The spleen and anæmia; experimental and clinical studies

Front matter

Class.

Book .

JO

Preface

In this volume splenectomy is considered, first, as a means of studying experimentally in animals the relation of the spleen to blood destruction and regeneration and, second, as a therapeutic procedure in the treatment of diseases of man accompanied by ansemia. No attempt is made to discuss injuries, infections and tumors of the spleen, or, except incidentally, the problems — leukocytosis and leucaemia — of the white blood-cells. The emphasis is on the side of the red blood-cell and the relation of the spleen to the quantitative and qualitative changes which the red cell may undergo.

The chapters on experimental and metabolic observations are based on some twenty odd studies carried out during the past five years in the John Herr Musser Department of Research Medicine of the University of Pennsylvania, and reported from time to time in medical periodicals, under the general title of " The Relation of the Spleen to Blood Destruction and Regeneration and to Hsemolytic Jaundice." These various papers have been rearranged and largely rewritten and brought into relation with the general literature so as to offer a consecutive comprehensive presentation of the general experimental problem.

Such experimental studies are obviously of importance in connection with the diseases of man characterized by splenomegaly, with ansemia or jaundice, or both, and in connection with which splenectomy, as a therapeutic procedure, has recently been so widely tried. Clinical studies of the splenomegalies and of the results of splenectomy in man are therefore presented by Dr. Krumbhaar. These chapters bring into one volume for the first time the modern vi PREFACE

views concerning the classification, diagnosis and treatment of the non-infectious splenomegalies characterized by blood destruction. The final section by Dr. Frazier gives details of the technic of the operation of splenectomy in man. This has been included, partly to complete our presentation, but chiefly to bring out new points concerning the operation which have been gained as the result of its widely extended use during the last few years.

Acknowledgments are due, and are gratefully made, to those assistants, — J.H. Austin, M.D. ; Harry Dubin, Ph.D. ; A. B. Eisenbrey, M.D.; Samuel Goldschmidt, Ph.D.; H. T. Karsner, M.D.; E. B. Krumbhaar, M.D.; J. H. Musser, Jr., M.D.; M. M. Peet, M.D., and O. H. Perry Pepper, M.D., — who assisted in the experimental work and thus made possible the many detailed studies, and likewise to the Board of Scientific Directors of the Rockefeller Institute for Medical Research, who by grants of money from time to time furthered the distinctly laboratory studies. To the editors of the Journal of Experimental Medicine, Archives of Internal Medicine, American Journal of the Medical Sciences, The Journal of the American Medical Association and the New York Medical Journal, we are also indebted for the privilege of reproducing in the present form material originally appearing in their journals.

The material presented under the headings of experimental and metabolic studies constitutes the substance of the Cartwright Lectures delivered in New York on October 24 and 25, 1916, under the auspices of the Association of the Alumni of the College of Physicians and Surgeons of Columbia University.

September, 1917. THE AUTHORS.

Part I

Experimental Studies by R. M. Pearce.

CHAPTER PAGE

I. The History of Extirpation of the Spleen 3

II. The Effect of Splenectomy in the Dog 11

(1) The Anaemia, (2) The Increased Resistance of the Red Blood-cells, (3) The Decreased Tendency of Haemolytic Agents to Cause Haemogiobinuria and Jaundice.

III. Concerning the Supposed Regulatory Influence

of the Spleen in Blood Destruction and Regeneration 58

A. In Relation to the Decreased Tendency to Hemoglobinuria and Jaundice: (1) The Relation of Spleen to the Liver and the Formation of Bile from Haemoglobin, (2) The Influence of the Course of the Blood to the Liver, (3) The Influence of Anaemia, (4) Influence of the Increased Resistance of the Red Cells, (5) Are Splenic Extracts Haemolytic? (6) Hemolytic Influence of Fatty Acids and Lipoids in Haemolysis.

IV. Concerning the Supposed Regulatory Influence of

the Spleen in Blood Destruction and Regeneration 87

B. In Relation to Anaemia: (1) A Comparison of the Arterial and Venous Blood of the Spleen, (2) Influence of Splenic Extract upon Blood Formation, (3) Influence of Feeding Spleen to Splenectomized Dogs, (4) The Repair of an Artificially Produced Anaemia in Splenectomized Animals, (5) The Influence of the Spleen upon Iron Metabolism.

V. Control Experiments: The Diversion of the Splenic Blood from the Liver Without Removal of the Spleen 121

vii viii CONTENTS

(1) By Ligation of the Splenic Vein, (2) By Transplantation of the Splenic Vein into the Vena Cava, (3) By Eck Fistula.

VI. The Changes in the Bone-marrow After Splenectomy 140 (1) Discussion of the Literature, (2) Histological Studies of the Dog's Normal Marrow, (3) Changes After Splenectomy.

VII. The Changes in the Liver and Lymph-nodes After

Discussion of the Literature. Changes in Lymph-nodes. Phagocytosis of Red Cells by Endothelial Cells of Lymph-nodes and Liver. Microchemical Test for Iron in Lymph-nodes and Liver. VIII. Metabolism Studied on the Dog Before and After

IX. General Summary of Experimental Studies 195

X. Metabolism Studies on Man Before and After

Part II

Clinical Observations by E. B. Krumbhaar XL Classification and Analysis of Types of Splenomegaly Accompanied by Anemia 241

Splenic Anaemia, Gaucher 's Disease, Banti's Disease, Von Jaksch's Disease, Acquired and Congenital Hsemolytic Jaundice, Pernicious Anaemia. XII. Methods of Value in the Diagnosis and Prognosis

of Splenic Disease 269

XIII. Treatment of Splenic Diseases by Methods Other

than Splenectomy 291

XIV. Treatment: Value of Splenectomy as a Therapeutic

Procedure 299

Part III

Surgical Observations by Charles H. Frazier XV. The Surgical Treatment of Lesions of the Spleen 333

(1) Preparation of the Patient for Splenectomy

(2) The Operation and (3) The After-care of the Patient.

ILLUSTRATIONS

COLOR PLATES

PLATE OPPOSITE PAGE

I. Lymph-nodes and Liver of Splenectomized Dogs Receiving Hemolytic Serum and Showing Phagocytic Cells

Containing Red Blood-corpuscles Frontispiece

II. Histology of Gaucher's Disease. Alveolar Arrangement

of Large Vesicular Cells with Small Concentric Nuclei 245

ILT. Spleen of Banti's Disease 248 '

IV. Histology of Spleen of Early Banti's Disease 250

V. Histology of Spleen of Late Banti's Disease 252 v

VI. Histology of Spleen of Congenital Hemolytic Icterus. . . 252

VII. Spleen of Pernicious Anaemia 265 v

VIII. Test for Resistance of Erythrocytes. Salt Solution (Nace)

Varying in Strength from 0.3 to 0.5 Per Cent 267 v

IX. Reticulated Red Blood-cells. From a Case of Hemolytic

Jaundice 276

X. The Relationship of the Tail of the Pancreas to the

Posterior Aspect of the Pedicle 346

XI. The Peritoneal Prolongation Between the Spleen and the Splenic Flexure of the Colon, Which Must be Divided Before the Organ Can be Completely Mobilized. . . . 347

XII. Left-side Bevan Incision for Splenectomy 350 •

Xni. First Step in the Mobilization of the Spleen 352

XIV. To Control Bleeding After Mobilization of the Spleen a Large Tampon of Gauze, Wrung out in Hot Water,

is Introduced into the Left Hypochondrium 352

XV. Fractional Ligation After Isolation of the Vessels of the Pedicle by Blunt Removal of Fat and Connective

Tissue 353

XVI. The Double-clamp Method of Dealing with the Pedicles 353

ix

ILLUSTRATIONS

TEXT CUTS

1. Composite Curve of the Red Blood-cell Count of Seven Dogs

2. Composite Curve of the Haemoglobin Estimation of Seven

Dogs After Splenectomy 15 •

3. Composite Curve of the Leucocyte Counts of Five Dogs After

PARTI

EXPERIMENTAL STUDIES BY R. M. PEARCE

Chapter I The History Of Extirpation Of The Spleen

The statement is frequently seen that the ancients practised removal of the spleen in the belief that it improved the wind of runners. It is also stated in the older literature that the swift giraffe is spleenless, an erroneous supposition that may have had something to do with the views of the ancients concerning the spleen and the speed of runners. Aristotle 21 assumed that the spleen is not necessary for the maintenance of existence, and Erasistratus insisted that it is of no use whatever. Galen more conservatively considered it an organ full of mystery (Mysterii pleni organon) and that it probably removed the melancholy of the blood going from the liver to the stomach. The first positive statement as to its extirpation (not excision) is made in Pliny's 357 Natural History. An old English 357 translation runs as follows : " This member (the spleen) hath a propriete by itself e sometimes, to hinder a man's running; whereupon professed runners in the race that bee troubled with the splene, have a devise to burne and waste it with a hot yron. And no marveile; for why? They say that the splene may be taken out of the body by way of incision, and yet the creature live neverthelesse ; but if it be man or woman that is thus cut for the splene, he or she looseth their laughter by the means. For sure it is that intemperate laughers have always great splenes." In connection with the last state-

s ment it is interesting that the modern German word for hypochondriasis is " Milzsucht." Pliny is said to have performed experiments involving the removal of the spleen from dogs, but this is probably merely an incorrect quotation of the foregoing. The belief that splenectomy improved the wind of runners was not lost sight of in the middle ages, as is shown by the couplet quoted by Brogsitter 60 from Murer's Belagerung von Babylon:

He also quotes Paracelsus, who considered the spleen " des Leibers und Lebens Unkraut," and advised physicians to excise it whenever possible. Van Helmont, on the other hand, attributed to it important and even vital functions.

The first authentic experimental splenectomy in the dog was performed by Zambeccari 482 in 1680, with apparently an uneventful recovery. Mar cello Malpighi, 272 the discoverer of the lymphoid follicles of the spleen, had previously described the effects of ligating the splenic vessels of a dog. It not only quickly recovered from the operation, with no noticeable injury to health, but became more voracious and much lazier and fatter. Nothing abnormal was noted in the stools. A second operation on this dog, performed some time later, showed almost complete disappearance of the spleen, but no other changes except slight enlargement of the liver and engorgement of the mesenteric vessels. Clarke 78 successfully extirpated a dog's spleen in 1676, and during the year following found no changes except that the animal became much fatter.

The celebrated pathologist, Morgagni, 299 states that he

EXTIRPATION OF THE SPLEEN 5

and Vallisnerius found during a period of five years' study no change in the size, disposition, or fertility of dogs whose spleens had been removed. J. H. Schultze 8M early practised splenectomy on dogs with a view to the application of the operation to human beings. Harvey and his pupils are frequently quoted as having extirpated the spleen in dogs, but we have not been able to find such accounts in Harvey's works.

Observations on experimental splenectomy are more numerous in the nineteenth century. Assolant, 20 found that in dogs the blood became more watery, with the appearance of scurvy-like symptoms and fatal peptic ulcer. He states that Dupuytren lost almost half of forty dogs after splenectomy. Those that survived recovered in two or three weeks and acquired abnormal appetites. Spitta and Mayo found increase in weight, and Mayer increased tendency to sleep. Saunders reported no change in bile formation. A. S. Schultze 3 " removed the spleen of twenty- four animals (dogs, cats, goats, rabbits), losing only one puppy. He states that the operation is followed by lessened fertility, greater inclination and ability to run far, and at first a decreased secretion of bile. Czermak, 85 working with dogs, rabbits and cats, found that two-thirds of the animals survived, and showed lessened fertility and enlargement of the mesenteric lymph-nodes. He noted that the spleen became greatly congested after feeding. Vulpian, 459 on the other hand, found no change in fertility. Enlargement of the lymph-nodes after splenectomy was noted by Tiedemann and Gmelin, 434 Hyrtl, 192 Mayer, 280 Fuhrer and Ludwig, 132 Eberhard, 100 and Simon. 409

Mayer maintained also that the extirpated spleen was easily replaced by a newly-formed organ. This was confirmed by Eberhard, working on the frog, and by certain French and Italian investigators (Philippeaux, 350 Eternod, 107 Tizzoni, 437 ). More careful later work (Peyrani, 348 Tizzoni, 438 Ceresole, 69 Tedeschi, 430 ), however, showed that when the spleen had been completely removed no regeneration took place; but, if a small portion was left in situ, it might hypertrophy and simulate complete regeneration ( Philippeaux, 351 Laudenbach 239 ) . Even this, however, has been denied by Peyrani 349 and Ceresole. 69 Bardeleben 34 found that extirpation of both spleen and thyroid was almost invariably fatal. Mosser 302 noted a stimulation of the bone-marrow.

Thus we find that before the year 1875 numerous experimenters, working on dogs, cats, goats, rats, mice, guinea-pigs, sheep, rabbits, frogs, and one (Eternod) on a fox, had found that the spleen was not necessary to life. Though one out of four splenectomized animals died (usually from peritonitis or pneumonia), the others quickly recovered and enjoyed good health. The most constant findings were increased appetite and eventual gain in weight. At autopsy, enlargement of the mesenteric lymph-nodes was frequently found, with occasionally enlargement of the liver, congestion of the splanchnic vessels, and, according to Mosser and Schindler, 303 stimulation of the bone-marrow. The power to regenerate after extirpation was denied, though it was shown that if small amounts of splenic tissue are left behind, these possess great capacity for hypertrophy.

The first recorded splenectomy on a human being is the celebrated operation performed in Naples in 1549, by Zaccarelli, at the instance of Fioravanti, 117 whose description follows:

EXTIRPATION OF THE SPLEEN 7

In the month of April I was called to a Greek woman, the wife of a Greek centurion, or war captain, who lived at Panormus, near the Garden of Marinus de Terra Nova. Her name was Maruella, and she was twenty-four years old. Her spleen was stopped up (oppilatus) and grew to such a size that the body could not have held a larger one. She had been visited by several doctors and had been told that if she wished to be cured it would be necessary to take the spleen out of the body. The captain himself came to me and took me with him to visit his wife; she desired of me the removal of the spleen. For this purpose I invited an old man named Adrian Zaccarelli, from the town of Palum, in the kingdom of Naples, who was very skilled in surgery. With him I proceeded to the operation. The old man made an incision in the body and immediately the spleen protruded from the body. After we had separated it from the membranes we pulled it entirely out and sewed the body up, leaving only a little hole (spiraculo exiguo relicto). This I cured with oleum hypericonis, incense powder, mastix, and so on. In this manner she was cured in twenty-four days. When taken out of the body the spleen weighed thirty-two ounces.

It should be said that some writers have doubted the veracity of this description, and Simon has suggested that on account of the discrepancy in the size of the tumor before and after removal it may have been an ovarian cyst.

Two other equally doubtful reports of successful splenectomy in the sixteenth century are at hand. Baillon 25 tells in a few words how, in 1578, an unknown operator removed the spleen,

" qui secuit prius superiore parte ligata; convaluit wger. Este igitur splentam necessarius? " (Which he cut after the upper portion had been tied; the sick man recovered. Is then the spleen so necessary to life?)

Rousset 388 also describes the successful removal, by a certain Doctor Viard, of a spleen which had already protruded through a wound in the left side.

In the seventeenth century two cases of total removal of the spleen are recorded. Timothy Clarke's 78 case was reported by an eye-witness, Dr. Dovbeny Turbevile. A certain William Panier, of Somerset, in an attempted suicide drove his butcher's knife into his left side. The spleen, part of the omentum, and the intestines protruded from the wound, and his companions left him for dead. Three days later a surgeon replaced the intestines, cut away the spleen and omentum, and sewed up the wound. The patient quickly recovered, was quite well a year later, and then migrated to New England, where he lived happily and in good health for some years. The second case was of like character. Nicolaus Matthia, 279 the town surgeon of Colberg, in 1678, was sent by the magistrate to a neighboring town to see a young man who had been injured by a knif e-thrust in the left side of the abdomen. The protruding spleen was pulled entirely outside the body and ligated. Three days later the spleen was removed and the bleeding controlled with styptics. The patient recovered completely in three weeks, and six years later was in good health.

Thus physicians began to realize that the spleen was not necessary for life. However, in spite of several similar successful splenectomies in the eighteenth century (Gerbezius, 1700 ; 112 Ferrerius, 1711 ; 112 South- Wilson, 1743 412 ), rest, diet, salves, and bloodletting were considered the proper treatment for injuries of this important organ. The first case of extirpation of the spleen reported in America is apparently that of O'Brien, 319 in 1816, for prolapse following a knife- wound. The patient recovered completely in the space of eight weeks.

Another proof that the spleen is not necessary for life is found in occasional reports of congenital absence of

EXTIRPATION OF THE SPLEEN 9

the spleen. In fact, these reports indicate that an individual may live to an advanced age and exhibit no abnormality traceable to the absence of the spleen. The case reported by Hodenpyl 181 exhibited a general lymphoid hyperplasia, and it is probable that, as after splenectomy there is a gradual adaptation of the blood-regulating organs, so also, in the congenital absence of the spleen, other organs may take on the function of the missing organ. Since the ten cases collected by Hodenpyl, other authentic cases have been reported by Kohlhass, 221 Sternberg, 410 and Riches, 373 making a total of 13. Unfortunately, modern methods of blood examination were not included in the study of any of these cases.

Karl Quittenbaum, 368 who introduced the practice of ovariotomy into Germany, was probably the first to plan deliberate splenectomy for disease of the spleen. Xumerous successful splenectomies on dogs and cats led him to believe that the omentum, whose vessels were always enlarged, took over the function of the spleen. In 1826 he had occasion to practise the operation on a young woman in an advanced stage of hepatic cirrhosis. Though she suffered from extreme ascites and weakness, he yielded against his judgment to the patient's entreaties, and removed the spleen. She died six hours later from shock.

More important in bringing the operation to the attention of the medical world was another unsucessful operation, by Kiichler 231 in 1855. Death occurred a few hours after operation, due to hemorrhage from a branch of the splenic artery that had not been ligated. This gave rise to a lengthy controversy between Kiichler and the Verein Hessischer Aerzte, represented by the surgeon, G. Simon. Efforts towards reconciliation by Adelmann, of the University of Dorpat, to whom the matter had been referred, were unsuccessful. On account of Simon's greater reputation, his opinion prevailed that the operation was justifiable only when necessitated by an otherwise fatal wound. Ten years elapsed before splenectomy was again reported, this time in England by Spencer Wells, 465 whose patient died one week after operation, probably from septicaemia. The nature of the enlargement of the spleen is not stated. In spite of the unsuccessful outcome of this case, attempts at splenectomy quickly became more numerous. Thus Schumann, 400 collected sixteen cases in 1868; Collier, 82 twenty-nine in 1882, and Adelmann, 4 fifty-three in 1887. Since that date the literature on splenectomy has been very thoroughly covered by three authors, Vulpius 460 (to 1894) , Laspeyres 238 (1894 to 1903), and Michelsson 290 (1903 to 1913) . These reports show that in later years the mortality after splenectomy has been materially reduced. This is due in part to improvement in technic and in part to the general abandonment of the operation in cases of leukaemia, in which condition surgical interference is nearly always disastrous. For the simpler conditions, such as cyst, torsion, or wounds uncomplicated by copious hemorrhage, the mortality is almost nil. The recent applications of splenectomy to other conditions, as the anaemias, will be discussed in later chapters.