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'.* -f.f.r.r.f.f.r.f .r.r.r ".rlr '.rlr'.i*'.. !.r It'1-'-f -*-'-' ' »■»»»■' .■•.-.■■"•;... •,vy- ■-■ .....'*••»...,.;.;.....•• ■•-.-!.».«....-.-;■• .'V •''.•..'■■.•■•.■■>.:.•■••■/.■••■' ••''•''•I't.t.,, ,-, , , , , r ,,,,','.','.'.*.' '.?*'.****• ' ■• ' v •■ »* , .»,•...*.. . . • * "»• . •• .. . --..,.,...'...*.,'.*.».'.r.r.j.„» _*•_■*_»■- . » « ft- ft . »- >-» »,i, LEUCOCYTHEMIA: TO WHICH WAS AWARDED THE BOYLSTON MEDICAL PRIZE OF HARVARD UNIVERSITY FOR 1863. HOWARD FRANKLIN ^AMON, A.M., M.D., FELLOW OF THE MASSACHUSETTS MEDICAL SOCIETY ; MEMBER OF THE BOSTON SOCIETY FOR MEDICAL IMPROVEMENT; MEMBER OF THE BOSTON SOCIETY FOB MEDICAL OBSERVATION; ONE OF THE PHYSICIANS, AND SUPERINTENDENT, OF THE BOSTON DISPENSARY. ANIMA OMNIS CARNIS IN SANGUINE EST. roon uen/'j. . LIBKABY. DE VRIES, IBARRA, & CO. LONDON: JOHN CHURCHILL. LEIPZIG: PARIS: WILH. ENGELMANN. V. MASSON ET FILS. 1864. Entered, according to Act of Congress, in the year 1863, by HOWARD EUANKI.IN DAMON, In the Clerk's Office of the District Court of the District of Massachusetts. VJH rovUftv^-^51", **-H ScconB Edition. Boston : Printed by John Wilson and Son. ORDER OF THE BOYLSTON MEDICAL PRIZE COMMITTEE. By an order adopted in 1826, the Secretary was directed to publish annually the following votes: — 1st, That this Board do not consider themselves as approving the doctrines contained in any of the dissertations to which premiums may be adjudged. 2c?, That, in case of publication of a successful dissertation, the author to be considered as bound to print the above vote in connec- tion therewith. PREFACE. A laege portion of the following Essay has been necessa- rily devoted to the difficult task of condensing into as small a compass as possible whatever is known in regard to the origin and formation of the cellular elements of the blood. While engaged in these studies, similar ones were pursued abroad; and Dr. William Roberts communicated to the Royal Society. Feb. 10, 1863, some observations upon the appearances of the blood-corpuscles under the influence of solutions of magenta and tannin. An account of these experiments is given in the " London Quarterly Journal of Microscopical Science" for July, 1863; and figures also of the blood-corpuscles. About the time of his discovery, similar phenomena were noticed by the author of this Essay in "pathological blood. It may be interesting to know something more of the history of the two cases of leucocy themia which were then under the care of the author. The following account of the removal of the large glandular tumor from the neck of the little boy, eight years of age, by Dr. David W. Cheever, was communicated by him to the Boston Society for Medical Improvement, April 13, 1863; and published in the " Boston Medical and Surgical Journal," April 30, 1863: — VI 1'KEF ACE. u This tumor, which was about as large as two closed fists, had exi>ted for twelve mouths, but had increased very rapidly in size in the last month. As it showed no signs of softening, but was steadily enlarging, and had begun to create dyspnoea by pressure on the nerves and trachea, it was deemed best to attempt its re- moval. The skin moved freely over it. A number of enlarged cutaneous veins ran over it in various directions. The tumor felt to the touch lobulated and movable, as if made up of an enlarged chain of lymphatic glands. It extended from near the middle line of the neck in front, back upon the edge of the trapezius on the left side, and above, from the lobe of the ear and angle and body of the lower jaw, down to and beneath the clavicle. The left shoul- der was depressed by it. The boy looked otherwise pretty healthy. "March ol. — He was etherized; and an incision made from just below the ear to near the cricoid cartilage, through the skin and platysma, disclosed a lobulated, hard, glandular mass, lying mainly beneath, and partly behind, the sterno-mastoid muscle. Contrary to expectation, it was found very adherent in all direc- tions, and the lobules bound together by strong, fibrous tissue. Considerable time and care were requisite to divide the adhesions, which were too strong to yield to any thing but the edge of the knife. It was found necessary to divide the sterno-mastoid, and dissect aside the external jugular which ran, somewhat displaced, over and through the tumor. The lower edge of the tumor ex- tended beneath the clavicle, into and below the subclavian triangle. The base lay over the sheath of the carotid, which was necessarily cxpo.-ed about two inches. Continuous dissection was required even to the last adhesion; for they could nowhere be made to yield at all." The boy recovered in a few weeks, a large part of the wound healing by first intention. It is now eight months since the operation was performed, and there is no appear- ance of a return of the tumor. The boy is still somewhat pale, and a microscopic examination of his blood gives a larger number of white corpuscles than is usual in the normal condition. Within a few days, a similar case has presented itself in a boy seven years old, the same side of PREFACE. Vll the neck being affected. The enlargement of the glands in this case commenced about five months ago; and there is a large, lobulated, movable mass of them extending from just below and behind the ear to the clavicle in front, and also somewhat backwards upon the neck. They are soft, elastic, not painful to the touch or otherwise. The boy seems to be in good health, and the blood is not yet per- ceptibly affected. Dr. Cheever has also met with a similar case since his removal of the tumor in the first one. These numerical hypertrophies of the lymphatic glands are of slow growth, and it is many months before the system becomes percep- tibly affected by the introduction of their elements into the circulation. The consequences of the local suppuration of large masses of these glands are much more to be dreaded than the immediate effects of the introduction of an exces- sive number of their cellular elements into the blood, or even of a surgical operation. The latter may co-exist with the red blood-corpuscles for a long time without any serious results. Nor should an operation be discouraged whenever it is practicable, since, by this means, life may be pro- longed, and the chances of recovery afforded. In regard to the author's case of splenic leucocythemia, much might be said, as its whole history is the most re- markable of any in the records of this disease. The boy died April 17, 1863, exhausted by the diarrhoea which never wholly left him. No post-mortem examination could be obtained; but the enlarged liver and spleen could be distinctly felt through the abdominal walls, extending low down into the abdominal cavity. Two days before the boy's death, some blood was taken from his finger, which presented, upon microscopic examination an hour or two afterwards, numerous large, nearly colorless, or but faint- ly yellow crystals, having very distinct outlines. They VI11 PRE FACE. consisted, as regards form, of hexagonal and pentagonal plates of unequal sides, of rectangular plates in the form of squares and parallelograms, and also of a few triangular plates. Some of these crystals were twice the size of the red blood-corpuscles in the same field of view. They differed entirely, in form, size, color, degree of resistance to atmospheric influences, refractive and other properties, from all known crystals of the human blood. They were not at all permanent when exposed to the atmosphere, and disappeared in a few days. The author, in communicating his discovery of these crystals to the Suffolk District Medical Society, April 25, 1863, gave them the name of Leucocrystallin. The photographs which accompany this Essay were taken from nature by Mr. William Hussey, of this city; and are exceedingly beautiful and valuable portraits of disease. The figures of the blood-corpuscles were also photographed by him from the original drawings. In closing these prefatory remarks, the author is fully aware that a vast amount yet remains to be done in this new field of pathological investigation. CONTEN T S. PAGE Leucocythemia ............... 1 The Blood : Hewson............4 The Blood-making Organs : — The Lymphatic Glands..........11 Thymus Gland.............14 Thyroid Gland............19 The Spleen..............21 The Liver..............24 Leucocythemia : Views of Bennett.......27 Case 1................2ft Case II................81 Case III................U Robertson's Analysis of Blood of Case III.....30 Bennett's Table of Eighteen Cases.......37 Molecular Physiology, &c, Bennett's Lectures on . 44 Burnett's Cell-Development..........45 Leucocythemia ; Leukaemia : Virchow......47 b \ CO NT F. NTS. r ai.k Or.M-'.i.YATioNs in Initio Stah>..........>•' Case I................:>:) Cam. II................M Cams III., IV..............•'•-' Views of Lebert..............,;l Cam: I................»;* Case II................<;s Case III................71 Conclusion................72 Author's Cases..............K7 1)11.LIOG i: a i• 11 v...............91 Illustrations...............•)•"> ILLUSTRATIONS. PAGE Photographs of the Author's Cases.........95 Case 1...................95 Case II...................96 Microscopical Illustrations............97 A. Blood-Corpuscles in Case I. B. ,, ,, ,, Case II. C. Blood-Corpuscles. Marasmus in an Adult. D. ,, ,, Marasmus in a Child. E. Blood-Corpuscles in Bronchocele. F. Crystals of Leucocrystallin found in the Blood of Case II. during Life. LEUCOCYTHEMIA. Scarcely twenty years have elapsed since Professor Bennett of Edinburgh first announced to the medical world the discovery of a new disease, which he called " Leucocythemia, or white cell-blood." This new and comparatively rare disease has been the subject of much interest and inquiry ever since. But little addi- tional light has been thrown upon its nature and symptoms, so fully were they delineated then. The most marked and fundamental characteristics of this disease are an augmentation of the white blood- globules and an hypertrophy of the spleen, not attri- butable to any anterior affection. A cachectic state, and a tendency to hemorrhages and diarrhoea, consti- tute some of its most frequent accompaniments. In the year 1852, Professor Bennett published a work containing thirty-seven cases, more or less illus- trative of the symptoms, pathology, and treatment of this disease. Since the appearance of his work, seve- 1 ') I.KrcoCYTIir.M.A. ral other cases of this disease have1 been reported in the various British, l'rcnch, (.erman, and other peri- odicals. At the suggestion of Dr. Bennett, analyses were made of the blood of several of these patients, which show a remarkable uniformity in their results. These analyses have been confirmed by able chemists and microscopists ; and the whole subject has passed through so searching an ordeal, that little is wanting to give it the character and precision of the facts and phenomena of positive science. A systematic accoimt of this disease was prepared by M. Yidal, and pub- lished in a number of the Gazette Hebdomad aire cle Jlecleciitc, April -1, 1S5(>. This account, although carefully prepared, is considered by Bennett to be based upon too small a number of cases for any exten- sive generalizations. The discovery of this disease has led to a more care- ful study of every thing which relates to the blood and the blood-making organs. Alany of the observations of the older writers upon the blood acquire a signifi- cant importance by this accession to our knowledge. The office of the lymphatics, as demonstrated by I lew- son nearly a century ago, receives additional confirma- tion from this source. His numerous papers and LEUCOCYTHEMIA. 3 experimental inquiries were the admiration of his con- temporaries, and continue to be, in many respects, one of the most reliable sources of our knowledge upon those subjects even at the present day. In the elaborate article upon the blood, in Simon's " Chemistry of Man," the opinions of Hewson stand side by side, in point of accuracy, with those of the most recent observers. The literature of this subject is very voluminous ; yet, in every modern work upon the blood or lymphatic system, we are sure, above all others, to find the name of Hewson. As his observations are to play so impor- tant a part in the consideration of our subject, let us make a rapid review of his works upon the lympha- tics and the blood, before inquiring into the nature and causes of leucocythemia. In reviewing the writings of Hewson, it would be unjust to pass over in silence those of his predecessors and contemporaries ; for it is by comparing the efforts of both that we can justly appreciate the value of either. By this very process, we shall arrive at a more definite idea of the office of the lymphatics, and their connection with the blood, and thus be the bet- ter prepared to study the intimate nature of leucocy- themia. 4 LECCO( YTHEMIA. THE BLOOD. HEWSON. The first of Hewson's papers on the " Lymphatic System in Birds, Amphibia, and Fishes," was read before the Royal Society on the 8th of December, 1768. In a paper read before the same society on the 19th of January, 1769, Dr. Monro claims the dis- covery of the vessels which correspond, in the lower vertebrate animals, to the lacteals of the mammalia. A long and somewhat exciting controversy upon the priority of the discovery followed, although this honor did not strictly belong to either; since, more than a century previous, Thomas Bartholin had observed the lacteals in fishes, but erroneously supposed that they terminated in the liver. But, whoever was the original discoverer, it is certain that Hewson did more to explain and illustrate the lymphatic system in animals and man than any one of his predecessors and con- temporaries. When his last two papers on the lymphatic system of amphibia and fishes were communicated to the Royal Society by Dr. "William Hunter, on the 16th of November, 1769, the following notice of them was placed upon record: " Mr. Hewson's descriptions leucocythemia. 5 were greatly illustrated by the exhibition of a series of preparations taken from turtles and divers fishes, wherein these vessels were injected, and shown to the naked eye in their rise, progress, communications, and insertions, to the great satisfaction of the society. Thanks were returned to Dr. Hunter and Mr. Hewson for these very ingenious communications." At a meeting of the Royal Society on the 22d of November, 1770, Sir Godfrey Copley's gold medal was awarded by ballot to Hewson " for his papers on the lymphatic system in birds, amphibious animals, and fishes." His three papers on the properties of the blood were published in the "Philosophical Transactions" for 1770; and that on the "Figure and Composition of the Red Particles of the Blood, commonly called the Red Globules," in 1773. This paper was fol- lowed by another, upon the " Red Particles of the Blood, the Lymphatic Glands, the Thymus, and the Spleen." To these papers we are indebted for many of our most valuable ideas upon the blood and the blood-making organs. Before the time of Hewson, the attention of obser- vers was mainly directed to the coagulation of the blood. Many difTerent opinions were held by the 6 I.I.I C( KYIII EMI A. older writers concerning this singular ])henomenon. Aristotle thought it was owing to the presence of a fibrous matter, having noticed that it did not coagulate when the fibres were removed. Harvey supposed, that, after death, the blood sepa- rated into two parts. — one dense and fibrous, the other ichorous and serous; the fibres connecting the whole. Sydenham thought the buffy coat was solid and fibrous, and that the fibres were formed of the red part divested of its coloring matter. Thus, it is evi- dent, he distinguished the blood-globules from the fibrine. Boerhaavc looked upon the fibrous portion of the blood as being chains of blood-globules; andllaller entertained a similar idea. Leeuwenhock, whose authority as a microscopist and whose speculative ideas had for so many years supplied the place of rigid experiments and careful deductions, appears to have regarded the blood as composed of globules and serum only ; the globules alone being spontaneously coagulable. About half a century after him, in 17*r>, Petit maintained, as a well-known phenomenon, that all the parts of the blood are not equally coagulable; that it LEUCOCYTHEMIA. 7 coagulates at first entirely; but, after a while, the serum separates from the clot " as whey does from curdled milk." From this he concluded that the lymph only coagulates, while the blood-globules and serum remain fluid. Gaubius, in 1758, had a partial knowledge of the three proximate constituents of the blood, — the fibrine, the globules, and the serum. Dr. Richard Davies, in 1760, had observed that the inflammatory pellicle was a kind of coagulated gluten, as he called it, belonging to the blood ; and that the red globules possess no strong cohesion for each other, without the interposition of this substance. The same opinion was held by Dr. William Hunter concerning the coagulable principle. Very little else was then known of the blood besides its coagulability, and its separation into its proximate principles, — the fibrine, the globules, and the serum. The origin, growth, and destination of its corpuscular elements were still shrouded in mystery. A wide field was open for discovery; yet many a writer was content to advance a theory, who lacked sufficient perseverance to search after the truth. Upon this field of labor, Hewson entered with a genius for observation and study hardly known in that s LEUCOCY IIIKMIA. age. The result is shown in the works which he has left behind him, and which constitute one of the brightest pages in physiological discoveries. What- ever changes time may have wrought in our ideas upon these subjects, still the essential facts which lie enunciated remain the same; and his theories of the origin and formation of the corpuscidar elements of the blood are still received with only slight modifica- tions. He was almost the first to observe, that the shape of the blood-globules is not spherical, as their name indi- cates, but differs hi different classes of animals, and, when out of the body, under different circumstances; the addition of water, for instance, converting them into spheres. He speaks of the general occurrence of tlie.se globules throughout the animal kingdom, and of the various colors which they assume in the insect tribes. Later observers have shown, that the color of insect blood is due, not to the corpuscles only, but to the liquor sanyiti/ti.s ; since the color is still preserved in absence of the corpuscles. Thus, in the greater part of the invertebrates, the blood is white, but red in the annelids, or worms; colorless in most of the mollusks ; milk-white in many of the snails; but, in the Helix romatia, sky-blue; and, in the .Plunorbis LEUCOCYTHEMIA. 9 corneas, of a dark amethyst. The blood of the or- thopterous msects is green; of the silk-worm, yellow; and of the coleopterous insects, or beetle tribe, dark brown. More is now known concerning the shape of the blood-corpuscles, and the changes which they undergo during their development. In the oviparous verte- brates, they are at first minute, rounded molecules, which become elliptical cells, in which a nucleus and nucleoli are formed. These perfected corpuscles are regarded as analogous to the white ones in the vivipa- rous vertebrates. Like them, when mature, their en- velope probably dissolves slowly, forming a portion of the plastic matter of the blood; while the nuclei are set free, and, in the viviparous vertebrates, at length become the red corpuscles. Thus do the white cor- puscles perform a duty somewhat similar to that of glands, in furnishing some of the plastic materials of the blood. Indeed, they have been called " the floating glands of the blood." Wharton Jones speaks of three phases in the de- velopment of the blood-corpuscle ; namely, that of the granule-cell, the nucleated cell, and the free cellse- form nucleus. It is found in all of these phases in the blood of man and the mammals only. In the 2 10 LEUttX YTHKMIA. lymph also of man and of the mammalia are found the granule-cell, the nucleated cell, and the free celhc- form nucleus; but. in the lymph of the oviparous ver- tebrata, only granule-cells and nucleated cells are found. Thus a perfect correspondence is shown be- tween the corpuscles of the blood and the lymph in these two great classes of the animal kingdom. This is, indeed, an important fact; and it will be much more clearly demonstrated, when we consider the office of the lymphatic glands in the formation of the blood- corpuscles. The earlier microscopists found great difficulty in seeing the blood-corpuscles, so thickly were they crowded together. Hewson remedied this by diluting the blood with scrum. He employed, in his examina- tions, single lenses of extremely short focal length. He gives plates of the blood-corpuscles of different animals, as seen with one of onc-twenty-third of an inch in focal length, and consequently not magnifying more than one hundred and fifty diameters. Still, with such a lens as this, much and important work could be done by a good observer. Hewson dis- covered that the size of the blood-corpuscles does not depend upon the size of the animal in which they are foimd : thus those of the elephant and whale are LEUCOCYTHEMIA. 11 very much smaller than those of some reptiles. He found that saturated solutions of the neutral salts con- tracted the vesicular substance closely around the nucleus, and that the fixed vegetable and volatile alka- lies corrugated the vesicles. From this he concluded, that Nature has set certain limits to the proportion between the water and salts of the blood, and that the latter are destined to preserve the peculiar disk-like form of the corpuscles. But this, we would rather suppose, is a vital phenomenon, from its constant occurrence and typical variations in the different classes of the animal kingdom, and not the direct result of chemical or physical forces. Thus Paget distinguishes vital force from all others by its power of generating typical organic forms. THE BLOOD-MAKING ORGANS. THE LYMPHATIC GLANDS. Little is known to us of these glands during health; and it is only in disease that they are rendered per- ceptible in the living body. They are of a pale rose- color, excepting those of the lungs and the bronchial glands, in which a black pigment is found deposited in \'> LEl'COCVUH.MIA. the adult. They are larger in infancy and childhood than in mature life or old age, and in the male than in the female. They are subject to acute and chronic enlargements, accompanied by a cachectic and aniemic state of the system. So common is amrmia in these enlargements, that the chalybcates are almost always indicated. It is evident, then, that these glands arc in some way connected with the blood-making system, and perform for it an important office. The security also of their general position, and the destination of their fluid and corpuscular contents to the thoracic duct and left subclavian vein, where they enter into direct communication with the lesser or pulmonary circulation, arc in favor of this view. After passing through the lungs, the altered contents of the thoracic duct become mingled with the general circulation, and form a portion of the reconstructive material of the system. Thus far. we have spoken of the lymphatic system only in the most general terms. There are several important organs of the body whose functions have been but very imperfectly known by physiologists, but which belong, without doubt, to this system. The thymus and thyroid glands and the spleen, with other lesser bodies, are now classed with the lym- LEUCOCYTHEMIA. 13 phatics, under the general name of " blood-making glands." We need no higher authority than that of Hewson, Simon, and Sir Astley Cooper, to vindicate their claims to this position. It is futile to suppose, that organs of this size were made for no purpose, or are useless, as has been asserted of the spleen, be- cause it can be excised in many animals without pro- ducing any obvious injury to their health. The thymus also, which assumes such wonderful propor- tions during foetal existence and the first years of infancy, has been considered by some as the mere packing material of the anterior mediastinum. No- thing could be more absurd than to suppose that the Creator should resort to so unusual an expedient as this for so simple a purpose. Would it not be far wiser to suppose, that this organ, with its bountiful supply of nerves and blood-vessels, in close connection with the great aerating and circulatory systems of the body, should perform some more important office than the one assigned it 1 We will consider, for the purpose of simplicity, each of the glandular organs separately; the office which it most probably performs hi the blood-making processes, and afterwards its connection with leuco- cythemia. It 1.1.1 aX YTHIMIA. THYMUS (ILAND. Sir Astley Cooper, in his beautiful monograph upon the thymus gland, describes it as composed of a cer- vical and a thoracic portion; the latter situated in the anterior mediastmum, the former extending upon the sides of the neck. It is just perceptible between the second and third months of foetal life. It grows very rapidly from the seventh month until the time of birth ; and even then continues to increase, or remain of the same size, during the first year. After this, it diminishes gradually until the time of puberty, when it usually disappears. Haller says, Ci In the foetus, it is an immense gland, and, together with the pancreas and thyroid, is the greatest of the glands, — hardly less than the kidney." Meckel says, " Notwithstanding its proportional volume is not so considerable at the end of the first year, and sometimes even at that of the second, it con- tinues to increase during all this period. It becomes effaced, in an inverse sense, to that in which it was formed ; that is to say, from below upwards. No trace is ordinarily found of it at the twelfth year; and the place which it occupied is then filled with fat." Hewson describes this gland as continuing to grow to the end of the first year after birth; remaining LEUCOCYTHEMIA. 15 nearly stationary during the next two years, and then decreasing until about the twelfth year, at which time it usually disappears. He never saw it, he says, at puberty. Cloquet's description is very similar to that of Meckel. Later observers have seen the thymus in adult life. The fluid from the thymus, according to Hewson, is the same as that found in the lymphatic glands. It consists of a " great number of small white, solid par- ticles, exactly resembling, in size and shape, the cen- tral particles in the vesicles of the blood, or such as are found in the fluid of the lymphatic glands. As to the excretory duct of the thymus, it was shown by him to consist of the lymphatic vessels connected with it, and ramifying throughout its substance. Large quantities of the white particles being found in these vessels, first led him to suspect that they were the excretory duct. This fact he afterwards demonstrated by several careful and conclusive experiments. In speaking of the physiology of this gland, Cooper says, " Hewson was of opinion, that the thymus gland formed the internal part of the red globules of the blood, and that the red particles were composed of two portions ; viz., a small central particle pro- 16 I.El'CCX YTHEMIA. duced by the thymus, and a vesicular part formed by the spleen." He quotes the following account of the use of the thymus from Hewson: — '• The thymus gland, then, we consider an append- age to the lymphatic glands, for the more perfectly and expeditiously forming the central particles of the blood in the ftrtus and hi the early part of life. The structure and uses of this gland are similar to those of the lymphatic glands, to which it may be con- sidered an appendage." In commenting upon the foregoing passages, Sir Astlev Cooper says, " It is quite at variance with my feelings to find fault with Hewson, who was an excel- lent anatomist and a highly ingenious man, and for whose memory I have the highest possible respect; but I cannot agree with the opinion, that the structure of the thymus and absorbent glands is similar: one is conglobate, and the other conglomerate ; one is firm and compact, and the other is loose and pulpy; the one contains cells of considerable magnitude when in a distended state, whilst in the absorbent glands the cavities are small, and with so much difficulty traced, that there is still a doubt if they be cellular or vascu- lar." Since the above was written, the nice distinc- tions drawn by Cooper between these glands are no LEUCOCYTHEMIA. 17 longer adhered to as of any essential importance. The name of vascular glands has been given to all of these glandular organs destitute of a proper excretory duct. Sir Astley Cooper concludes his chapter upon the physiology of the thymus with the following query: " As the thymus secretes all the parts of the blood, — viz., albumen, fibrine, and particles, — is it not pro- bable that the gland is designed to prepare a fluid well fitted for the fcetal growth and nourishment from the blood of the mother before the birth of the foetus, and consequently before chyle is formed from food 1 And this process continues for a short time after birth, the quantity of fluid secreted from the thymus gradually declining as that of chylification becomes perfectly established." It is evident from the foregoing query, as well as from other portions of his essay, that Sir Astley Cooper indorses, on the whole, the opinions of Hew- son, even if he does not his precise language. The rapid progress of comparative anatomy and physiology tends to give us more correct ideas of the functions which different organs perform in the animal economy. Shape and size alone cannot determine definitely, beforehand, the office of any organ or part. Disease or some well-directed experiment may en- 3 is l.hTClK YTIH.MIY. lighten us upon its functions, which might otherwise be obscure ; but who shall say, from mere examina- tion, why the liver should secrete the bile, the kidneys the urine, the salivary glands the saliva, or the spleen, thymus, and lymphatic glands, the nuclei and corpus- cles of the blood ? Cooper mentions only one case of disease of the thymus. This occurred in a girl seventeen years old, and was accompanied by bronchocele, or enlarged thyroid. Death took place from pressure upon the trachea. The disease is described as of a " fungoid " nature and yellowish-white color. Nothing is said about its microscopical appearance ; and it was pro- bably not examined. Wcdl mentions premature atrophy of the thymus as occurring particularly in children affected with marasmus. Its entire absence* has been observed only in cases of acephalism. Inflammation of this body is rare. Hasse mentions two cases, in one of which an abscess opened into the trachea. In tuberculosis, the thymus occasionally becomes affected : it sometimes, also, suffers from hypertrophy. Thus, from the ordinary diseases of this organ, it would be very difficult to determine its functions. Its embryology throws more light upon the subject. LEUCOCYTHEMIA. 19 THYROID GLAND. Happily, our knowledge of the thyroid is of a much more positive nature. The most common dis- ease of this gland is hypertrophy, or bronchocele. Erichsen speaks of this disease in the following man- ner: "There is a remarkable connection between tumors of the thyroid gland of this kind and a gene- ral anaemic condition of the system. In London, nothing is more common than to find a certain degree of bronchocele in pale and bloodless women and girls. Indeed, so frequent is the coincidence, that it is impos- sible not to regard it in the light of cause and effect." Hasse speaks of simple enlargement of the thyroid as frequent. Handfield Jones says, "The affection is almost wholly confined to youth, and is frequent about the age of puberty in both sexes; more so, however, in the female, in whom enlargement is espe- cially apt to prevail at the approach of the menstrual period." All we can learn from the above authorities is, that the enlargement of the thyroid is generally associated with some change or derangement of the blood. Ben- nett has recorded a case of diseased thyroid, in which microscopical examinations were made of the contents 20 LEUCOCYTHEMIA. of this gland, and also of the blood of the patient. In this case, which was that of a female1 who died at sixty with cancer of the lung, the thyroid body and lymphatic glands of the neck were involved, and the blood was leucocy thank. Besides the cancer-cells found in these organs, were a considerable number of round, colorless corpuscles, varying in diameter from the hundred and fiftieth to the hundredth of a milli- metre. An unusual number of these cells also existed in the blood, as was determined both before and after death. The most remarkable feature of the ease was this: " The cells and included nuclei of the thyroid body were considerably smaller than usual; and it was ascertained that the colorless bodies in the blood, and their nuclei, were smaller also." Thus, he con- tinues, " It was seen, that the colorless corjmscles in the blood were of two distinct sizes, —the smaller cor- responding with the nuclei of the larger^ ones; and the lymphatic glands were found to be crowded with cor- puscles, also of two distinct sizes, exactly correspond- ing to those in the blood." What better evidence could we have, that the colorless corpuscles are formed in these appendages to the lymphatic system, from which they readily find their way into the blood] The fact of the smaller corpuscles exactly correspond- LEUCOCYTHEMIA. 21 ing in size with the nuclei of the larger ones cannot be merely accidental. This increase in the number of the white corpuscles in the blood, has, in every known instance, been preceded by hypertrophy of some of the lymphatic glandular organs, more especially the spleen. Thus it is shown most conclusively, that it is the diseased glands which give rise to an excess in the number of white corpuscles in the blood. THE SPLEEN. In health, the spleen ordinarily weighs from six to ten ounces, and is situated on the left side, between the eighth and tenth ribs, and next to the diaphragm. Soon after death, it resembles the blood in color, but gradually becomes of a dark, leaden hue. It may, with propriety, be regarded as a mere congeries of arteries, veins, nerves, and lymphatic vessels. It has no proper excretory duct; but this office is fulfilled by the lymphatic vessels and veins with which this organ is so amply supplied. Hewson found the lymphatic vessels so numerous in the spleen of fishes, that the gland was equally well colored by injecting them as by injecting the arteries. The secreting cells of the spleen are covered by a network of veins and arteries which ramify over their ■)) LEUCOCYTHEMIA. surfaces. Into the veins and lymphatic vessels its proper secretions are carried, after they have been elaborated by the gland from the arterial blood, and thus find their way into the portal circulation. Were the white corpuscles are found most abundant; but, after the blood has passed through the pulmonary cir- culation, it is not usual to find, except hi cases of leucocythemia, more than one white to three hun- dred and fifty red blood-corpuscles. The production of plasmic, or colorless blood-corpuscles, is very active hi the spleen ; and the extirpation of this organ is followed by a diminution in their number, although it is most probable that its function, in this case, is supplied, in a measure, by the increased activity of the other blood-making organs. Funke has noticed the great abundance of these corpuscles in the healthy spleen ; as has also Yirchow. Gray has observed the same phenomenon, and considers them identical with those that are ordinarily found in the blood, and insists on their perfect resemblance to the constituent cells of the spleen. Yierordt has found the white corpuscles in the splenic blood to be from one-fourth to one-ninth as numerous as the red ones. Ilirt gives the relative number of red globules to one white one in the arte- rial and venous blood of this organ, as follows: — LEUCOCYTHEMIA. 23 Arterial Blood. Venous Blood. 1st observation . . . 2600.....74 2d „ ... 1843.....54 3d „ ... 2095.....82 Thus, for the same number of red globules, there was over thirty times as many white ones in the blood which left the spleen as in that which arrived at this organ. Gray has observed, that the blood generally contains less solid matter after its passage through the spleen than before entering it, and that this impover- ishment is confined to the diminution of the number of its red globules. In horses badly nourished, or deprived of food, this diminution in the relative num- ber of the red blood-globules in the spleen became less apparent. Fiihrer has noticed the rapid destruc- tion of blood-globules in the spleen in its enlarge- ments after intermittent fever. What interpretations shall we give to these state- ments ? Do they not show an astonishing diminution of the red corpuscles in their passage through the spleen, and, at the same time, the formation of the white ones there in greater abundance than elsewhere; or, in other words, both a destructive and a reconstruc- tive metamorphosis in the same organ? But do we not have something quite analogous to this in the liver ? Does not this organ secrete sugar and excrete J 4 lli eocYi hlmia. bile, and with it a portion of the coloring matter of the blood, as well as assist in the elimination of differ- ent substances introduced into the system I If the red globules of the blood arc destroyed in the spleen, as has been asserted of them, then will their destruc- tion be the more rapid, the more numerous the con- stituent elements or cells of that organ become ; and, finally, in place of the utricles or perfectly developed blood-cells, we shall have only the nucleated or imma- ture plasmic cells, or, in other words, the white blood- corpuscles. All of these conditions are found in leu- cocythemia. THE LIVER. OKK.IN" OF TJIK BLOOD-COUPl SULKS. Tho^e micrographers who have studied most pro- foundly the origin of the blood-globules in batrachians and fishes have nearly all agreed, that the primitive blood-cells bear a close resemblance to the cells of the surrounding tissues. Many, indeed, have gone so far as to declare them identical. Among those who have done most to establish this idea arc Baumg'artner and Schultz, who suppose these primordial globules to be spherules from the vitellus ; the latter supposing them LEUCOCYTHEMIA. 25 to become surrounded by an utricular membrane,— an opinion which has been combated by Valentin. Reichert has also endeavored to show, in the tadpole and chick, the close analogy between the blood-cells and tissue-cells of the embryo. Vogt believes that the origin of the blood-corpuscles is in the blastoder- mic layer, which reposes directly upon the vitellus, and which is designated by him under the name of hema- togenic layer. The formation of the coloring matter of these corpuscles — which is regarded by chemists as an animal dye — is the result of a physiological process which is closely allied to, if not identical with, secretion. Thus each one of these corpuscles is a living organ or organite, endowed with important and peculiar functions, and furnishing to the economy its elaborated products. In their earliest stages, in oviparous vertebrates, their included nuclei undergo fissiparous multiplication; the diaphanous cell-wall becoming constricted as the nucleus becomes divided, so as to form new enclosures for the separated nuclei. Hugo Von Mohl and Braun have shown a similar mode of cell-division in the vegetable kingdom. The above observations are also equally applicable to the formation of the blood-corpuscles in the embryos of viviparous vertebrates and man. 4 ■>(\ Ll.inX YTHl.MIA. After the formation of the liver, the multiplication of the blood-globules by fissiparation ceases. From this fact, Prevost and Dumas have drawn the infer- ence, that the typical blood-globules have their seat of formation in this organ. Kollikcr has seen all the stages of transformation between the colorless and colored corpuscle in the blood of the liver in the embryos of the mammalia; and he is of opinion, that, at a certain period of fertal life, the blood-globules are formed solely in this organ. He is probably, in a great measure, correct; but it cannot be denied, that other organs at the same time share extensively in the formation of these elements of the blood. Weber is of opinion, that these globules arise out of the epithelial cells of the delicate walls of the capillaries of the liver. Remak thinks that they are not derived from the constituent cells of the liver; as they coidd not enter the circulation, on account of the limitary membrane of the hepatic vessels. Later observations tend to show that the colored are derived from the colorless corpuscles, and that their formation in the human blood is due to a large number of glandular organs. LEUCOCYTHEMIA. 27 LEUCOCYTHEMIA. BENNETT. Having spoken of the blood and the blood-making organs in a somewhat general manner in relation to this subject, let us now consider leucocythemia in a clinical, microscopical, and physiological point of view. It will be necessary, for the purpose of simplicity, to review the principal writers upon this subject sepa- rately, and in the chronological order of their publica- tions, as nearly as it can be ascertained. In this manner, much discussion as to the priority of discovery will be avoided. As regards the clinical history of leucocythemia, a few cases from Bennett are sufficient to characterize this as a newly-discovered disease. It has probably been confounded by previous writers with pyaemia, or pus in the blood. As there is no ready way of dis- tinguishing blood containing pus from white cell-blood, it is easy to see how this mistake could have often been made. But the history of pyaemia, which is always connected with some local inflammation and suppuration by which pus is introduced into the blood, is sufficient to distinguish it from leucocythemia, which comes on in a very gradual and insidious manner, 2* I.Kl (OCYTHLMIA. accompanied by altogether different symptoms, and invariably preceded by chronic enlargement of some of the lymphatic or blood-making glands. Case I. — The first case of leucocythemia was pub- lished by Professor Beiinett in the Edinburgh Journal for the Ut of October. 1S4.">. The. subject of it was John Montcith, a slater, aged twenty-eight years ; com- plexion dark ; usually healthy and temperate ; admitted into the Royal Infirmary, Feb. 27, IS 1.3. The follow- ing is a condensed history of the case: For the last twenty months, a tumor appeared in left side of abdo- men, which has gradually increased in size until with- in four months, — not painful. Other tumors have since appeared hi neck, axilla*, and groins; at first, painful. Previous to June last, vomited frequently in the morning ; usually constipated ; appetite and diges- tion good. On admission, the tumor extends from ribs to groin, and spinal column to umbilicus, on left side. Dull on percussion, and painful near upper part on pressure. Pulse 90; slight (edema of legs; urine turbid, natural in color; acid to litmus, sp. gr. 1013, unaffected by nitric acid. March 9, oedema of legs has increased. March 10, tormina and diarrhoea. March 13, thirsty; skin hot; pulse 110; diarrhoea leucocythemia. 29 checked by opium ; urine, a hundred ounces. March 14, diarrhoea continues; pulse 100; tongue dry and brown; countenance of typhus. March 15, died sud- denly, in the morning. Sectio Cadaveris. Prominence of tumor well marked externally. As- cites and oedema, of limbs gone. Blood throughout the body separated into a yellow and brick-red portion. Blood-vessels, substance of brain, and lungs, healthy. Heart somewhat enlarged; weighed eleven and a half ounces; texture healthy; valves normal. Firm co- agula in right auricle, ventricle, and pulmonary artery. Liver enormously hypertrophied; structure healthy. Gall-bladder enlarged ; contents, pale yellow ; weight of both, ten pounds and twelve ounces. Spleen also greatly enlarged, fusiform; weight, seven pounds and twelve Ounces ; length, fourteen inches ; breadth, seven inches; and thickness, four and a half inches. Kidneys healthy. Lymphatic glands everywhere much enlarged. Several of the inguinal glands the size of a walnut, and even larger. So also of the axillary glands. Bronchial glands enlarged; dark purple and black in places, from pigmentary deposit. The mesenteric and lumbar glands also much enlarged. No pus found in any of the tissues. 30 LEI C(M YTHI.MIA. Mi< -nisropic Examination. Numerous colorless corpuscles were found in the yellow coagula. These varied in size, from the eighti- eth to the hundred and twentieth of a millimetre in diameter. Acetic acid showed a distinct nucleus in some, about the two hundredth of a millimetre hi dia- meter ; in others it was divided into three smaller ones. White corpuscles and granules were found in the dif- ferent lymphatic glands. In relation to this case, Professor Bennett says, "There was no pridebitis, abscess, or purulent collection, to irhich the appearances within the ressels could be ascribed.'1 He thinks the only bodies which they resemble are the colorless blood-corpuscles, but that no instance was known in which they were found in such numbers; that they originated hi the blood sys- tem itself, as M. Bouchut has shown in various chronic diseases. About six weeks after this, Professor Yirchow, of Berlin, published a similar case, in which he con- firmed the opinion of Bennett, that these were the colorless corpuscles of the blood. Thus was he en- abled, from his previous pathological studies, to con- firm what Bennett had already surmised. The discovery, then, of leucocythemia belongs almost LEUCOCYTHEMIA. 31 equally to both writers. Nor are these singular coin- cidences uncommon in the history of medical discove- ries. Thus were the discoveries of Schwann, in regard to the origin and development of the animal cell, made almost simultaneously with those of Schleiden in relation to the vegetable cell. Case II. — Let us give, in a condensed form, two more characteristic cases from Bennett. Barney Fin- ley, aged seventeen, farm-servant. Admitted into the Royal Infirmary, Jan. 25, 1850. About three years ago, had scarlet fever. With this exception, has had perfect health until one year ago. Then noticed a tumor in abdomen somewhat painful, which has since increased in size so as to cause dyspnoea in walking. On admission, pale and cachectic. A hard tumor can be felt occupying the whole left side, from the false ribs to within an inch and a half of the symphysis pubis, and extending backwards to within three inches of the spinous processes of the lumbar vertebrae. Liver, on percussion, found natural; tongue clean; appetite good. Has had profuse diarrhoea for the last three or four weeks. Pulse 80 ; weak; some vertigo; sounds of heart natural. Has occasional epistaxis, and hemorrhage from the gums. Respiratory and 32 LEl'UX YIIIKMIA. urinary systems healthy. Blood drawn from finger contained the colorless corpuscles in great numbers. Acetic acid brought into view a single nucleus in some; but. in the majority, two, three, and even four nuclei with depressed centres. Occasionally the nucleus was crescent ic. Jan. 27, diarrhoea diminished; less pain. Examination of Blood. Specific gravity of the blood.....1041..") Specific gravity of the scrum.....102(!.5 (''imposition of 1000 Parts. Fibrine............ (>.0 Serous solids..........72.0 (.lobules............07.5 Total solids........II").5 Water.........854.5 1000.0 Feb. 2, urine loaded with lithatcs ; diarrhaa returned. March 24, during the last few Aveoks, recurrence of hemorrhage from nose and gums ; ascites not abated. Aug. 7, more or less recurrence of diarrhoea and epistaxis during the last six months. Ascites not all gone. Dismissed, and returned home. Died July 22, 1*51, extremely emaciated. LEUCOCYTHEMIA. 33 Post-mortem Examination and Report of Dr. Sandwith. Heart very small ; lungs healthy ; liver Aveighed three pounds and tAvelve ounces; spleen weighed three pounds and fourteen ounces; mesenteric glands en- larged and pale ; kidneys small, — weighed together six ounces. Microscopic examination of the blood showed numerous white corpuscles. This case was remarkable for its duration, and the persistent recurrence of the diarrhoea under energetic treatment and most favorable hygienic circumstances. The spleen was the principal organ involved; but the lymphatic glands Avere also somewhat enlarged. As- cites was a marked feature of the case. There was no perceptible change in the number of white corpus- cles in the blood while under treatment. During the progress of the disease, the fibrine increased to twice the amount usually found in healthy blood; the albu- men and salts remained normal; the globules were diminished to one - half their usual number; the Avater was proportionally increased. Thus Ave have a condition of the blood peculiar to no other knoAvn dis- ease ; at least, to the same extent. We have a disease, too, Avhich has thus far been singularly fatal; AArhose 5 34 LEICOC YTHF.MIA. diagnosis admits of very little doubt; and the prognosis of which, when Avell marked, is any thing but favora- ble. Is it not singular, then, that this disease should have so long escaped the attention of observers . It is to the microscope, as a means of diagnosis, that avc OAve its discovery. The relations between these differ- ent glandular enlargements and the multiplication of the Avhite corpuscles in the blood would never have been known Avithout it. In the twTo instances of leucocythemia already quoted, the spleen, liver, and lymphatic glands, were all hypertrophied in one ; and the spleen and mesen- teric glands, in the other. In the latter case, there was ascites, and the kidneys were someAvhat atrophied. In the one Avhich we are about to condense from the same author, the spleen and liver were both enlarged, and the patient had ascites. The urine, in both cases where ascites existed, was loaded Avith the lithates. Case III. — Thomas Welsh, sailor, aged twenty. Admitted into the Royal Infirmary, Sept. 22, 1851. In June, 1847, first experienced pain and SAvelling in splenic region; shortly afterwards, had SAvelling also in right side of abdomen, folloAved by jaundice. The latter disappeared, and he regained his health. Had LEUCOCYTHEMIA. 35 occasional attacks of jaundice since, and abdomen has slowly enlarged. On admission, is generally emaciated; abdomen en- larged ; no ascites. Extensive hepatic and splenic dulness. BoAvels loose ; respiration embarrassed ; impulse of heart feeble ; pulse 78. Of small sta- ture and sallow skin. Urine healthy. The relative number of colorless and colored corpuscles, thus far, unchanged. Had occasional diarrhoea and epistaxis until October. During this month, had a severe attack of laryngitis. In the latter part of December, ascites came on: the urine was diminished in quantity, and loaded Avith lithates. The blood was examined from time to time; and, on the 3d of January, a decided increase of the colorless corpuscles was observed. The ascites was diminished by diuretics: but the color- less corpuscles continued to increase; considerable groups of these bodies being seen between the rolls of colored disks under the microscope. His strength became much diminished; but he left the infirmary, Feb. 27, 1852. He died two days after reaching Berwick. There Avas no post-mortem examination. The fol- lowing analysis of his blood was made by Dr. W. Robertson on the 7th of January: — 3(5 LKl VO( YIHEM1A. Density of blood.........10-I.J... Density of serum........102<.0 Composition of 1000 Parts. Fibrine............ 3.2 Serous solids { °rganiC'. 1™] • • • 80.7 ( inorganic, 10.6 ) Globules........... (). To these is added a somewhat elabo- rate discussion of the subject from a physiological pomt of view. Name. Age. Degree. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 15 43 13 16 19 25 56 23 28 17 50 27 60 35 32 32 29 50 Advanced. Advanced. Well marked. Moderate. AVell marked. Moderate. Advanced. Slight. Moderate. Slight. Moderate. Well marked. Advanced. Well marked. Slight. Slight. Advanced. Well marked. Liver. Spleen. Abdominal Glands. Remarks. lbs. oz. 3 10 6 14 4 7 3 5 3 2 2 8 2 7 2 0 Natural. Natural. 5 10 6 8 5 11 5 9 4 0 lbs. oz. 2 4 0 22 2 14 0 6 0 5 0 6 Natural. Natural. 14 oz. dense. 8 lbs., with deposit. 0 27 22 oz.deposit. 0 16 3 13 8 oz. dense. Little enlarged. Twice natural size. Enlarged. Highly Tubercular. Greatly enlarged. Mucous coat of ileum thickened. Enlarged. Not mentioned. Not mentioned. Little enlarged. Not enlarged. Little enlarged. Much enlarged. Enlarged. Not enlarged. Not examined after death. Dismissed from the house; did not return. Tubercular Peritonitis. Not examined after death. Cancer in various organs. Cancer in Lung. Tubercular Peritonitis. Aneurism. Waxy kidneys. Cerebral Hemorrhage. Glanders ? Pneumonia. Tubercle in Lungs. Bright's Disease. Melsena. Acute Tuberculosis. Bright's Disease. 3^ LEUCOCYTHEMIA. Let us, then, examine the peculiar views of Bcn- nett, before passing to the consideration of the labors of others. In this manner. Ave shall give more unity to our subject; since each author's cases must neces- sarily serve to illustrate his ideas of the disease. Let us examine, for a moment, his ideas of its patho- logy. Among the hypertrophies, Avhich are always more or less present, the spleen has most usually been affected. The enlargement hi these cases was chiefly OAving to numerical hypertrophy. Xext in frequency, the liver has been found enlarged. In a few instance's, it Avas found in a state of cirrhosis, or even cancerous. The lymphatic glands are also prone to be similarly affected. Hypertrophy of the thyroid gland, or bron- chocele, has, in a few cases, given rise to leucocythe- mia. Bennett gives the details of a very interesting case of this kind. He also mentions others in Avhich the blood was found in this condition by l)rs. Holland and Xeale. Disease of the supra-renal glands is mentioned as sometimes associated Avith a leucocythemic condition of the blood. Considerable difference is found in the relative proportion between the white and red corpuscles in different cases. Sometimes they are LEUCOCYTHEMIA. 39 nearly equal in number; at others, the white ones exceed the red: but, in the majority of instances, the red ones are found in the largest numbers. Different fields of the microscope are found to present the two kinds of corpuscles in somewhat different relative proportions. Sometimes the white corpuscles Avill cluster more thickly along the borders of the streak of blood, and thus appear much more numerous than they otherAvise would. It requires much time and care to approximate even to their relative num- bers. The white corpuscles differ also considerably in size. They are from two to three times the dia- meter of the red ones. In two cases mentioned by Bennett, they were of the same size as the red cor- puscles ; in one of which, there was also the larger variety at the same time. They contained from one to four nuclei; or, in some cases, an elongated and crescentic nucleus. This is ultimately divided into two or more nuclei. From an analysis of the blood in several of the foregoing cases, the fibrine was generally found to be increased, and the corpuscles diminished. The fibrine ranged betAveen three and. seven parts, and the cor- puscles from one hundred to fort} -nine parts in a thou- sand. 10 I.EUCOCA THEMIA. It is, according to Bennett, the opinion of many physiologists, that the colored corpuscles are fonned directly from the colorless corpuscles of the blood. Others suppose, that, Avhilst this may be the case in fishes, reptiles, and bhds, in mammals the colored corpuscle is the liberated nucleus of the colorless one. This latter vieAV accords with the observations of Bennett upon the blood-corpuscles in leucocythemia. The folloAA'ing is his idea of the process of transforma- tion : The nucleus of the colorless cell becomes divided into two, three, and four nuclei; the cell-Avail gradually dissolves, and the nuclei escape into the cir- culation, and become the colored corpuscles, whilst still in the nuclear stage of groAvth. Some of them, how- ever, acquire cell-walls. " Under such circumstances," says Bennett, " the nuclei increase endogenously by a process of fissiparous division, in the manner formerly described ; circulate in the blood within colorless cells ; and, on the solution of the cell-Avail, also become colored blood-disks." Let us noAv, for a moment, apply this theory of cell- groAvth to the rational explanation of leucocythemia. In this disease, then, Ave have an excessive multiplica- tion of the Avhite corpuscles of the blood, and, at the LEUCOCYTHEMIA. 41 same time, a persistence of their cell-membrane, even after entering the systemic circulation; or, in other Avords, we have an excessive growth of imperfectly developed blood-cells. In such cases, the cell-mem- brane, or parent cell, still encloses its multiple nucleus. Sometimes these nuclei present a distinct depression, or shadowed spot in their centres; at others, the nu- cleus becomes oval, elongated, or even crescentic, con- taining, at the same time, two or three granules with depressed centres. " On one occasion," says Bennett, " the colorless bodies in the blood were of two distinct sizes. The smaller were evidently free nuclei, such as could be observed within the larger." The lymphatic glands in this case were observed to contain the smaller bodies in great numbers, associated with a few of the larger ones. Thus it would seem, that the white corpuscles of the blood are only lymph- corpuscles with the addition of a cell-membrane. If this position be acceded to, and certainly it is in har- mony with the observations of the latest and best writers upon these subjects, what more can we desire for the rational explanation of the causes of leucocy- themia \ Is it not the tendency of modern investiga- tions to trace all pathological back to physiological 6 42 LEUCOCYTHEMIA. processes? Do avc not sec in the enlarged glands, Avhich are always met with in leucocythemia, a suffi- cient cause for the increased production of cell ele- ments ? Thus has the power of forming white blood- corpuscles been increased in proportion to the extent of this glandidar hypertrophy. In those mstances hi which the progress of leucocythemia has been ob- served from the first appearance of any increase of the white corpuscles in the blood, the enlargement of the spleen or some other lymphatic glandidar organ has always preceded this change. Thus the hypertro- phy of the spleen and other lymphatic glandular organs must be considered as the cause, and not as the consequence, of leucocythemia. The cause, then, of leucocythemia, is so intimately connected with the origin of the blood-corpuscles, that a thorough consideration of this disease necessarily involves an inquiry into the sources from which they are deiived. Whatever light may be thrown upon this obscure point by comparative physiology, Bennett has made use of to illustrate his theories. The origin and mode of development of the blood-corpuscle, as at present known, in fishes, reptiles, and bhds, are carefully com- pared with the origin and development of those in LEUCOCYTHEMIA. 43 man. He concludes the subject of leucocythemia in the following brief paragraphs: — 1st, "The blood-corpuscles of vertebrate animals are originally formed in the lymphatic glandular sys- tem ; and that the great majority of them, on joining the circulation., become colored in a manner that is as yet unexplained. Hence the blood-corpuscles may be considered as a secretion from the lymphatic glands; although, in the higher animals, that secretion only becomes fully formed after it has received color by exposure to oxygen in the lungs." 2d, " That, in mammalia, the lymphatic glandular system is composed of the spleen, thymus, thy- roid, supra-renal, pituitary, pineal, and lymphatic glands." 3d, " That in fishes, reptiles, and birds, the colored blood-corpuscles are nucleated cells, originating in these glands: but that, in mammals, they are free nuclei, sometimes derived as such from the glands; at others, developed within colorless cells." 4th, " That, in certain hypertrophies of the lympha- tic glands in man, then cell-elements are multiplied to an unusual extent, and under such circumstances find then Avay into the blood, and constitute an increase in the number of its colorless cells. A corresponding 44 LEUCOCYTHEMIA. diminution in the formation of free nuclei, and conse- quently of colored corpuscles, must also occur. This is leucocythemia." In the London "Lancet" for Jan. 3, 1863, Avill be found the first of a course of lectures now being delivered by Professor Bennett, " On Molecular Phy- siology, Pathology, and Therapeutics." In these lec- tures, which are an exposition of his latest views upon cell-development, he advances the well-known theory of the agency of molecules in growth and disintegra- tion. He characterizes these processes of formation and disintegration by the names of histogenetic and histolytic processes. He speaks of these molecules as bemg of three different kinds, — albuminous, fatty, and mineral compounds. He illustrates, by a figure from Rainey, the process by Avhich mineral molecules coalesce into cell-forms. Several of these forms are shown, which bear a striking resemblance to what we observe in the growth of vegetable and mineral cells. Whether this is a mere casual resemblance or not, is a matter well worthy of the attention of physiologists. In the " Lancet" of Jan. 17, 1863, is the second of Bennett's course of lectures. In this lecture he brings forward three prominent theories of cell-development, — that of Schleiden and Schwann (1839), of Goodsir LEUCOCYTHEMIA. 45 (1845), and of Huxley (1853). The first of these is known to every physiologist: the second does not essentially differ from the first. This theory regards the nucleus as the centre of nutrition and germination. The third theory, or that of Huxley, considers the nucleus as a comparatively unimportant element, and ascribes all morphological and chemical changes to the periplast, or cell-wall. This last theory is not strictly one of cell-genesis, but of the morphological growth of cells. Bennett's theory in regard to the reproduction of cells is this: There are four different modes in which cells may arise: — 1st, Endogenously, or cell within cell. 2d, Exogenously, or outside of cells by extrusion of contents. 3d, Fissiparously, or by division. 4th, Gemmiferously, or by the process of budding. These may all be seen in one plant, proceeding together. The first and second modes are most common in adult animals; the third, in the embryo. Previous to the publication of Huxley's views, the late Dr. Waldo I. Burnett, of Boston, made an elabo- rate study of cell-development in animals, and, to some 46 LKUCOCATHLMIA. extent, in plants. In his admirable prize essay upon this subject, he shows very clearly, at least in animal cells, that the nucleus is a hollow vesicle, or utricle, which becomes enlarged by cndosmosis; the contents of Avhich may afterwards become condensed to form a nucleolus or another similar utricle. A similar mode of cell-origin has been shown hi plants by Braun and other physiologists. Dr. Burnett regards the embryonic blood-cell of both the oviparous and mammalian vertebrates as " of an cpithchal nature, and simply provisional." He thinks that adult blood, A\iiich is elaborated from the food alone, contains typical corpuscles. As regards the blood-corpuscles of the mammalia, he is of opinion that they " are formed around the granules Avhich con- stitute the compoimd nucleus of the chyle-cell; the nucleus afterwards becoming dissolved, and, in nearly every instance, entirely passing aAvay." This theory is confirmed, in a great measure, by the transition stages which have been found in many of the blood-corpus- cles of leucocythcnua. In closing this reAieAv of Professor Bennett's labors, it is but just to say, that he has already done more than any one else, of late years, to excite a lively interest in the study of the pathology of the morpholo- LEUCOCYTHEMIA. 47 gical elements of the blood; and it is to be hoped, that his present course of lectures will not be without their good effect in this direction. VIRCHOW. From a careful comparison of the writings of Ben- nett and of Virchow upon leucocythemia, it is impossi- ble to find any essential difference in the views of either as regards the origin or nature of this disease. Both are agreed, that numerical hypertrophy of the spleen, or multiplication of its cellular elements, is the principal cause of the increased number of white corpuscles in the blood. Both are equally agreed, that the same kind of hypertrophy of other lymphatic glands is also the cause of a leucocythemic condition of the blood. Bennett makes no distinction between the different varieties of leucocythemia as regards its origin, but considers them all essentially the same. Virchow divides this disease into two distinct varieties, — the splenic and lymphatic, according to the organs affected. Both authors regard numerical hypertrophy of the spleen as the most common cause of this disease. Let us now consider more fully the views entertained by Virchow upon this subject. These views are given 4H LEUCOCYTHEMIA. at some length and Avith great clearness in his recent work on " Cellular Pathology." So interwoven are they, however, Avith his cell-doctrines, that then unity and beauty are, in a measure, lost by being separated. Nevertheless, in the hniited space Avhich must be allotted to them in this essay, let us give an adequate idea, if possible, of these views. That remarkable change by Avhich the blood for a time contains more than its usual number of white corpuscles has been denominated by Virchow, leukocy- tosis. This temporary condition of the blood is not an unusual one. After every full meal, there exists, ac- cording to this author, Avhat may be properly called a j)hysiological leucocytosis, or augmentation of the white blood-corpuscles in the circulation. This phenomenon is attributed by him to the irritation of the mesenteric glands during digestion by the large quantities of material passing through them, and is considered a strictly normal one. In disease, however, of these or any other of the lymphatic glands, provided that the disease has not proceeded so far as to interfere with their functions, there is also a more or less permanent leucocytosis, or increase of the Avhite-blood corpuscles. To this more permanent condition of the blood, he has given the LEUCOCYTHEMIA. 49 name of " Leukaemia," or " Avhite blood." It must be remarked, that, in the physiological leucocytosis, there is but a very inconsiderable and transitory in- crease in the number of Avhite blood-corpuscles ; Avhile, in the permanent or pathological leucocytosis, their number is gradually augmented, until it almost equals, in some cases, that of the red blood-corpuscles. As to the amount of this increase of the Avhite corpuscles during digestion, Virchow has given us no approximate idea. Milne Edwards states, that, in a series of experiments upon the numerical relation between the red globules and the white, before and after meals, Donders and Moleschott found, that, in the rabbit, the proportion of the latter augments considerably during the process of digestion. Thus, urjon counting the number of white globules which were found in the field of the microscope, arranged so as to contain about two thousand red globules, they have seen one or two of these globules (corpuscles) hi the morning, AAiien the animal had fasted during the night; a little Avhde after he had eaten, the num- ber increased to four, then to ten; three hours after the meal, it diminished again; and, after an interval of nine hours, fell to nearly the same rate as in the morning. 50 I.r.rcOCYTHEMIA. Iii man, the influence of meals Avas equally marked by an augmentation in the proportion of the white globules ; but the difference was not so great. In another series of analogous observations. Mole- schott has also seen that the proportion of white globules is diminished by abstinence, and augmented by starchy food. Dr. E. Ilirt has published a more extended work upon the same subject; and he has represented by curves the relative numbers of the red globules and of the plasmic or lymphatic cells observed in the blood during different periods of the digestive process. Indeed, under these circumstances, the absolute number of red globules docs not seem to vary notably ; and, consequently, the differences in the proportion of the Avhite corpuscles can be considered as being the expression of the variations in their real number. In the morning, fasting, the proportion of these corpuscles Avas about one Avhite globule for eighteen hundred red ones ; an hour after his break- fast, Avhich took place at eight o'clock, he found one Avhite for scAen hundred red globules; and, bctAvcen eleven and one o'clock, the relative number of these plasmic cells had decreased again to one for fifteen hmidred red globules. He dined at one o'clo-k ; and soon afterwards the plasmic cells became more abun- LEUCOCYTHEMIA. 51 dant than they had been after breakfast, — one for about four hundred red globules. These experiments have been verified by other observers; nor Avould they have been given so fully, did they not seem to have an important bearing also upon that singular yet Avell-attested phenomenon, the gradual enlargement of the spleen during the process of digestion. Thus Dr. William Dobson found this organ to be increased in size from the third up to the fifth hour after feeding ; at which period it had attained its maximum, and afterAvards began to diminish. This active congestion and enlargement of the spleen during digestion is now a well-known pheno- menon. Thus, indeed, are two widely separated and seemingly unimportant facts brought together in the close relation of cause and effect, and mutually made to corroborate each other. So, in the ever-varied book of Nature, are Ave tracing those wonderful rela- tions in the phenomena which are constantly recur- ring around us. The fall of an apple suggests to a philosophical mind the law which gives harmony to the system of worlds. An occasional pebble thrown into the great ocean of thought leaves its ripple upon the sands ; and the adventurer who comes afterwards sees in its impress the indications of some widely per- 52 1.1 rcoCYTHl.MI \. vading law. Step by step, by the slow process of accretion, have all of the inductive sciences been built up. Thus, in a manner, has the knowledge of the physiology of the blood and the blood-making pro- cesses been acquired from widely separated and seemingly disconnected phenomena. Observation, in physiology, has taught but little; generalization, much. An age of observers has generally been fol- loAvcd by an age of theorists ; but hardly ever, as in the case of VirchoAV, do Ave see the genius of the observer and the theorist combined. In the masterly manner Avith A\iiich he has handled not only the sub- ject of leuka?mia in all its bearings, but the Avhole theory of cellular pathology, avc have a guaranty of the truth and the importance of his doctrines. It is of the utmost necessity, in a discussion like this, to leave no step untaken Avhich will lead to a more thorough knowledge of the facts upon Avhich each author's vicAvs are. in a measure, based. As long ago, then, as 1S47, the theory of Sclrwann, in regard to the animal cell, Avas someAvhat modified by Vir- chow. As the matter then stood, Avhat really appeared to constitute a vegetable cell, Avas the presence, Avithin a non-nitrogenized membrane, of nitrogenized con- tents differing from it. Virchow has shown, that, in LEUCOCYTHEMIA. 53 all the essential constituents of animal cells, there are nitrogenized matters. But, in the lowest grade of animal cells, cartilage stands, in every respect, in the closest relation Avith vegetable tissue; and thus the ordinary membrane of the animal cell corre- sponds to the primordial utricle of the vegetable cell. We have, then, in the primitive vegetable and ani- mal cell, a structure of wonderful simplicity and con- stant recurrence in every living organism. There are certain laAvs, Avhich it follows in its origin, develop- ment, and decay, Avhich are necessary to it for its very existence. It is a vital entity of itself, Avhatever may be its position or its surroundings. Thus the blood- corpuscle enjoys a purely cellular existence. And as, according to Virchow, " all those cellular formations Avhich lose their nuclei have a more transitory exist- ence, they perish, they disappear, they die away, or break up;" so the red blood-corpuscle, which has already lost its nucleus, has run its appointed race, at least as a nucleated cell. Indeed, Virchow thinks there would be some doubts of the cellular nature of the red blood-corpuscle, were it not known to have a nucleus in the embryo. The red blood-corpuscles are compared by him to 51 LLTCOCYTHKMIA. the uppermost cells of the cuticle. Avhich have also lost then nuclei and arc about to perish. Nothing could be more just than this comparison ; since there is ample testimony to show that all embryonic blood, at least in the vertcbratcd series, abounds in corpus- cles of an epithelial character and origin. Kcillikcr also admits of a complete identity betAveen the earliest blood-globules and the histogenic cells of other parts of the embryo, and thinks that they arc derived from the substance of the Avails of the great acsscIs, as avcII as of the heart. Remak has arrived at the same conclusion, and has demonstrated the presence of blood-globules in the t. Sur le Developpemcnt du Cirur ft. la Forma- tion du Sang (Annates des Sciences Xaturellos, 1824). Edward?. II. Milne. Lecons sur la Physiologic ot l'Anatomie comparee de 1'IIomme et des Animaux. Paris, 1857. ,; 0 d (3 (^ (,vr >^ o c. ^ (S J» ci <# o) © ijj ^ @ -J) @ O a ^ 5 a .' ^J C O \> '' i . -> A^ <2 .-. r \>:c\ .:=?;. U . illv,,,-y. !' • !'.;'»!>.%••;•;;■. . . i i «-'* * • • ». . •>•! s. '-• ■-. >-»- ••- ■' ■— V •«• •■»•' :-:«:«;«ni<*v