., Art. " Diphtheritis," " Realencyclop. d. ges. Heilk.Letze- rich, "Virch. Arch.," vol. Ixviii.; Nassiloff, "Virch. Arch.," vol. 1.; Eberth, "Zur Kenntniss d. bacter. Mycosen," 1872 ; Wood and Formad, "Rep. of Nat. Board of Health (U. S.)," 1881-82. Brieger ("Zeitsch. f. klin. Med.," iii.) has lately pointed out the fact that in pyaemia, erysipelas, diphtheria, and scarlatina, certain processes take place in the tissues nearly allied to those in bacterial putrefaction. He therefore calls the diseases in question putrefactive diseases. (5) Scarlatina and Measles. We have no certain knowledge as to the causation of scarlatina. Coze and Feltz (" Malad. infect.," 1872) and Riess (" Reichert's Arch.," 1872) have seen micrococci in the blood, and by inoculation have gener- ated a fever-like disease in rabbits. Coze and Feltz also found micro- cocci in the blood of patients affected with measles ; Keating ^Philadel- phia Med. Times, August 12, 1882) recently found them in an epidemic of malignant measles ; Ransome, and Braidwood and Vacher {Brit. Med. Journ., January 21, 1882) found them in the breath as well as in the tis- sues. PARASITES. 303 (6) Endocarditis. In many forms of endocarditis the affected patches are covered with an abundant layer of micrococci. These are also found in metastatic patches if there be any. It is very probable that endocarditis may be set up by various causes, and, as it would seem, by various forms of micrococcus (Art. 282). References: R. Maier, "Virch. Arch.," vol. Ixii. ; Eberth, "Virch. Arch.," vol. Ivii. ; Klebs, "Arch. f. exp. Path.," x. ; Koster, "Virch. Arch.," vol. Ixxii. ; Koch, "Mitth. a. d. k. Gesundh.," Berlin, 1882. (7) Variola and Vaccinia. In both affections micrococci have been found in the vesicles. As to their real significance nothing certain is known. References: Keber, "Virch. Arch.," xlii.; Ziilzer, "Berl. klin. Woch.," li., 1872 ; Weigert, "Anat. Beitr. z. Lehre v. d. Pocken," 1874 ; Klebs, "Arch. f. exp. Path.,"x. (8) Haemophilia Neonatorum. Klebs ("Arch. f. exp. Path.," iv.) and Eppinger (" Beitriige zur path. Anat. v. Klebs," 1878) have described a micrococcus in this disease, and have given it the name of Monas hoemorrhagicum. (9) Acute Yellow Atrophy of the Liver. Klebs, Waldeyer, and Eppinger (" Prag. Viertelj.," 1875) have pub- lished papers on the micrococcus found in this disease. (10) Croupous Pneumonia. Klebs ("Arch. f. exp. Path.," iv.), Koch (" Mitth. a. d. k. Gesundh.," Berlin, 1881), and Friedlander ("Virch. Arch.," vol. Ixxxvii.) have seen micrococci in cases of this disease. (11) Acute Catarrhal Pneumonia. Micrococci are very often found in the alveoli and lung-tissue. They probably reach the lungs with other bacteria from the mouth-cavity (pneu- monia by aspiration). The fungus so called occurs chiefly in the stomach, lungs, pharynx, and urine. In the lungs it has been found by Nauwerck in various pneu- monic affections (" Corresp. f. schweiz. Aerzte," 1881). It is much smaller than the sarcina of the stomach. Nothing is known of its significance. We may here refer to a disease of silkworms, which throws light on (12) Sarcina. 304 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the development of bacteria within the body. It is called pebrine, gattine, or " spotted disease." It formerly produced enormous destruction among the silkworms in silk-producing districts. Investigations made in 1853-56 showed that it was associated with the presence of a micrococcus. Nagel called the fungus Nosema bombycis. Pasteur proved experimentally that these organisms produced the disease, and also showed by what means it could be averted. The micrococcus is transmitted to the eggs ; the moths are therefore isolated, and after laying their eggs are microscopically ex- amined. If the moths are found to be diseased the eggs are destroyed. Another disease of the silkworm, maladie de morts-blancs, which annually causes great losses to silk-growers, is very probably a bacterial affection. Toussaint and Pasteur have shown (" Comptes Rendus," nos. 6, 17, 18, 1880) that fowl-cholera is caused by an invasion of micrococci. The organism can be cultivated in alkalized chicken-broth, which has previ- ously been sterilized by being raised to a temperature of 110° to 115° C.] 205. The two representatives of the class of Microbacteria, namely, Bacterium termo and Bacterium lineola, can only develop in dead tissues and liquids. B. termo is frequently found in the human body at places where necrosed tissue is accessible to the air. Putrefaction is in fact conditioned by the presence of this organism. It may become dangerous by setting free products of decomposition which excite inflammation or gangrene around the putrefactive focus, and when absorbed act poison- ously on the system generally or on remote organs. [Gaffky recently discovered a specific microbacterium (" Mitth. a. d. k. Gesundh.," Berlin, 1881) which he was able to cultivate separately in sterilized gelatine impregnated with blood-serum, and in a cold infusion of boiled beef. He found the organism in river-water much polluted with sewage. The same bacterium is occasionally found in meat-wash- ings and blood, as putrefaction sets in. It is a short rodlet which takes up aniline dyes at its poles only, the middle remaining clear. It is very like B. termo. Its spores have not been observed. Rabbits inoculated with it remain unaffected for ten or twelve hours, then high fever sets in, and death in twenty hours. The blood of the infected animals contains bacteria. Guinea-pigs, white rats, cats, and dogs are not susceptible, but sparrows, canaries, and chickens are. This bacterium does not set up putrefaction when " purely " cultivated ; it is therefore distinct from JB. termo.] 206. Of the Desmobacteria the typical example is the best known of all microparasites, the Bacillus anthracis. It is found in the blood of animals affected with anthrax or splenic fever, and it is certain that it is the sole cause of the affection. The organism can be cultivated out- side the body (Art. 186), and anthrax can be produced by means of the cultivated specimens. All that is needful is to introduce the bacillus or PARASITES. 305 its spores into the blood. No auxiliary conditions, such as the formation of septic products or the presence of chemical poisons, are necessary. The spores are the commonest medium of infection, as they are hardier than the bacillus itself. Such spores develop in the blood of animals dead of anthrax even after burial (Koch). If they are not deeply buried the spores may ultimately reach the surface of the ground. Cattle are then infected through wounds (such as scratches of the mouth caused by stubble or by insects), through the alimentary canal, or through the lungs. Death seems to result chiefly from abstraction of oxygen, and disturb- ance of the circulation. In man the disease is only produced by transmission of the virus from infected animals, living or dead. In England the infection is chiefly con- veyed by means of the fleeces of diseased animals to persons engaged in handling them (woolsorters' disease). Anthrax in man usually contin- Fig. 80.-Bacillus Tuberculosis in Phthisical Sputum, x 800 circa. (Stained by Gibbes's method with ma- genta and methylene-blue ; the pus-cells appear blue, the bacilli crimson). ues as a local affection for a longer time than in the lower animals. Pap- ules, vesicles, and pustules on a red and swollen base are developed in the skin. Numerous dark-red button-like nodulescrammed full of bacilli then appear in the intestine. This hemorrhagic intestinal form also occurs in cattle. In human anthrax the blood usually contains much fewer bacilli than in the case of cattle. Armauer Hansen and Neisser have lately succeeded in demonstrating the presence of a bacillus (B. leprae) in the nodes and tubercles of lep- rosy. The constancy with which it occurs in leprous patches would in- dicate that it is the exciting cause of the disease (Art. 131). Klebs and Tommasi-Crudeli have likewise found a bacillus (B. mala- riae) in cases of malarious or intermittent fever, and have experimentally investigated its properties. They assert that it is to be met with in the soil and air of malarious districts, and can be demonstrated in the blood of affected patients. The significance of the bacillus has not, however, been fully made out. 20 306 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. In cases of typhoid fever Klebs and Eberth have discovered a bacillus lodging in recent infiltrations of the mesenteric and intestinal glands. Koch and Friedlaender have verified the discovery, but the life-history of the bacillus is as yet unknown. Koch has recently made comprehensive researches into the etiology of tuberculosis. He finds that bacilli (B. tuberculosis) are constantly present, not merely in tubercles, but in various diffuse inflammatory in- filtrations and granulomatous growths, and in the sputa of phthisical patients (Fig. 80). He is also able to cultivate the bacilli in gelatine impregnated with blood-serum, and to produce tuberculosis with striking success by inoculation with the cultivated bacilli (Art. 127). It is prob- able that the bacillus is unable to develop outside the animal body ; and that it forms spores within the body of its host (Art. 127). [(1) Anthrax {Splenic Fever, Malignant Pustule, Charbon}. The Bacillus anthracis was first discovered by Pollender in 1849 ("Casper's Viertelj.," viii., 1855) and Brauell (" Virch. Arch.," vol. xi., 1857). Davaine was the first to recognize it as the specific virus of splenic fever (" Comptes Rendus," vols. Ivii. (1863) and Ixxvii. (1873) ; " Archiv. gen.," February, 1868). Since then many investigators have examined the question of the significance of the bacillus (see Bollinger, " Splenic Fever," "Ziemssen's Cyclopaedia," vol. iii.). Koch has made the most careful researches on the subject (" Beitrage z. Biol. d. Pflanzen von Cohn," ii., p. 277, and " Mitth. a. d. k. Gesundh.," Berlin, 1881), and his experiments have thrown much light on the biology of the bacillus. Toussaint also has lately published some elaborate researches ("Re- cherches experimentales sur la maladie charbonneuse," Paris, 1879). Spear and Greenfield have investigated anthrax in man as it occurs in the form of "Woolsorters' Disease" ("Med. Off. Report to Local Gov. Board " for 1880). The life-history of the anthrax-bacillus has already been given in Art. 186. It can only develop at a temperature over 18° C. and in presence of a free supply of oxygen. Hence no spores are found in the bodies of animals buried more than a metre deep. Spores may, however, very readily be produced, if in burying the animal its blood or secretions (such as urine) be allowed to contaminate the superficial soil; in summer the temperature there may rise above 18° C. (Koch). Pasteur (" Bulletin de l'acad. de med.," xxviii., 1880) thought that earthworms might carry spores from buried beasts to the surface, and eject them with their excreta. But Koch regards this hypothesis as un- likely and unnecessary to explain the spread of the disease. The con- tamination of the surface-layers in the process of burial is enough. Koch's experiments show that the transmission of the spores through the bodies of worms does not play the important part assigned it by Pasteur, but they do not exclude it altogether. Other experiments prove that PARASITES. 307 the bacillus may be cultivated on potatoes, in alkaline or neutral hay or pea-straw infusions, on crushed oats or barley, on turnip-juice, maize, beans, lentils, and many varieties of dead vegetable matter, if only suf- ficient water be provided. It is therefore probable that they may nor- mally grow and develop outside the body of an animal. This takes place most readily in marshy spots and river-banks (Koch). Spores are formed in summer, and persist through the winter. Inundations then carry the germs into the pasture-lands. If Koch's views are correct, the invasion of the animal body by the bacillus is as it were an accidental in- cursion of an ectogenous organism. Pasteur has shown that birds enjoy no immunity against anthrax. (2) " Symptomatic " Anthrax (Bauschbrand). This disease is probably due to a bacillus found in the affected ani- mals. It is shorter and thicker than the anthrax-bacillus, forms local aggregations in the tissues, and is accompanied by the development of gas. See Koch (loc. cit.), and Arloing, Cornevin, and Thomas on "Charbon symptomatique" ("Paris Acad.," June, 1881). (3) Malignant (Edema. Koch has occasionally found in putrefying matters a bacillus which produces in animals an affection resembling anthrax. He describes the affection as malignant oedema, and the bacillus as B. oedematis. It is fatal to mice and guinea-pigs. The site of inoculation becomes oedema- tous, and is beset with bacilli. These spread into the serous cavities, but except in mice the blood remains free of them. If mice be inocu- lated at the tip of the ear, they survive. The bacilli are somewhat nar- rower than anthrax-bacilli. It is possible that the bacilli found in cer- tain affections due to poisonous meat (Huber, " Arch. f. klin. Med.," xxv.) are oedema-bacilli. (4) Intestinal Mycosis. This is a term which includes several bacterial affections. Sometimes the affection is due to anthrax-bacilli, sometimes to oedema-bacilli. It is possible that other bacilli and micrococci (Art. 477) may give rise to similar disorders. References : E. Wagner, "Arch. d. Heilk.," xv. ; Leube and Muller, " Arch. f. klin. Med.," xii. ; Bollinger, " Beitrage zur vergl. Path. d. Hausthiere," Munich, 1872 ; Buhl, " Zeitsch. f. Biol.," vi. ; Waldeyer, " Virch. Arch.," vol. lii. ; Fischl, " Arch. f. exp. Path.," xvi. Many instances of so-called " meat-poisoning " are to be reckoned as cases of intestinal mycosis. They are very probably produced by various micro-organisms and their products. In some cases the poisoning is simply septic (Art. 204 (3)) ; in others it is apparently specific, and in 308 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. some of these latter bacilli are certainly concerned. Exact investigations on the subject are still to be desired. References : Zangger, " Arch. f. Thierheilk.," xxiv., 1871 ; Albrecht, " Wochensch. f. Thierheilk.," 1878 ; Kussmaul, " Arch. f. klin. Med.," iv.; Huber, "Arch. d. Heilk.," xix.; Walder, "Berl. klin. Woch.," 1878 ; Wyss, " Corresp. f. schweiz. Aerzte," 1881 ; Bollinger, " Zur Aetiol. d. Infect.," Munich, 1881 ; Ballard and Klein, " Report of Med. Off. of Local Govt. Board," 1880. (5) Syphilis. Klebs has a paper on a bacillus connected with syphilis in the " Arch, f. exp. Path.," x. He found microscopic rods and spherules in indurated chancres. From these he obtained bacilli by cultivation. Inoculating a monkey with these, he produced an inflammatory affection in some respects resembling syphilis, in other respects resembling tuberculosis. Ziegler made many similar experiments, but was unable to corroborate Klebs's statements. In 1878 he and von Rinecker attempted to cultivate the substance removed with all care from indurated buboes, the attempt was repeated many times, but always with negative results. Various nutritive substances were used in the cultivation-experiments. See also Aufrecht, "Cent. f. med. Wiss.," 13, 1881 ; Birch-Hirschfeld, ibid., 44, 1882. (6) Malaria. The Bacillus malarias was taken by Klebs and Tommasi-Crudeli from the air over the Italian marshes by means of a special apparatus. Its properties were tested by culture and inoculation. They also found the fungus in samples of soil taken from the same districts. They con- clude-that malarious disease can be reproduced in rabbits ; that it is caused by an organism ; that this is present in the soil of the malarious district before it produces fever in man ; and that its passage into the air can be observed under favorable conditions. Marchiafava found the bacillus in the blood, marrow, and spleen of patients who had died of malarious fever. The Bacillus malarias is an aerobious organism, which flourishes in soils of various kinds and may occur in places that are not marshy. It forms spores, and for its development requires a temperature of 20° C. Laveran found "filaments mobiles " in the blood of ague-patients. References : Klebs and Tommasi-Crudeli, "Arch. f. exp. Path.," xi.; Ceci, ibidem, xv.; Tommasi-Crudeli, "La Malaria de Rome," Paris, 1881, "Nuovi studj sulla natura della Malaria," Rome, 1881, "Malaria and the Ancient Drainage of the Roman Hills," Practitioner, 2, 1881, " Istituzioni di anat. pat.," vol. i., Turin, 1882 ; Marchiafava and Cuboni, " Nuovi studj sulla natura della Malaria," "Acad, dei Lincei," January 2, 1881 ; Mar- chand, " Virch. Arch.," vol. Ixxxviii.; Laveran, "Nature parasitaire des accidents d'impaludisme," Paris, 1881 ; Richard, " Comptes Rendus," 1881 ; Sternberg, " Rep. Nat. Board of Health (U. S.)," 1881. PARASITES. 309 (7) Leprosy. Bacillus leprae was found in all the leprous nodules they examined by Armauer Hansen (" Virch. Arch.," vol. Ixxix., and Quarterly Journ. of Micro. Sei., 1880) and Neisser (" Breslauer arzt. Zeitsch.," 1879, and " Virch. Arch.," vol. Ixxxiv.). The bacilli are rather longer than the semi- diameter of a red blood-cell ; they lie partly within and partly without the cells of the leprous nodules. Neisser cultivated them in blood-serum and extract of meat, and observed them develop into filaments. They form spherical spores which are seated at the ends of the rodlets, or form bright vacuoles in the middle of them. They spread through the system by way of the lymphatics, not of the blood-vessels. They are surrounded by a gelatinous envelope and at times seem to be motile. Cornil and Suchard (" Annales de Dermat.," 1881) have confirmed the statements of the first observers. (8) Typhoid Fever. Klebs ("Arch. f. exp. Path.," xii.,xiii.) and Eberth (" Virch. Arch.," vol. Ixxxi.) have found bacilli in the diseased patches of the intestine, and in the mesenteric glands, in cases of typhoid fever. Koch has con- firmed the statement (" Mitth. a. d. k. Gesundh.," 1881). In the sloughs from the intestinal ulcers long and short bacilli have been seen, in the lymphatic glands only the short ones. The latter are found also in the vessels of various organs, especially the spleen, kidneys, and liver. They are probably the exciting cause of the disease. Maragliano has found similar bacilli in the blood of living typhoid patients (" Cent. f. med. Wiss." 41, 1882). The above results seem at first sight to disagree with those of Fischl and Eppinger (" Beitrage z. path. Anat.," ii., Prague, 1880), Letzerich ("Arch. f. exp. Path.," ix.), and Tizzoni (" Studj di pat. sperim. sulla gen. d. tifo abdom.," Milan, 1880). These observers detected micrococci. It is possible that micrococci may settle in the typhoid ulcers by way of a secondary invasion. (9) Tuberculosis. Koch's Bacillus tuberculosis, mentioned already in Art. 127, grows in gelatine impregnated with blood-serum between the temperatures of 30° and 40° C., but not beyond these limits. It cannot therefore complete its development outside the body, at least in temperate climates. In most cases tuberculosis starts in the lungs, which become infected from the inspired air. The chief agent in contaminating the air is the sputum (Fig. 80) of phthisical patients, which invariably contains the specific bacillus, either with or without spores. The infective power of the sputum is not destroyed by drying. It is highly probable that the spores are likewise unaffected thereby. 310 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. The tubercle-bacilli grow very slowly, and therefore do not readily succeed in making a settlement on the surface of mucous membranes. Healthy tissues are, besides, at all times difficult to infect. The settle- ment is favored by wounds, loss of epithelium, stagnating secretions, etc. The tuberculosis of domestic animals and the " pearly-disease " of cattle are due to the same bacillus as the human disease (Koch, " Berl, klin. Woch.," 15, 1882). The bacilli grow well in sterilized ox-serum, but they develop and multiply very slowly. The colonies of fungi are only visible to the naked eye after ten days' growth ; they then appear as dry whitish scales. These are made up of delicate rodlets. Each patch attains in three to four weeks the size of a poppy-seed, and then ceases to grow further until transplanted to a fresh substratum. This is owing to the fact that the bacilli have no power of locomotion, and so cannot spread over the nutrient gelatine.] 207. Of Spirobacteria two forms are known to occur in man. The one, apparently quite innocuous, is the Spirochaeta denticola ; it inhabits the mucous membrane of the mouth and nose. The other, the Spirochaeta (or Spirillum) Obermeyeri, is found in the blood of patients suffering from relapsing fever, during the attacks. It is almost beyond doubt that the disease is caused by its invasion and multiplication within the blood. Quite lately the disease has been transmitted to monkeys by inoculation with the spirillum. Nothing certain is known of the habitat of the spirillum outside the body. It is easily detected by the microscope in the blood by reason of its lively movements ; these sometimes cause the red blood-cells to be driven and pushed about in the field of view. [The spirillum of relapsing fever was discovered by Obermeyer in 1873 (" Centralb. f. med. Wiss.," 10, 1873, and "Berl. klin. Woch.," 33,1873). Since then it has often been examined and described. See Weigert, "Deutsche med. Woch.," 1876 ; Heydenreich, " Der Parasit des Ruck- fallstyphus," Berlin, 1877 ; Moczutkowsky, " Arch. f. klin. Med.," xxiv.; Geddes and Ewart, "Proc. Roy. Soc.," xxvii. The successful inoculation of the monkey was performed by Carter ("Deutsche med. Woch.," 16, 1879, Lancet, 1, 1880, and "Spirillum Fever," London, 1882).] 208. If we accept for a moment the hypothesis that all or most in- fective diseases (other than those due to animal parasites) are caused by the development of bacteria in some tissue or fluid of the body, we are met at once by the question whether in that case each specific form of disease has a corresponding specific bacterium. From a clinical stand- point this question must be answered in the affirmative. The most marked feature of the infective diseases is just this, that they run a typi- cal and special course. Even though this may, in individual cases, be modified by various influences, it is in general so characteristic, so pathog- PARASITES. 311 nomonic, that the disease can often be diagnosed by its course alone. We should, therefore, have no hesitation in inferring from the specific course of the disease that the virus which excites it is also specific. Histological examination of the tissues of patients affected with bac- terial disease has shown that in some cases (relapsing fever, anthrax, tu- berculosis, leprosy) well-marked forms of fungi are always detected ; and further, that these forms of fungi, or at least forms belonging to one or other of their developmental stages, are the only ones constantly found. In other cases such histological distinction has not yet been possible. The micrococci occurring in various infective diseases do not as yet afford us characters sufficiently well-marked to form a basis for distinguishing them into species. It must not, however, be assumed that these various micrococci are identical, and that it is merely the accidental association with them of this or that poison which makes them seem to have differ- ent properties. If the micrococcus that is found be in fact the exciting cause of the disease, we must admit that it must be endowed ab initio with distinct properties. From the pathological point of view as well as from the clinical, we must regard it as belonging to a distinct species. As we pointed out in Art. 183, we are compelled to classify the bacteria into species on other grounds than those that apply to the higher plants. Our classification is based as yet on their morphological and physiologi- cal peculiarities. In the case of the micrococci we are confined almost entirely to the latter. We are compelled to set up physiological species. Thus, as the chromatogenous micrococci are classified according to the color they produce, so the infective micrococci are classified into species according to their pathogenous properties. [Koch has shown that in the case of many bacterial affections it is possible to discover in the fungi well-marked morphological differences corresponding to the physiological differences (" Traumatic Infective Diseases," 1880). Struck's papers also contain many valuable contribu- tions of this nature. See Arts. 204-207 for further references.] 209. Each specific microparasitic disease presupposes a specific excit- ing cause, that is, a bacterium with special physiological properties. In affirming this proposition we do not imply that the specific bacte- rium constitutes a distinct species in the biological sense. This is a ques- tion which cannot be answered by the physician ; it belongs to the biolo- gist. He will have to make out whether the properties attributed to the bacterium are constant, and whether these properties are the only ones possessed by the corresponding biological species. On these points observers differ widely. Koch, from his culture-ex- periments, has come to the conclusion that the pathogenous bacteria, like the non-pathogenous, do not alter in their properties. If bacteria be cul- tivated for several generations, the same developmental forms continually 312 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. recur, and their physiological properties remain in every respect the same. Even when the nutrient medium is altered from time to time no recogniz- able differences are produced. Koch does not dispute that mutability of species is possible among bacteria, but he holds that no adequate evi- dence has yet been brought to prove it. This view has now many adherents, especially among clinical observers. Some go even further and assert that mutability of species is impossible. The most important opponents of Koch on this point are Nageli, Davaine, Buchner, and Wernich. Nageli thinks that both the mor- phological and the physiological characters of the bacteria are mutable.' A given bacillus does not invariably produce bacilli of the same struct- ure, and does not always pass through the same developmental stages. A bacterium which under given conditions gives rise to a definite kind of fermentation, may lose this property when cultivated under different con- ditions (Art. 192). Thus the same fungus can set up butyric acid fer- mentation or lactic acid fermentation according to circumstances. Nageli regards the various species of bacteria above described not as biological species, but as vegetative forms of a few as yet undetermined species. [References : Nageli, " Die niederen Pilze," Munich, 1877 and 1882 ; Buchner, "Die Nageli'sche Theorie," Leipzig, 1878 ; Birch-Hirschfeld, "Schmidt's Jahrbiicher," 1875 ; Wernich, " Die accommodative Ziichtung der Infectionsstoffe," " Kosmos," 4, 1880; "Die Entwickelung der or- ganisirten Krankheitsgifte," Berlin, 1880 ; " Desinfectionslehre," 1880; Pasteur, " De l'attenuation des virus et de leur retour a la virulence," " Comptes Rendus," vol. xcii.; Klebs, " Arch. f. exp. Path.," xiii.; Buch- ner, "Exp. Erzeug. d. Milzbrandbacillen aus Heubacillen," Munich, 1880; " Miinchener Acad. d. Wiss.," January 12, 1882, and Nageli's " Untersuch. ub. n. Pilze," Munich, 1882 ; Urlichs, "Arch. f. klin. Chir.," xxiv.; Koch, "Traumatic Inf. Dis.," 1880 ; "Mitth. a. d. k. Gesundh.," Berlin, 1881 ; Gaffky, ibidem: Fokker, " Virch. Arch.," vol. Ixxxviii.; Wolff, "Virch. Arch.," vol. Ixxxi.; Semmer, "Virch. Arch.," vol. Ixxxiii.; Davaine, "Acad, de med.," Paris, 1872; Greenfield, "Proc. Roy. Soc. Edin.," 1880, " Journ. Roy. Agric. Soc.," 1880 ; Klein, " Rep. Med. Off. Loc. Gov. Board," 1881 ; Miquel, " Bull. Soc. Botan.," 1881. Wolff maintains that micrococci and short bacilli change into each other, and seeks to support this by showing that transitional forms exist. What he takes for transitional forms may very easily, however, be nothing more than germinating spores, or even rodlets viewed obliquely. His statement-that he obtained bacilli from a rabbit into whose peri- toneal cavity he had injected micrococci-is explicable by supposing the injected matter to be impure. Wernich also asserts that the various forms may be interchanged, and speaks of the circumstance as evidence of " unstable morphological equilibrium." He gives no other evidence in support of his idea. With regard to Klebs and Billroth, and their views in this connection, see Art. 185.] PARASITES. 313 210. The defective state of our knowledge makes it for the present impossible to give a definite answer to the question of the mutability of the bacteria. It would, however, appear, from the researches of Nageli and others, that we are not absolutely justified in regarding all the various forms as representing distinct biological species. The idea of a species must be based on characters that are constant, not on those which may alter with the surroundings. The researches of Koch and his pupils do not prove that the proper- ties of the bacteria examined by them are perfectly constant. They only show that the morphological and physiological qualities possessed by a bacterium at a given time are retained by it with some tenacity, even when a certain amount of variation takes place in its environment. On the other hand, the researches of Nageli, Buchner, Wernich, and others seem to afford evidence that this constancy is not shown under all con- ditions ; that changes of the nutrient medium may have some effect on the form and size of the cells, on their mode of multiplication, and on their physiological or fermentative properties. Changes of this kind and extent do not, however, indicate that one species is transformed into another. We must rather conclude that one or other of the properties possessed by a biological species of bacterium may be brought into prom- inence by proper modifications of the external conditions. The mutability manifested by a given bacterium will thus have defi- nite limits. The bacterium cannot, in any period of time within the ex- tent of our observation, acquire properties different from any of those possessed by the species to which it belongs. As to the extent of the cycle of varieties through which any one of the known bacteria may pass, we know indeed but little. It is possible that the properties of many of them admit of only the slightest variations from those with which we are acquainted. It is, moreover, probable that many of the varieties known to us constitute true biological species. 211. If we accept the hypothesis that different vital properties of the bacteria may be brought out by different external conditions, we have next to inquire whether the pathogenous bacteria may not be peculiar varieties of non-pathogenous forms. It is conceivable that in certain circumstances a bacterial virus might be developed from an innocuous bacterium, and might ultimately be transformed back to the innocuous form again. This view has been maintained by several authors (Nageli, Buchner, Wernich) and has been supported by various experimental re- sults. They have chiefly relied on the observation that many bacterial poisons appear to become more virulent by transmission from animal to animal (e.g., that of Davaine's septicaemia), in other words, that by con- tinual inoculation the parasite learns to accommodate itself more and more completely to the conditions in w'hich it is placed. The opponents of the theory of mutability diminish the force of this argument by show- ing that the increase of virulence corresponds with an increase in the " purity " (or freedom from admixture with other bacteria) with which 314 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. the fungus is cultivated. If a mass of mixed bacteria be injected into an animal, there will be at first several forms which develop simultan- eously, and it is only after the virus has been transmitted through the living body twice or thrice that one form gets the upper hand, and develops to the exclusion of the others. The theory of mutability, and especially that of the transformation of non-pathogenous into pathogenous forms, receives stronger support from an experiment of Buchner's, in which he seemed to show that anthrax- bacilli can be bred from hay-bacilli (B. subtilis) and conversely. Koch, Gaffky, and Klein dispute the validity of the experiment, but Buchner stands by it and claims to have confirmed it by fresh results of a like kind. The weight of evidence is for the present against him. At present we are unable to draw any certain conclusion regarding the relation of non-pathogenous to pathogenous bacteria. Clinical ex- perience would indicate that the activity of the infective virus may vary within certain limits. And we must apparently admit that the infective bacteria have not always possessed their noxious qualities, but have acquired them somehow in the course of ages. But this is not enough to convince us that harmless bacteria can acquire infective properties rapidly, that is to say, in the course of comparatively few generations. They appear rather to hold by their properties with a certain tenacity. We may, therefore, provisionally conclude that the transformation of in- nocuous into noxious bacteria can occur but rarely and under special con- ditions. In other words, the pathogenous bacteria, even if they do not represent biological species, are wont to maintain the pathogenous form for long periods of time. [Davaine, Coze, and Feltz experimented on the septic poison obtained from putrefying blood. They at first asserted that its virulence increased with extraordinary rapidity, so that in the twenty-fifth generation one- trillionth of the amount of matter originally used in the inoculation was all that was necessary to produce the same infective results. Davaine became afterward convinced that the virus attained its full power in the second or third generation. Koch confirmed this, and explained it by showing that the original matter used in the inoculation was impure, i.e., contained other bacteria, and that the repeated inoculations gradually eliminated the admixture. Gaffky's experiments brought out the same result. Rosenberger (" Centralb. f. med. Wiss.," 4, 1882) has lately found that the gradual increase of virulence is more protracted in the case of the Bacillus cedematis. Wernich finds that the potency of the Micrococcus prodigiosus (that is, its faculty of multiplying and producing red coloring-matter) can be increased by modifying the mode of cultivation. Gaffky regards this fact as likewise due to the elimination of impurities. Buchner first announced in 1880 that hay-bacilli could be transformed into anthrax-bacilli. If hay-bacilli are injected into the blood of animals PARASITES. 315 they do not give rise to anthrax. If, however, they are bred for several generations in meat-extract and then in the arterial blood of a rabbit, they acquire noxious qualities and give rise to anthrax in mice after two to nine days' incubation. Conversely, if anthrax-bacilli are properly cul- tivated they can be transformed into bacilli whose properties are identi- cal with those of hay-bacilli. Koch (loc. cit.) disputes the correctness of Buchner's observations, and suggests that he has been experimenting with the oedema-bacillus (Art. 206 (3)) instead of the Bacillus anthracis. According to Koch the an- thrax-bacillus and the hay-bacillus do not resemble each other. Hay-bacilli are rounded at the ends and possess cilia or flagella ; anthrax-bacilli are as it were cut off square. Buchner's cultures were impure, they contained germs of other bacilli, and these by degrees suppressed the original forms. While the hay-bacillus was supposed to be breeding in the blood the oedema- bacillus, or some other of similar action, was developed ; in the converse process the so-called anthrax-bacilli were gradually suppressed by others. In a later memoir (" Akad. d. Wiss.," Munich, 1882) Buchner main- tains his position and mentions fresh experiments bearing on it. In his view Cohn's Bacillus subtilis includes several varieties ; namely (1) hay- bacilli, (2) Pasteur's butyric acid ferment, (3) Fitz's bacterium (" Ber. deutsch. chem. Gesellsch.," ix., 1878), which converts glycerine into ethylic alcohol, (4) anthrax-bacilli. This fungus, which he regards as constitu- ting a biological species, he calls Bacterium subtile. The properties of the variety which produces anthrax may be retained or withdrawn at pleasure by proper modes of cultivation. In the process of transforma- tion transitional varieties appear representing intermediate stages be- tween anthrax-bacilli and hay-bacilli. The middle forms only produce anthrax when injected in very large quantities. The process of trans- formation may be completed by cultivation in an alkaline solution of egg- yolk for twenty-four to forty-eight hours. The transformed bacillus (hay- bacillus) is distinguished by its energetic fermentative activity, and causes albumen to coagulate. It is inert when injected into the blood. Nageli, in his recent book entitled " Untersuchungen uber niedere Pilze," (Munich, 1882), takes up the same position as Buchner with re- gard to the mutability of the bacteria. He believes that one an^ the same species may assume different forms according to the nutriment it is supplied with. These forms may exhibit different physiological and even morphological characters. The pathogenous bacteria are " nutrimental " modifications of non-pathogenous species. Klein, in an important report just published (" Report of Medical Officer to the Local Government Board for 1881), communicates the results of a series of researches undertaken to test Buchner's hypothesis. He points out the probable sources of error in Buchner's work, and concludes that the anthrax-bacillus retains its full power to produce specific disease so long as it retains any power at all. References : see under Arts. 209 and 219.] CHAPTER XXXI. HYPHOMYCETES AND BLASTOMYCETES (MOULDS AND YEASTS). 212. Mould-fungi and yeast-fungi, with their congeners, belong like the bacteria to the achlorophyllous Thallophytes. They appear to have no nearer affinity than this to the bacteria, and they have no phylogene- tic relation to them. The mould-fungi and the yeast-fungi are, however, more nearly akin to each other, for it is probable that the yeast-fungi are the primitive forms from which the higher fungi have developed (Brefeld). Moulds and yeasts, like bacteria, can only draw their nutriment from organic carbon-compounds. These they mostly find in dead organic mat- ters, and they are therefore classed as Saprophytes. Some of them, how- ever, are able to abstract nutriment from living tissues, and are therefore to be reckoned as Parasites. Both forms are met with in connection with the human body. The mould-fungi or Hyphomycetes are well known outside the body. They form the familiar flocculent covering or pellicle seen on decaying organic substances, and variously known as mould, mildew, mother, etc. They belong to several distinct genera, and even to distinct sub-classes of the Thallophytes. The yeast-fungi or Blastomycetes are also familiar organisms. They set up alcoholic fermentation, and form the yeasty scum which appears on the surface of alcoholic liquors. [The systematic classification of the Thallophytes has, in the last year or two, undergone considerable modification. The earlier classification, based on certain obvious characters of form and habit, was into Algae, Lichenes, and Fungi. This subdivision has been modified since the disco ery of the reproductive organs, and in many cases of the entire life-history, of the various forms. No sharp line divides the algee from the fungi. Many families of so-called algae and fungi are really correlated, inasmuch as they agree in the characters of reproduction and " alternation." The lichens have been regarded as ascomycetous fungi, which are parasitic on particular algae, the gonidia. The absence of chlorophyll, and the variety of external forms (poly- morphism) which occurs, are secondary characters ; the latter especially PARASITES. 317 being influenced by parasitism (Sachs, " Text-book of Botany," Oxford, 1882 ; Brefeld, " Botanische Untersuchungen tiber Schimmelpilze," Leip- zig, 1874-77.) Brefeld's classification is-(1) Phy corny cetes=algoid fungi; (2) J/y- comycetes-true higher fungi; (3) Myxomycetes-gelatinous fungi; (4) 7?fo^omyce^es=yeast-fungi ; (5) Schizomycetes-bacteria. For pathological purposes it seems more convenient to retain, as we have done, the older and well-marked classes of bacteria, moulds, and yeasts.] The Hyphomycetes or Moulds. 213. Morphology and physiology. The mould-fungi are hypho- mycetous, i.e., they are fungi characterized by the formation of a myce- lium. As they occur in man they appear in the form fl) of simple or branched, jointed or unjointed filaments of various thicknesses, and (2) of ovoid or spherical cells. These filaments are the hy- phue (Fig. 81) ; the compact masses or tufts which they form are my celia ; the spheri- cal, ovoid, or cylindrical cells, often strung into a kind of chaplet, are the spores, or rather the conidia. Spores are more com- monly found within the human body than a,ny other of the vegetative forms ; fructi- fication is rarely observed. These fungi are classified according to the place in which they are found, and the affection which they produce. Their names are de- rived from the name of their discoverer, from the name of the disease they produce, or otherwise. Such a classification can only, of course, be a temporary expedient. The filaments and spores are not the plant, they represent merely a de- velopmental stage of it, and by no means determine the species. To settle this the plant must be purely cultivated on a proper soil, and its various stages traced out. In all cases the cell which we call the spore or conidium grows into a germinal tube or cylinder, and from it spring a greater or less number of ramifying unicellular or multicellular filaments or hyphse. These form a mass which, taken as a whole, is called the mycelium. This again may give rise asexually to reproductive cells, which develop into fresh myce- lia. In other cases sexual organs are formed, and the product of the congress of the male and female elements is either a single spore {zygo- spore}^? a fructification in which numerous spores {ascospores) are devel- oped. From the zygospore, or from the ascospores, the new generation Fig. 81.-Fungi from a Favus-patch. (Neumann.) 318 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. springs. The former is the case in Mucor Mucedo ; the latter in Asper- gillus glaucus, and Penicillium glaucum-the commonest of the ordinary moulds. 214. The genus Oidium exhibits the processes of growth and multipli- cation in their simplest form. It forms a white downy covering on de- caying organic substances, especially on animal excreta, fruit, grapes (Oidium Tuckeri), and sour milk. According to Grawitz (" Virch. Arch.," vol. Ixx.) Oidium lactis, which grows upon the surface of milk, passes through the following stages of development. The conidia or spores, which are ovoid cells, lengthen out into one or more germinal tubes, which very soon become jointed and throw out lateral branches. These branches are at first cylindrical, but later on they become rounded off, and then appear as lengthened ovoids. Sooner or later they break up by transverse subdivision into chains or chaplets of conidia. The sev- eral conidia-cells then recommence the developmental cycle, which pro- ceeds as before. No true sporangia or spore-capsules are formed, and no kind of sexual reproduction has been observed. 215. Mucor Mucedo is a mould-fungus which grows on all kinds of substances, but chiefly on excreta and on articles of food. It forms the familiar white mouldy covering. When the spores are numerous it takes on a brownish-yellow powdery look. If these spores be sown on the sur- face of a decoction of horse-manure, for instance, they proceed to germi- nate within a few hours. The long ovoid spores become larger and more spherical. Then they throw out their germinal tubes or hyphae in one or more directions. In twenty-four hours a dense interlacing weft of mycelium is already formed, made up of non-septate filaments (Fig. 82, P, m), branching indefinitely into finer and finer expansions. The entire mycelium is thus one enormously branched cell. When it reaches a certain point this vegetative growth ceases. The contents of the filaments become turbid, and draw toward the middle, from which springs a stouter branch than the rest, the conidiophore or sporangiophore (g). When this has grown somewhat, a button-like pro- tuberance appears at its apex ; this is the sporangium. It consists of an enclosing membrane and a protoplasmic core. The protoplasm becomes segmented, and thus are formed a multitude of conidia {A). Septa then begin to develop in the filaments of the mycelium. These sporangia are non-sexual structures. When ripe they consist of a membranous spherical envelope, containing a mass of spores agglu- tinated by a sticky intercellular substance. In water the membrane gives way, and the conidia are set free. The mode of multiplication just described is the commonest ; but there is also a sexual mode of propagation by means of what are called zygospores. The process is this :-the tips of two filaments rising from the mycelium are each marked off by a septum, so that each ends in an apical cell (Fig. 82, D, ad). These tips meet and the cells coalesce, and by absorption of the separating membranes the contents flow to- PARASITES. 319 gether. The single new cell thus produced is the zygospore. Its mem- brane becomes thickened and it grows to a considerable size. The thick- ened membrane is divisible into a blackish exosporium and a colorless endosporium. From this zygospore, which in the case of Mucor is also a resting-spore, there springs, after some weeks of cultivation, a germinal hypha ( C k), which then develops a hypha bearing a sporangium (g). Fig. 82.-Development by Conidia and Zygospores. A, the conidiophore or conidia-bearing hypha of Mucor Mucedo in optical section ; B, mycelium of Phycomyces nitens; g, conidiophore ; m, unicellular my- celium (three days old; grown in plum-decoction and gelatine ; the finest ramifications are left out in the drawing; from Sachs); C, germinating zygospore («) of Mucor Mucedo ; the germinal tube or hypha (ft) throws out a conidiophore (a); D, free conjugating branches (b, b) whose tips (aa) have not yet coalesced, but are marked off by septa; the zygospore results from the coalescence of the cells (aa). [We owe most of the details of our knowledge on this part of the subject to Brefeld (" Botan. Untersuch. uber Schimmelpilze," Leipzig, 1874-77) ; the foregoing account is taken from him. The mycelium of Phgcomgces^ in the figure taken from Sachs, agrees generally with that of Mucor ; in the latter, however, only a single conidia-bearing hypha is developed.] 216. The life-history of Eurotium Aspergillus (Aspergillus glaucus') and Eurotium repens is somewhat different. These two fungi are found 320 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. on various substances, but chiefly upon cooked fruit. They form a finely filamentous-jointed mycelium (Fig. 83, A), from which rise a great num- ber of aerial hyphas or conidiophores (c). These end in a spherical knob, from the upper part of which sprout numerous densely packed radial peg- shaped protuberances or sterigmata {st). Each sterigma gradually devel- ops a long chain of conidia, so that the head of the conidiophore is at length covered with a sheaf of such chains. Fig. 83.-Development of Eurotium repens, and of Aspergillus glaueus (after De Bary). A, small part of mycelium with a conidiophore (c) and young carpogonium (as); B, the spiral carpogonium (as) and pollinodium (p) ; C, the same, with commencing growth of filaments to form the wall of the perithecium; D, a mature perithecium; E and F, young perithecia in optical section; w, wall-cells;/, "packing-cells"' or pseudo-parenchyma; as, ascogonium ; G, ascus ; E, ascospore. While the conidia are developing, the sexual organs are being formed within the same mycelium. The end of a mycelial filament becomes twisted like a corkscrew (yl as) ; and the spiral turns come closer and closer to each other, till at last they touch and form a hollow spiral tube. This is the female organ or carpogonium {as). From the lowermost turns of the carpogonium thin branches sprout out, which grow up over the outside of the spiral. One of these, growing more quickly than the rest, reaches the uppermost turn and applies its point closely to it {B p). This is the male part or pollinodium. Conjugation takes place between PARASITES. 321 it and the carpogonium ; the bounding membranes give way, and the contents coalesce. Thereupon from the lower part of the pollinodium and carpogonium spring new filaments, which increase rapidly in number and cling closely to the spiral ( C), so as at length to cover it up com- pletely. These tubular filaments subdivide transversely, and so an en- velope of polygonal cells (7)) is finally formed. This envelope is the perithecium, and it forms a hollow sphere (E w) containing the carpogo- nium. The cells multiply so as to fill up the cavity (F). Meanwhile numerous septa are formed in the carpogonium, and from the joints spring lateral branches (ascogerwus hyphae), which ramify and subdivide (Fas) between the surrounding cells. Their terminal twigs form the asci ( G) (whence the fructifying carpogonium is named the ascogonium). The asci are tubular, and in each of them eight spheres (ascospores) are developed. As the ascogenous filaments develop, the "packing cells"or pseudo-parenchyma of the perithecium disappear. Ultimately the asci also vanish, and we are left with a hollow receptacle filled with spores. When ripe these last are lenticular or biconvex (77). On germinating they again form a mycelium, which produces both conidia and perithecia. There is no true alternation of generations between the sexual and asexual varieties. 217. The commonest of all mould-fungi, Penicillium glaucum, de- velops in a similar way. It grows on the most meagre soils. Until lately the mycelium with its conidia was the only form of it which had been recognized. Brefeld showed, however, that it is an ascomycetous fupgus allied to the Tuberaceoe or truffles. The mycelium consists of jointed, much-branched, uniform filaments. Some of these rise as conidiophores, which branch at the apex into ste- rigmata, and produce rows or chains of greenish-colored conidia. Peni- cillium may pass through several generations, all following this mode of propagation. But there is also a sexual mode. As in Eurotium, a spiral female carpogonium and a male pollinodium are developed. In the former the germs of the new plants are produced. After fructification the carpogonium throws out thin sterile filaments which interlace to form an envelope for it ; and also a thicker filament lying in the centre and constituting the germinal or sporiferous element, which takes the form of a branching tube. The densely packed envelop- ing filaments subdivide freely, so as to produce a compact and coherent mass of cells. The cells increase greatly in size, and their walls become firm and hard ; so that the structure appears at last as a firm ball or tuber, looking like a yellow grain of sand. This is called the sclerotium, and may be preserved in the dry state for many months together. On germinating ascogenous filaments are developed within the carpo- gonium and grow out into threads, some of which are stout, while others are slender. The latter have to do with the absorption of nutriment from the enveloping capsular tissue, the former with the process of fruc- 21 322 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. tification. Clusters of asci are developed upon them, each containing eight spores. The whole of the enveloping tissue is ultimately absorbed, with the exception of the brownish outer layers. The asci and the fila- ments likewise vanish, and after some months we have left merely a hol- low capsule filled with a multitude of bright yellow spores. From these spores or ascospores an ordinary mycelium is again reproduced. 218. The life-history of a few of the most common of the filamentous fungi, some of them occurring in the human body, exemplifies the fact that the various forms have various modes of development and reproduc- tion. In some the process of reproduction is very simple. The mycelium gives rise by subdivision and abstriction to separate cells or conidia, which have the faculty of existing independently, and of developing a fresh mycelium. In others a second, more complex but still asexual, mode obtains ; the mycelium shoots out specially constructed conidiophores or sporangiophores, and these bear sporangia, or sterigmata. In or upon these receptacles are developed reproductive cells,which we term conidia or spores. But there is a third or sexual mode of propagation. In this two equivalent cells unite to form a new cell-the zygospore (as in Jfucor) or true resting-spore ; or a female organ develops-the carpogonium- which, fructified by the agency of a male organ or pollinodium, develops a germinal or ascogenous organ ; and this again, by a process of branch- ing and subdivision, produces asci or spore-tubes containing the true spores or ascospores. From these the cycle of development may begin once more. This sexual reproduction may either go on simultaneously with the asexual modes, or an alternation of generations may take place. That is to say, from a conidium a mycelium is developed which possesses sexual organs, and from these is sexually generated an asexual plant. This bears ascospores, and they again form a mycelium which produces coni- dia. It is not to be forgotten, however, that strict alternation of this kind rarely occurs. Without prejudice to the plant the alternation may be pretermitted for many successive generations, as is the case with Penicillium. In any case, indeed, the number of asexual generations is much greater than the number of sexual ones. Such an alternation of sexual with asexual generations is not peculiar to the fungi ; it occurs in a much more definite manner among higher plants. No peculiar polymorphism is exhibited by the fungi. The idea of polymorphism has arisen from the fact that the asexual mode of re- production is very common among fungi, while the sporangiophores or conidia-bearing organs assume very various forms. Moreover, in all of the fungi there is more than one mode of asexual reproduction. The statement of various authors (like Hallier)-to the effect that fungi pos- sess a special and peculiar habit of polymorphism or " pleomorphism "- rests mainly on error. They have either failed to cultivate "purely " the plants studied, or they have been ignorant of the diverse modes in which they may be propagated. PARASITES. 323 [The account just given by no means exhausts the various modes of sexual and asexual reproduction among the fungi. We have, for exam- ple, said nothing of the formation of oospores. Here a female cell or oosphere develops in an oogonium, and is fructified by a male cell or sper- matozoid developed in an antheridium. From this is bred a plant like the parent-plant, or else a multitude of germs which go to produce a new generation. For such details and others we must refer the student to Sach's "Text-book of Botany," or to Brefeld's papers above cited. All we have here attempted is:-to give such an account as would make clear the general modes of growth and reproduction of the mould-fungi, and en- able the student to understand the allusions to them that are constantly occurring in articles on the fungous parasites of man.] 219. The form and texture of the mycelium and the mode of multi- plication depend greatly on the nature of the nutrient substratum. Thus the filaments of Oidium ladis may be short or long, thin or thick, ac- cording to the proportion of sugar present and the reaction of the solu- tion. If there is a dearth of nutriment, the formation of conidia is gen- erally favored. The free access of oxygen is also of import. According to Brefeld sexual reproduction can be induced in Penicillium if the ac- cess of air and light is prevented after the mycelium is formed. If spores of Mucor be sown in a saccharine liquid with access of air, the mycelium developed on the surface is made up of branched non-sep- tate hyphae, and the liquid absorbs oxygen (Reess, " Botan. Untersuch. uber Alkoholgahrungspilze," 1870 ; and Fitz, " Ber. d. deutsch. chem. Gesell.," Berlin, 1873). If the mycelium be immersed, or oxygen with- drawn, the hyphae develop septa and break up into longer and shorter segments ; these then multiply by budding like the yeast-plant, and form a kind of large-celled yeasty scum. This yeast has the power of decom- posing sugar into alcohol and carbonic acid, but the fermentation ceases when a small proportion of alcohol is formed. The same is true of Mucor racemosus, but not of Penicillium glaucum. If the composition of the nutrient substratum be gradually altered, the fungi may be got to grow on substances which they do not usually affect. Thus Eurotium and Penicillium may be transplanted from bread to solution of peptone, and can ultimately be made to grow on the sur- face of blood (Grawitz). The limits of temperature, within which the mould-fungi can flourish, vary with the different forms. Some species of Aspergillus (A. flaves- cens, fumigatus^ nigrescens) and some of Mucor grow very well at tem- peratures between 35° and 40° C.; while A. glaucus and Penicillium only thrive below 34 C°. The spores bear high degrees of heat ; to kill them outright they must be kept at a temperature of 110° to 115° C. for an hour. [References: Grohe, "Berl. klin. Woch.," 1, 1871 ; Loftier, "Mitth. a. d. k. Gesundh.," Berlin, 1881; Grawitz, " Vircb. Arch.," vol. Ixxxi.; 324 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. Lichtheim, " Berl. klin. Woch.," 9, 1882 ; Leber, " Grafe's Arch.," xxv., and "Berl. klin. Woch.," 19, 1882; Duclaux, "Ferments et Maladies," Paris, 1882 ; Koch, "Berl. klin. Woch.," 52, 1881 ; Kaufmann, "Lyon medicale," 1882.] 220. The action of the mould-fungi on the nutrient soil on which they grow is slow, and limited in extent. Thus the mouldy covering which forms on preserved fruit extends only to a slight depth below the surface. Mouldy articles of food acquire a peculiar, unpleasant, " musty " taste. If the mycelium of a fungus gains access to an apple, for instance, the apple becomes rotten ; i.e., a process of change and decay sets in ac- companied by purely chemical decompositions. Timber in which mould- fungi develop becomes soft and brittle, and breaks down into a dry "mouldering " dust. Fungi which are specifically distinct may give rise to similar or identical decompositions in articles of food, timber, etc. The mycelium of Mendius lacrimans (dry-rot) destroys the wood-work of houses. Moulds may likewise attack living plants, i.e., they may thrust their mycelia into living vegetable tissue. The changes they occasion are va- rious. Sometimes they seem to exert no disturbing influence on the nor- mal development of the tissue. In others they induce abnormal growths. The so-called "witches' brooms " of the silver fir are produced by the set- tlement in the tree of the Aecidium elatinum. Often the cell-contents become altered ; thus starch and cellulose may be converted into turpen- tine. Hartig thinks the moulds may also act as organized ferments. Not infrequently the fungi destroy altogether the plants they attack. Thus the Oidium Tuckeri (vine-mildew) seizes on the green parts of the vine, and destroys it. If the spores of Peronospora infestans reach the tubers of the potato-plant, they drive their germinal hyphae into their substance, form a mycelium there, and so ruin the potato (De Bary) ; this constitutes the " potato-disease." The " leaf-rust " which destroys fruit-trees is likewise due to a fungus (Roestelia cancellata). [References : Sachs, "Text-book of Botany," 1882 ; De Bary, "Die gegenwartig herrschende Kartoffelkrankheit," Leipzig, 1861, Journ. of Botany, 1876, " Botan. Zeitung," 1881 ; Hartig, " Ueber die durch Pilze bedingten Pflanzenkrankheiten," Munich, 1881.] 221. Pathological significance. The mould-fungi do not act as producers of disease to anything likn the same extent as the bacteria. The fact that they require abundance of oxygen and flourish best at tem- peratures below that of the body hinders their development within it. Moreover, their growth and reproduction are much slower than in the case of the bacteria, and this also is a hindrance to the invasion of living tissues by them. Lastly, they do not usually find in living tissues their proper nutriment. At the same time the products of the decompositions PARASITES. 325 set up by them are by no means so poisonous as those which result from the development of bacteria. For these reasons the effect of mould- fungi or their germs on the system is either nil, or very limited. Multitudes of fungus-germs are received into the accessible cavities of the body with the air, water, and food. Most of these germs fail of development and perish, or are removed from the body. It is only now and then that they produce hyphae, and that only when they reach spots accessible to the air and containing necrotic tissues or other like matters. Such spots are the mouth, nostrils, and pharynx, and the external audi- tory meatus, the cornea, trachea, bronchi, and lungs. In the "fur" of the tongue of patients whose mouths are not kept clean we often find not only bacteria but also the spores and hyphae of various filamentous fungi. In cases of bronchiectasis, vomicae, and pulmonary gangrene various forms of mycelial growths, such as Mucor, Eurotium, and Asper- gillus, have been frequently described. They produce hyphae and co- nidia, and (rarely) the more complex conidiophores. These fungi are not, however, to be regarded as the specific causes of the diseases in question. They are merely secondary growths developing on the dead tissues produced by antecedent morbid processes. They have merely sprung up on a soil which they found already prepared. They are not parasites, they are merely saprophytes. But their devel- opment in the necrotic matters, and the further decay they set up, may nevertheless tend to excite inflammatory action in the neighboring tissues. The fungi found occasionally in the stomach are in like manner to be regarded as secondary formations. They are not causally connected with the disease which they accompany. They are sometimes observed in cases where the gastric functions are gravely impaired, as in carcinoma and in dilatation of the stomach. The form of vegetative growth then met with is not the ordinary one ; the fungi multiply by subdivision into short cells resembling those of the yeast-plant. This phenomenon we have already seen exemplified in the case of Mucor when grown under the surface of the nutrient liquid. [On mycoses (or fungus-affections) of the lungs see Virchow, "Virch. Arch.," vol. ix. ; Kiichenmeister, "Die in dem und an dem Kbrper des Menschen vorkommenden Parasiten ; " Friedreich, " Virch. Arch.," vol. x. ; Pagenstecher, "Virch. Arch.," vol. xi. ; Cohnheim, "Virch. Arch.," vol. xxxiii. ; Furbringer, "Virch. Arch.," vol. Ixvi. ; Lichtheim, "Berl, klin. Woch.," ix., 1882; Bollinger, "Zur Aetiol. d. Infect.," Munich, 1881 ; Kitt, "Deutsche Zeitsch. f. Thiermed.," vii. The Aspergillus which is found in the lungs is, according to Licht- heim, the A. fumigatus. It was formerly believed that A. glaucus oc- curred within the body. This cannot be the case, however, for the body- temperature is too high. A. glaucus forms rounded conidia-spores 12-13 micromm. in diameter, with a thick, warty, yellowish envelope. Those of 326 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. A. fumigatus are only 3-4 micromin. across, and are smooth. Invasions of the Aspergillus are very often observed in birds. In the external meatus and middle ear the following are found-As- pergillus fumigatus, nigricans, flavescens, and Trichothecium roseum. They excite inflammation. The instillation of oil favors their develop- ment (Bezold, " Ueber Otomycosis, Zur Aetiol. d. Infect.," Munich, 1881). Aspergillus may grow on the injured surface of the cornea and lead to suppurative inflammation. Leber (" Grafe's Arch.," xxv.) has culti- vated it on the cornea and in the anterior chamber of rabbits. Asper- gillus also occurs in the pelvis of the kidney.] 222. Filamentous fungi are the exciting causes of certain skin dis- eases. In Favus, Tinea tonsurans, Tinea versicolor, Tinea sycosis, and Onychomycosis deposits of hyphas and conidia are found in the epithelial layers of the skin. In Favus, for example, the root and root-sheath of the affected hair (Fig. 84, a, 6) are beset with jointed filaments and spores. The other parts of the hair and skin are also interpenetrated with filaments and spores, and these tend to separate the constituent epidermoid cells by loosening their cementing substance. Inflammation is set up and scales and crusts are formed on the surface. Grawitz asserts that the hyphae and conidia, which are met with in the above-named mycoses of the skin, all belong to the same species of fungus, which is identical with the Oidium lactis ; the differences observed in the various diseases being simply due to differences in the nutrient substratum. Most authors, however, maintain that they belong to different species. The fungus of Favus is called Achorion Schonleinii, that of Tinea tonsurans (or ring- worm) is Trichophyton tonsurans, and that of Tinea or Pityriasis versi- color is Mierosporon furfur. Most of the parasitic filamentous fungi infesting man seldom pene- trate beyond the superficial layers of the tissues affected. They can only do so under special and uncommon conditions, as in deep wounds. Some few, like Aspergillus fumigatus saAflaveseens, can germinate and throw out filaments into the blood, if they succeed in entering the vessels ; but they do not multiply. As they grow they excite inflammation and ne- crotic changes. Only two fungi referred to this class are known to multi- ply in the substance of the tissues, and they cause widespread and highly destructive inflammations. One of these is the so-called Actinomyces or " ray-fungus " which causes the disease known as Actinomycosis (Arts. 134-135). Its botanical position is not yet determined ; if it is a myce- lial fungus at all, it differs in many respects from its congeners. Some pathologists go so far as to question whether it is a vegetable. The other is the Chionyphe Carteri, which is found in tissues affected with the Indian disease known as " madura-foot " or Mycetoma. Its myce- lium penetrates the skin and subcutaneous tissue, and suppuration and ulceration are set up. PARASITES. 327 [The earliest observation of filamentous fungi in the deeper organs was made by Zenker (" Jahresb. d. Gesell. f. Natur- und Heilk.," Dresden, 1861-2). He found them in cerebral abscesses. Fig. 84.-Hair ACected with Favus (after Kaposi), a, hair bulb and shaft; 6, root-sheath beset with hyphas and conidia. Grohe ("Berl. klin. Woch.," 1, 1870) and Block (" Ueber Pilzbildung in thier. Geweb.," In. Diss., Stettin, 1871) made the first experimental re- searches on the behavior of mould-spores introduced into the blood. They affirmed that the spores of Aspergillus glaucus and Penicillium glaucum germinate when injected into the blood, so that the tissues be- come penetrated with their filaments. Their experiments were again and again repeated, but their results were not confirmed until Grawitz took 328 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. up the subject (" Virch. Arch.," vol. Ixxxi.). He found that to obtain positive results the fungi must first be adapted to the conditions of the human body by cultivation in an incubator. Koch, Loftier, and Lichtheim (Art. 219), however, showed that this is not always necessary, for the conidia of various moulds, such as Asp. fumigatus, A. flavescens, and several of the Mucorini, have the power of developing within the body. Experiments made with a view to acclimatize other varieties to the con- ditions of the body were unsuccessful. Grawitz's results are vitiated by the fact that his cultures were probably " impure." On Madura-foot see Vandyke Carter "On Mycetoma," London, 1874, and Lewis and Cunningham, " The Fungus-Disease of India," Calcutta, 1875, and " Quain's Diet, of Med.," 1882. The affections induced by the mould-fungi have a totally different significance from those induced by the bacteria. No transmissible infec- tive disease has yet been produced by the former class of organisms, for they do not multiply within the body. In all the experiments referred to what was obtained was at most the germination of conidia-never their fructification. Among invertebrate animals diseases due to mycelial fungi are by no means rare. Botrytis bassiana sets up the so-called muscardine-disease in silkworms. Cordyceps militaris destroys the noxious pine-spider {Gastropacha pini). Tarichium megaspermum, a black fungus, is fatal to the noxious caterpillar Agrotis segetum. The genus Empusa is well known ; one of its species (E radicans) attacks the caterpillar of the white cabbage-butterfly, another (E. muscai) the ordinary house-fly. These are often found completely beset and permeated with mycelial filaments.] The Blastomycetes or Yeasts. 223. The yeast-fungi consist of round or ovoid cells of various sizes (Fig. 85). The cell-protoplasm is granular, and often vacuolated. It is contained within a cell-wall. Multiplication takes place by gemmation and abstriction. An out- growth springs from some point of the surface of the parent-cell ; this grows till it is about the size of the parent, and then it is abstricted. In some conditions (Cienkowsky, Grawitz) the cells grow out into filaments, but these do not become jointed or subdivided. If joint- ed threads seem to be formed, it is by a process of gem- mation, like that which produces the rounder cells. Di- lution of the nutrient liquid favors the development of filaments ; abundance of sugar favors the development of spherical cells. Reess asserts that new cells may also be formed endogenously, by means of so-called brood-cells. The organism which sets up alcoholic fermentation is a yeast-fungus Fig. 85.-Saccharomv- ces Cerevisiae. x 400. PARASITES. 329 (Torula). When it multiplies in a liquid containing sugar, alcohol and carbonic acid are generated. It has therefore been described as Saccha- romyces. The scum which forms on the surface of alcoholic liquors and leads to their transformation into vinegar also contains a yeast-fungus ; it is distinguished as Mycoderma vini or " mother of vinegar." Nageli maintains that Torula and Mycoderma are not distinct species. [Sachs classes the yeasts with the bacteria as Protophyta. Brefeld regards them as probably mere low forms of the moulds or filamentous fungi. Cienkowsky's paper on My coder ma is in the " Melanges biolo- giques de l'acad. de St. Petersbourg," vol. viii.; Grawitz's in " Virch. Arch.," vol. Ixx. On Saccharomyces and alcoholic fermentation see Reess, " Bot. Untersuch. ub. d. Alkoholgahrungspilze," Leipzig, 1870 ; Pasteur, Op. cit. (Art. 191), "Studies on Fermentation," London, 1879 ; Mayer, " Lehrbuch d. Gahrungschemie," 1876 ; Schiitzenberger, " Fer- mentation," London, 1876 ; Brefeld, " Phys. med. Gesellsch. zu Wurz- burg," v., 1873 ; Hiller, " Die Lehre von der Faulniss," Berlin, 1879. On the various theories of fermentation see Art. 191. Yeast-cells not only set up fermentation directly, but they yield an unorganized ferment which changes cane-sugar into grape-sugar.] 224. The yeast-fungi have but little pathological importance. They havp no power of invading living tissue, and therefore they are only to be found in parts that are accessible from without. Even there it is only under specially favorable conditions that they are able to grow freely. There is usually no great supply of fermentable saccharine mat- ter available for them. It is in the stomach that they are oftenest found, and there they may set up fermentation ; the presence of the gas- tric acids does not check their development. If fermenting " wort" or " must " be drunk, the fermentation goes on in the stomach. According to Grawitz the white patches known as 11 thrush" (or aphthae) which form in the mouth, pharynx, and oesophagus of weakly children and debilitated patients are due to the presence of Mycoderma vini. The mycelial filaments and spores found in these patches have usually been regarded as belonging to an Oidium distinguished as 0. albicans. Grawitz has shown that on cultivation the filaments gemmate like Torula and Mycoderma. He has further proved experimentally that the latter can be grown in the epithelium of the mucous membrane. The subepithelial fibrous tissue is not usually invaded, and then only when by antecedent changes, constitutional or other, the resisting power of the tissues has been considerably diminished. CHAPTER XXXII. ANIMAL PARASITES. Arthropoda. 225. Arachnida. The arachnoid parasites are mostly ectozoa ; they inhabit the skin for a shorter or longer time. Only a single species, Pen- Fig. 86.-Female Acarus Scabiei, Dorsal Surface, x 200. (From Hebra's Atlas of Skin Diseases.) tastoma, is found (in the larval form) within the substance of the deeper tissues. (1) Acarus scabiei (Sarcoptes hominis), or itch insect. This mite is PARASITES. 331 about the size of a small pin-head, and somewhat turtle-shaped. It has four pairs of legs springing from the ventral surface, each being fur- nished with bristly hairs (Fig. 86). The anterior pairs are prolonged into stalked suckers, as are also the posterior pairs in the male. The foremost of the two posterior pairs in the male and both posterior pairs in the female end in a long bristle. The border of the body behind is likewise furnished with bristles, and the dorsal surface is beset with tooth-like hooks and spines. The head is blunt and rounded, and beset with bristles. The female is about twice the size of the male. The mite lodges in the epidermal layer of the skin, in which it excavates burrows or cuniculi that may run to 10 mm. in length. In these burrows the female lays her eggs. From the eggs the young acari are hatched in loco ; they proceed to burrow further into the epi- dermis, and after changing their skin several times be- come sexually mature. The irritation caused by their presence produces inflammation of the skin. This again is greatly intensified by the scratching induced by the intolerable itching of the affected parts. (2) Leptus autximnalis^ or harvest-mite. This like- wise infests the epidermis. It is red in color, and thus is readily seen in spite of its smallness. It gives rise to the formation of papules and wheals. Two allied American species are the Leptus Americamis and L. irritans. (3) Acarus (Demodex) folliculorum (Fig. 87). A third mite, which is found solitary or in small numbers in the sebaceous matter of the follicles in perfectly healthy skin. It is about 0.2 mm. long, and bears four pairs of short stumpy feet on the tho- rax. The head bears a proboscis and a pair of short antennae. It has no pathological significance. (4) Ixodes ricinus (hominis), or wood-tick, is also an occasional para- site of the skin. It buries its proboscis in the tissues and sucks its fill of blood. It belongs to the Acarina, as do also the American I unipunc- tata and I. bovis. (5) Pentastoma denticulatum (Fig. 88). This is an arachnoid, which in its larval state lodges in the internal organs. Its body is 4-5 mm. long, 1.5 mm. broad, squat and rounded, and possessing some ninety an- nular segments which are beset with spines at their margins. The mouth is surrounded by four large hooks in chitinous sheaths. The larva chiefly inhabits the liver, more rarely the spleen, intestine, lung, or kidney. When looked for post-mortem the animal has generally been dead for some time ; it then appears as a nodule as big as a pea, made up of a mortar-like chalky mass with a fibrous capsule. The mass often contains booklets, but seldom the whole animal. Fig. 87. - Acarus Folliculorum. x 300. (From Peris.) 332 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. According to Leuckart, Pentastoma denticulatum is the larva of Pen- tastoma toenioides, a lanceolate arachnoid inhabiting the frontal sinuses of various animals, chiefly the dog. The female is 60-85 mm. long, the male 16-18 mm.; the breadth of each is about 3 mm. The mature ani- mal resembles the larva, but it has no booklets. Fig. 88.-Head-end of Pentastoma Denticulatum. x 40. (From Peris.) \Pentastoma constrictum has also been met with as a larva in the liver and in the lungs (von Siebold ; Aitken, " Science and Pract. of Medi- cine," 1882).] 226. Insecta. The parasites belonging to this class are nearly all epizoa. Some settle on the skin for a brief time only, in order to extract nutriment from it ; others are stationary and make use of the epidermal structures for the deposit of their eggs. Of the many insects which afflict man we need name only the following : (1) Pcdiculus capitis, or head-louse. This inhabits the hairy scalp, and extracts from it, by means of its proboscis, the blood on which it feeds. It fastens its eggs to the hairs by means of a chitinous covering. The "nits" are easily seen as small grayish oval bodies, tightly affixed to the hair. The young louse emerges in about eight days, or less. The irritation induces scratching, which may set up somewhat severe inflam- mation or eczema. (2) Pcdiculus pubis, or crab-louse, inhabits the hairy parts of the body and extremities, more especially about the genitals. Its mode of life is much like that of the head-louse, but it is smaller, and often more difficult to detect. (3) Pcdiculus vestimentorum, or body louse, infests the underclothing and lays its eggs there. It passes to the surface of the body merely in order to feed. It is somewhat larger than P. capitis. (4) Cimex lectuarius, or bed-bug, infests bedding, bedsteads, old floors and walls, cupboards, etc., and betakes itself to its human victim at night in order to suck blood from him. It produces wheals on the skin. (5) Pulex irritans, or common flea, also draws blood from the skin. At the point attacked is found a small punctiform hemorrhage surrounded PARASITES. 333 by a reddened areola. More marked swellings or wheals are sometimes formed. The eggs are laid in the crevices and cracks of flooring-boards, in saw-dust, etc. (6) Pidex penetrans, or sand-flea (chigoe or chigger), is found in the sands of South Africa. The female buries itself arid lays its eggs be- neath the skin, and so produces intense inflammation. (7) Culicida and Tipulida (midges and mosquitoes), Tabanida (gad- flies), and Stomoxys calcitrans also take blood from the skin and excite transient exudative inflammations. Some flies (Oestrida) lay their eggs occasionally in accessible body-cavities or in wounds. This occurs oftener among the lower animals than among men. Oestrus hominis (a doubtful species) lays its eggs beneath the human skin, and the larvae (maggots or bots) set up violent inflammation. Ilcematopota pluvialis is the Scotch " clegg ; " it attacks men and beasts indifferently. [The above account has been chiefly taken from Leuckart, " Die menschlichen Parasiten," Leipzig, 1863-76, and second edition, vol. i., 1879-81 ; Heller, " Ziemssen's Cyclopsedia," vols. iii., vii.; Klebs, " H. d. path. Anat.Peris, " Lehrb. d. allg. Path.," ii., Stuttgart, 1879. Other comprehensive works are-Kiichenmeister and Zurn, " Die Parasiten d. Menschen," Leipzig, 1882 ; Davaine, "Traite des Entozoaires," Paris, 1877 ; Muller, " Statistik d. menschlichen Parasiten," Erlangen, 1874; Stein, "Die parasitaren Krankheiten d. Menschen," vol. i., Lahr, 1882 ; Perroncito, "Parasiti d. uomo e d. animali utili," Milan, 1882 ; Cobbold, "Parasites," London, 1879.] Scolecida, or Worms. 221. Nematoda. The parasitic round-worms and thread-worms are all nematoids. They have slender cylindrical elongated (sometimes filiform) bodies, without segments or appendages. The cuticle is thick and elastic. The mouth is placed at the anterior extremity, and is pro- vided with soft or horny lips according to the species. The intestine is straight and, with the pharyngeal and gastric portions, extends from end to end of the body-cavity, terminating on the ventral surface just in front of the acuminate tail. The genital organs and their orifices are on the ventral side. The female genital orifice is usually placed at about the middle-point of the length ; more rarely it is anterior or posterior to this. The male orifice coincides with that of the anus ; it is provided with a chitinous investment, which serves also as a prehensile organ during copulation. The males are usually smaller than the females Development is direct, and the metamorphic variations slight. The nematoids parasitic on man are some of them harmless inhabitants of the intestine, while others are highly dangerous when they invade the deeper organs. 228. Ascaris lumbricoides, the common round-worm or maw- 334 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. worm (Fig. 89), is a cylindrical worm with pointed ends ; it is light brown or red in color. The female (A) is 25-40 ctm. long; the male (U) is con- siderably smaller, and its tail-end is bent into a hook provided with two spicula (c) or chiti- nous spines. The mouth is surround- ed by three muscu- lar lips bearing very delicate teeth. The female genital orifice (a) is anterior to the mid- dle of the length. The eggs, which the female bears in enormous numbers, have when mature a double shell (Fig. 90) surrounded by an albuminous coating. It is about 50-60 micromm. in diameter. The worm is found in all parts of the alimentary canal, but chiefly in the small intestine. When the females are mature great numbers of eggs are shed and are found in the faeces. They are very tenacious of life, and are not killed by drying or freezing. The life-history of the worm is not fully known. It is possible that the eggs, after ejection from the intestine, require to pass through the body of an intermediate host before they can take up their abode in another human body. Their presence in the intestine does not usually give rise to any serious trouble. Only when they are very numerous do they cause intestinal catarrh, vomiting, and nervous irritation, chiefly in children. At times they pass through normal or morbid openings in the intestinal wall, and give rise to more serious disturbances. Thus an ascaris in the common bile-duct ma\| obstruct the outflow of bile and so in- duce jaundice. Or if it pass through an ulcerated opening into a hernial sac, or into the peritoneal cavity, it may excite inflammation in the corresponding tis- Fig. 90.-Egg of Ascaris Lumbricoides with its shell and albuminous coating. Fig. 89.-Ascaris Lum- bricoides. Natural size. (From Peris.) A, female; B, male, a, female genital orifice; b, head-end with the three lips, magnified : c, male orifice with spicula. PARASITES. 335 sues. According to Leuckart it may even penetrate the wall of the in- testine where there is no pre-existing wound. It is often voided per anum, and occasionally per os during vomiting. \Ascaris mystax, or round-worm of the cat, is a very rare inhabitant of the human intestine. It is considerably smaller than the common round-worm (Cobbold, " Entozoa," 1864-69).] 229. Oxyuris vermicular is, the thread-worm, seat-worm, or maggot- worm (Fig. 91). is a small round-worm. The female (A) is 10 mm. long, and acuminate at the tail ; the male (li') is 4 mm. long and blunt at the tail, which is furnished with a single spiculum at the anus. The eggs (C), often seen in great multitudes within the body of the fe- male, are 50 micromm. long and 24 mi- cromm. broad. One side is flat and the other rounded. The shell is covered with a thin albuminous coating. The thread-worm inhabits the upper part of the colon and lower part of the ileum. According to Zenker and Heller the mature egg-bearing females affect the colon and caecum, the younger ones and the males affect the ileum. They are of very common occurrence and are often found in vast num- bers. They are apt to migrate from the rectum into neighboring parts, and may so enter the vagina. The irritation they cause induces violent scratching, and this again brings about inflammation of the skin and other disagreeable consequences. When the eggs have been ejected from the body with the faeces, they must be taken up into the stomach of an animal before they can develop. It is not improbable that the individual host may reinfect himself ; for eggs may stick under his finger-nails after he has been scratching himself and may thus be inadvertently carried to the mouth. The eggs are not destroyed by being dried, and in this condition-they may be carried from place to place. 230. Trichocephalus dispar, or whip-worm (Fig. 92), is a common but innocuous parasite inhabiting the caecum and neighboring parts of the intestine. Davaine says that half the inhabitants of Paris are infested with it. Both male and female are 4-5 cm. long. The anterior part of the body is very fine and thread-like. The posterior part, which contains the genital organs, is much thicker ; in the female (Z?) it is straight and cylindrical, in the male (A) it is rolled into a flat spiral and furnished with a spiculum. The eggs (Fig. 93) are prolate spheroids, 50 micromm. in length. Fig. 91. - Oxyuris Vermicularis. (From Leuckart). A, female, and B, male, magnified fivefold, C, egg, magnified 350-fold. 336 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. They have a thick brown shell, with a peg-shaped glassy-looking projec- tion at each pole. The first stage of development is passed in water or moist earth. It is very protracted, lasting even in the warm season for four or five months ; and in cold weather for a longer time still. The eggs resist cold and drying extremely well. Fig. 93. Fig. 92.-Trichocephalus Dispar. A, male; B. female. Somewhat magnified. (From Lenckart.) The male is anchored in the mucous membrane by means of his whip-like anterior part. Fig. 93.-Egg of Trichocephalus Dispar, x 350. (From Heller.) Fig. 94.-Head-end of Dochmius Duodenalis. Magnified. (From Lenckart.) Fig. 92 A. Fig. 92 B. Fig. 94. 231. Ancliylostoma or Soler ostoma duodenale {Dochmius or Strongy- lus duodenalis) is a small worm infesting the upper part of the small in- testine. The female is cylindrical and 6-18 mm. long, the male 6-10 mm. The head-end (Fig. 94) is bent toward the dorsal surface and is fur- nished with a bulging oral capsule. This is cleft almost throughout on the dorsal surface, the cleft being covered by two chitinous lamellse. On the ventral lip are four curved teeth, on the dorsal lip are two straight ones. These are all held together by chitinous clasp-like structures. Beneath the dorsal cleft a conical projection rises from the interior of the capsule. The male at its posterior end has a three-lobed bursa, and two thin spicula looking like slender fish-bones. The posterior part of the female becomes gradually thinner and ends in an awl-shaped spine. The vulva lies behind the middle point. The oval eggs are 44-67 micromm. long and 23-40 broad. They pass through their first developmental stages in the human intestine ; in the next stages they inhabit dirty or muddy waters ; thence they again obtain access to the alimentary tract, and there grow to maturity. Their presence in the small intestine is not free from danger. The worm gnaws into the mucous membrane with its PARASITES. 337 teeth until it reaches the submucous coat, and thence it sucks its fill of blood. The point attacked is recognizable as a small ecchymosis, in the middle of which is a white spot with a central punctate aperture. This aper- ture has contained the head. Occasionally small blood-filled cavities are found in the mucous mem- brane, each containing a coiled-up worm. When present in number these parasites give rise to serious hemorrhages, which produce intense anaemia in the patient (the Egyptian chlorosis). The parasite is common in the tropics. According to Griesinger and Bilharz a great proportion (something like twenty-five per cent.) of the natives of Egypt suffer from it. Wucherer says it is also common in Bra- zil. McConnell has met with it in India {Lancet, 1, 1882). Within the last few years it has been very frequently observed among the workmen en- gaged in the St. Gothard tunnel. [References to Anchylostoma: Griesinger, " Arch. f. phys. Heilk.," 1854 ; Wucherer, " Arch, f. klin. Med.," xii., 1872; Bilharz, "Zeitsch. f. wiss. Zool.," iv. ; Leuckart, op. cit. ; Grassi and Parona, " Anhali univ. di med.," 1878 ; Bozzolo and Pagli- ani, " Giorn. d. Soc. ital. d' igiene," ii., Milan, 1880 ; Sonderegger, " Corresp. f. schweiz. Aerzte," 1880 ; Bugnion, " Anchylostome duodenal et anemie du St.-Gothard:" "Rev. m^d. de la Suisse rom.," i., 1881 ; Perroncito, " Arch. p. 1. scien. med.," v., Turin, 1881; Long, " Trans. Int. Med. Congress," i., 1881; Megnin, "Soc. de Biologie," March, 1882; Cobbold, " Human Parasites," 1882, Art. " Scleros- toma," " Quain's Diet, of Med.," 1882. Among the rarer nematoid parasites are the fol- lowing. Eustrongylus gig as or palisade-worm ; the female attains a length of 1 metre, the male of 35 cm. ; the color is blood-red. It has been found a few times in the pelvis of the human kidney ; but it is commoner in the seal, marten, wolf, and dog. The immature worms dwell chiefly in fresh-water fishes. Strongylus longevaginatus {bronchialis), a thread-like worm 26 mm. long. It has once been found in the lung of a boy. Anguillula {Rhab- ditis) stercoralis, a minute round-worm 1 mm. long, indigenous in Cochin-China. It infests the entire alimentary tract, bile-ducts, and pancreatic duct, 22 Fig. 95.-Mature Trichina. Magnified. (From Leuckart.) A, female ; B, male. 338 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. and gives rise to chronic diarrhoea. Perroncito (loc. cit. and Mier. Soc. Journ., 1882) found it in the tunnel-workmen at St. Gothard. See Peris, " Allg. Path.," ii. ; Davaine, " Traite des Entozoaires," 1877 ; Liebermann, " Dysenteric chronique de Cochin-chine: " " Gaz. des Hop.," 1877 ; Normand, " Arch, de Med. Navale," 1877.] 232. Trichina spiralis, or flesh-worm of pork, appears in two forms, according? as it inhabits the intestine or the muscles. The intestinal form (Fig. 95) is the sexually mature worm. It is a minute filiform creature, scarcely visible with the naked eye, and white in color. The female (yl) is 3 mm. long ; the male is considerably smaller. In both sexes the hinder part of the body is straight ; the male (2?) has on the dorsal side of its tail two mammillary protuberances which are turned toward the ventral aspect and include between them four wart- like nodules. There is no spiculum ; in copulation the muscular cloaca is everted and protruded. Fig. 96.-Trichinae Encysted in Muscle, showing the capsule and its contents. Magnified. (From Leuckart.) The alimentary canal begins with a muscular pharynx which widens as it passes into the oesophagus. This latter is surrounded throughout its length with a series of large cellular masses. The stomach passes without notable change of structure into the intestine. In the male this terminates, with the seminal ducts, in the cloaca. The testis consists of a tube which commences cfecally at the tail-end, extends forward to the cellular bodies round the oesophagus, and then bends back to be joined by the seminal ducts. The genital organs of the female (yl) consist of a simple ovary, uterus, and vagina ; the latter opens at a quarter of the whole length from the head-end. The ovary, like the testis, is a tube commencing posteriorly and passing forward to join the tubular uterus. The eggs develop into embryos in the uterus, and these are born in the free state. The trichina of muscle (Fig. 96) is a small worm 0.7 to 1.0 mm. in PARASITES. 339 length ; it inhabits the fleshy muscles. It is usually coiled up into a spiral, and lies in a fibrous capsule or cyst, which sometimes also contains calcareous matter. A finely granular substance surrounds the coils of the worm. One capsule may enclose two to five trichinae. 233. The following is the life-history of the trichina. When a piece of muscle containing live encysted trichinsereaches the stomach of a host, human or other, the capsule is dissolved and the trichinae set free. They come to maturity in the intestine in about two and one-half days ; when they proceed to pair. The birth of embryos begins on the seventh day and continues for some time, it may be for weeks. A single worm may bring forth one thousand to thirteen hundred young. These then migrate from the intestine in search of striated muscle. They do so in various ways. Most of them seem to pass directly through the wall of the intes- tine, the peritoneal cavity, and the subperitoneal connective tissues. Others gain access to the lymph and blood, and are thus conveyed to re- mote organs. Once in the muscle they penetrate the primitive bundles, reduce the contents to mere detritus, and in fourteen days or so become mature muscle-trichinae. At first they are only enclosed by the evacuated sarcolemma. Afterward a cyst is formed, consisting partly of a chitinous secretion of the animal, partly of hyperplastic fibrous tissue. The intestinal trichinae live but a short time (five to eight weeks). The muscle-trichinae, on the other hand, may live for a very long time, perhaps indeed for a time limited only by the death of their host. After a while calcareous salts are generally deposited within the cyst; this gives the cyst a lustrous white appearance by reflected light, and a dark or turbid appearance by transmitted light. If for any reason the trichina dies, the contents of the capsule become calcified. Trichinae are met with in man, in the pig, cat, rat, mouse, hamster, pole-cat, fox, marten, badger, hedgehog, and racoon. By feeding on trichinous flesh, muscle-trichinae may be acquired by rabbits, guinea-pigs, sheep, dogs, etc. Human beings are infected by eating uncooked pork. Trichinosis in man is attended with very various symptoms. Intestinal catarrh follows upon the introduction of the trichinous flesh into the ali- mentary tract. The invasion of the muscles is marked by swelling, oedema, partial paralyses, and not uncommonly fever. The symptoms are at their height in the fourth or fifth week. Death not unfrequently en- sues. The violence and gravity of the symptoms depend generally on the number of trichinae which have entered the muscles. The trichinae are found most abundantly in the diaphragm, intercostal, cervical, and laryngeal muscles ; they are least abundant in the muscles of the limbs. They are usually crowded together at the points of attach- ment of the muscle to its tendon. [The worm was first discovered by Paget, at St. Bartholomew's Hos- pital, in 1834 ; see Lancet, 1, 1866. Owen named and described it shortly afterward. 340 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. The literature of trichinosis is very abundant ; we can only refer to a few of the chief works on the subject. Owen, " Zool. Soc. Trans.," 1835 ; Zenker, " Virch. Arch.," vol. xviii,, " Arch. f. klin. Med.," viii.; Virchow, "Die Lelire von denTrichinen," Ber- lin, 1866; Leuckart, " Die Parasiten des Menschen;" Heller, "Ziemssen's Cyclopaedia," vol. iii.; Cobbold, "Entozoa," 1869 ; Glazier, "Report on Trich.," Washington, 1881 ; Wendt, "Chronic Affect, fol- lowing Trich.:" New York Medi- cal Record, 1879. For further references see Cobbold, " Hu- man Parasites," 1882.] 234. Iliana (Dracunculus) medinensis (Fig. 97), or Guinea- worm, is a fine thread-like worm from sixty to one hundred cm. in length. Only the female is known. The anterior end is rounded ; the posterior termi- nates in a pointed tail curved over ventrally. The outer cov- ering consists of a firm cuticle thickened at the head-end into a kind of shield. The intestine is narrow, and there is no anus. The gravid uterus occupies near- ly the whole of the body-cavity. The embryos have no envelope ; they have a stout cuticle and an acuminate tail. They use as in- termediate hosts certain small crustaceans (Cyclops) that in- habit drinking-water, and so they ultimately reach the human stomach. In Africa and Asia they are very common. They develop to maturity under the skin, giving rise to cutaneous abscesses. They are most commonly found in the legs and feet, espe- cially in the neighborhood of the heel. Fig. 98-Embryo of Fi- laria Sanguinis Hominia. x 400. (From Lewis.) [See Leuckart, op. cit.; Davaine, " Entozo- aires," etc. ; Cobbold, " Entozoa," 1864. The Guinea-worm disease has been identified with the dracontiasis of Plutarch, and with the endemic disorder attributed to " fiery serpents " in the book of Numbers.] Fig. 97.-Filaria (Dra- cunculus) M e d i n e n s i s. Natural size. (From Leuck- art.) PARASITES. 341 235. Filaria sanguinis hominis (Lewis), or sanguinolenta, in its sexu- ally mature form is a filiform worm 8 to 10 ctm. long. According to Manson it inhabits the lymphatics, especially those of the scrotum and lower limbs. It gives rise to obstructions of the lymph-current and to peculiar inflammations, which end in elephantiasis of the tissues with oedema and lymphangiectasis. Suppurative inflammations, lymphatic abscesses, buboes, chylous hydrocele, and chylous ascites have all been observed as consequences of its presence. The embryos, which are about 0.35 mm. long (Fig. 98), pass from the lymphatics into the blood and induce haamaturia and chyluria. Both conditions result from the lodgement of the embryos in number within the kidneys. The embryos may be ejected with the urine. Manson finds that they are spread by the agency of mosquitoes, who take up the fila- riae with the blood they suck. The filariae pass through an intermediate developmental stage in the body of the mosquito ; thence they pass into water, and thence again into the human body. It is thus probable that they reach the vessels and tissues from the intestine. The Filaria sanguinis appears to be indigenous only within the trop- ics (Brazil, Egypt, India, Guadaloupe, etc.). [See Lewis, " On a ILematozoon Inhabiting Human Blood : its Rela- tion to Chyluria and other Diseases," Calcutta, 1872 ; Lancet, 2, 1877 ; Quarterly Journal of Microscopic Science, 1879 ; Art. " Chyluria : " " Quain's Diet, of Med.," 1882 ; Bancroft, " Trans. Path. Soc.," 1878 ; Manson, Lancet, 1,1878, and " Trans. Path. Soc.," 1881 ; Cobbold, " Para- sites," 1879, and " Human Parasites," 1882 ; Journal Quekett Micro- scopic Club, 1880 ; Barth, " Annales de Derm, et Syph.," 1881. Several other rare species of Filaria are known. References to them will be found in the standard works of Leuckart, Davaine, and Cobbold, already cited.] 236. Trematoda. The flukes, or suctorial worms, are flattened or tongue-shaped worms. They possess suctorial pores by which they can adhere to surfaces, and in some cases they have also hook-like processes. The intestine is usually bifurcated, and terminates caecally. The develop- ment is direct or by alternate generations. In the latter case an inter- mediate host is necessary. This is usually a mollusc ; while the mature worms almost all find lodgement in vertebrate animals. The interme- diate larval stage is usually preceded by a period of active locomotion. The trematode larvae are furnished with a propelling tail, and swim about freely as cercaria. 237. Distoma hepaticum, the liver-fluke (Fig. 99), is a leaf-shaped trematode 28 mm. long and 12 mm. broad. The head-end projects like a beak, and bears a small suctorial disc in which the orifice of the mouth is visible. Immediately behind this, on the ventral surface, is another suc- torial disc. The genital orifice lies between the two discs. 342 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. The uterus is a convoluted tube lying behind the posterior disc. The ovaries lie on each side of the hinder part of the body, and between them lie the deeply bifurcated testes. The intestinal canal is also bifurcated and much branched. Fig. 99.-Distoma Hepaticum, with Male and Female Genital Organs, x 2X- (From Leuckart.) The eggs (Fig. 100) are oval, 0.13 mm. long and 0.08 mm. broad. When placed in water a globular embryo is developed, which swims freely by means of its ciliated envelope. The details of its life-history are not certainly known. The adult animal infests the biliary ducts ; more rarely it is found in the intestine or in the vena cava. It is rare in man. Fig. 100.-Egg of Distoma Hepaticum. x 200. (From Leuckart.) but very common among the ruminants ; it causes the " rot " in sh$ep. The consequences of its invasion, especially in great numbers, are ob- struction of the biliary ducts, accumulation of bile, dilatation and incrus- tation of the ducts with biliary matters, inflammation around them, and hyperplasia of the hepatic connective tissues, with associated atrophy of the liver-cells. 238. .Distoma lanceolatum is only 8 or 9 mm. long and 2 to 2.5 mm. broad. It is lancet-shaped, and the head-end does not markedly project. The integument is naked. The two lobulated testes lie close behind the posterior disc and in front of the ovary and uterus ; the coils of the lat- Fig. 101.-Distoma Lanceolatum, with its Internal Organs, x 100. (From Leuckart.) PARASITES. 343 ter are seen through the transparent body-walls. The more anterior coils, which are filled with eggs, look black, the remaining coils are russet- colored. The yellowish-white ovaries lie about the middle of the lateral margin. The eggs (Fig. 102) are 0.04 mm. long. The embryo is visible in Fig. 102.-Eggs of Distoma Lanceolatum shortly after the Shell is formed, x 400. (From Leuckart.) them before they have left the uterus, but it only escapes some weeks after they are deposited. Jis metamorphoses are unknown. This fluke, like the other, infests the biliary ducts, but it is rarely found in man. It is commonest in sheep and cattle, but as it is usually present in small numbers, it rarely gives rise to any grave disturbances of health. 239. Distoma, haematobium, or Bilharzia, haematobia (Fig. 103), is a species of fluke in which the sexes are distinct. The oral and ventral discs are close to each other, and the fore-end of the body is slender. The sexual orifice in each sex lies just behind the ventral disc. The male is 12-14 mm. long. The body is flattened, but its posterior part is rolled laterally into a kind of tube or gynaecophoric canal (Fig. 103) into which the female is received. The female is 16-19 mm. long and almost cylin- drical in form. The eggs are prolate (Fig. 104) and 0.12 mm. long. They are furnished with a spine which may be either terminal or lateral. Fig. 103.-Distoma Hiematobium, Male and Female, the latter within the Gynaecophoric Canal of the former, x 10. (From Leuckart.) Fig. 104.-Eggs of Distoma Haematobium, x 150. (From Leuckart.) a, with terminal spine with lateral spine. Fig. 103. Fig. 104. These worms are found in the branches and main stem of the portal vein, in the splenic vein, in the mesenteric veins, and in the vessels of the rectum and bladder. They feed on the blood, and infest man and the monkey. They are very common in Egypt and Abyssinia, the Cape, 344 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. and Natal, where they give rise to the disease known as "endemic hae- maturia." The cercaria abound in canals and rivers, and gain access to the body in drinking-water. The embryos mature quickly and permeate the mucous and submucous coats of the ureters, bladder, and rectum, and occasionally the substance of the liver. They set up inflammation of the bladder and ureters, associated with ulcerations, incrustations, and concretions. Haematuria is always produced. Cylindrical ciliated em- bryos may develop within the urinary tract. [References: Griesinger, "Arch. f. phys. Heilk.," xiii., 1854 ; Bil- harz, " Wien. med. Woch.," 4 and 5, 1856, and JBrit. and For. Aled.- Chir. Rev., 1856-58 ; Sonsino, "Arch. gen. de med.," 1876; Cobbold, "Para- sites," 1879 ; Guillemard, " Endemic Haematuria," London, 1882.] 240. Cestoda. The cestoids, or tape-worms, are flat compound " worms," destitute of a mouth or alimentary canal. They multiply by gemmation from a pyriform " head " or " nurse." The budded individu- als or segments remain for a long time connected with the head, forming a jointed chain. The several members {proglottides) of this colony are hermaphrodite. The older segments increase in size as they are gradu- ally pushed away from the place at which they were formed by the con- stant development of new segments. In other respects they resemble each other exactly ; while the head is distinguished by possessing two or four suckers or oscula, and generally a circlet of claw-like hooks. By means of these the tape-worm fastens itself to the intestinal wall of its host, which is probably always a vertebrate. The head develops from a rounded embryo having four to six booklets. These embryos {proscolices, hydatids) are found in the various parenchymatous organs of the inter- mediate host ; and thence by what we may call passive migration they reach the intestine of their final host. The cestoids parasitic on man belong to the families of Tceniada and Bothriocephalida. The former infest man both as hydatids and as tape- worms ; the latter only as tape-worms. [The development of the Cestoda is exhaustively treated in the hand- some work of Hein, " Die parasitaren Krankheiten des Menschen," 1882 ; see also Davaine, "Les Cestoides : " "Diet. ency. sciences med.," 1874; Cobbold, "Tapeworms," 1874.J 241. Tosnia solium when fully developed is two to three metres long. The head (Fig. 105, A) is the size of a small pin-head ; it is globular and the suckers project somewhat. The vertex is not uncommonly pig- mented, and is surrounded with a pretty large rostellum or circlet of some twenty-six hooks (Fig. 105, JB). The hooks are short, broad, and appressed, with a small projection at the root. The head is followed by a filiform neck an inch or so in length. At a certain dis- PARASITES. 345 tance from the head the joints begin to be traceable. The first joints are very short, the more advanced ones are longer (Fig. 106) ; they then become square, and finally the length is greater than the breadth. About 130 ctm. beyond the head the mature segments begin, though the sexual organs have been fully developed in earlier segments. The ripe segments (Fig. 107) are 9-10 mm. long and 6-7 mm. broad; their corners are rounded off. The genital opening lies at the side, somewhat behind the middle. The ovary has seven to ten lateral branches, separated by considerable intervals; each branch breaks up into a series of dendritic ramifications. The ovary is filled with eggs. The parenchyma of the body, both in ripe and unripe segments, is divisible into a peripheral and a central layer. The central layer contains the generative organs and the Fig. 105.-A, head of Tania Solium, with rostellum protruded, x 50. (Carmine staining; mounted in Canada balsam.) Ji, circlet of hooks magnified. (Leuckart.) water-vascular system. The latter is an excretory apparatus ; it takes the form of two lateral canals running along the margins of the entire chain of segments, and connected by cross-canals at both ends of each segment. Fine ramifications pass from these into the parenchyma. The male and female sexual organs lie close to each other. The tes- tis is a clear or whitish convoluted tube with vesicles, lying in the fore- part of the segment. It passes into the vas deferens, and this into a cirrus or retractile extremity, which is rolled up within a muscular pouch or cloaca at the middle of the lateral margin. The cirrus can be everted and protruded through the genital orifice. The opening of the female organ lies close behind the male opening in the same genital cloaca. From this the vagina passes backward toward the hinder border of the segment. Before reaching the border it communicates with a copulative 346 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. sac or receptaculum seminis, and receives the duct of the germ-bearing organ or true ovary. Then turning forward it passes into an oviduct, into which opens the duct of the so-called vitelligenous organs. The entire ovigenous organ (which must be studied in unripe segments) is thus made up of an unpaired germ-bearing portion or true ovary, and a pair of yolk-bearing or vitelligenous glands, all lying in the hinder part of the segment. The oviduct having received the ducts of these glands passes then into the dilated matrix or uterus, which in sexually mature segments forms a simple straight tube. The egg-germs, leaving the true ovary, become impregnated by spermatozoa from the seminal receptacle, and passing onward are invested with yolk-substance from the vitelli- genous glands. Being then complete ova they pass into the uterus, Fig. 106.-Immature and Mature Proglottides. Natural size. (From Leuckart.) Fig. 107.-Two Proglottides, showing the Uterus, x 2. (From Leuckart.) Fig. 106. Fig. 107. which as it gradually fills throws out the numerous lateral caeca charac- teristic of the ripe segment. As this happens the other generative or- gans gradually disappear. The peripheral layer is essentially muscular, but it contains a greater or less number of calcareous granules. These, indeed, are not entirely absent in the central layer. The muscular tissue is made up of non- striated fibres ; in the neighborhood of the sucking-discs of the head they form peculiar bunches or groups. The surface of the tape-worm is covered with a transparent cuticle, from which the booklets of the head are developed. 242. The egg-germs, as they leave the ovary, are pale, thin-walled, spherical cells. In the oviduct they are transformed into yellowish glob- ules, which become covered over with a somewhat opaque envelope or shell thickly beset with minute spicula (Fig. 108, a). It is frequently found to be invested by a second covering (b), made up of an albuminous PARASITES. 347 layer with granules, and enclosed in a fine membrane (primitive vitelline membrane). Without this envelope the egg is 0.03 mm. in diameter. With the second envelope the egg already contains the partly developed embryo, whose six booklets can be distinguished. Thus the embryonic development begins within the uterus ; the ripe segments are in fact viviparous animals. The further development of these embryos, which are now enclosed in a brownish envelope, does not take place within the body of the orig- inal host ; they must pass into a new one. When they reach the stom- ach of a pig, the envelope is dissolved, and the liberated embryo bores its way into the wall of stomach or intestine. Thence it migrates, either by way of the vessels or directly, into one or other of the organs. When at last it settles, it passes through various metamorphoses, and at the end of two or three months is transformed into a vesicle filled with serum (Fig. 109), from the inner surface of the wall of which springs a new head or scolex, enveloped in a second membrane or receptaculum scolicis. Fig. 108.-Eggs of Taenia Solium, x 300. (From Leuckart.) a, without the primitive vitelline mem- brane ; &, with it. Fig. 109.-Cysticercus Cellulosae, with the head and its membrane. Natural size. (From Leuckart.) Fig. 108. Fig. 109. This cyst or vesicle containing the head of the tape-worm is called a " measle " or cysticercus celluloses. The scolices have already their circlet of hooks, sucking-discs, water-vascular system, and calcareous granules. If the scolex reaches the stomach of a man, the cyst-membrane is dis- solved, and from the scolex is developed a chain of proglottides, forming a new tape-worm. 243. Tesnia solium inhabits the small intestine of man, and is acquired by eating ill-cooked pork. The corresponding measle is found in man and in the pig exclusively, or nearly so. In the intestine the worm is generally solitary, but cases in which two or more have co-existed are not very rare. In some instances from thirty to forty have been found in one person. The tape-worm gives rise to irritation of the mucous membrane, colic, and reflex nervous disturbances. The measle or cysticercus also occurs in man, as we have already indi- cated. It is found in the most various tissues, in the muscles, brain, eye, skin, etc. Its pathological significance depends on its seat ; but it is usually slight. Even in the brain it does not always give rise to serious consequences. It excites a local inflammation which induces a fibrous thickening of the tissues round the cyst. It maintains its vitality for 348 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. years. After the death of the scolex the cyst shrinks, and chalky masses are deposited within its cavity. The booklets may be found long after- ward. Cystic infection depends necessarily on the introduction of eggs or proglottides into the stomach. Fig. 111. Fig. 110.-Fragments of a Taenia Saginata. Natural size. (From Leuckart.) Fig. 111.-Head of Taenia Saginata Retracted, with Dark Pigment in and between the Sucking-discs, x 30. (Unstained glycerine preparation.) Fig. 112.-Segment of Taenia Saginata. x 1%. (From Leuckart.) Fig. 110. Fig. 112. [ Cysticercus racemosus is a measle of the brain. It is distinguished by the fact that it remains sterile and forms grape-like bunches of vesi- cles (Heller, " Ziemssen's Cyclopasdia," vol. iii.; Zenker, "Henle's Bei- trage," Bonn, 1882). Abnormalities of development are very often observed in individual tape-worms.] PARASITES. 349 244. Toenia mediocanellata or saginata exceeds T. solium not only in length (it may reach four metres) but in width and thickness, as well as in the size of the separate proglottides (Fig. 110, p. 348). The head (Fig. Ill) has neither booklets nor rostellum. Its vertex is smooth and furnished with four large sucking-discs, usually surrounded with a dark pigmented border. The eggs are like those of T. solium. The uterus (Fig. 112) has a large number of lateral diverticula, running close to each other and branching dichotomously, not like T. solium in dendritic ramifications. The genital opening lies below the middle of the lateral margin. The segments which break loose are generally empty of eggs. The corresponding cysticerci infest the muscles and organs of cattle. The development follows the same course as in the case of T. solium. Malformations of the worm are very frequently observed. Man acquires this tape-worm by eating uncooked beef. It is more widely diffused than T. solium. [Taenia cucumerina or elliptica is fifteen to twenty ctm. long ; its head has a circlet of hooks and a rostellum. It is often found in cats and dogs, rarely in man. Its cysticercus infests the dog-louse. Taenia nana is a small tape-worm fifteen mm. in length ; its head has four sucking-discs and a circlet of hooks. It has been found in Egypt. The frequent malformations to which Taenia is subject have led to the multiplication of species, or rather of spe- cific names. Many of these refer to what are at best mere varieties.] 245. Taenia echinococcus inhabits the intestine of the dog. It is 4 mm. long, and possesses only four segments, of which the last is larger than all the rest of the body (Fig. 113). The booklets have a blunt process at the base, and are seated on a somewhat prominent rostellum. There are some thirty or forty of them. Only the cystic form or hydatid is known to occur in man ; he acquires it by the introduction of the eggs into the alimentary canal. When the embryo migrates from the intestine to some other organ, it is transformed into a cyst incapable of active motion. The hydatid cyst consists of an ex- ternal lamellar highly elastic cuticle, and an internal lining of body-par- enchyma consisting of granular matter, cells, muscle-fibres, and a vascular system. When the cyst reaches the size of a walnut (or in some cases sooner) it begins to develop from the parenchymatous layer a series of smaller vesicles (brood-capsules). The wall of these is likewise twofold ; but the cuticular layer is within and the parenchymatous layer without. Fig. 113. -Full- grown Taania Echi- nococcus. x 12. (From Leuckart.) 350 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. On these brood-capsules develop numbers of heads or scolices (Fig. 114). According to Leuckart they are formed out of sacculated outgrowths from the external wall of the capsules (see the left side of Fig. 114). When the rudimentary head has become fully developed into a scolex (sometimes even sooner), it is retracted within the cyst, which it thereby invaginates (Fig. 114). What was before the internal or cuticular surface of the head now becomes the outer surface. The original outer surfaces, which are parenchymatous, come now into contact and adhere to each other. The head is then about 0.3 mm. long, and has a rostellum with tiny blunt booklets, four sucking-discs, a water-vascular system, and nu- merous calcareous granules in its parenchyma. The fore-part of the body is often invaginated within the hind-part. Fig. 114.-Brood-capsules of Echinococcus in connection with the Parenchymatous Layer of the Cyst, x 50 circa. (From Leuckart.) Some of the capsules are closed, some have been burst open in making the preparation. In many cases these echinococcus-cysts remain single. The only change they undergo is that they grow larger as fresh capsules and sco- lices are formed, so that they at length reach the size of a big orange, or of the closed fist. The surrounding tissues form, by condensation and thickening, a pseudo-cyst round the cuticular membrane. The cavity of the cyst is filled with clear liquid, which is not coagulable by heat or acid. The brood-capsules are always seated on the inner surface, unless they are shaken loose mechanically. They appear as small white points lying in the transparent parenchyma. Occasionally the cyst may remain alto- gether sterile. 246. In many cases " daughter-cysts " are formed. They develop in the thickness of the cuticle independently of the proper parenchymatous layer. Between two lamellae of the cuticle is formed an aggregation of granules which becomes surrounded with a secondary cuticle. This forms the starting-point of a new series of layers. As the layers multiply the inner cavity increases in size and its contents at length become clear and liquid. As the daughter-cyst grows it forces out the wall of the parent cyst like a hernial sac, until it at length gives way and sets the daughter-cyst free. Escaping thus into the tissues round the parent cyst it receives from them an external fibrous envelope, and proceeds to de- velop brood-capsules in the same way as the primary cyst derived from the six-hooked embryo. PARASITES. 351 An echinococcus which is thus reproduced exogenously is called Echinococcus granulosus or scolecipariens (Kiichenmeister). It is also described as E. veterinorum, as it often occurs in domestic animals. A second compound echinococcus is the E. hydatidosus. It is char- acterized by the formation of internal daughter-cysts. Naunyn (" Dor- pat. med. Zeitsch.," 1870) asserts, and Leuckart agrees with him, that the scolices and brood-capsules may undergo a cystic transformation, and so become daughter-cysts. Naunyn goes on to say that these endogenous daughter-cysts may migrate from the parent cyst and so produce the E. granulosus ; but this Leuckart disputes. The internal daughter-cysts sometimes develop daughters of their own or " granddaughter-cysts." Each of the cystic forms of which mention has been made may reach to a very considerable size. 247. The third form, or Echinococcus multilocularis, only forms small cysts, from the size of a millet-seed to that of a pea. They are always present in very large numbers. The E. multilocxdaris appears as a hard tumor, seated in the liver. It is built up of a multitude of alveoli separated by dense scar-like fibrous tissue. The contents are transparent and jelly-like or semi-fluid. The alveoli are spherical or irregular in form. Here and there the tissues may have softened and broken down, and thus ulcerated cavities are formed. In other places the vesicles are shrunken and calcified, or the tissues are bile-stained. The distinct alveolar texture of the growth led to its being regarded as a tumor, and it was described as alveolar colloid of the liver. Virchow ("Verb. d. phys. med. Ges. zu Wurzburg," vi., 1855) was the first to make out its real nature, and he showed that the colloid masses were made up of echinococcus-cysts. The smallest vesicles merely contain granular matter, the larger contain liquid. The granular pseudo- parenchymatous covering of the cuticle seldom contains scolices, most of the cysts being sterile. E. multilocularis is possibly an abnormal variety or sport " from the exogenous form. [References : Virchow, "Virch. Arch.," vol. vi. ; Leuckart, " Parasi- ten," vol. i ; Klebs, " Handb. d. path. Anat.;" Bollinger, "Deutsche Zeitsch. f. Thiermed.," ii., 1875 ; Proujeansky, "Die multiloculare Echin- ococcusgeschwulst," In. Diss., Zurich, 1873; Morin, "Deux cas de tumeurs a echinocoques," In. Diss., Berne, 1875 ; Huber, "Arch. f. klin. Med.," i., iv., v., xxix.; Waldstein ("Virch. Arch.," vol. Ixxxiii., with beautiful illustra- tions) brings forward evidence to show that the dissemination of the ech- inococcus may be effected through the lymphatics of the liver. He gives full references to previous memoirs.] 248.' The occurrence of hydatids in man implies that the eggs of the corresponding canine tape-worm have somehow gained access to his body. The liver is the commonest seat, but hydatids are found in all organs. 352 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. Apart from the local inflammation and fibrous hyperplasia they induce, they often cause no trouble to the patient. When a hydatid reaches a certain size, it sometimes dies and the cyst shrivels up. Its contents are changed to a fatty or cheesy mass, often becoming mortar- like as it calcifies. The hooks remain for a long time unchanged. In other cases the hydatid becomes larger, especially when it forms exogenous or endoge- nous daughter-cysts. It may then become dangerous by its mere size. Sometimes if the cyst is wounded or bursts, its contents pass into one or other of the body-cavities and set up severe inflammation. It may even break into a blood-vessel. In the most favorable case it breaks into the intestine or upon the exterior of the body. The Echinococci are widely diffused, but not very frequent ; they are commonest in Ice- land, where the inhabitants are in constant con- tact with their dogs. It is somewhat surpris- ing that the multilocular variety is chiefly ob- served in Switzerland and Southern Germany. [Neisser gives a summary of the various cases of hydatids that have been published ("Die Echinococcus-krankheit," Berlin, 1877). See also Peris, "Handb. d. allg. Path.," ii.] 249. Bothriocephalus latus is the largest of human tape-worms. It measures five to eight metres in length, and' consists of three to four thousand short wide segments (Fig. 115). The largest segment is about 3.5 mm. long and 10 to 12 mm. broad. Toward the "tail" the breadth diminishes and the length increases. The body is thin and flattened like a ribbon. The central part of each segment projects somewhat ; it is here that the uterus lies, in the form of a simple tube coiled into numerous convo- lutions. When this is full of eggs the coils lie in contiguous loops, forming a kind of rosette. The genital openings are in the mesial line of the ventral surface, somewhat anteriorly ; the female opening being- close behind the male. The testis consists of a series of sacculations lying along the lateral margins of the central layer of the body. The general structure of the body resembles that of the Tceniada. Fig. 115.-Fragments of a Bothrio- cephalus Latus. Natural size. (From Leuckart.) PARASITES. 353 Anteriorly the worm becomes gradually more and more slender and at length thread-like. The head, which is 2.5 mm. long and 1 mm. broad, is club-shaped or oval in outline, and somewhat flattened. Along each lateral margin is a chink-like suctorial groove. The eggs (Fig. 116) are oval ; they measure 0.07 mm. by 0.045 mm. They have a thin brown shell furnished at the an- terior pole with a lid or cap, which is in general easily seen. J?, latus occurs chieflv in Switzerland and in the northeast of Europe ; it is occasionally met with in Ireland. It lives like the Tseniada, in the small in- testine. The first development of the eggs takes place in water. After some months an embryo is hatched, which is provided with six booklets and a ciliated cuticle. This enters the body of the pike, the trout, or the eel- pout {Lota vulgaris} (Braun, " Virch. Arch.," vol. Ixxxviii.), and de- velops in the muscles or viscera into an asexual tape-worm. If it thence reach the alimentary canal of man, it proceeds to develop further and becomes sexually mature. Fig. 116.-Eggs of Both- riocephalus Laius. (Leuck- art.) One is emptied of its contents and shows the lid. [It has been maintained that R. lotus represents the mature form of the cestoid of the trout, known as Ligula nodosa. See Duchamp, "Les Ligules," Paris, 1876 ; Kiessling, "Troschel's Arch.," 1882. , In Greenland another form, R. cordatus, occurs. It is only one metre long and has a heart-shaped head. R. cristatus, two to three metres long, with a crest-like rostellum, has been found in France.] Protozoa. 250. Protozoa are not rarely found in the cavities of the body acces- sible from without, such as the mouth, lungs, intestine, vagina, etc.; they are most common in patients suffering from chronic disease. The forms observed belong to the Rhizopoda, Infusoria, and Psorospermia or Sporozoa, respectively. Of parasitic Amoebae one species only has been described, the Amoeba coll. It occurs in the intestine, and is simply a motile cell with a granu- lar protoplasm containing a nucleus and several vacuoles. [Lbsch and Sonsino found the Amoeba coli in the dejections of a pa- tient suffering from dysentery.] Among Infusoria the Ciliata and the Flagellata are represented. Paramoecium (or Balantidium) coli is a large ciliated organism occa- sionally met with in the large intestine and in the faeces. Cercomonas intestinalis (Davaine) is a pvriform infusorian, with a spine-like process 23 354 A TEXT-BOOK OF PATHOLOGICAL ANATOMY. at its smaller end and a flagellum at its larger end. It is found in the intestine in cases of catarrh, of typhoid, and of cholera. Kannenberg discovered Cercomonas in the sputa from a patient affected with gan- grene of the lungs. In the same sputa he also found Monas lens, a spherical flagellate infusorian. Trichomonas is another flagellate infu- sorian ; it is oval in shape and provided with a comb-like row of cilia. One species (71 vaginalis) is found in the vagina, another (T. intestina- lis) in the intestine. These protozoa are not to be regarded as the exciting cause of the affections with which they are associated. They may possibly, however, maintain or intensify the morbid processes, when present in considerable numbers. Of parasitic Psorospermia we have here to mention the Coccidia. According to Leuckart, they are when young simple non-capsulated in- habitants of the epithelial cells. When they reach maturity they become invested with a kind of membranous capsule. In this condition they leave their first lodg- ing, and generally their host at the same time. Their contents are then transformed into "spores" containing granular masses and peculiar rod-like embryonic forms. The spores are round or ovoid. Coccidi- um oviforme (Fig. 117) is a parasite of the intestine and bile - ducts, especially those of the rabbit. In a few cases it has been found in the human subject. It leads in the liver of the rabbit to the formation of whitish nodules, which may be as large as a hazel-nut. The nodules consist of a puriform or cheesy mass, containing multitudes of coccidia. The granular contents of the coccidium are uniformly spread throughout its body, or rolled into a ball in the middle of it. The changes produced in the human liver by the presence of the parasite, in the few cases observed, have been similar to those met with in the rabbit. Our knowledge of the organisms known as " Miescher's cylinders" or "Rainey's corpuscles " is still very defective. They are cylindrical or tube-like bodies, found not infrequently in the muscles of the pig, ox, sheep, and mouse. They contain an innumerable multitude of small oval or reniform corpuscles. Nothing is known of their effect on the human system. Fig. 117.-Coccidia, from the human liver, c is magnified 300-fold; b and c, 1000-fold. (From Leuckart.) [References to memoirs on Coccidia and Psorospermia generally : Leuckart, " Die Parasiten des Menschen," second edition ; Lieberkuhn, "Arch. f. Anat. u. Phys.," 1854 ; Eimer, " Ueber die ei- oder kugelfbr- migen Psorospermien der Wirbelthiere," Wurzburg, 1870 ; Klebs, " Virch. Arch.,''vol. xxxii.; Stieda, "Ueb. die Psorospermien d. Kaninchenleber PARASITES. 355 "Virch. Arch.," vol. xxxii.; Waldenburg, ibidem, vol. xl.; Rivolta, "Dei parasiti vegetali," Turin, 1873. According to our present information the parasitic protozoa take no important share in the production of human disease. It is, however, not impossible that further research may considerably alter our views in this regard. This is perhaps suggested by the fact that animal parasites are every now and then detected in the blood of vertebrate animals. Thus Rattig (" In. Diss.," Berlin, 1875) describes a ciiiated infusorian in frog's blood. Klebs ("Eulenburg's Realencyclop.," Art. " Flagellata ") has found in the blood of scurvy-patients very minute organisms, which he refers to the Infusoria and names Cercomonas globulus and C. navicula. Lieberkuhn ("Ueb. Bewegung. d. Zellen," Marburg, 1870) found an amoeba (A. rotatoria) in frog's blood. Lewis (Quart. Journ. Micros. Science, xix., 1879) found in rat's blood, and Wittich (" Centralb f. med. Wiss.," iv., 1881) in hamster's blood, a mobile organism resembling the spermatozoon of the frog. Koch (" Mitth. a. d. k. Gesundh.," Berlin, 1881) describes a fusiform granular-looking structure with one or two flagella found in hamster's blood. He regards it as a flagellate infusorian.] INDEX OF AUTHORS CITED. {The numbers refer to the articles.) Abelin, 10 Ackermann, 7 Adams, 11 Addison, 96 Ahlfeld, 1, 5, 9, 12, 13, 179 Albrecht, 206 Anderson, 18 Andral, 94 Anger, 152 Appert, 96 Arloing, 206 Armauer-Hansen, 117, 131, 185, 206 Arndt, 63 Arnold, 13, 27, 74, 84, 86, 89, 97 Arnstein, 152 Aufrecht, 85, 108, 127, 206 Auspitz, 128 Boser, 196 Bostrom, 153 Bottcher, 79, 99, 108 Bouley, 201 Bowman, 94 Bozzolo, 231 Braidwood, 204 Brauell, 206 Braun, 249 Braune, 13 Brefeld, 186, 212, 215, 217, 219, 223 Brieger, 191, 192, 197, 201, 204 Bristowe, 153 Brodowski, 109, 153 Briicke, 94 Bruns, 154 Buchholtz, 190 Buchner, 186, 190, 193, 201, 209, 211 Budge, 94 Bugnion, 231 Buhl, 9, 11, 120, 206 Burkhard, 84 Burow, 61 Busch, 18, 88 Butlm, 165 v. Baer, 11 Baillie, 118 Baker-Brown, 10 Balfour, 74, 75, 86, 89 Ballarl, 206 Bambeke, 10 Bancroft, 235 Barbieri, 54 Barth, 235 Bary (de), 216, 220 Bauer, 52 Baumgarten, 8, 108, 127 Biiumler, 128 Bayle, 118 v. Becker, 61 Bence Jones, 52 Bergmann, 191, 197, 201 Bezold, 221 Bilharz, 231, 239 Billroth, 86, 109, 149. 156, 159, 161, 163, 171, 183, 184, 185, 209 Binz, 52 Birch-Hirschfeld, 69, 204, 206, 209 Bizzozero, 35, 81, 108, 114, 156 Blix, 10 Block, 222 Bogehold, 177 Bohm, 13 Boll, 177 Bollinger, 125, 127, 133, 134, 135, 197, 206, 221, 247 Caton, 96 Carter, 201, 207, 222 Cayley, 31 Ceci, 193 Chamberland, 188 Charcot, 28 Chauveau, 42, 125, 127, 201 Cheyne, 201, 204 Chiari, 179 Christoph, 145 Cienkowsky, 223 Claudius, 13 Clelland, 5 Cobbold, 226, 228, 233, 234, 235, 239, 240 Cohn, 183, 184, 185, 186, 189, 191, 192, 211 Cohnheim, 18, 19. 21, 22, 25, 27, 30, 38, 36, 47, 62, 79, 80, 84, 94, 95, 97, 99, 117, 119, 125, 136, 140, 153, 177, 179, 180, 221 Colin, 127, 201 Cordua, 68 Cornevin, 206 358 INDEX OF AUTHORS CITED. Cornil, 58, 66, 76, 84, 120, 128, 156, 206 Courty, 153 Coze, 204, 211 Creighton, 127, 174 Cuboni, 206 Cullen, 94 Cunningham, 74, 193, 222 Curling, 18 Curnow, 31 Czerny, 154 Gaffky, 189, 204, 205, 206, 209, 211 Galen, 93 Gamgee, 35, 54, 68 Gannet, 135 Gartner, 190 Gaule, 120 Gautier, 191 Geddes, 207 Gee, 120 Gerlach, 5, 17, 127 Gibbes, 127, 206 Giorgewic, 152 Glax, 97 Glazier, 233 Gluge, 112 Golubew, 86 Goodsir, 87, 94, 174 Gordon, 178 Grancher, 118 Grassi, 231 Grawitz, 11. 214, 219, 222, 223, 224 Greenfield, 130, 204. 206 Griesinger, 231^ 239 Griffine, 84 Grohe, 219, 222 Gruber, 10, 11, 75 Guillebeau, 37 Guillemard, 239 Gull, 63 Giimher, 127 Guilt, 1, 5 Gussenbauer, 67, 174 Dallinger, 185 Danzel, 178 Dareste, 3, 7, 10 Davaine, 204, 206, 209, 226, 230, 231, 234, 235, 240, 250 Day, 31 De la Croix, 190 Demme, 42 Depaul, 13 Dickinson, 58, 62 Dittmer, 5 Donitz, 5 Drasch, 74 Drysdale, 185 Duchamp, 249 Dudaux, 191, 201, 219 Duzan, 179 Eberth, 56, 59. 74, 79, 84, 87, 99, 153, 204, 206 Ebstein, 28 Ecker, 17 Ehrlich, 127 Eidam, 189 Eimer, 55, 250 Eisenmann, 94 Emmert, 94 Engelmann, 190 Eppinger, 63, 161, 204 Etard, 191 Ewart, 184, 186, 189, 204, 207 Ewetzky, 87, 108, 163 Haab, 204 Haberkorn, 185 Haff ter, 178 Haller, 3. 94 Hallier, 185, 186, 218 Hall wachs, 115 Hamilton, 27, 96, 108, 120 Hamlet, 190 Harms, 127 Hartig, 220 Hasse, 180 Hayem, 35 Hebra, 152 Hegar, 115 Heidenhain, 108, 115 Hein, 240 TTaima Qzt Heller, 226, 229, 233, 243 Henle, 94 Hennings, 62 Heppel, 61 Hering, 27, 97, 120 Hermann, 52 Hertwig, 89 Heschl, 59, 178 Heubner, 130 Heusinger, 8 Heydenreich, 207 Hickmann, 11 Hill, 31 Hiller, 191, 197, 201, 223, 226, 233 Hink, 135 Fagge, 62 Fehleisen, 204 Feltz, 125, 204 Fischer, 18 Fiscbl, 206 Fitz, 211, 219 Fleming, 133 Flemming, 46, 74, 75, 84 Foerster, 1, 4, 5, 7, 10, 13 Fokker, 209 Formad, 204 Fox (Wilson), 125, 178 Fraenkel, 125 Friedberg, 18 Friedlander, 204, 206 Friedreich, 18, 58, 59, 61, 221 Frisch, 199 Fronista, 174 Fuerst, 3 Furbringer, 221 INDEX OF AUTHORS CITED. 359 Hirsch, 125, 146 Hoffman, F. A., 94, 96 Hoppe-Seyler, 52, 96, 191 Horwath, 190 Houston, 13 Huber, 153, 162, 206, 247 Hueter, 11, 204 Hunter, 94 Laycock, 67 Lebedeff, 9 Leber, 61, 219, 221 Lebert, 125, 173, 178 Legg, 28 Leichtenstern, 17 Leopold, 140, 179 Letzerich, 204 Leube, 194, 206 Leuckart. 225, 226, 228, 231, 233, 234, 235, 245, 246, 247, 250 Lewin, 52 Lewis, 222, 235, 250 Lichtheim, 25, 219, 221 Lieberkuhn, 250 Liebermann, 231 Liebig, 190 Lippe', 125 Lister. 94, 97, 185, 186, 194 Litten, 30, 37, 64 Little, 18 Lockwood, 9 Loffler, 189, 201, 219 Long, 231 Lowne, 1 Lubbock, 94 Lubimoff, 63, 120 Lucae, 161 Lucas, 18 Liicke, 136, 149, 171, 173, 178, 204 Ludwig, 55 Lukkornsky, 204 Liitkemdller, 13 Immermann, 28 Israel, 134, 135 Jeiin, 28 Jensen, 3 Johne, 35 Joubert, 188 Julliard, 10 Jurgens, 29 Kannenberg, 249 Kaposi, 152 Kassowitz, 87, 88 Kaufmann, 219 Keating, 204 Keber, 204 Kekule, 58 Kern, 186 Kessler, 18 Key, 79, 99 Kiener, 125 Kiessling, 249 Kitt, 221 Klebs, 84. 117, 125, 127, 128, 145, 161, 174, 178, 183, 184, 185, 186, 188, 201, 204, 206, 209, 226, 247, 250 Klein, 63, 74, 76. 86, 119, 120, 125, 186, 206, 209, 211 Klemensiewicz, 97 Kobner, 131 Koch. 94, 117. 120, 125, 127, 183, 184, 185, 186, 188, 189, 190, 193, 196, 199, 201, 204, 206, 208, 209, 211, 219, 222, 250 Kocher, 153, 171, 177, 204 Kohlrausch, 178 Koiaczek, 161 Kolhker. 5, 7, 88, 115 Konig, 11 Koster, 119, 120, 143, 163, 171, 204 Kraske. 89 Kronlein, 11, 177 Kiichenmeister, 221, 226, 246 K ihne, 58, 69 Kunkel. 67, 68, 69 Kuss, 107 Kussmaul, 206 Kyber, 58, 61, 62, 64 Maas, 88. 140, 179, 180 Macewen, 88 Maier, 152, 156, 161, 163, 204 Maizel, 74 Manson, 235 Maragliano, 206 Marchand, 5, 7, 153, 206 Marchiafava, 206 Martin, 74, 125, 126 Martini, 178 Maurer. 161 Mayer, 223 McConnell, 231 Meckel, 5, 8 Megnin, 231 Meier 136 Miquel, 193 Mitchell-Bruce, 17 Moczutkowsky, 207 Moleschott, 35 Monod. 18, 149 Montegazza, 35 Moore, 181 Morin, 247 Moxon, 165, 174 Miiller, 127, 147, 165, 206, 226 Laennec, 118 Lancereaux. 130 Langhans 61, 67, 68, 82, 115, 119, 120, 125, 153 Lankester, 185 Lassar. 25. 96 Laveran, 206 Nageli. 186. 188. 190, 191, 192, 193. 2C1, 204. 209 , 211, 223 Nassiloff, 204 Naunyn, 246 360 INDEX OE AUTHORS CITED. Nauwerck, 204 Neelsen, 63 Neisser. 117, 131, 204, 2e6, 248 v. Nencki, 183, 184, 191, 194, 197 Nepveu. 204 Neumann, 8, 79, 85, 89, 161 Nieden, 152 Normand, 231 Reverdin, 84 Richard, 206 jRiess 204 RindOeisch, 42, 59 , 66, 76, 81, 84. 85, 86, 109, 114, 117, 119, 120, 125, 150, 165, 173, 174, 204 Rivolta, 250 Roberts, 190, 194 Rohrer, 179 Rokitansky, 58, 149 Rosenbach, 194 Rosenberger, 115, 196, 211 Rossbach, 196 Roszahegyi, 201 Roth, 9 Roustan, 125 Rudneff, 58 Rumler, 143 Ryneck, 97 Obermeyer, 207 Oellacher, 5 Oemler, 201 Oertel, 204 Oldham, 153 Oordt (Van), 128 Orth, 1, 8, 13, 69, 114, 125, 127, 204 Owen, 233 Pagenstecher, 331 Paget, 43, 71, 80, 86, 89, 94, 107, 136, 146, 147, 149, 165, 171, 173, 178, 181, 333 Pagliani, 331 Pannm, 3, 5, 7, 13, 178, 190, 197 Parona, 331 Pasteur, 183, 186, 188, 191, 301, 306, 309, 333 Paulizky, 61 Payne, 150 Peris, 1, 3, 7. 9, 13. 13. 68, 85, 153, 154, 156, 173, 174, 194, 199, 304, 336, 231, 348 Perroncito, 336, 361 Peters, 63 Pflug, 135 Pinner, 153 Poland. 133 Pollend er, 206 Ponfick, 81, 114, 135 Pospelow, 152 Prazmowski, 186, 188 Prou jeansky, 247 Priestley, 74 Piltz, 133 Sachs, 213, 215, 218, 220, 223 Salkowski, 191, 197 Samuel, 80, 94, 95, 96, 97 Sanderson (Burdon), 94, 95, 99, 119, 120, 125, 183, 186, 189 Sattler, 163 Schede, 8, 108 Schklarewsky, 27, 96 Schmidt, 35 Schmiedeberg, 191, 197 Schotte, 190 Schroeter, 191 Schron, 171 Schuller, 133 Schultze, 5 Schulz, 53 Schulze, 54 Schdppel, 119, 120, 127 Schiitzenberger, 223 Schweninger, 84, 125 Semmer, 196, 201, 304, 209 Senftleben, 108, 115 v. Siebold, 235 Simon, 94, 125, 174 Simpson, 14 Smith, 154 Sokolow, 156 Sonderegger, 231 Sonnenburg, 13 Sonsino, 239 Soyka, 154, 193 Spear, 206 Stein, 226 Sternberg, 194, 204, 206 Steudener, 88, 156 St. Hilaire (Geoffroy), 3, 5, 7 Stieda, 250 Stilling, 94 Strasburger, 74, 75, 76, 84 Strelzoff, 88 Stricker, 79, 86, 95, 99 Struck, 208 Struthers. 17 Suchard. 205 Sutton, 63 Quain, 52 Ranvier, 52, 66, 76, 84, 89, 120, 128,146, 156 Rattig, 250 Rauber, 5 Raynaud. 204 v. Recklinghausen, 63, 99, 154, 205 Redfern. 87 Reess, 219, 223 Rehn, 8 Reichel, 13, 153 Reid, 18 Reinhardt, 51 Reinke, 190 Remak, 76, 174, 178 Retzius, 79 Reuss, 96 INDEX OF AUTHORS CITED. 361 Tappeiner, 125 Thiersch, 109, 171, 181 Thoma, 95, 96, 97, 131 Thomas, 206 Tiegel, 185 v. Tieghem, 185, 186, 189 Tillmanns, 5, 11, 85, 108, 109, 115, 204 Tills, 85 Tizzoni, 204, 206 Tommasi-Crudeli, 204, 206 Toussaint, 201, 206 Traube, 101 Travers, 86 Trelat, 18 Trendelenburg, 204 Treves, 120 Turner, 17, 62 Tyndall, 193 Waldenburg, 118, 125, 250 Walder, 206 Waldeyer, 84, 161, 171, 173, 178, 204, 206 Waldstein, 247 Waller, 96 Wallis, 99 Wartman, 87 Wasserthal, 13 Weber, 86, 125 Wedl, 9 Wegner, 115, 120, 152 Weigert, 13, 36, 96, 123, 179, 204, 207 Weil, 174 Weissgerber, 194 Weicker, 17 Wendt, 161, 233 Wernich, 193, 201 209, 211 Wieger, 63 Wilks, 165, 181 Williams, 96, 153 Wilson, 125 v. Winiwarter, 97, 117 Winslow, 3 Wittich, 250 Wolff, 88, 177, 197, 201, 204, 209 Wolff hiigel, 189, 190 Wood, 204 Wooldridge, 35 Wucherer, 231 v. Wyss, 84, 108, 125, 206 Unna, 128 Urlichs, 209 Vacca, 95 Vacher, 204 Vallienne, 11 Valsuani, 11 Vandyke Carter, 222 Verneuil, 13, 154 ViHemin, 125, 133 Virchow, 5, 8, 13, 14, 30, 35, 48, 56, 58. 61, 62, 68, 72, 76, 77, 78, 80. 81, 84. 85' '87, 89, 90, 94, 114, 117, 118, 125, 127, 128, 131, 136, 138, 145, 146, 147, 149, 150, 152, 153, 154, 156, 165, 171, 177. 179, 201, 221, 233, 247 Vogel, 94 Vogt, 179 Voigt, 10 Voit, 52, 191, 201 Vrolik, 1 Yeo (Burney), 125 Youatt, 133 Zahn, 61, 140, 179 Zangger, 206 Zenker, 38, 153, 222, 229, 233, 243 Ziegler, 28, 37, 59, 61, 68, 85, 86, 88, 108, 109, 110, 115, 119, 120, 123, 140, 145, 150, 156, 173, 174, 179, 184, 193, 204 Ziilzer, 204 Ziirn, 226 Wagner, 56, 59, 62, 120, 128, 129, 206 INDEX OF SUBJECTS. fThe numbers refer to the articles.) Abra chins, 10 Abscess, 102, 116 metastatic, 116 Acardiacus, 13 Acarus folliculorum, 225 scabiei, 225 Achirus, 10 Achorion Schonleinii, 222 Acrania, 7 Actinomyces, 222 Actinomycosis, 134, 135. 222 Acute miliary tuberculosis, 123 Acute atrophy of the liver, 204 Adenocarcinoma, 169, 173 Adenoma, 166, 167 sqq Adipose tissue, growth of, 85 Adiposity, 50 2Ec'dium elatinum, 220 Aerobious fungi, 188, 206 Agnathia, 8 Agrotis segetum, 222 Air, bacteria in the, 193 Albuminoids, putrefaction of, 191, 192 Alcoholic fermentation, 212 set up by mucor, 219 set up by yeasts, 223 Algae, 212 Alternation in mould-fungi, 218 Alveolar colloid, 247 sarcoma, 161 Amelus, 10 Amoeba coli, 250 rotatoria, 250 Amputation, intra-uterine, 10 Amputational neuroma, 154 Amyloid concretions, 61 Amyloid degeneration, chap. xiii. results of. 60 seat of, 59, 62 Amyloid substance, nature of, 59, 62 reactions of, 58 Anaemic necrosis, 40 Anaemia, 19 collateral, 22 Anaerobious fungi, 188 Anasarca. 23 Anastomotic varix, 151 Anencephalia, 7 Aneurism by anastomosis, 151 Anchylostoma duodenale, 231 Angioma, 148 lymphatic, 152 congenital, 179 Angiosarcoma, plexifcrm, 161 myxomatodes, 163 Anguillula stercoralis (rhabditis), 231 Anomaly, congenital, 1 Anthrax (see Bacillus Anthracis), 199 symptomatic, 206 ' genesis of, 206 history of, 206 vaccination in, 201 Antheridium, 218 Aplasia of the limbs, 10 Apoplexy, 27 Aprosopia, 8 Apus, 10 Araohnida, 225 Argyrism, 70 Arsenic, causing fatty change, 52 Arteries, syphilis in, 130 Arthropcda, 225 sqq Ascaris lumbricoides, 228 mystax, 228 Ascites, 23 chylous, 31 Ascococcus, 185 Ascogonium, 216 Ascospore, 213, 216 Ascus, 216 Aspergillus glaucus, 216, 221 flavescens, etc., 219, 222 Atheromata (congenital!, 8 Atrophic proliferation, 46 Atrophy, active, 47 of inaction, 47 passive, 47 pigmentary, 45, 46 serous, 46 simple, 43, 45 trophoneurotic, 47 Attenuation of virus, 201, 211 Attraction theory of inflammation, 94 Autosite, 13 364 INDEX OF SUBJECTS. Bacillus amylobacter, 186 anthracis, 185, 186, 188, 190, 199, 206 transmutation of, 211 leprae, 131, 185, 186, 206 malarias, 185, 206 cedematis, 206 of typhoid, 206 subtilis, 185, 186, 211 tuberculosis, 120, 127, 186,- 206 (Fig. 80) detection of, 127 Bacon-liver, 57 Bacteria, chap. xxx. biology of, 188 sqq. classification of, 183 diffusion of, 193 effect of agitation on, 190 effect of heat on, 189 effect of light on, 190 effect of poisons on, 190 effect on nutrient liquid, 191 in air, soil, etc., 193 inflammation excited by, 198, 199 in health, 194 mutability of, 192, 208, 209, 211 non-path<'genous, 197 pathogenous, 195, 196, 198 specific nature of, 208, 209 textural changes caused by, 200 Bacterial action, theories of, 210 Bacterium lineola, 185, 205 subtile, 211 termo, 185, 189, 192, 2C5 Balantidium coli, 250 Bed-bug, 226 Bed-sores, 33 Bile-pigments, 69 Bilharzia haematobia, 239 Birds'-nest body, 172 Blastomycetes, 223 sqq. Bleeders. 28 Blood-pigments, 68 Blood-vessels, growth of new, 86 Blut^lAttchen, 35 Bones, growth of, 88 metaplasia of, 91 regeneration of, 88 Bothriocephalus cordatus, 240 crisfatus, 249 latus, 249 Botrytis bassiana, 222 "Bots," 226 Bovine tuberculosis, 127, 206 Bronzing, 67 Brood-capsules (echinococcus), 245 Brood-cells, 76 Cancer-cells, 170 Cancer-stroma, 170 Canker in cattle, 135 Capillaries, growth of, 86 Carcinoma, 166, 170 sqq. etiology of, 181 growth of, 171 metastases in, 174 varieties of, 173 Carpogonium, 216 Carrier-cells, 114 Cartilage, growth of, 87 metaplasia of, 91 Caseation, 39 after necrosis, 34 in tubercle, 118 Catarrh, 55 desquamative, 103 purulent, 102 serous, 102 Cavernous angioma, 150 metamorphosis, 150 Cells, division of, 74, 75 multiplication of, 80, 81 Cell-nests, 170, 172 Cellulitis, micrococci in, 204 Cercaria, 236, 239 Cercomonas, 250 Cestoda, 240 sqq. Chalky concretions, 65 Chancre, 128 Cheilognathopalatoschisis, 8 Chigoe or chigger, 226 Chionyphe, Carteri, 222 Chloroma, 162 Chlorosis, Egyptian, 231 Cholesteatoma, 161 Cholesterin, 54 Chondroma, 146 Chylous hydrothorax, 31, 235 ascites, 31 Chyluria, from filariae, 235 Cicatricial tissue, 82, 105 growth of, 108, 109 Cicatrix, after necrosis, 34 Ciliata, 250 Cimex lectuarius, 226 Cleft palate, 8 " Clegg," 226 Clostridium butyricum, 186, 188, 192 Cloudy swelling, 48 Club-foot, 11 Coagulative necrosis, 35, 36 Coccidium, 250 Coccobacteria, 185 Cohnheim's embryonic theory of tumors, 177 sqq. Colliquative necrosis, 40 Colloid degeneration, 56 Concentric globes, 172 Condyloma, 129 Congenital hypertrophy, 18 tumors, 178 Congestion, 21 Conidia, 213 Cachexia of tumor, 141 Cadaveric poison, 197 Calcaneus (talipes), 11 Calcareous deposits, 64, 65 Calcification, after necrosis, 34 Cancellous osteoma, 147 INDEX OF SUBJECTS. 365 Conidiophore, 215 Connective tissue, regeneration of, 85 metaplasia of, 91 Connective-tissue tumor, 138 Contagious disease, 202 evidence of organic na- ture of virus in, 203 Cordyceps militaris, 222 Cornea, mould-fungi on, 221 Crab-louse, 226 Craniopagus, 12 Craniorachischisis, 7 Cranioschisis, 7 Croupous exudation, 102 Culicida, 226 Cultivation of bacteria, 186, 211 Cuniculi in scabies, 225 Cyclopia, 7 Cyclops, host of Guinea-worm, 234 Cylindrical epithelial cancer, 173 Cylindroma, 163, 173 Cystadenoma, 168 Cysticercus cellulosae, 242, 244 racemosus, 243 Cystoma, 168 Cysts, 71 dermoid, 178 following necrosis, 34 Distoma haematobium, 239 hepaticum, 237 lanceolatum, 238 Dochmius duodenalis, 231 Dracontiasis, 234 Dracunculus medinensis, 234 Dropsical degeneration, 49 Dropsy, 23 Dry-rot, 220 Duplicitas anterior, 14 posterior, 15 Duplication of limbs, 17 mammary glands, 17 viscera, 17 Dwarfs, 6, 43 Ear, mould-fungi in the, 221 Eburnated osteoma, 147 Ecchondroses, 146 Ecchymoses, 26 Echinococcus cysts, 245 granulosus, 246 hydatidosus, 246 multilocularis, 247 scolecipariens, 246 taenia, 245 veterinorum, 246 Ectogenous virus, 203 Ectophytes, 182 Ectopia cordis, 9 (ecstrophia) vesicse, 9 Ectozoa, 182 Effusions, 26 Egyptian chlorosis, 231 Elephantiasis grascorum, 131 Embolic infarction, 37 Embolism, 29 Embryonic hypothesis, 177 sqq. tissue, 180 Empusa, 222 Encephalocele, 7 Encephaloid cancer, 173 Enchondroma, 146 Endocarditis, micrococci in, 204 Endogenous gemmation, 76 virus, 203 Endosporium, 215 Endothelioma, 161 Engastrius, 13 Engorgement. 21 Enostosis, 147 Entophytes, 182 Entozoa, 182 Epidermic globes, 172 Epigastrius, 13 Epignathus, 13 Epipygus, 13, 14 Epistaxis, 26 Epithelial tumors, 138, chap, xxvii. Epithelioid cells in granulations, 108 in tubercle, 119 Epithelioma,170, 172 Epithelium, growth of, 84 regeneration of, 84 Epizoa, 182 Daughter-cysts (echinococcus), 246 Davaine's septicaemia, 204 Decubitus, 33 Definitive inflammation, 34 Degeneration, amyloid, 57 colloid, 56 dropsical, 49 fatty, 50 hyaline, 63 "hyalin-fibrous," 63 lardaceous, 57 mucoid, 55 parenchymatous, 48 vitreous, 63 waxy, 38 Demarcation, line of, 34, 41, 115 Demodex, 255 Dermoid cysts, 71, 178 Desmobacteria, 183, 186, 206 Desquamative catarrh, 103 Development of blood-vessels, 86 Diapedesis, 27, 96 Dicephalus, 14 Diphtheria, coagulative necrosis in, 38 micrococci in, 204 Diphtheritic inflammation, 38, 103 Diplobacteria, 185 Diplococcus, 184, 185 Diprosopus, 14 Dipygus, 15 direct cell-division, 76 Disinfectants. 190 Disinfection by heat, 189 Disintegration, cysts of, 71 Dislocation, congenital, 11 Dispora Caucasica, 186 366 INDEX OF SUBJECTS. Equinus (pes), 11 Erectile tumors, 150 Erysipelas, micrococci in, 204 Eurotium aspergillus, 216, 2M Eustrongylus gigas, 231 Excitability of cells, 78 Exosporium, 215 Exostosis, 147 Extravasation, 26 cysts of, 71 Exudation-corpuscles, 112 Exudations, inflammatory, 96 re-absorption of, 112 varieties of, 102 Giant-cells, 76 in granulations, 108 in tubercle, 119 in syphilis, 128 Glanders, 133 Gliacoccus, 185 Glioma, 145 Gluge's corpuscles, 112 Gonorrhoea, 204 Gout, deposits in, 66 Granulation-tissue, 105 growth of, 108 Granule-carrying cells, 51 Granuloma, 117 Granulomata, infective, chap. xxiv. Guinea-worm, 234 Gumma, 129 Gummatous node, 130 Gynaecophoric canal, 239 False membrane, 35, 102 Farcy, 133 Fatty degeneration, chap. xi. cause of, 52 Fatty infiltration, 50, 53 Favus, 222 Fermentation (see Bacteria), 191, 223, 224 Fibrin, 35 Fibrinous exudation, 102 necrosis, 35, 36 Fibroblasts, 85 in granulations, 108, 109 Fibroid, uterine, 142, 153 Fibroma, 142 Fibromyoma, 153 Fibroplastic degeneration, 135 Fibrosarcoma, 157, 160 Fibrous tissue, growth of, 85 regeneration of, 85 Filaria medinensis, 234 Filaria sanguinis hominis, 235 Filobacteria, 186 Fissura abdominalis, 9 Fistula colli congenita, 8 Fixed tissue-cells in cicatrisation, 111 Flagellata, 250 Flea, 226 Flukes, 236 Foetus papyraceus, 13 Fomites, 202 , Foreign substances, re-absorption of, 113, 114, 115 Fowl-cholera, 201, 234 Fungi, classification of, 212 Fungous tumor, 137 Fungus disease of India, 222 Fur of the tongue, 221 ELematemests, 26 Haematin. 68 Haem ato Masts, 35 Haematocele, 26 Haematoidin, 68 Haematoma, 26 Haematometra, 26 Haematopota pluvialis, 226 Haematuria, 26 endemic, 239 from filariae, 235 Haemoglobin, 68 # Haemopericardium, 26 Haemophilia, 28 neonatorum, 28, 204 Haemoptoe or haemoptysis, 26 Haemorrhoids, 149 Haemothorax, 26 " Hard sore," 128 Hare-lip, 8 Hay-bacilli, transmutation of (see bacillus subtilis), 211 Head of tape-worm, 240 Hemicephalus, 7 Hemorrhage, 26 by rupture (apoplexy), 27 Hemorrhagic diathesis, 28 exudation, 102 infarct, 26 Hernia cerebri, 7 funis, 9 Heterologous tumor, 138 Heteroplasia, 83 Heteroplastic tumor, 138 Histioid tumor, 138 Homoeoplastic tumor, 138 Homologous tumor, 138 Hyaline degeneration, 63 necrosis, 35, 36 , " Hyalin fibrous " degeneration, 63 Hydatid, cyst, 245 , 248 Hydatids, 240, 245 Hydraemic plethora, 25 Hydrobilirubin, 68 Hydrocele colli, 8 Gad-flies, 226 Gangrene, dry, 41 moist, 42 Gangrenous emphysema, 42 Gastroschisis, 9 Gattine, 204 Gemmation in cells, 76 in yeasts, 223 Genesis of tumors, chap, xxviii. Germ-theory, evidence for, 203 Giant-celled cancer, 173 INDEX OF SUBJECTS. 367 Hydrocephalus (causing acrania), 7 Hydroencephalocele, 7 Hydrops, 23 Hydrorachis, 7 Hydrothorax, chylous, 31 Hyperaemia, 19 appearances of, 20 collateral, 21 idiopathic. 21 passive, 21 Hyperostosis, 147 Hyperplasia, cell-processes in, chap, xviii. Hypertrophy, congenital, 18 cell-processes in, chap. xvii. numerical, 72 simple, 72 Hyphae, 213 Hyphomycetes, chap. xxxi. Hypostasis, 21 Intention, second, 110 Interstitial inflammation, 101 Intestinal diverticula, 9 mycosis, 206 Inversio vesicae, 9 Iron in morbid pigmentation, 68 h i itabilitat, 78 Ischaemia. 21 Iscbiopagus, 12 Itch insect, 225 Ixodes ricinus, 225' Janiceps, 12 Jaundice, 69 Karyokinetic cell-division. 74 Karyolytic figures, 75 Lardaceous degeneration, 57 Leaf-rust, 220 Leiomyoma, 153 1 Leprosy (see Bacillus Leprae), 131, 206 | Leptothrix, 186 ( Leptus autumnalis, 225 Leucocytes, diapedesis of. 96 dissolve in infective diseases. 201 in granulations, 108 migration of, 96, 90. 108 peripheral disposition of, 96 Leukaemia, 52 Lice, 226 Lichenes, 212 J Ligula nodosa, 249 ; Lipofibroma, 144 i Li porno, 144 Lipomatosis, 50 Lipomyxoma, 144 Liquefaction, after necrosis, 40 Lithopaedium, 6, 64 Liver, acute atrophy of, 204 cavernous tumor of, 150 ; Liver-fluke, 237 ■ Livores, 21 I Lupus, 132 Lymph transudation of, 23 Lymphadenoma, 155 Lymphangioma, 152 Lymphatic glands, tubercle in, 122 Lymphatics in oedema, 24 Lymphoma, 155 Lymphorrhagia, 31 Lymphorrhoea, 152 Lymphosarcoma, 155, 158 Icterus, 69 neonatorum, 69 Inclusio fcetalis, 13 Incrustation, 64 Indirect cell-division, 74 Infarct, 26, 30 Infarction, embolic, 37 Infective diseases, classification of, 202 organisms in, 203 Infective granulomata, chap. xxiv. Infectiveness, marks of, 117 Infiltrating tumor, 137 Infiltration with salts, 64 Inflammation, chaps, xxi., xxii. altered blood-current in, 96 attraction theory, 94 causes of. 98 definition of, 93 diapedesis in, 96 dilated vessels in, 96 exudation in, 96 later stages of, chap. xxii. migration of blood-cells in, 96 necrosis after, 100 neuropathic, theories of, 94 recovery after, 104 repair after, 98 stasis in, 93 symptoms of, 93 temperature in, 97 terminology of, 101 textural changes in, 99, 1C3 varieties of, 101 vascular changes in, 95, 96 Inflammatory infiltration. 101 oedema, 102 stimulus. 99 tissue, 105 Infusoria, 250 Inoculation in anthrax, 201 in fowl-cholera, 201 in septicaemia, 196, 201 Insecta, 226 Intention, first, 110 Madura-foot, 222 Maggots, 226 Maggot-worm, 229 Malaria (see Bacillus Malariae), 206 Malformations, artificially produced, 3, 5 congenital, Sect. I. fissural, 7, 8, 9 of the organs, 11 origin of, 2, 3, 12 Malignant oedema, 188, 204, 206 368 INDEX OF SUBJECTS. Malposition of the organs, 11 Margaric acid, 54 Margarin-crystals, 54 Matter or pus, 102, 108 Maw-worm, 228 Measle of pork, 242, 243 Meat-poisoning, 206 Meckel's diverticulum, 9 Medullary cancer, 173 Melanin, 67 Melanocarcinoma, 173 Melanoma, 162 Melanosarcoma, 162 Meningitis, 204 Meningocele, 7 Merulius lacrimans, 220 Mesoblastic tumor, 138, chap. xxvi. Metamorphosis (see Degeneration) Metaplasia, chap. xx. Metastases in cancer, 174 Metritis, 204 Metrorrhagia, 26 Miasmatic disease, 202 Miasmo-contagious d sease, 202 Microbacteria, 183, 185, 205 Microbrachius, 10 Micrococci in lupus, 132 pathogenous, 204 Micrococcus, 184 cyaneus, 191 diphtheriticus, 185 erysipelatis, 204 luteus, 184, 191, 195 prodigiosus, 191, 211 septicus, 185, 199, 204 variolas, 204 Micromelus, 10 Microparasitic theory of contagium, 203 Micropus, 10 Microsporina, 185 Microsporon furfur, 222 Miescher's cylinders, 250 Migration of leucocytes, 96, 99, 108 Mikrosomia, 6 Mildew (vine), 220 Miliary tubercle, 118 tumors, 137 Miner's lung, 70 Mixed connective-tissue tumors, 164 sqq. cancerous tumors, 176 mole, congenital, 179 fleshy, 6 hydatidiform, 6 Molluscum, fibroma, 142 Monadina, 185 Monas haamorrhagicum, 204 Monobrachius, 10 Monopus, 10 Monsters, double, 1, 5, chap. iii. origin of, 5, 12 Monsters, single, 1, chap. ii. Monstrosities by defect, 3 by perversion, 4 Mortification (see Gangrene) Mosquitoes, 226 Mosquitoes, hosts of filaria, 235 Mould-fungi, chap. xxxi. in invertebrates, 222 in moist gangrene, 42 mutability of, 219 pathology of, 221 reproduction of, 218 Mucoid degeneration, 55 Mucor mucedo, 215, 221 mutability of, 219 Mucor racemosus, 219 Mucous membranes, tubercle of, 124 patch, 129 tissue, growth of, 85 Multiplication of cells, causes of, 80, 81 Mummification, 41 Muscle, growth of, 89 regeneration of, 89 Mutability of bacteria, 208 sqq. Mycelium, 213 Mycetoma, 222 Mycoderma, 223 Mycomycetes, 212 Mycoprotem, 183, 184 Mycosis, intestinal, 206 of lungs, 221 Myeloid cancer, 173 sarcoma, 159 Myoma, 153 Myosarcoma, 153 Myxosarcoma, 103 Myxoma, 143 Myxofibroma, 143 Myxolipoma, 143 Myxomycetes, 212 N^evi, 149 Nanosomia, 6 Necrosis, chap. viii. after inflammation, 100 anemic, 33, 40 coagulative, 35, 36 colliquative, 40 Necrotic inflammation, 103 Nematoda, 227 sqq. Nerve-tissue, growth of, 89 regeneration of, 89 Neuroglia, growth of, 85 Neuroma, 154 Neuropathic theories of inflammation, 94 New blood-vessels, growth of, 86 in granulations, 109 "Nightingale" (two-headed), 14 Node, syphilit'c, 130 Nodular tumor, 137 Non-pathogenous bacteria, 197 Nosema bombycis, 204 Nuclear figures, 74, 75 Nucleolus (nuclear or nucleolar corpuscle), 74 Nucleus-division, 74 Nucleus, structure of, 74 Obesity, 50 (Edema, 23 INDEX OF SUBJECTS. 369 CEdema, cachectic, 25 hydrannic, 25 inflammatory, 25, 102 malignant, 206 purulent, 102 varieties of, 24 CEdema-bacilli, 206 transmutation of, 211 (Estrida, 226 Oidium, 214, 220, 222 identical with mycoderma, 224 Oil-drops in fatty degeneration, 51 Oligaemia, 21 Omphalopagi, 12 Ondontoma, 147 Onychomycosis, 222 Oogonium, 218 Oosphere, 218 Oospore, 218 " Organization," 86 Organoid tumor, 138 Osteoblasts, 88 Osteoclasts, 115 Osteoid chondroma, 165 Osteoma, 147 Osteophyte, 147 Osteosarcoma, 165 Ovigenous organ in taenia, 241 Oxyuris vermicularis, 229 Phycomyces, 215 Phy corny cetes, 212 Pigmentary atrophy, 45 Pigments, haematogenous, 68 normal, 67 Pigment-spots, congenital, 179 Piles. 149 Pityriasis. 222 Plagues, 203 Pleomorphism in fungi, 218 Pneumonia, catarrhal, 204 croupous, 204 Pollinodium, 216 Polymelia, 15 Polymorphism in fungi, 212, 218 Polypous tumor. 137 Posc-mortem staining, 21 Potato disease, 220 Proglottis, 240 Proliferation, cell-processes in, 73 factors of, 80, 81 Proscolices, 240 Prostatic concretions, 61 Protection by inoculation, 201 Protophyta. 223 Protozoa, 250 Psammoma, 162 Pseudo-parenchyma, 216 Psorospermia, 250 Puerperal peritonitis, 204 Pulex irritans, 226 penetrans, 226 Purulent catarrh, 102, 204 exudation, 102 oedema, 102 Pus, origin of, 99, 102, 107, 108, 112 Putrefaction in moist gangrene, 42 Putrefactive diseases, 204 Putrid decomposition, 191, 192, 197 exudation, 102 Pyaemia, 204 Pyelitis, micrococci in, 204 Pygopagus, 14 Packing-cells, 216 Papilloma, 137 Paramcecium coli, 250 Parasites, Sect. VII. animal, chap, xxxii. vegetable, chaps, xxx., xxxi. Parasitic twin, 13 Parenchymatous inflammation, 101 Parostoses, 147 Pasteur's septicaemia, 188, 204, 206 Pathogenous bacteria, 195, 196, 198, 210 sqq- Pearly disease, 127, 206 tumor, 161 Petrine, 204 Pediculi, 226 Penicillium glaucum, 217 Pentastoma constrictum, 225 denticulatum, 225 taeniodes, 225 Perodactylus, 10, 18 Periostitis, infective, 204 Peripheral disposition of leucocytes, 96 Perithecium, 210 Perobrachius, 10 Perochirus, 10 Peromelus, 10 Peronospora infestans, 220 Petalobacterium, 185 Petalococcus, 185 Petechiae, 26 Petrification, 64 Phocomelus, 10 Phosphorus, causing fatty change, 52 Phthisis, bacilli in sputum of, 206 24 Rainey's corpuscles, 250 Re-absorption, 104 imperfect, chap, xxiii. Recovery after inflammation, 104 Regeneration after inflammation, 104 after necrosis 34 cell-processes in, chap, xviii. Relapsing fever, spirillum of (see Spiro- chaeta Obermeyeri), 207 Resting-spore, 215 Retention, cysts of, 71 Rever din's skin-grafting, 84 Rhabdomyoma, 153 Rhizopoda, 250 Rigor caloris in bacteria, 189 frigoris in bacteria, 189 Ringworm. 222 Rcestelia cancellata, 220 Rostellum of taenia, 241 "Rot" in sheep, 237 370 INDEX OF SUBJECTS. Bound-celled sarcoma, 158 Round-worm, 228 Spirillum volutans, 185, 187 Spirobacteria, 184, 187, 207 Spirochaeta, denticola, 187 Obermeyeri, 185, 187, 207 Sporangia, 214, 215 Sporangiophore, 215 Spores of mould-fungi, 213 Sporozoa, 250 Squamous epithelial cancer, 173 Staining, post-mortem, 21 Stasis (as a cause of necrosis) 33 Sterigma, 216 Sternopagi, 12 St. Gothard tunnel, anchylostoma in, 231 Stigmata, 27, 97 Stimuli, action of, on cells, 79 Stomach, fungi in the, 221 Stomata, 27, 97 Stomoxys calcitrans, 226 Storage-fat, 53 Streptobacteria, 185 Streptococci, 185 Strongylus duodenalis, 231 longevaginatus (bronchialis), 231 Strumous inflammations, 204 Suctorial worms, 236 Sugillations, 26 Supernumerary hones and muscles, 16 mamma-;, 16 Suppuration (see Pus), 112 Symptomatic anthrax, 206 Sympus, 10 Syncephalus, 12 Syndactylus, 10 Synophthalmia, 7 Synotia, 8 Syphilis, 128 sqq. micrococci in, 206 Saccharomyces, 223 Sago-spleen, 57 Saliva, causing septicaemia, 204 Sanious exudation, 102 Saprophytes, 221 Sarcina, 184, 185, 204 Sarcoma, 156 sqq. alveolar, 161 myeloid, 159 myxomatodes, 163 peculiar, 161 roundcelled, 158 spindle-celled, 160 varieties of, 157 Sarcoptes, 225 Scarlatina, micrococci in, 204 Schistomycetes, chap. xxx. Schistoprosopia, 8 Schizomycetes, chap, xxx., 212 Scirrhous cancer, 173 Sclerosis (fibrous hyperplasia), 82, 111, 129 Sclerotium, 217 Scolecida, 227 sqq. Scolex, 242 Scrofula, 127 Seat-worm, 229 Senile retrogression, 45 Sepsin, 191, 197 Septicaemia, Davaine's, 204 from saliva, 204 micrococci in, 204 of mice. 201, 204 Pasteur's, 188, 204, 206 Septic poison, 191, 197 Sequestrum, 115 Serous catarrh, 102 exudation, 102 Siamese twins, 12 Silkworm disease, 204 Silver-staining, 70 Simple cancer, 173 Siren-monster, 10 Situs transversus (inversus) 11 Skin diseases, fungi in, 222 Skin grafting, 84 Slough, 115 Small-pox, micrococci in, 204 Softening, 40 Soil, anthrax-spores in, 206 Soil, bacteria in, 193 Somatic death, 32 " Specific inflammations," 117 Specific natures of tissues, 77 Spermatozoid, 218 Sphacelus, 42 Sphaerobacteria, 184 Spina bifida, 7 Spina ventosa, 135 Spirillum of relapsing fever (see Spiro- chaeta Obermeyeri) 207 tenue, 187 undula, 187 Tabanida, 226 Taenia cucumerina, 244 echinococcus, 245 elliptica, 244 malformations of, 243, 244 mediocanellata, 244 nana,244 saginata, 244 solium, 241 Tape-worms, 240 sqq. Tarichium megaspermum, 222 Tattooing, 70 Telangiectasis, 152 Temperature, effect on bacteria, 189 effect on moulds, 219 Teratoma, 13, 178, 179 Textural changes in inflammation, 99 varieties of, 103 Thallophytes, 212 Thoracic duct, rupture of, 31 Thoracogastroschisis, 9 Thoracopagus, 12 parasiticus, 13 Thread-worm, 229 Thrombosis, 29 • 371 INDEX OF SUBJECTS. " Thrush," 224 Tinea, 222 Tipulida, 226 Torula, 223 Trematoda, 236 Tricephali, 16 Trichina spiralis, 232, 233 Trichocephalus dispar, 230 Trichomonas, 250 Trichophyton tonsurans, 222 Triplets, homologous, 16 Tuberaceae, 216 Tubercle, 118 sqq. clinical characters of, 125 crude, 121 definition of, 118 inoculability of, 125 miliary, 118 Tuberculosis (see Bacillus Tuberculosis), 118 sqq. acute miliary, 123 bacillus of, 120,127, 186, 206 diffusion of, 121, 122, 124 of lymphatic glands, 122 transmissibility of, 125 Tuberous tumor, 137 Tumors, Sect. VI. etiology of, chap, xxviii. cachexia of, 141 Cohnheim's theory of, 177 , congenital, 178 definition of, 136 growth of, 189 malignancy of, 140 metastasis of, 149 Tumors, varieties of form in, 137 Twins, homologous, 12 Typhoid fever, bacilli in, 206 Tyrosis, 39 Umbilical cord, withering of, 41 Umbilication in cancer, 175 Urobilinuria, 68 Uterine fibroid, 142, 153 Vaccination, 201 in anthrax, 201 Vaccinia, micrococci in, 204 Valgus (pes), 11 Varicocele, 151 Variola, micrococci in, 204 Varix, anastomotic, 151 Varus (pes), 11 Vibrio, 186 serpens, 185 Vibrion butyrique, 186 Vessels, dilated in inflammation, 96 Vessel-walls in inflammation, 97, 98 Virus, attenuation of, 201, 211 of tubercle, 126, 127 Viscera, transposition of, 11 Vitelligenous organ in taenia, 241 Vitreous degeneration, 63 Warts, congenital, 156, 179 Waxy degeneration, 38 liver, 57 Whip-worm, 230 Witches'-brooms, 220 Wood-tick, 225 Woolsorters' disease, 206 Worms, 227 sqq. Wound-infection, 204 Wounds, healing of, 107 Xiphopagi, 12 Ulcer, 102, 115, 116 cancerous, 175 tuberculous, 121 sqq. Yeast-fungi, 223, 224 ZOOGLCEA, 184 Zygospore, 213, 215