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 THE SPLEEN 
 
 AND SOME OF ITS DISEASES
 
 THE SPLEEN 
 
 AND SOME OF ITS DISEASES 
 
 BEING 
 
 ffirafcsbaw Xcctnrc 
 
 of the Royal College of Surgeons of England, 
 
 1920. 
 
 BY 
 
 SIR BERKELEY MOYNIHAN, 
 
 LEEDS. 
 
 WITH 13 FULL-PAGE DIAGRAMS 
 
 PHILADELPHIA : 
 
 W. B. SAUNDERS COMPANY. 
 
 11Z
 
 1C 
 
 Wfl 
 
 600 
 
 IUI 
 
 TO 
 
 THE PRESIDENT 
 
 AND MEMBERS OF THE COUNCIL 
 
 OF THE ROYAL COLLEGE OF SURGEONS 
 
 OF ENGLAND 
 
 624032
 
 PREFACE. 
 
 THIS book contains the material upon which I based the 
 Bradshaw Lecture delivered at the Royal College of 
 Surgeons of England in December, 1920. 
 
 The surgery of the spleen has hitherto enjoyed only a 
 very restricted field. The removal of the enlarged or injured 
 organ, or of the normal organ whose pedicle has twisted, or 
 the opening of abscesses or cysts within the spleen, has been 
 all that it was possible to do. 
 
 But in recent years the part played by the spleen in 
 many other diseases has gradually been recognized, and an 
 extension of surgical treatment to cases of cirrhosis of the 
 liver, pernicious anaemia, haemolytic jaundice, etc., has taken 
 place. 
 
 We are beginning to realize that the spleen, too, plays 
 its part, perhaps a considerable one, in the etiology of 
 diseases whose most conspicuous symptoms are evoked 
 by associated or consecutive affections of other organs. We 
 can 110 longer consider diseases which affect one abdominal 
 organ as being restricted to that organ. In the provocation 
 and in the development of the morbid affections of any of 
 these viscera, many of them may take a share. The spleen, 
 which has been little regarded in this connection, may 
 now justly claim a measure of attention. 
 
 I am much indebted to Dr. Gruner for his help in the 
 preparation of the diagrams, and of the list of references ; 
 and, generally, for his wise counsel. He is in charge of my 
 private laboratorj^, and the interstices of my surgical life 
 are filled in by visits to him there, and by most helpful 
 discussions at all times. 
 
 BERKELEY MOYNIHAN. 
 LEEDS, 67. Patrick's Day, 1921.
 
 CONTENTS. 
 
 CHAPTER PAOK 
 
 I. ANATOMY OF THE SPLEEN - 1 
 
 Relations Peritoneal attachments Blood-supply Surface 
 markings Significance of anatomical features Occasional absence. 
 
 II. THE SURGERY OF THE SPLEEN 4 
 
 History Association of spleen with laughter, and with speed in 
 running Early records of splenectomy Experimental observations ; 
 Cases of absent spleen Splenectomy in modern times. 
 
 III. ON THE FUNCTIONS OF THE SPLEEN - 17 
 
 Brief consideration of the minute anatomy and physiology of 
 the spleen and liver Lines of inquiry and research Results of 
 splenectomy in animals Questions suggested thereby Connections 
 of the spleen with other organs The spleen as a member of the 
 haemopoictic system Reticulo-endothelial system Digestive system 
 Sympathico-endocrine system. 
 
 IV. THE PATHOLOGY OF SPLENIC DISEASES - 89 
 
 Pathological changes grouped according to affinities between 
 causal agents and parts of spleen-liver system affected Varieties of 
 toxins entering or leaving spleen, and their actions. 
 
 V. THE CLINICAL AND ASSOCIATED PHENOMENA IN SPLENIC 
 
 DISEASE - 48 
 
 Anaemia Jaundice Petechial haemorrhages Muscular weak- 
 ness Pyrexia Splenomegaly Leucocytosis Spleen and hsemor- 
 rhagic diathesis Urobilin in the urine. 
 
 VI. PERNICIOUS ANAEMIA (ADDISON'S ANEMIA, IDIOPATHIC 
 
 ANAEMIA) - - - - - 54 
 
 History 'Primary' and 'secondary' misleading as applied to 
 anaemia The blood in anaemia Pathology of pernicious anaemia 
 Source of toxin Important signs and symptoms Treatment by 
 splenectomy. 
 
 VII. LEUKAEMIA - - - - - - -69 
 
 History Development of science of haematology Pathology 
 Symptoms Acute leukaemia Chronic leukaemia Treatment. 
 
 VIII. HODGKIN'S DISEASE - 79 
 
 History Pathology Disorders of the reticulo-endptheliaj 
 system Symptoms Treatment ,
 
 x CONTEXTS 
 
 CHAPTER PAGE 
 
 IX. SPLENIC ANEMIA (BANTI'S DISEASE) - 84 
 
 History Clinical features Differential diagnosis Pathogenesis 
 Treatment. 
 
 X.- -H.EMOLYTic JAUNDICE - 95 
 
 History Congenital and acquired types Symptoms Patho- 
 genesis Treatment. 
 
 XI. GAUCHER'S DISEASE, VON JAKSCH'S DISEASE, POLYCY- 
 
 TII.EMIA - - 102 
 
 XII. DIFFERENTIAL DIAGNOSIS - - 108 
 
 XIII. ON THE LIVER IN SOME OF ITS RELATIONS TO THE SPLEEN 109 
 
 Multiple pathological classifications of cirrhosis a source of 
 confusion Further consideration of minute anatomy and physiology 
 of liver Method of production of cirrhosis Circulatory and infective 
 causes Relationship of spleen Conception of liver acinus as divided 
 into solid and tubular portions with different functions Portal and 
 biliary cirrhosis as variants of a single type Surgical treatment and 
 its aims. 
 
 XIV. CONCLUSION - 124 
 
 Splenic diseases not isolated entities but local manifestations of 
 systemic disorder Search to be made for site of lesion and type of 
 infective agent at work.
 
 LIST OF PLATES. 
 
 FACING PAGE 
 
 Plate I. THE SPLEEN : ITS PEDICLES AND BLOOD-VESSELS - 1 
 
 Plate II. To SHOW THE RELATIONS BETWEEN LIVER, SPLEEN, 
 
 AND BONE-MARROW - 17 
 
 Plate III. THE CHIEF CHANGES IN PERNICIOUS ANAEMIA - 54 
 
 Plate IV. THE CHIEF CHANGES IN LEUKEMIA - 69 
 
 Plate V . THE CHIEF CHANGES IN HODGKIN'S DISEASE - 79 
 
 Plate VI. THE CHIEF CHANGES IN SPLENIC ANAEMIA - 84 
 
 Plate VII. THE CHIEF CHANGES IN H.EMOLYTIC JAUNDICE - 95 
 
 Plate VIII. THE CHIEF CHANGES IN VON JAKSCH'S DISEASE - 103 
 
 Plate IX. THE CHIEF CHANGES IN POLYCYTH^MIA VERA - - 105 
 Plate X. SCHEME SHOWING THE RELATIONS OF THE STRUCTURES 
 
 CONCERNED IN THE PRODUCTION OF ClRRHOSIS THE ESSEN- 
 TIAL EFFECTS OF PORTAL CIRRHOSIS THE ESSENTIAL 
 
 EFFECTS OF BILIARY CIRRHOSIS - 111 
 
 Plate XL PORTAL CIRRHOSIS (LOW-POWER VIEW) - - 114 
 
 Plate XII. BILIARY CIRRHOSIS (LOW-POWER VIEW) - - 115 
 
 Plate XIII. To SHOW THE ANASTOMOTIC CONNECTIONS BETWEEN 
 THE PORTAL (GREEN) AND THE SYSTEMIC (BLUE) VEINS 
 
 APPEARING IN CASES OF PORTAL OBSTRUCTION - - 119
 
 PLATE 1 
 
 THE SPLEEN: ITS PEDICLES AND 5LOOD-VESSELS
 
 THE SPLEEN 
 AND SOME OF ITS DISEASES 
 
 CHAPTER I. 
 ANATOMY OF THE SPLEEN. 
 
 THE SPLEEN is almost entirely covered with peritoneum, and 
 is situated behind the fundus of the stomach, being covered 
 by the lower ribs. Its outer or phrenic surface is convex and lies 
 against the diaphragm, which separates it from the ninth, tenth, 
 and eleventh ribs. In its upper part it is separated from the 
 costal wall by the left pleura and lung. The gastric surface is 
 concave and rests upon the fundus of the stomach. Within the 
 confines of this surface lies the hilum for the entry and departure 
 of the splenic vessels. The renal surface is applied to the upper 
 and outer part of the anterior surface of the left kidney, and 
 usually overlaps the summit of the suprarenal capsule. 
 
 The basal end of the spleen bears a varying relationship to 
 the splenic flexure of the colon and tail of the pancreas. The 
 extent to which the tail of the pancreas comes into relationship 
 with the spleen may vary considerably ; it very frequently 
 encroaches on the gastric surface in its lower part as far forward 
 as the hilum. 
 
 The peritoneal attachments of the spleen are three (Plate I) : 
 
 1. The lienorenal ligament, a double fold of peritoneum 
 which passes from the intermediate border of the spleen to the 
 anterior surface of the left kidney. This peritoneal attachment 
 only partakes of the nature of a ligament when the spleen is drawn 
 forward ; in situ, the two folds forming it pass off to the right and 
 to the left on the posterior abdominal wall, the tail of the pancreas 
 and the splenic vessels separating them widely. 
 
 2. The gastrosplenic omentum is a longer and more delicate 
 fold which passes from the hilum of the spleen to the fundus of 
 
 1
 
 2 THE SPLEEN AND ITS DISEASES 
 
 the stomach : between its layers run the left arteria gastro- 
 epiploica and the vasa brevia, branches of the splenic artery. This 
 fold is continuous below with the gastrocolic omentum. 
 
 3. The lower end of the spleen is supported by a peritoneal 
 shelf, the costocolic ligament, formed by a fold of peritoneum 
 passing from the diaphragm opposite the tenth and eleventh ribs 
 to the splenic flexure of the colon. 
 
 The spleen receives its blood-supply from the splenic artery, 
 a branch of the coeliac axis. This vessel breaks up between the 
 layers of the lienorenal ligament into five or six branches which 
 enter the hilum of the spleen. The blood returning from the 
 spleen is poured into the portal system through the splenic vein. 
 
 The spleen may be marked out upon the surface of the body 
 by drawing two horizontal lines from the spinous processes of the 
 ninth dorsal and first lumbar vertebrae ; these are joined by a 
 vertical line 4 centimetres (l inches) to the left of the mid-line 
 of the body, and another corresponding with the left mid-axillary 
 line. Within this quadrilateral space the spleen lies obliquely 
 beneath the ninth, tenth, and eleventh ribs. 
 
 Such are the bald anatomical facts about the spleen. The 
 connections of the organ with the sympathetic system are intimate ; 
 they are of an importance and a significance that as yet we are 
 quite unable to measure. The vascular arrangements of the gland 
 are interesting. Why is the splenic artery in its tortuous course 
 so different from all other arteries ? What is the importance to 
 be attached to the junction of the tributary veins with the splenic 
 vein ; and is the order in which they join an index of the processes 
 that go on in the splenic blood before it reaches the liver ? The 
 vein from the tail of the pancreas, which is the first to send its 
 current into the splenic vein, comes from that part of the gland 
 which is richer in the islands of Langerhans than any other. The 
 blood from the hind-gut goes into the splenic vein before that 
 which flows from the mid-gut. Does the current in the portal 
 vein from these many tributaries observe any degree of separation 
 of their constituent parts, or is there a free mingling of all the 
 blood from all the tributaries ? The relation of the spleen to 
 the lymphatic system deserves inquiry. Though the spleen is 
 associated primarily with this system, it differs materially from 
 any other organized part of it. It is not a modified lymphatic
 
 ANATOMY OF THE SPLEEN 3 
 
 gland, nor is it an aggregation of lymphoid tissues, like the tonsil 
 or the lymphoid element of the vermiform appendix. Though it 
 is evolved out of the great tract of lymphoid tissue along the 
 alimentary canal, it is, on the one hand, deliberately developed 
 outside the physically restrictive influence of the wall of the canal ; 
 and on the other, it acquires and retains vascular and nervous 
 connections which can only mean a careful provision for functional 
 association with a certain part of that canal and the organs which 
 developmentally owe their origin to it. The fact that every drop 
 of splenic venous blood passes through the liver must surely be 
 of the profoundest significance. 
 
 The spleen is not always present in man, though its absence 
 is excessively rare. Its occasional absence is noticed in animals. 
 In the vertebral kingdom its position is not constant. In 
 Protopterus annectens it is embedded in the stomach wall ; in 
 Siren it extends along a great part of the intestinal canal, as does 
 lymphoid tissue in man. In the majority of animals it is outside, 
 but associated with, the gastric segment ; but there are instances 
 of its development in connection with the lower end of the canal, 
 and others where it is scattered. 
 
 With the rarest exceptions the spleen is constant in man. It 
 can be removed without apparent harm to the economy ; life has 
 been maintained, and good health experienced, for over thirty 
 years after its loss ; it lies completely outside the alimentary 
 canal, though it is developed from the mesoblastic tissue of the 
 mesogastrium ; it is nourished by those same arteries and nerves 
 which supply a certain segment of the canal ; it has an exceed- 
 ingly liberal vascular supply which comes to it along a vessel of 
 unique appearance ; its venous blood is a part of the portal system, 
 the constituent portions of which are united in a manner significant 
 and suggestive. Every drop of its venous blood passes through 
 the liver. If Macalister was right when he said that the " question 
 in modern anatomy has become not What, but Why ", we may 
 hope that the anatomists may some day help to elucidate these 
 hidden mysteries : for it has often fallen to them to be the first 
 to throw light into dark places, and to lead a crusade in search 
 of truth.
 
 CHAPTER II. 
 THE SURGERY OF THE SPLEEN. 
 
 IT was known to the ancients, and their knowledge has been 
 confirmed in all later times, that the spleen is not essential to life. 
 Aristotle wrote : " It is the position of the liver on the right side 
 of the body that is the main cause for the formation of the spleen ; 
 the existence of which thus becomes to a certain extent a matter 
 of necessity in all animals, though not of very stringent necessity ". 
 Erasistratus took the view that the spleen was wholly devoid of 
 use. Galen spoke of it as an organ " full of mystery ". In an old 
 English translation by Holland of the Natural History of C. Pliny 
 (23 to 79 A.D.) the following statement is found : " This member 
 hath a proprietie by itself sometimes, to hinder a man's running : 
 whereupon professed runners in the race that be 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 nevertheless : 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 ". 
 Shakespeare speaks of both these functions of the spleen : 
 
 " Such fantastic tricks 
 
 As make the angels weep ; who, with our spleens, 
 Would all themselves laugh mortal." 
 
 Measure for Measure, n, ii, 121. 
 
 And, again, Maria, in Twelfth Night, as she ridicules Malvolio before 
 Sir Toby, says : 
 
 " If you desire the spleen and will laugh yourself into stitches, follow me." 
 
 Twelfth Night, in, ii, 72. 
 
 Of its effect upon the pace of a runner the Bastard speaks in King 
 John : 
 
 " I am scalded with my violent motion 
 And spleen of speed to see your Majesty." 
 
 King John, \, vii, 49.
 
 THE SURGERY OF THE SPLEEN 5 
 
 In ancient literature the statement is made more than once 
 that the giraffe, noted for a turn of high speed, is spleenless an 
 interesting example, of which evidences are still to be discovered 
 in the literature of to-day, that statements lacking in truth, cap- 
 able of verification or refutation, but never so tested, are slavishly 
 copied by one author from another. In the Middle Ages, as 
 Brogsitter has told us, the belief in the inhibitory effect of the 
 spleen upon the pace of runners is found in Murer's Belagerung von 
 Babylon : 
 
 " Ich han mir Ion dass milz Schnyden 
 Dass ich mag laufen wegt und veer." 
 
 It is interesting to note that, if records are to be trusted, the 
 removal of the spleen from a human being preceded the removal, 
 for experimental purposes, from animals. The following account 
 of the first recorded case of splenectomy is given in The Treasure 
 of Human Life, by Leonardo Fioravanti, Chapter 8. A translation 
 has been kindly made for me by Mr. L. A. Sheppard, of the British 
 Museum. 
 
 " Treatment of a woman whose spleen I removed. This same 
 year (1549) in the aforementioned month of April, I was called 
 to visit a Greek lady who lived near the garden of the Marquis 
 of Terranuova. She was the wife of the Greek Captain Matio, 
 who died afterwards in the year 1551, in the African War. This 
 young woman, twenty-four years of age, had a very great enlarge- 
 ment of the spleen. It grew so large in her body that you could 
 not conceive it larger. It caused both legs to be very badly 
 ulcerated, and the poor woman could hardly live longer. 
 
 " Having been visited by various doctors, she was told that 
 if she wished to recover it was necessary to remove the spleen ; 
 that it was an easy matter, without danger, and so on. So the 
 poor woman, who had been the most beautiful lady of that town, 
 and a great favourite, pondered whether she wished to die or 
 recover, and began to beg the captain, her husband, to find some- 
 one who would remove her spleen. She beggged so hard that the 
 poor gentleman began to look for a doctor to perform such an 
 operation, and while he was searching I was recommended to him. 
 He came to see me at my house and took me to his home to see 
 the lady. I saw her and talked to her, and cheered her as best I 
 could. She asked me if I felt capable of removing her spleen. I
 
 6 THE SPLEEN AND ITS DISEASES 
 
 said 'Yes' readily, although I had never before removed one. 
 But since then, in Naples, I have removed another, as I shall 
 describe when I come to that place. 
 
 "So I promised to perform the operation, and having 
 promised, every day she urged me to do so. But to tell the truth, 
 although I had promised, I did not want to treat her for fear of 
 making some blunder. But notwithstanding, I sent for a certain 
 old man, of the kingdom of Naples, of a town called Palo. This 
 old man, named Andriano Zaccarello, operated with the knife, 
 removed cataracts and such things, and was much experienced in 
 this profession. The old man soon came to my house, and I said 
 to him, Dear Messer Andriano, a strange thing has come into the 
 head of the wife of Captain Matio, the Greek she wishes to have 
 her spleen removed I should like to know from you if it is a thing 
 that could be done without danger ? ' ' Yes ', answered the old 
 man, 'one can do it, because it is a thing that has been done many 
 times in my life time'. 'Then do you feel capable of undertaking 
 it ? ' I asked. He replied that he would do it with me, but not 
 otherwise ; so we agreed to do it. 
 
 " I went to see the lady, and made preparations with her and 
 her husband, and having done so, went to the Justices, to give her 
 up for dead, as is usually done. 
 
 " And having permission, we went one morning to the lady's 
 house. The good old man took a razor and cut the flesh above 
 the spleen, which, being cut, came out of the body. We went on 
 separating it from the reticulum, and took it all out, and sewed 
 up the flesh, leaving only a small opening. I dressed it with mixed 
 oil of hypericum, incense powder, mastic, myrrh, and sarcocolla, 
 and ordered her a drink of boiled water with ordinary honey, 
 comfrey, betony, and holy-thistle, and every day I made her take 
 a dose of theriac. 
 
 " So I continued to relieve her in such a way that the poor 
 woman in twenty-four days was cured and went to mass at the 
 Madonna dei Miracoli near the Dogana, and was safe and sound. 
 The spleen that was removed weighed 32 ounces. It was taken 
 to the Loggia of the Merchants, and there remained three days, 
 when all the town saw it, and the honour of such an experiment 
 was given to me. Wherefore the people came to me as to an 
 oracle ; and every day I debated with various people and learned 
 many things in my subject, so that beyond the gain and experience
 
 THE SURGERY OF THE SPLEEN 7 
 
 I learned yet many secrets, and, to tell the truth, there is no better 
 way of learning than by going about the world, for every day one 
 sees new things and learns various important secrets." 
 
 The veracity of this description has been challenged more 
 than once, chiefly because of the discrepancy between the alleged 
 bulk of the tumour and the insignificant weight of the mass 
 removed. Simon, chiefly for this reason, suggests that the tumour 
 was an ovarian cyst from which much fluid had leaked between 
 the time of removal and the time of weighing. If the description 
 is true, it is certain that earlier cases than this had occurred in 
 the practice of Zaccarello. Baillon* very briefly mentions the 
 successful removal of the spleen in the year 1578 by an operator 
 whose name is not given. Rousset described, in 1581, the suc- 
 cessful removal by Viard, on two occasions, of spleens which 
 protruded through wounds on the left side. Two similar cases are 
 recorded in the 17th century. 
 
 OBSERVATIO CXCV. Cruger, Daniel. De exciso liene ex homine, sine 
 noxa. Miscellanea curiosa sive ephemeridum medico-physicarum Germanicium 
 Academiaz naturce curiosorum. Decuriae ii, Annut. Lertini anni M.D.C.LXXXIV. 
 Norinbergrae, 1684, p. 378. 
 
 " A man named Scultetus, of Henickhagen, was knocked 
 down by a rustic, and severely wounded in the left side by him 
 with a knife. The wound made by the knife caused the prolapse 
 of a large portion of the spleen. The man subsequently vomited, 
 and wallowed in his own blood, and was left without any assistance 
 during the night. In the morning, at the request of the magistrate, 
 Nicolaus Matthias, a surgeon of Colberg, arrived, and found the 
 unhappy man immersed in blood and the swollen spleen protruding 
 from his body. All who were present, with the priest, saw the 
 spleen, and were astonished at seeing so large a viscus protruding 
 from the wound. By the aid of milk and herbs of a nature suitable 
 for fermentation, the surgeon proceeded to tend the wound, and 
 about sundown had the patient transferred to Colberg. On the 
 following day a physician was called into consultation, and the 
 surgeon showed him the swollen and protruding spleen, and in- 
 quired of him whether he should excise it. The physician, who 
 
 * Opera Omnia Med., i, 183.
 
 8 THE SPLEEN AND ITS DISEASES 
 
 said that the authorities had taught that no one could live without 
 the spleen, was averse to this being done ; the blood flowing from 
 the organs within the abdomen in large amounts would be without 
 a proper passage for or method of exit. The surgeon, on the con- 
 trary, because the spleen was protruding considerably through 
 the wound, said that he could not see that it was possible to re- 
 place the spleen in its proper position in the body, and that he 
 considered it would be better that it should be removed. The 
 patient consented to this ; he turned in this critical moment 
 of impending death, and said that he was prepared to suffer 
 everything patiently. The surgeon then ligatured the protrud- 
 ing portion of the spleen with a silk cord and withdrew the 
 entire viscus from the cavity of the body. Next, that portion 
 where it was adherent to the body he constricted with a cord, and 
 on the third day afterwards he resected the whole spleen, and 
 checked the abundant haemorrhage with styptic powder. By the 
 employment of suitable medicaments he restored the patient to 
 health within the space of three weeks, although there remained in 
 the wound a small swelling resembling a hazel nut, because at that 
 place the vessels were adherent to the divided tissues. To this day 
 the man lives happily with his wife, not deprived of offspring, and 
 carries on his ordinary occupation. 
 
 " The following is the testimony of an eye-witness : 
 
 " I declare that I have seen with my eyes the spleen of a 
 young man, age 23, projecting from a wound in the left side ; that 
 the spleen was of the usual size, and that it was detached from all 
 its connections ; I have also felt and touched the spleen with my 
 hands. 
 
 " That on the third day after the receipt of the wound it was 
 excised by a surgeon summoned from the town, named Nicolaus 
 Matthias. I know, because the same surgeon held a conference 
 with me, and brought the same spleen recently excised. The 
 burgomaster, Edw. Kundenreichen, and the pastor, Herm. Thorn 
 Hoppen, were also visited by the surgeon and were shown the 
 spleen. Before it was excised the spleen hung out from the wound ; 
 about the stomach it was torn from all its connections, also from 
 the splenic artery and vein, and it resembled a rigid and gangrenous 
 limb. 
 
 " The injured man soon recovered from this and other wounds ; 
 and was able to carry on his usual avocations ; and is in good
 
 THE SURGERY OF THE SPLEEN 9 
 
 health at the present time ; this I have observed with astonish- 
 ment in company with those people with whom he is accustomed 
 to mix. 
 
 (signed) Joh. Auenius." 
 
 OBSERVATIO CLXV. Clarke, D. Timotheus. De lienis resectione in 
 homine vivo. Ibid. p. 209. Miscellanea curiosa medico-physica academics 
 naturce curiosorum, sive ephemeridum medico-physicarum ; Annus IV, V. 
 Francofurti et Lipsiae, 1676, p. 208. 
 
 " A butcher, named William Panier, living in the village of 
 Wayford, near Crookhome, in the County of Somerset, being greatly 
 in debt, and fearing lest he should be arrested, was constrained to 
 go into hiding. The constables were about to capture him, and 
 becoming desperate, and in order to avoid them, he drove his 
 butcher's knife into his abdomen on the left side, thus causing a 
 great wound through which part of the omentum, and of the intes- 
 tine, and also the spleen, protruded. The constables were horrified, 
 and left the man for dead, as they believed. For three days the 
 wound remained without a suture, but at last a surgeon was 
 summoned. The surgeon replaced the intestines, and cut away 
 part of the omentum, along with the spleen. The man rapidly 
 recovered from the effects of the wound, and for the whole of the 
 following year remained in good health and spirits. He soon after- 
 wards emigrated to New England, where not long ago he was so 
 far living a healthy life. Doubeny Turbervile, M.D., a man worthy 
 of high credit, and a witness of the occurrence, renouned among 
 our fellow-countrymen for his treatment of diseases of the eyes, 
 has collaborated with me in communicating this observation." 
 
 The first experiments made upon the spleen were carried out 
 in 1669, by Malpighi, who ligatured the splenic artery and vein 
 in a dog. A subsequent operation showed that the spleen had 
 undergone almost complete atrophy, and that the liver had 
 enlarged. Malpighi's name is, of course, for ever associated with 
 the lymphoid follicles of the spleen. In 1676 Clarke (vide supra) 
 performed the first experimental splenectomy in a dog. The 
 animal recovered, and the only subsequent change noticed in it 
 was that it became much fatter. Morgagni describes a successful 
 case of splenectomy in the dog, performed by Zambeccari, at 
 Florence, in 1680. It is evident that he performed this operation
 
 10 THE SPLEEN AND ITS DISEASES 
 
 himself quite frequently after this date, for he observes that, after 
 studying the matter for five years, he found that the dogs under- 
 went no special change in consequence of such an operation ; the 
 dogs did not grow fatter, had no loss of fertility, and no change 
 in their manners or disposition was noted. 
 
 In the nineteenth century experimental observations increased 
 rapidly in number. In 1828 Schultz records that he had removed 
 the spleen from 24 animals, 23 of which survived the operation. 
 After the operation the fertility of animals was reduced, there was 
 a greater inclination and ability to run far, and a diminished 
 secretion of bile. Czermak also observed the lessened fertility of 
 animals, and remarked upon the enlargement of the lymph-glands 
 in the mesentery. In the year 1841 A. Bardeleben published 
 the results of his experiments, which were directed towards the 
 discovery of the functions of the spleen. They were the first well- 
 considered and fully-recorded operations to be performed, and 
 they have become classical. For the first time they showed with 
 complete proof that animals could live and thrive after the removal 
 of the spleen, and that certain changes, possibly compensatory in 
 character, followed upon the loss of this organ. The changes noted 
 were in the blood and the lymphatic glands. Vulpius, who followed 
 in 1894, summarized his observations as follows : 
 
 1. Extirpation of the spleen produces a transitory decrease 
 in the number of red, and an increase in the number of white,, 
 blood-corpuscles. 
 
 2. The thyroid gland cannot vicariously assume the function 
 of the spleen. 
 
 3. The lymphatic glands and the bone-marrow show an 
 increased blood-forming activity after removal of the spleen. 
 
 4. The regeneration of the blood, after the loss of blood, is 
 probably less rapid in individuals in whom splenectomy has been 
 performed. 
 
 A great many observers confirmed these observations subse- 
 quently. 
 
 That the spleen is not essential to life is also shown by the fact 
 that it is occasionally absent. Aristotle wrote : " The spleen is 
 not invariably present ; and in those animals that have it, it is 
 only present of necessity in the same sense as the excretions of the 
 belly and of the bladder are necessary, that is, of being an in- 
 evitable concomitant ". Rokitansky and Ziegler in the middle of
 
 THE SURGERY OF THE SPLEEN 11 
 
 the nineteenth century asserted that the spleen was not always 
 present, but neither gave any specific instance of its absence. At 
 the close of the century Hodenpyl* found records *of nine cases 
 of alleged absence of this organ, and related a tenth case observed 
 by himself. Two of the cases occurred in infants six weeks and 
 one hour old respectively ; the remaining eight instances were in 
 adults, the oldest being a woman, age 57, who had no unusual 
 symptoms during her lifetime. The records of at least three of 
 these are disputable. Indubitable cases of congenital absence of 
 the spleen are related by Sternberg, Kohllass, and Riches.f 
 
 By the middle of the last century it was, therefore, clearly 
 established by experience which was beyond cavil that the spleen 
 was an organ not necessarily present in normal individuals, that 
 its removal, when successful, did not seriously impair the chances 
 of life and of good health, and that after its removal certain 
 changes assumed to be of a compensatory character followed in 
 due course. The way was then prepared for the question of the 
 deliberate removal of the spleen fvom man in conditions in which 
 it was enlarged by disease. The first instance of such an operation 
 is related by Quittenbaum, of Rostock, in 1826 (the father of 
 ovariotomy in Germany), who, after a series of experiments in 
 which the spleen was successfully removed from cats and dogs, 
 undertook the removal of the organ from a human being. The 
 patient, it is interesting to note in connection with recent develop- 
 ments of ( the surgery of the organ, was a woman suffering from 
 cirrhosis of the liver and ascites. It was " the patient's urgent 
 entreaty rather than the surgeon's judgement " which led to the 
 performance of the operation in a woman so ill. She survived 
 the operation only six hours. 
 
 Controversy in surgery may often tend to be coarsening, but 
 we cannot gainsay its occasional advantages. It serves to 
 challenge opinions which might too readily be accepted, to oppose 
 reason to authority, to destroy prejudices, or to support a truth 
 which otherwise might long pass unnoticed. In the year 1855 it 
 raged round the question as to whether the operation of splen- 
 ectomy could be justified. The story is told by Simon. J Kiichler, 
 of Darmstadt, had removed the spleen from a patient, age 36, 
 
 * Med. Record, 1898, ii, 695. ^Jour, of Ment. Sci., 1914, Ix, 630. 
 
 J Die Extirpation der MHz (Giessen, 1857).
 
 12 THE SPLEEN AND ITS DISEASES 
 
 who fourteen years before had suffered for nine months from 
 malarial fever. The spleen on palpation was estimated to have a 
 length of 13 inches and a breadth of 7 inches. Death four hours 
 after the beginning of the operation was due to haemorrhage from 
 a branch of the splenic artery, which had either escaped ligature 
 at the time of operation or from which the ligature had subse- 
 quently slipped. Post-mortem examination showed cirrhosis of 
 the liver, and about 250 c.c. of serous fluid was present in the 
 peritoneal cavity, with 625 grms. of coagulated blood. The 
 matter was taken up by the Surgical Association of Hesse, repre- 
 sented by Simon, and a long and bitter controversy resulted. 
 Simon's greater experience and authority seemed to prevail, and 
 he decided that the operation was only justified in cases where a 
 wound had been inflicted which threatened otherwise to be fatal. 
 Kiichler, in his defence, published a pamphlet, entitled, Extirpation 
 of a Tumour of the Spleen. Light upon the Question of Extirpation 
 of the Spleen in Man, its Practicability and its Justification.* In 
 this publication he gives details of the operation he performed, 
 and draws a parallel with six previously recorded cases of splen- 
 ectomy in human beings. In three of these cases the operation 
 had been performed for hypertrophy or abscess, and in three for 
 prolapse of the organ through an abdominal wound. Kiichler 
 sent this pamphlet to the Medical Faculty of the University of 
 Dorpat with the request that they would communicate to him 
 their opinion of the operation of splenectomy. Adelmann was 
 appointed by the Faculty to draw up their report. He searched 
 the earlier literature for examples of this operation, and formed 
 an opinion favourable to Kiichler's view. His report was pub- 
 lished in Deutsche Klinik for 1856. Adelmann also inspired a 
 thesis by Johannes Braun, of Warsaw, Lienis in nomine extirpatio, 
 published in 1857, in which the literal text of the earliest recorded 
 cases was given. In this year, 1857, there appeared also the paper 
 of Gustav Simon, which has been a storehouse of information 
 upon the history of the operation for all subsequent writers. In 
 this publication, the author, possessed of an extensive acquaint- 
 ance with the literature dealing with the physiology, pathology, 
 and surgery of the spleen, but deeply prejudiced by his controversy 
 with Kiichler, expressed the opinion that removal of the diseased 
 
 * Darmstadt, 1855, Dietatall.
 
 THE SURGERY OF THE SPLEEN 13 
 
 spleen under any circumstances was an unwarrantable operation. 
 Kiichler's reply was to point out that " the conclusions of Simon 
 are in themselves unreliable and illogical, and throw doubt upon 
 incontrovertible facts ". Adelmann* gives a full account of this 
 discussion, and decides : " From such expressions we may con- 
 clude that there was personal friction between the two Darmstadt 
 surgeons. In September, 1858, when I made the personal acquain- 
 tance of both of these colleagues in Karlsruhe, I endeavoured, 
 unfortunately without success, to bring about a reconciliation 
 between them ". 
 
 The first splenectomy deliberately performed in England (the 
 fifth in the history of the operation) for an enlargement of the 
 organ, is related by Spencer Wells. | The patient was a married 
 woman, 34 years of age, who was " evidently dying from a large 
 spleen ", and who had no other disease. The following is the 
 account of the operation given by Spencer Wells : 
 
 " I made an incision along the outer border of the left rectus 
 abdominis which extended five inches above and two below the 
 umbilicus. Two arteries were tied before the peritoneum was. 
 opened. In opening the peritoneum a rather large artery was cut 
 across in a piece of omentum, which was loosely adherent between 
 the surface of the spleen and the abdominal wall. The vessel was 
 tied. The adhering portion of omentum was separated, and by 
 putting in my hand and turning the lower edge of the spleen first 
 through the opening, the whole of it was easily removed. The 
 intestines were prevented from escaping by Dr. Wright, who kept 
 the edges of the opening carefully together behind the spleen, 
 which was held only by the vessels and the gastrosplenic omentum. 
 I was beginning to twist the spleen round to bring the vessels into. 
 a sort of cord preparatory to applying a ligature, when the splenic 
 vein, which was as large as a small finger, gave way, and blood 
 ran freely from the spleen ; but none was allowed to enter the 
 abdomen, and I at once enclosed the vessels in a large clamp, and 
 cut away the spleen. Before tying the vessels temporarily secured 
 by the clamp, I passed eight silk sutures to keep the edges of the 
 incision well together. The peritoneum was thus protected and 
 the viscera retained while I was dealing with the vessels. These 
 were tied in two bundles above the clamp, which was then loosened, 
 
 * Arch. /. Win. Chir., 1887, xxxvi, 442. f Mcd - Times and Gaz., 1866, i, 2.
 
 14 THE SPLEEN AND ITS DISEASES 
 
 .and two arteries and a vein were also separately tied before it was 
 finally removed. On taking it off, I found that a part of one 
 end of the pancreas, as large as the end of a thumb, had been 
 bruised by it. All the ligatures, except those on vessels in the 
 abdominal wall, were cut off close and returned with the included 
 tissues. The sutures were then tied, and the abdomen was well 
 supported by plaster, pads of lint, and a bandage." 
 
 The patient died of septicaemia 158 hours after the operation. 
 
 By this time the position of Spencer Wells in the surgical 
 world was such that his authority was an absolute warrant for 
 the performance of any abdominal operation. His sagacity, 
 integrity, prudence combined with intrepidity, and technical skill 
 were^such as to command the respect of all men. And it was 
 accordingly not very long before other operations involving the 
 removal of the enlarged spleen were attempted. T. Bryant, of 
 Guy's JHospital, performed the operation twice, in 1866 and in 
 1867, in cases of leucocythsemia. Both patients died rapidly from 
 haemorrhage, one fifteen minutes, the other one and a half hours, 
 after operation. Koeberle, of Strasburg, performed a similar 
 operation for a like condition in 1867; the patient died 'soon 
 after', of haemorrhage. Spencer Wells in 1873 and again in 1876 
 removed the spleen for this disease, and both patients died, one 
 of peritonitis, one of haemorrhage. 
 
 In the year 1882 H. Collier* reviewed the position of the 
 operation of splenectomy, and gave a brief account of all the cases, 
 29 in number, submitted to operation up to that date. Of 13 
 operations performed for various conditions, 'wandering spleen', 
 hydatid cysts, simple enlargement, 'ague cake', 8 were success- 
 ful, the patients making perfect recoveries. Of 16 cases in which 
 leucocythaemia was present, there was no instance in which the 
 patient recovered even from the primary effects of the operation. 
 Bryant's comment upon his two cases was as follows : " We have 
 learnt two things from the cases related. Firstly, that enlargement 
 of the spleen in leucocythaemia appears to be only a part of a 
 general disease affecting the glandular system as a whole ; and, 
 secondly, that in splenotomy for such a disease there is a predis- 
 position to haemorrhage with which surgery is incompetent to deal. 
 It can neither be foreseen by any amount of care, nor coped 
 
 * Lancet, 1882, i, 219.
 
 THE SURGERY OF THE SPLEEN 15 
 
 with by any amount of skill. Under these circumstances there is 
 no shirking the conclusion that the operation is physiologically 
 unsound and surgically unsafe, and, for leucocythaemia, should not 
 be performed ". 
 
 From this date up to the last few years the operation was 
 reserved for cases of injury, for spleens with a rotation of the 
 pedicle, for cysts of the spleen, or for cases of enlargement of the 
 organ due to causes which were not always discoverable. In the 
 year 1898 Van verts, in a Paris thesis, collected the records of 274 
 cases of splenectomy with 170 recoveries. 
 
 In the last few years splenectomy has been performed in 
 certain of the anaemias associated with splenomegaly. The tech- 
 nique of the operation has been greatly improved, and the 
 mortality in all classes of cases very considerably reduced. 
 
 Dr. W. J. Mayo has most kindly given me the records of 
 the Mayo clinic up to September 20, 1920. They show better 
 than any other record the modern position of the operation of 
 splenectomy. 
 
 SPLENECTOMIES FOR SPLENIC ANAEMIA. 
 Total number of cases to Sept. 20, 1920. . 73 
 Total number of hospital deaths . . . . 9 = 12-3 per cent. 
 
 Out of a total of twenty-seven cases operated on 5 years or more ago, 
 seventeen patients lived over 5 years ; of these patients, sixteen are still living. 
 
 The results in splenic anaemia, generally speaking, have been 
 good, but the operation is more difficult than in other conditions, 
 and the mortality is considerable. 
 
 SPLENECTOMIES FOR PERNICIOUS ANAEMIA. 
 Total number of cases to Sept. 20, 1920.. 53 
 Total number of hospital deaths . . . . 3 = 5-6 per cent. 
 Five patients living 4 to 5 years after operation. Eleven patients living 
 3 to 4 years after operation. 
 
 The fact that 22 per cent of patients have lived two and one- 
 half times as long as the average, shows that in early cases of 
 pernicious anaemia the operation is at least justifiable. 
 
 SPLENECTOMIES FOR MYELOGENOUS LEUKAEMIA. 
 Total number of cases to Sept. 20, 1920. . 26 
 Total number of hospital deaths . . . . 1 = 3-8 per cent. 
 One patient died 5 years and 4J months after operation. Seven patients 
 Tvere living 3 to 4 years after operation. Six of these are still living.
 
 16 
 
 THE SPLEEN AND ITS DISEASES 
 
 The results are poor in myelogenous leukaemia, but five 
 patients are in good condition and two in fair condition after 
 periods of time beyond the life-expectancy of these cases. The 
 patients are at least relieved of the weight of the spleen, and in 
 two instances supposed to be early cases of myelogenous leuka?mia, 
 not counted in this series, the patients have been cured, or at 
 least they have lived a number of years following operation. The 
 operation is not difficult after radium treatment, and in selected 
 cases should be further considered. 
 
 SPLENECTOMIES FOR ILEMOLYTIC ICTERUS. 
 
 Total number of cases to Sept. 20, 1920.. 32 
 
 Total number of hospital deaths . . . . 1 = 3*1 per cent. 
 
 One patient living over 9 years after operation. 
 
 The results in haemolytic icterus have been excellent. Splcn- 
 ectomy is a real cure in a high percentage of cases. 
 
 SPLENECTOMIES FOR SEPTIC SPLENOMEG ALIAS. 
 Total number of cases to Sept. 20, 1920.. 10 
 Total number of hospital deaths . . . . 2 = 20 per cent. 
 
 Splenectomy is undoubtedly indicated in some of these cases. 
 
 DIAGNOSIS 
 
 No. or CASES 
 
 HOSPITAL DEATHS 
 
 Portal cirrhosis 
 
 9 
 
 4 
 
 Biliary cirrhosis 
 
 
 
 1 
 
 Lymphoma 
 
 3 
 
 
 
 Luetic splenomegalies 
 
 G 
 
 1 
 
 Lymphosarcoma . . . . 2 
 
 
 
 Gaucher's disease . . . . 4 
 
 1 
 
 Tuberculosis . . . . . . 4 
 
 
 
 Wandering spleen . . . . 2 
 
 
 
 Splenomegaly with eosinophilia . . 1 
 
 
 
 Splenomegaly with neutrophilia . . 1 
 
 1 
 
 Miscellaneous, questionable 
 
 11 
 
 2 
 
 
 49 
 
 10 
 
 Thus the total number of cases is 243, with 26 hospital deaths,
 
 17 
 
 CHAPTER 111. 
 ON THE FUNCTIONS OF THE SPLEEN. 
 
 (See Plate II.) 
 
 The coeliac axis, the first visceral branch of the abdominal 
 aorta, supplies those organs, the stomach, the liver, and the 
 pancreas, which are especially concerned in disorders of the spleen. 
 The largest of its three branches is the splenic artery. Each 
 branch of this artery within the spleen supplies a different compart- 
 ment of the organ, and its main subdivisions each end rather 
 abruptly in a small pencil of arterioles near the periphery of the 
 organ. Close to its termination each of the subdivisions of the 
 artery is enveloped by a small mass of lymphoid tissue, the so- 
 called Malpighian body, in which the manufacture of lymphocytes 
 takes place. This small mass of tissue is supplied by a coil of 
 minute arteries springing at right angles from the main course of 
 the vessel. In this way the large germinal cells of the follicle are 
 provided with arterial blood, and give rise to successive generations 
 of lymphoid cells until a colony of ordinary lymphocytes results. 
 These lose their attachments and drift outwards into the sur- 
 rounding splenic tissue. 
 
 The pencil of arterioles finally gives place to the spongework 
 of which the spleen essentially consists. ' Taken broadly, it may 
 be said that the spleen consists of a meshwork of delicate fibres 
 which serve to retard the flow of the blood, and to allow its con- 
 stituents to come into thorough contact with the specific cellular 
 elements which are attached to the network in large numbers. 
 These cells are similar to the cells lining the capillaries of all parts 
 of the body. In the capillaries they are orderly in arrangement 
 and definite in position, and they appear as the lining of com- 
 plete tubes. In the spleen-tissue or spleen-pulp they are larger, 
 they are disorderly, and they cease to form definite channels. 
 Since it is admitted that the endothelial cells of capillaries are 
 capable of phagocytosis, it is not difficult to see a close resem- 
 blance between them and the so-called reticular cells of the spleen. 
 
 2
 
 18 THE SPLEEN AND ITS DISEASES 
 
 These latter cells, it is true, exhibit a certain sort of arrange- 
 ment, since the blood runs more vigorously in some directions 
 than in others, allowing a distinction to be made, on close 
 examination, between blood-channels and pulp-cords. The latter 
 are perhaps twice as broad as the more open channels which 
 separate them, but cannot be regarded as solid tissue. The blood 
 flows more slowly through them than through the adjoining 
 channels. When, however, a pathological change occurs, it is not 
 infrequent to find the channels become relatively more distinct, 
 and the pulp-cords more indefinite in character. 
 
 Various authors describe a number of types of cell as entering 
 into the cellular composition of the pulp ; but if we exclude the 
 purely supporting cells (which provide the reticulum proper), it is 
 possible to group all the others in one category that of modified 
 endothelial cells. There is an abundant literature dealing with the 
 question of the specific pulp-cells of the spleen, from which it is 
 possible to draw the following simple picture : that these modified 
 endothelial cells which cling to the reticular meshwork are occupied 
 in different ways at different times. Sometimes they remain 
 stationary and gather up passing particles suitable as food ; at 
 other times they separate from the meshwork and wander among 
 it likewise for the purpose of engulfing solid particles (notably 
 effete red blood-cells) ; at other times still they undergo prolifera- 
 tion. It is very probable that they remain stationary for this 
 purpose, and produce daughter cells and granddaughter cells which 
 adhere to one another for a time, but ultimately separate (either 
 in the daughter or in the granddaughter stage), and remain in the 
 spleen as, apparently, a special type of cell, or else pass away in 
 the blood of the splenic veins. 
 
 It is especially important to notice that the blood in this 
 meshwork is venous, since it is asserted that the processes of multi- 
 plication of the pulp-cells, and the varieties of cell which result 
 therefrom, are particularly modified by the carbon-dioxide atmo- 
 sphere in which they reside (Loele). The purely lymphatic cells of 
 the Malpighian bodies, which lie in a medium richer in oxygen, 
 give rise to a very different progeny. 
 
 The blood as it leaves the spleen carries with it some of these 
 pulp-cells, or their descendants, but leaves behind it a certain 
 number of red corpuscles and other solid particles. As it emerges 
 by the splenic vein it immediately meets two streams of venous
 
 THE FUNCTIONS OF THE SPLEEN 19 
 
 blood, one coming from the cardiac end of the stomach, and the 
 other from the tail of the pancreas, facts no doubt of great physio- 
 logical significance. Nearer the liver it meets successively a stream 
 of blood from the descending colon, and the great mass of blood 
 returning from the alimentary tract bearing with it the products 
 of digestion, such as sugar and the amino-acids of protein, etc. 
 
 It is probable that a mingling of these various portions of 
 blood occurs in the wide portal vein, but the degree to which this 
 takes place is uncertain. There is evidence to show that, like the 
 Rhone and the Arve, the two streams long remain separate parts 
 of a great common stream. And the view is taken by many 
 authorities, upon what appears reasonable evidence, that the larger 
 part of the splenic blood goes to the left lobe of the liver. Tested 
 experimentally by injecting in the cadaver a continuous stream of 
 red fluid through the splenic vein and a continuous stream of blue 
 fluid by the superior mesenteric vein, the mingling of the two 
 streams appears to be complete when the issue from the severed 
 portal vein is watched. The stream of blood in the portal vein 
 finally comes in contact with the liver tissue, whose cells exert 
 upon it their metabolic activity. If we regard the matter as con- 
 cerning a single liver-cell, the following events occur. The blood 
 flowing from the free surface of the liver-cell becomes mixed with 
 a small stream of blood derived from the hepatic artery, the next 
 largest branch of the coeliac axis. Oxygenated and venous blood 
 thus come in contact with the free surface of the liver-cell, which, 
 if represented in a diagram, would appear to be protruding into a 
 dilated vascular channel a 'sinusoid'. All other surfaces of the 
 latter are lined with endothelium, the cells being of conspicuous 
 size, endowed with phagocytic powers, and known as Kupffer's 
 star-cells. The liver-cells are now regarded as containing a net- 
 work of intracellular canaliculi emptying into a small ampulla from 
 which a minute duct issues. This, joining with other ducts simi- 
 larly arising, forms at last a tiny bile-duct visible to the naked eye. 
 Since the liver-cell forms bile out of the blood flowing in the portal 
 vein, the ingredients of the bile must enter the liver-cell and appear 
 within the minute canaliculi. If these substances enter, so also 
 may other substances conveyed by the blood, and, by penetrating 
 the liver-cell, finally obtain access to the bile-duct beyond. It is 
 a fact that the liver-cell takes up other substances which never 
 pass into the bile-ducts, and stores them in the protoplasm without
 
 20 THE SPLEEN AND ITS DISEASES 
 
 any risk of their emerging by that system of vessels. It is also 
 known that the liver-cell is capable of discharging ferments into 
 the blood-space around it, a fact which makes it reasonable to 
 suppose that many changes can and do take place in the blood 
 without the substances concerned entering directly into the liver- 
 cell at any time. 
 
 In the spleen-pulp, the endothelial cells share one of the 
 properties of all cells that of making ferments. The blood may 
 undergo definite change in chemical composition as it lingers among 
 the meshes of the spleen. Then, before it enters the liver, it has 
 become mixed with products from the stomach, and with ferment 
 from the tail of the pancreas, \vhere the islands of Langerhans are 
 three times as numerous as elsewhere. Obviously some change 
 must take place if and when the two become admixed ; and, 
 indeed, the observations of Herzen and Bellamy* on the action of 
 the splenic and gastric blood strongly indicate the existence of 
 such changes. Finally, attention may again be drawn to the fact 
 that this blood undergoes a still further change in composition 
 by receiving the blood from the large intestine, and from the small 
 intestine with its products of digestion, \vhich necessarily include 
 ferment substances absorbed with food. 
 
 The spleen has long been thought of as a blood-forming 
 organ ; and during foetal life it appears certainly to be con- 
 cerned in the formation of red cells ; in consequence, dominant 
 attention has been directed to the fact of its enlargement in many 
 so-called diseases of the blood. It is therefore desirable to add 
 to the picture so far drawn, details in reference to the chief of the 
 blood-forming organs namely, the bone-marrow. Arterial blood, 
 entering the nutrient arteries, passes through the minute capillaries 
 of the marrow of the long bones and enters into dilated cavities 
 recalling those into which the liver-cells project. These also are 
 called 'sinusoids'. The endothelial cells projecting into them are 
 modified into large sustentacular cells, from which sprout the 
 various cells described as concerned in the formation of red and 
 white cells respectively. It has been said that the red cells form 
 on such buds where they are bathed in arterial blood, while the 
 white cells appear in those portions where the blood has become 
 richer in carbon dioxide. As in the spleen-pulp, the daughter and 
 
 * Lancet, 1900, ii, 371.
 
 THE FUNCTIONS OF THE SPLEEN 21 
 
 granddaughter generations remain adherent to the sustentacular 
 cell until they are ripe, after which they become loose and float 
 away in the blood-stream. 
 
 The ground having been cleared by these very brief anatomical 
 and physiological considerations, it now becomes possible to review 
 the large amount of work which has been done by many investi- 
 gators in reference to the functions of the spleen, and perhaps to 
 elucidate some of the difficulties of contradictory observations. 
 
 The lines of inquiry and research have been broadly as follows : 
 
 1. Study of the effect of splenectomy in man and animals 
 upon the general health, upon the blood, and ultimately upon 
 the various tissues. 
 
 2. Study of the action of extracts of the spleen, when 
 administered in various ways. 
 
 3. Study of the action of splenic extracts on various phases 
 of artificial digestion in the laboratory. 
 
 4. Biochemical investigations upon the spleen, upon the meta- 
 bolic activities of the body, and upon the several secretions. 
 
 5. Microscopical studies of the spleen and other organs in 
 case of diseases of the spleen, as well as in normal and splenec- 
 tomized animals subjected to the action of various drugs. 
 
 6. Consideration of clinical cases in which the spleen was 
 known to be diseased, any special phenomena being carefully 
 observed in order to decide to what extent the spleen was to be 
 held responsible for them. 
 
 Of all these methods, the study of splenectomized animals has 
 been most widely followed. 
 
 Even when allowance is made for the ultimate differences 
 which are shown by the cases of splenectomy in man, due to the 
 varying reasons for the performance of the operation, there re- 
 main certain changes in the blood which agree with those found in 
 splenectomized animals. There is a temporary anaemia, gradually 
 subsiding in approximately two months' time, and there is an in- 
 crease in leucocytes, whose numbers return to the normal very 
 slowly. An increase of lymphocytes persists for about a year, and 
 gives place to a moderate eosinophilia, which increases up to about 
 8 per cent during the third year. Apart from these laboratory dis- 
 coveries there is no particular change to be noticed in the condition 
 or in the health of the patient. It has been asserted that a certain
 
 22 THE SPLEEN AND ITS DISEASES 
 
 degree of asthenia persists, and that the patient shows an increased 
 liability to become infected with epidemic diseases, such as influ- 
 enza. But in these respects there is no uniformity of evidence, 
 doubtless owing to lack of knowledge of the normal resisting power 
 of the patients, to differences of age, to the various diseases for 
 which the operation may have been performed, and to the condition 
 of health in other respects. When the extirpation has been for 
 trauma, the general health of the patient may not have been 
 previously impaired. 
 
 After the experimental removal of the organ from animals, 
 certain additional observations have been made. The red cells 
 have been found to become more resistant to hypotonic saline 
 solutions, and the administration of drugs capable of causing 
 haemolysis has been found to cause jaundice less easily than 
 before. Study of the animals after death has shown proliferation 
 of the endothelial cells in the lymph-glands and in the liver, and 
 a reddening of the bone-marrow has been disclosed. 
 
 Briefly stated, these are all the salient facts relative to the 
 effects of splenectomy. They are meaningless unless the matter 
 is carried further in order to force answers to certain definite 
 questions which may now be asked. 
 
 1. How much of the effect of splenectomy is due to the mere 
 operation ? Pearce and his co-workers,* whose work is the most 
 recent, and is distinguished throughout by great care and pains- 
 taking analysis, incline to attribute much to the operation. They 
 point out that a certain amount of blood is lost with the spleen, 
 and that the appearance of increased resistance of the red cells, 
 and even of their susceptibility to hsemolytic drugs, may be related 
 to the consecutive anaemia, or to the processes engaged in the 
 repair of the anaemia. Banti has insisted that any such explana- 
 tion is unsatisfactory, and asserts that the increased resistance 
 persists long after the anaemia has passed away ; and he further 
 points out that in an animal rendered anaemic by appropriate 
 drugs this change in the resistance of red cells does not occur. 
 
 2. Does the spleen destroy red cells ? There is a general agree- 
 ment that phagocytosis does go on in the spleen. The agents 
 which carry on this work are the same kind of large mononuclear 
 
 * The Spleen and Anaemia, Philadelphia, 1919.
 
 THE FUNCTIONS OF THE SPLEEN 23 
 
 cells which are found in the sinuses of the lymph-glands. It has 
 been found that these cells are very much increased in numbers 
 in the lymph-glands when drugs acting on the red cells are adminis- 
 tered to a splenectomized animal. This suggests that these cells 
 are carrying out vicariously the functions previously performed 
 by the spleen in other words, the spleen normally destroys red 
 cells. Then, too, the occurrence in the spleen of phagocytes con- 
 taining red cells in severe anaemias in man, can hardly have any 
 other meaning than that the organ in these conditions fulfils that 
 destructive purpose. 
 
 3. Does the spleen make a substance which weakens the red cells 
 prior to their being engulfed by the phagocytes ? This action has been 
 called 'the haemocatatonistic function' (Bottazzi), and belief in its 
 existence was based on the observation that the resistance of the 
 red cells begins to increase at once after splenectomy, rising to a 
 certain maximum, at which level it is maintained. But when it 
 was found by other workers, including Pearce, that the same result 
 will occur in the presence of the spleen, by treating an animal with 
 a haemolytic immune serum, it became evident that the problem 
 is not as simple as Bottazzi assumed. It receives its true answer 
 when the import of the following further questions is understood. 
 
 4. Does the spleen pass on the blood-pigment for conversion into 
 bile-pigment ? Removal of the spleen does not lead to absence of 
 bile-formation, nor to the accumulation of blood-pigment in the 
 blood. The explanation of these observations may be found in the 
 fact that red cells may be taken up by phagocytes anywhere in the 
 body and carried round to the liver. Material for the manufacture 
 of bile-pigment is therefore still available. Pearce, evidently believ- 
 ing, I think, that the blood-pigment is free in the splenic blood, 
 has endeavoured to discover what quantity of haemoglobin must 
 accumulate before it will overflow into the kidney or appear as bile 
 in the urine. There appears to be a definite limit beyond which 
 the colouring matter fails to be dealt with by the liver ; and there 
 is a limit to the amount of bile which can flow out of the liver-cell. 
 If so much haemoglobin is converted into bile-pigment that it 
 cannot leave the bile-channels quickly enough, the excess of bile- 
 pigment accumulates in the blood and jaundice appears. The 
 amount of bile-pigment formed after splenectomy is at first approxi- 
 mately only one-half of that which is formed prior to the operation, 
 and, as Martinotti and Barbacci have shown, this delay accounts
 
 24 THE SPLEEN AND ITS DISEASES 
 
 for many of the phenomena arising in the course of experimental 
 work upon haemolytic poisons, and upon the short-circuiting of 
 the splenic vein. All this work is based on the belief that haemo- 
 lysis in the body must be the same as haemolysis in a test-tube, 
 namely, a process of liberation of free haemoglobin into the sur- 
 rounding medium (that is, the blood-serum). But the splenic blood 
 cannot be proved to contain free haemoglobin, and the microscope 
 shows that the red cells are not dissolved in the stream, but are 
 consumed by phagocytic cells facts of the greatest significance, 
 which have been ignored or too little considered in this line of 
 inquiry. 
 
 5. Similarly with reference to the question, Does the spleen 
 hcemolyse red cells by means of a ferment action ? Expressed in a 
 more technical form, this means, Does the spleen manufacture a 
 ' haemolysin ' ? The literature on this point is very extensive, all 
 of it showing how general is the belief that ' haemolysis ' in the body 
 is comparable to a test-tube phenomenon. Yet all observers 
 Pearce included have failed to find proof of this ferment action, 
 which was first suggested as possible by Nolf. That the dissolution 
 of red cells within the bodies of phagocytes takes place by an intra- 
 cellular ferment action is obvious, but it is not in this sense that 
 the question has been raised. 
 
 6. A further question often asked, as to whether the spleen 
 contributes an immune substance, veils the same belief. The 
 researches of immunology seek to establish the existence of 
 chemical substances circulating as such in the blood-stream. Con- 
 sequently, viewing these substances as secretions from cells, it is 
 supposed that some of them are formed by the splenic cells, and 
 would be likely to appear in more concentrated form in the splenic 
 juice or in the blood of the splenic vein. In order to stimulate 
 the cells of the spleen to greater activity, various substances have 
 been used or devices adopted to bring about a greater destruction 
 of the red corpuscles, in the hope that the spleen may be induced 
 to secrete more of this immune substance. This accounts for the 
 experiments devised to show the presence and purpose and mode 
 of action of fatty acids and lipoids. These substances dissolve the 
 red corpuscles. Is it that the spleen prepares such reagents, or 
 that the spleen needs the co-operation of the liver, since the liver 
 is an acknowledged source of both these substances ? Eppinger 
 found that the total fats and cholesterin of the blood are increased
 
 THE FUNCTIONS OF THE SPLEEN 25 
 
 after splenectomy, and King confirmed his work ; but Pearce failed 
 to substantiate it. Anitschkow, taking another side of the problem, 
 sought to show that if the spleen makes a substance for the express 
 purpose of dissolving the red cells, removal of the spleen should 
 diminish the tendency to jaundice. As a matter of fact this does 
 happen if the splenic vein is diverted into the inferior vena cava 
 without removal of the spleen, and is, I think, to be explained by 
 the longer route traversed by the splenic blood, which gives the 
 liver more time to deal with the liberated blood-pigment, seeing 
 that in the new arrangement this becomes distributed over the 
 whole body, instead of being contained only in the portal vein. 
 
 Another argument in favour of there being such a function 
 of the spleen is afforded by the fact that exposure of the spleen 
 to x rays results in a diminished output of haemolysin in the 
 experiments on dogs (Hektoen). There are great difficulties in 
 interpreting the experiments relative to this part of the subject, 
 since the bone-marrow also must inevitably be influenced by the 
 substances used to produce haemolysis. 
 
 The whole subject assumes an entirely different aspect when it 
 is discussed from the cellular side, as Sajous has fully done in his 
 work on Internal Secretions. Haemolysis in a normal animal is 
 carried out by cells within cells ; immunity-reactions are secured 
 by the same means. These views are fully supported by the 
 results of all the experiments to which reference has been made. 
 
 7. Does the spleen secrete a substance capable of acting on the 
 bone-marrow ? D anile wsky was the first to assert that this was the 
 case, and others corroborate his view. The rapid anaemia after 
 splenectomy, out of proportion to the loss of blood, suggests that 
 some such substance has temporarily ceased to be formed. In one 
 of Pearce's experiments a splenic extract, administered to a dog 
 dying from anaemia after splenectomy, saved its life. A single dose 
 of splenic extract given intraperitoneally will induce a rise in the 
 red cells and haemoglobin content in dogs who are not dangerously 
 anaemic. The effect, it is interesting to note, is not produced when 
 the splenic tissue is given by the mouth. Another argument in 
 favour of this view, fortified by Pearce, is that regeneration of 
 blood takes place much more slowly than usual when a splenecto- 
 mized dog has been bled, or has been rendered anaemic in some 
 other way. 
 
 As regards the part of the bone-marrow concerned with the
 
 26 THE SPLEEN AND ITS DISEASES 
 
 formation of white cells, it has been suggested that there is 
 normally a restraint of its activity through some substance 
 secreted by the spleen. Increased activity of the spleen leads to 
 increased formation of ' leucosplenins ', and therefore, consecu- 
 tively, to a diminution in the number of white cells in the blood. 
 After splenectomy, there is leucocytosis due to the removal of this 
 restraint. Undue restraint occurs, as Schmincke points out, in 
 typhoid, syphilis, malaria, Banti's disease, Gaucher's disease, kala- 
 azar, and Hanot's cirrhosis. When x rays are applied to the 
 spleen, they stimulate the splenic cells, cause them to form more 
 leucosplenins, and thus indirectly interfere with the action of the 
 bone-marrow. 
 
 Pearce has decided that the relation between the spleen and 
 bone-marrow is rather a matter of the changes which take place in 
 the storage and utilization of the iron of the body than a specific 
 hormone action. Bone-marrow becomes red after splenectomy 
 because it begins to take on the function of storing iron. It is 
 certain that animals suffer largely from loss of iron after this opera- 
 tion, and it is evident that red cells cannot be produced in the 
 absence of iron. Hence the anaemia may have a perfectly simple 
 explanation, making it unnecessary to introduce the notion of 
 special ferment substances into a discussion of the pathology of 
 this subject. 
 
 8. A final question : Is the spleen concerned -with the activation 
 of digestive ferments ? Tarulli and Pascucci compared the digestive 
 power of the gastric juice before, and some days or weeks after, 
 extirpation of the spleen in dogs. They also studied the effect of 
 administering watery infusions of 'engorged' spleens (that is, 
 spleens removed from dogs in full digestion), observing at the same 
 time whether the animals lost weight or not. The result of their 
 experiments is to show that the digestive power is constantly 
 weakened after loss of the spleen during a period of two or three 
 months. The use of a congested spleen-infusion eight hours before 
 the meal restored the digestive power. Infusion of spleen removed 
 in the intervals following active digestion failed to replace the 
 loss of activity of the gastric juice of such dogs. The authors 
 therefore conclude that the spleen provides a substance which 
 causes the gastric glands to produce more pepsin. Hedin and 
 Rowland, however, in 1901, found similar results with extracts of 
 other organs.
 
 THE FUNCTIONS OF THE SPLEEN 27 
 
 The conspicuous feature of all this work and the quantity of 
 it is very considerable is the attempt to study the organ almost 
 entirely as a separate entity working in isolation. In future the 
 most eager attention must be given to tracing up, and laying bare, 
 every possible connection it may possess with other organs. The 
 analogy with the work of the surgeon is interesting. In our earlier 
 experience we were concerned with the clinical recognition and the 
 operative treatment of diseases of one organ the stomach, the 
 duodenum, the gall-bladder, the intestine, or the appendix. We 
 now realize that the diseases in these several organs are secondary, 
 and that some common underlying cause for many of them may 
 be present. Any operation upon one of the organs now involves 
 not merely the examination of that one, but also the scrutiny, 
 and possibly a further operation upon, any one or more of the 
 others. Future experimental work must consider the spleen, not 
 as an organ whose functions are confined to its own activities, but 
 as a member of a group of organs each concerned with, and influ- 
 enced by, the activities of the others. And clinical work must 
 regard the problems of its disease in the same manner. Micro- 
 scopical examination of the organ, showing as it does exactly what 
 are the tools with which the spleen works, or the tools that go to 
 make up the organ itself, demonstrates very clearly that we have 
 to deal with cell-structures which other blood-forming organs also 
 possess and use ; indeed, the capillaries of many parts of the body 
 in genera] show similar structures. 
 
 Intimate connections with the spleen can be found in four 
 important systems of the body : (1) The hcemopoietic system ; 
 (2) The reticulo-endothelial system ; (3) The digestive system ; (4) The 
 sympathico-endocrine system. Each of these systems has a depot, 
 so to speak, in the spleen ; but this organ also contains within 
 itself a histological system into which the other four merge. 
 Although the spleen constitutes a link in each one of these systems, 
 they are all able to dispense with its service ; and although the 
 presence of the spleen is not by any means a matter of indifference 
 to any of them, yet they are not permanently or irreparably 
 affected by its loss. 
 
 1. The Spleen as a Member of the Haemopoietic System. 
 The part played by the spleen in the formation of red blood- 
 cells and neutrophile leucocytes in embryonic life is everywhere
 
 28 THE SPLEEN AND ITS DISEASES 
 
 admitted. In adult life the connection is usually only demon- 
 strable under the influence of infections and in the various forms of 
 splenic enlargement, and rarely is there a reversion to the capacity 
 of forming red cells. Leukaemia affords an instance of post-natal 
 resumption of white-cell formation, though the process is, of course, 
 enormously exaggerated. The mechanism of the change is the 
 same in the infections as in leukaemia. The cells of the spleen - 
 pulp become transformed into parent cells tending to give rise to 
 neutrophile leucocytes as they originally did in the embryo. And 
 the process is now the same as in ordinary bone-marrow, where 
 endothelial cells, specially endowed, still give rise to these 
 leucocytes. 
 
 A connection between the spleen and the bone-marrow has 
 already been spoken of as dependent upon a hormone, elaborated 
 by the spleen and expended in stimulating the bone-marrow ; a 
 hypothesis which explains certain facts. But, as has been suggested, 
 the same facts can be explained more simply. The destruction 
 of red cells by the spleen enables this organ to liberate effete iron 
 in a form capable of reconstruction into a complex albuminous 
 substance by the aid of the liver-cells. In this synthetic process 
 the first step is checked by excision of the spleen ; and sufficient 
 iron to make the usual hourly complement of red cells is not 
 then available for the bone-marrow. I think Krumbharr expresses 
 this view when he asserts that the spleen furnishes a substance 
 which is activated by the liver. But neither the substance, nor 
 the activated products, need be new and additional ; they are 
 pre-existing substances, temporarily parted, and united again in 
 rejuvenated form on the distal side of the liver. 
 
 In the same way, the theory of Horbaczewski that the spleen- 
 pulp secretes a substance normally restraining white-cell formation 
 may be looked on as too superficial, and experimental evidence to 
 support it is not at all conclusive. 
 
 2. The Spleen as part of the Reticulo-endothelial System. - 
 We owe the conception of this system of the body to Aschoff. It 
 has evoked numerous investigations, and as time goes on it is 
 regarded more and more as important, once again raising to 
 supreme interest a sphere of action in the body the consideration 
 of which has been neglected for nearly forty years. 
 
 Wherever the tissue surrounding capillaries is loose, the endo-
 
 thelial cells are found to be closely connected with the surrounding 
 reticular cells. The endothelium and the perithelium form parts 
 of a meshwork, and this again becomes connected with the reticular 
 meshwork familiar in connective tissue. The spleen-pulp furnishes 
 a very good picture of this arrangement, for the meshwork is made 
 of reticular cells which can be traced continuously into the network 
 formed of the fraying edges of the blood-vascular channels where 
 they open out or, on the venous side, close up into the spongework 
 of the organ. 
 
 In the liver, certain large cells, the star-cells of Kupffer, excited 
 much speculation for many years. They are essentially phagocytic 
 in function, and are really to be regarded as endothelial in nature.. 
 After splenectomy they undergo proliferation. In haemolytic 
 diseases they become filled with iron pigment. The endothelial 
 cells of the lymphatic glands are also phagocytic, and undergo 
 proliferation after splenectomy. They exactly resemble the corres- 
 ponding cells in the spleen. Similarly, the bone-marrow provides 
 a meshwork of cells exactly comparable to the cells of the 
 splenic pulp, though characteristically active in their own special 
 direction. 
 
 A complete histological system can therefore be easily traced 
 in many important parts of the body. It is traceable, if less 
 easily, as a generally distributing form of tissue, not specially 
 noticed hitherto, yet performing one of the most important parts 
 in the physiology of the body. It is rightly attracting increasing 
 attention at the present time. 
 
 The nature of the spleen-pulp cell ; the changes it may 
 undergo in different diseases and under different forms of stimulus ; 
 its relations to the connective tissue of the organ ; its chemical 
 characters, and the powers of taking up certain 'vital' and other 
 dyes have all been carefully worked out during recent years, and 
 give a satisfactory insight into the minute processes which collec- 
 tively constitute the functions of the spleen. It is the phagocytic 
 proclivities of these cells which account for the harbouring of 
 micro-organisms in the spleen-pulp ; and it is the great vitality of 
 these organisms, even after ingestion, which accounts for the latency 
 of many infections. The malarial parasites notoriously find here 
 a home, from which they only emerge under provocation. The 
 same is true of the pallid spirochaete. Whatever truth there may 
 be in the view that cirrhosis of the liver is due to bacterial
 
 30 THE SPLEEN AND ITS DISEASES 
 
 infection finds its explanation in the two phenomena of phago- 
 cytosis together with persistent vitality of the engulfed particles. 
 
 But these phenomena are not restricted to the spleen. When 
 poisons capable of dissolving the red blood-cells are administered, 
 the pigment is found scattered through all the organs in which this 
 reticulo-endothelial system occurs, especially in the liver and in 
 the lymphatic glands, less conspicuously (because less often exam- 
 ined ?) in the bone-marrow. When Eppinger realized that the 
 endothelial cells of the liver were identical in function with those 
 in the spleen, he called them " the splenic tissue of the liver ", 
 .and seemed to suggest that they are carried bodily from the spleen 
 to the liver, whenever the former is overburdened or maimed. 
 Lintwarew has shown that such a procedure actually occurs ; and 
 it is histologically evident that there is a permanent tissue as well. 
 Aschoff's conception is, however, much more useful and suggestive. 
 
 The relation of the spleen to immunity is not merely a matter 
 of its behaviour to the introduction of haemolysins ; its pulp-cells 
 ;are concerned in the manufacture of the immune substances with 
 which the body is furnished in the course of infections. Herein lies 
 a, very important practical bearing in regarding the spleen as a 
 member of the reticulo-endothelial system. The question is worthy 
 of ample consideration. 
 
 In the early literature of splenic diseases the statement is not 
 seldom found that the organ possesses, among its many functions, 
 that of offering resistance to systemic infection. Its enlargement 
 during some of the acute specific fevers, and in other conditions 
 in which grave infections are present, was held to be an evidence 
 that it was conspicuously active in defence. And experimental 
 evidence, which was early sought, did at times appear to support 
 this view ; but such evidence was often conflicting. It was neces- 
 sarily so ; for no care appears to have been taken to choose healthy 
 .animals for experiment, and such results as were obtained, were in 
 part due, in all probability, to the existence in many of the animals 
 of such diseases as would inevitably vitiate any conclusions. Of 
 the early work, that of Pfeiffer and Marx* was the soundest. In 
 investigating the formation of immune bodies in cholera, these 
 authors found that the spleen and the medulla of the long bones 
 contained a far larger proportion of these substances than any 
 
 * Zeils. /. Hygiene, 1898, xxvii, 272.
 
 THE FUNCTIONS OF THE SPLEEN 31 
 
 other part of the body ; and this reservoir, so to speak, of defen- 
 sive substances continued for many months, until the bactericidal 
 properties of the blood were slowly brought up to the standard 
 found in the spleen and the bones. They also found that immunity 
 could be developed in an animal whose spleen had been removed 
 some months before ; but if the production of immunity was 
 attempted and the spleen then at once removed, the immunity 
 failed to develop. This suggests that the early removal of the 
 spleen had afforded time for the vicarious functions possessed by 
 the medulla of the long bones or other parts to have developed. 
 
 In 1891, Bardach* injected 25 normal dogs, and 25 dogs from 
 whom the spleen had been removed, with 1 c.c. of an anthrax 
 culture (rabbits are normally resistant to infection by anthrax). 
 Of the 25 spleenless dogs, 19 died ; of the 25 normal dogs, 5 died. 
 Similar results were obtained when normal and spleenless dogs 
 were immunized against anthrax before injection of the culture. 
 The deaths in the spleenless dogs were more numerous. 
 
 Tizzoni and Cattanif injected cultures of the tetanus bacillus 
 into three groups of rabbits : normal vaccinated, normal unvac- 
 cinated, and vaccinated spleenless. Animals in the first group 
 resisted the inoculation ; those in the last two groups succumbed. 
 They were unable to render rabbits whose spleens had been 
 removed immune against tetanus. It therefore appeared possible 
 that the manufacture of a substance causing immunity was manu- 
 factured by the spleen. In their later work they seemed to realize, 
 with Righi, that the removal of the spleen merely acts as any other 
 major operation would, in reducing the general systemic resistance 
 to infections. These results are not confirmed by some other ex- 
 perimenters, but, as a rule, too few animals were used by them 
 to avoid the chance of error. 
 
 The most careful experiments hitherto conducted are those 
 of Morris and Bullock. J The following is a portion of their 
 account : 
 
 " Thirty-six apparently healthy young brindle rats, weighing 
 from 50 to 100 grms. each, were splenectomized under ether 
 anaesthesia. Great care was taken to guard against any operative 
 'Complications, such as haemorrhage or infection, and the subsequent 
 
 * Ann. de Vlnst. Pasteur, 1891, iii, 571. f Centralb. f. BakterioL, 1892, xi, 325. 
 % Ann. of Surg., 1919, Ixx, 513.
 
 32 THE SPLEEN AND ITS DISEASES 
 
 autopsies showed that none had occurred. A similar number of 
 control rats of like weight and breed were subjected to a laparo- 
 tomy in which one testicle was removed. As the testicle is larger 
 than the spleen, and the blood-vessels entering it are about equal 
 in size to the splenic vessels, its transabdominal removal furnishes 
 a very fair basis of comparison as to the effect of the operative 
 trauma alone upon the subsequent health of the animals. 
 
 " Both sets of animals were found to be active and thriving 
 on the day following the operation. They were then exposed to 
 chance laboratory contagion and kept under observation for several 
 months. Whenever an animal in either series died, an animal 
 of the other group was killed, and both were completely autopsied. 
 Microscopical sections were made from all important organs, and 
 cultures were taken from the heart's blood and from the peritoneal 
 cavity or lung. 
 
 " It w r as then observed that the splenectomized animals almost 
 invariably died before the controls, and that the death-rate among 
 them was 80-5 per cent as compared with 38-9 per cent in the 
 normal rats. Necropsy showed the following lesions : Congestion 
 and parenchymatous degeneration of nearly all the important 
 organs, varying from injection of the vessels and slight cloudy 
 swelling to focal necroses or extensive disintegration of the paren- 
 chyma. If the animal had survived long enough for a reparative 
 process to set in, there was replacement of the degenerated areas 
 by newly-formed granulation tissue." 
 
 They conclude from these results that the spleenless rats were 
 more prone to contract the prevalent rat plague, and that, having 
 contracted it, they showed less resistance to its ravages. A second 
 experiment with 72 rats confirmed these results, and showed that 
 under ordinary laboratory conditions spleenless rats were far less 
 resistant to a common infection than normal rats. The conclusion 
 is therefore drawn that the spleen must in some way help to protect 
 the animals against infection, since removal of another organ of 
 equal size and weight, by a similar operative procedure, caused 
 no impairment of the defensive mechanism. 
 
 In a further experiment, two groups of 88 rats each were 
 treated, the one by splenectomy, the other by abdominal castration, 
 and were then injected subcutaneously with a sublethal dose of 
 broth culture of the bacillus of rat plague. Of the castrated rats, 
 22*7 per cent died ; of the spleenless rats, 87'5 per cent died.
 
 THE FUNCTIONS OF THE SPLEEN 33 
 
 The conclusions which flow from these most careful and 
 exhaustive experiments are that the spleen affords great aid in 
 resisting infective processes in rats, and that its removal robs the 
 body of its resistance, or diminishes that resistance until such time 
 at least as compensatory processes have had a chance to establish 
 it once again in its original strength. Hektoen's experiments* 
 appear to show that antibodies are produced in the spleen, 
 lymphatic tissues, and bone-marrow. 
 
 So far as I am aware, no observations to support these conclu- 
 sions have yet been made on man. But the evidence as to the 
 defensive properties of the spleen which these experiments reveal 
 is so strong that remembrance of this function of the spleen should 
 always be borne in mind when the operation of splenectomy is 
 under consideration. 
 
 3. The Spleen as a Member 'of the Digestive System, Although 
 it is well known that the spleen undergoes variations in volume 
 during the day, becoming larger up to a period of about four hours 
 after every meal, diminishing subsequently as a result of muscular 
 action, there is much difference of opinion as to the purpose of 
 these changes. Some regard the spleen as a reservoir for surplus 
 blood, while others believe that the periodic enlargement is con- 
 cerned with the digestive processes in the duodenum and small 
 intestine. This last view is supported by two observations : (a) 
 That the blood shows a leucocytosis during the period of digestion ; 
 and (&) That the blood of the splenic vein is richer in leucocytes 
 than that of the artery. 
 
 We owe our early knowledge of the relationship between the 
 leucocytes and digestion chiefly to Hoffmeister and Pohl. The 
 great increase of lymphocytes in the intestinal mucous membrane 
 during digestion was demonstrated by the former ; and the 
 relationship existing between this and the kind of food taken was 
 indicated by the latter. The leucocytosis is most evident after a 
 protein diet. Examination of the blood of the superior mesenteric 
 artery shows a great increase of leucocytes during digestion, 
 although the increase is due to the neutrophiles and not to lympho- 
 cytes. Subsequent observers have sought to belittle these observa- 
 tions. There are some who deny the existence of an increase of 
 
 * Jour, of Infect. Dis., 1915, xvii, 415.
 
 34 THE SPLEEN AND ITS DISEASES 
 
 the blood-cells during digestion ; others, who admit that such an 
 increase does occur, consider it to be merely a part of a natural 
 cyclic phenomenon having no direct relationship to any food 
 ingested. It has been suggested that the increase may be in the 
 nature of a protective mechanism, whose purpose is to ensure the 
 detoxication of the products of protein digestion. The evidence 
 on the whole seems to indicate that there is a definite relationship 
 between the type of the dominant cell in the blood, and the quality 
 of the food ingested. Neutrophile leucocytosis follows a meal of 
 proteids and fats ; lymphocytosis follows a meal rich in carbo- 
 hydrates. 
 
 It may be that the spleen is concerned with the destruction 
 of the surplus lymphocytes liberated during the process of diges- 
 tion. If so, this would account for the undoubted enlargement of 
 that organ which then occurs, and also for the lymphocytosis which 
 follows splenectomy, the agent responsible for the destruction of 
 these cells being then absent. 
 
 The relation of the spleen to the liver must be of the most 
 intimate character, for every drop of splenic blood passes into and 
 through this organ. The connection is well shown in regard to 
 bile secretion, for it is everywhere admitted that the bile-pigment 
 is derived from haemoglobin, though the exact mechanism of the 
 conversion is not understood. Assuming that the haemoglobin must 
 be carried to the liver in the free state, Banti and Furno searched 
 for it in that form in the splenic vein. They claimed positive 
 results, but Pearce does not confirm their observations. In the 
 belief that the spleen contributes a substance which dissolves red 
 cells, the blood of the splenic vein was then searched for evidence 
 of 'fragile' red cells. Hammersten, Chalin and Charlet, and more 
 recently Pearce, have all failed to find evidence of such a condition. 
 This work, as well as the experiments of Pearce made to determine 
 the 'threshold' for haemoglobin, and the work of Anitschkow and 
 many others, including Widal, would appear, as I have previously 
 urged, to be quite irrelevant when once it is admitted that the 
 haemoglobin reaches the liver within the bodies of wandering cells, 
 and not in the free state. 
 
 The fact that splenectomy in dogs lessens the liability to 
 jaundice from the introduction of haemolytic substances, has 
 suggested that the spleen prepares a substance directly concerned 
 in aiding the work of the liver; and the fact that the urobilin
 
 THE FUNCTIONS OF THE SPLEEN 35 
 
 becomes less plentiful in the urine when a case of pernicious anaemia 
 has been treated by splenectomy, points in the same direction. 
 The urobilin is the evidence of increased hsemolytic activity in the 
 portal blood. But the attempt to explain certain clinical pheno- 
 mena of diseases of the spleen in terms of a ' hypersplenia ' 
 (Eppinger) or 'dysfunction of the spleen' (Hirschfeld) is due to a 
 misconception either as to the purpose of the spleen or as to the 
 significance of haemolysis. 
 
 It is probable that in splenic anaemia the benefits of splen- 
 ectomy are due to the liver receiving less work to accomplish in a 
 given unit of time. The cirrhosis in the later stages results from 
 the presence of the same toxic substances which excite the fibrosis 
 of the spleen ; the liver shuts off, and entombs within a fibrous 
 wall, those substances with which it fails adequately to deal. 
 
 In those cases of splenic anaemia in which gall-stones are 
 developed concurrently, the irritant traverses the liver-cells and 
 enters into the bile, causing precipitation and encapsulation within 
 the gall-bladder. It may also be that the composition of the bile 
 itself is altered, the raw material supplied to the liver being short 
 of some constituent, so that the product subsequently precipitates 
 more readily around organisms within the gall-bladder. 
 
 The relation of the spleen to the pancreas is suggested by the 
 anatomical features. The blood from the tail of the pancreas 
 meets the splenic blood soon after leaving the organ. The classical 
 work on this subject is that of Herzen, who sought to establish 
 the existence of a ' trypsinogenic function' of the spleen. All the 
 bearings of this work were ably set forth by Bellamy in 1900. It 
 seems quite clear that the splenic blood is definitely different in 
 composition according to the digestive period in which it is 
 collected. The experiments devised to show this were exception- 
 ally clear and convincing. 
 
 More recently, Sajous* emphasizes the importance of what he 
 calls the ' spleno-pancreatic ferment' which comes into action 
 between the spleen and liver, apparently detoxicating the blood 
 which bears the food products. The albuminoid substances are 
 converted into benign products in the liver circulation, and are 
 passed on to the body at large in order to supply the tissues with 
 a high percentage of phosphorus. This author, as I have said, 
 
 * Internal Secretions, 8th ed., 1919, 531.
 
 36 THE SPLEEN AND ITS DISEASES 
 
 strongly emphasizes the view that the functions of the spleen, in 
 so far as they are to be revealed by a study of the blood of the 
 splenic vein, will be found to be connected with the cellular and 
 not with the fluid portions. 
 
 A relation of the spleen to the small intestine is shown by the 
 fact that splenic extracts powerfully excite intestinal peristalsis. 
 Such extracts are the basis of the preparation 'hormonal', which 
 has been so much vaunted as a remedy for constipation, for 
 lethargic appetites, and so forth. 
 
 The position of the spleen as part of the digestive system is 
 also demonstrable in terms of the chemical composition of the organ, 
 and of the phenomena of purin metabolism. Horbaczewski drew 
 attention to the endothelial cells as the visible link between cellular 
 changes and the formation of the purins shown by chemical 
 analysis. Many eminent chemists have elucidated this part of the 
 subject. The subject of iron metabolism has constituted an impor- 
 tant chapter in the story of researches into the functions of the 
 spleen. Asher principally, in addition to Schmey, Kruger, Bayer, 
 and others, has shown by many experiments that variations in 
 output of iron go with variations in the activity of the spleen. 
 Splenectomy results in increased loss of iron from the body. The 
 part played by the spleen in fat metabolism has been studied micro- 
 chemically, and it seems clear that this organ provides a link in 
 that very complicated process of body metabolism. Experiments 
 which have been made to show such a connection have not 
 succeeded in Pearce's hands. 
 
 4. The Spleen as a part of the Sympathico-endocrine System. 
 
 The endocrine organs are those which produce an internal secretion. 
 They belong to two main groups. In the first are those which 
 now produce, or have at some time produced, an external secretion 
 also. The pancreas is the best instance of this type ; others are 
 furnished by the testis and the thyroid. The second group con- 
 tains those organs which do not yield an external secretion, and 
 have never done so. The former exert their action through the 
 circulation ; the latter operate through the sympathetic nervous 
 system. 
 
 The spleen has never yielded an external secretion ; it is 
 intimately connected with the blood-stream, and at the same time 
 it has extensive connections with the sympathetic nervous system.
 
 THE FUNCTIONS OF THE SPLEEN 37 
 
 The splenic sympathetic plexus forms a dense network round the 
 splenic artery and its ramifications within the spleen. This plexus 
 is closely connected with the solar plexus, and therefore comes 
 into connection with the adrenal glands. Besides this, the spleen 
 receives branches from the vagus nerve which supply the muscular 
 tissue of the capsule and the trabeculse. The French writers have 
 named this system ' parasympathetic ' ; the American writers ' the 
 autonomic-sympathico-endocrine complexus' ;* but before we can 
 accept or make use of the term ' autonomic instability ' to explain 
 the action of certain phenomena in connection with the spleen, 
 much more detail is required upon the whole subject. 
 
 When Cohen asserts that 'gall-duct crises' are started by 
 changes in the splenic end of the vasomotor chain, he reminds us 
 not to omit the action of the nervous system from our calculations, 
 without affording us that adequate knowledge which we crave. 
 
 Extracts of the spleen, including the proprietary substance 
 called 'hormonal', have been shown by Berlin to have a similar 
 action to that of cholin upon vasomotor nerves. Stern and Rothlin 
 have found that extracts of the spleen are also capable of acting 
 specially on smooth muscle, even in very minute doses. The active 
 agents in the extracts are called ' lienins ', and it is suggested that 
 the spleen is concerned with the preservation of the tonus of the 
 stomach, and of the intestinal and other smooth muscles. The 
 action is aided by the presence of adrenalin. 
 
 The relations between the spleen and thyroid have been 
 studied by many observers, from 1883 onwards. Zander (1893) 
 found that removal of the thyroid will not produce a fatal result 
 if the spleen be removed first, though other experimenters found 
 that the fatal result was only deferred. Massenti and Coronadi, 
 quoted by Luciani, found that thyroidectomy is associated with 
 subsequent atrophy and fibrosis of the spleen. Klingerj* did not 
 find much definite evidence of interaction between the spleen and 
 thyroid. Asher and Streuli's observation that these two organs 
 both influence the bone-marrow and the consumption of oxygen 
 by the body was not confirmed by him. He thought the varia- 
 tions which these and others had found were not necessarily 
 attributable to the spleen. Hauri,J evidently working under the 
 
 * Osier Memorial of 1919 (S. S. Cohen). t Biochem. Zeits., 1919, xcii, 376. 
 J Biochem. Zeits., 1919, xcviii, 1.
 
 38 THE SPLEEN AND ITS DISEASES 
 
 influence of Asher, studied the respiratory metabolism in animals 
 deprived of the spleen, or thyroid, or both, and is satisfied that 
 there is some interaction between the two organs. Streuli* also 
 adduces evidence to support the view that the spleen ' balances 
 up ' the thyroid. 
 
 Investigations have also been made to ascertain if there are 
 any special relationships between the spleen and the thymus 
 gland. According to Bayer, the activity of the thymus is re- 
 awakened after the spleen has been removed. 
 
 *Biochem Zeits., 1918, Ixxxvii, 359.
 
 39 
 
 CHAPTER IV. 
 THE PATHOLOGY OF SPLENIC DISEASES. 
 
 THE pathological changes found in the spleen can best be grouped 
 according to the affinities which exist between the causative agents 
 and the various parts of the spleen-liver system which they directly 
 affect. 
 
 1. In the first type the provocative agent excites either a 
 mechanical effect, or a local lesion, of the exact kind produced in 
 other organs. The results will be expressed by the formation of 
 an abscess, by a deposit of tuberculous nodules, by a metastatic 
 new growth, and so forth. 
 
 2. In the second type, an organism lodges firmly in the pulp 
 of the spleen without actually producing a gross lesion there. Like 
 any irritant of chronic character, it induces changes in the reticu- 
 lum akin to, or actually constituting, fibrosis. The best example 
 of this condition is afforded by the chronic malarial spleen, wherein, 
 according to modern experience, the parasites lie apparently inert 
 for long periods, to appear from time to time in the general circula- 
 tion as a consequence of some excitant, suspected or unknown. 
 The tropical splenomegaly may be regarded as a similar example, 
 since here also the parasites are found embedded in the splenic 
 pulp. It is probable that many other chronic enlargements of the 
 spleen may be regarded in the same light, and it seems not unlikely 
 that spirochaetal infections, whether syphilitic or of an unknown 
 type, may account for many forms of fibrosis and of chronic 
 disease. The work of W. J. Mayo on cases of splenomegaly 
 associated with incoercible manifestations of syphilis is referred to 
 elsewhere. 
 
 3. The third type of process is that which is set in motion by 
 toxic substances reaching the spleen from some nidus elsewhere in 
 the body. Foci in the mucosa or submucosa of various parts of 
 the alimentary canal, in which there is no frank suppuration, 
 but merely a subacute inflammatory cell-infiltration of slight or 
 moderate extent, are easily overlooked, especially in the examina- 
 tion of the dead body. In pernicious anaemia, of course, definite
 
 40 THE SPLEEN AND ITS DISEASES 
 
 lesions of this kind have been discovered by means of a special 
 technique, and have been considered by Hunter, who first recog- 
 nized them, as the portal of entry of the causative infection. 
 
 Given the primary infected lesion, the course of the toxic 
 substances continually poured out into the vascular system is 
 identical (for a part of the circuit) with that of the blood through 
 the spleen, liver, and bone-marrow. The toxic substances may be 
 of various kinds, which may be named according to their action. 
 They may remain in the blood-stream and act on the floating cells, 
 or they may pick out certain tissues of the body. The selective 
 power of streptococci (as shown by Rosenow) and of toxins is well 
 recognized, and mutual affinity of soil and seed may also be present. 
 There is nothing impossible, therefore, in conceiving that some 
 toxins will affect the cells of the spleen-pulp exclusively, either 
 causing degeneration in them, or stimulating them to increased 
 activity. In either case the material which leaves the spleen may 
 consist not only of the original toxin, but also of the products of 
 degeneration or over-activity of the existing splenic cells. The 
 poison contained in the blood leaving the spleen comes almost at 
 once into contact with the blood from the stomach and the tail of 
 the pancreas. In this way it may become altered enough to cease 
 to have any deleterious action upon the cells next encountered, 
 namely, the Kupffer star-cells and the other endothelial cells of 
 the hepatic sinusoid, or the liver-cell itself. On the other hand, 
 the toxic substance or substances may arrive at the liver unaltered, 
 and there set up changes in the respective elements which go to 
 make up the unit of liver-tissue. These changes are usually of a 
 degenerative nature ; but in some cases, owing to the toxins 
 passing through the endothelium, reactive changes are excited in 
 the fibre-cells enclosing the lobule. This is the beginning of 
 cirrhosis. 
 
 Another series of changes results when the brunt of the action 
 of the poisonous substances is borne by the hepatic cell itself. As 
 occurs in other parts of the body, the passage through the cell may 
 cause no damage, but may provoke changes in the parts beyond ; 
 in this case in the smallest beginning of the bile-channel. Here 
 the bile itself may lose its fluidity, precipitates may form, which 
 in the minute channels cause blockage and a mechanical biliary 
 retention (with or without jaundice). Or it may be that, without 
 acting in any way upon the bile, the noxious substances first affect
 
 THE PATHOLOGY OF SPLENIC DISEASES 41 
 
 the endothelial lining of the bile-channels, and so set up some form 
 of cholangitis. 
 
 In other cases, however, the liver-cell is itself affected, and a 
 series of clinical phenomena dependent on failure of the hepatic 
 function takes place. After that, the stereotyped secondary 
 cirrhosis may occur. 
 
 Leaving the liver, the poisoned blood may pass through the 
 heart and lungs without losing its toxic character, and may finally 
 come in contact with the cells in the sinusoids of the bone-marrow, 
 and interfere with their function, if there is any affinity between 
 them. Where repression of function occurs, a certain type of 
 anaemia results, or a diminution in the number of the white cells 
 which are being made there. Conversely, increase of white cells 
 may occur, and leucocytosis form a conspicuous feature. 
 
 Sufficient evidence has now been accumulated to enable us to 
 form some idea of the varieties of toxins which may enter or leave 
 the spleen ; they are grouped according to their supposed actions : 
 as causing anaemia, haemolysis, asthenia with muscular wasting, 
 cirrhosis of the liver, fibrosis of the spleen, or proliferation of 
 various cells capable of active increase (for instance in the germ 
 centres of lymphoid follicles, or in the bone-marrow in myeloid 
 leukaemia). Banti invoked the first three types to explain the 
 disease which goes by his name. 
 
 1. The most active poisons causing ancemia ('anaemizing') are 
 such as prevent the red cells from being formed. There is little 
 doubt, however, that many substances are comprised in this group 
 which produce anaemia rather by destroying the red cells or by 
 rendering them vulnerable. In this case the phagocytes of the 
 spleen-pulp become unduly active, and a complication is intro- 
 duced, inasmuch as these pigment-laden cells carry their burden 
 to the liver, disintegrate there, and overburden this organ, besides 
 producing another and peculiar type of change siderosis and 
 proliferation of endothelial cells. 
 
 2. The hcemolysing poisons are important. They play the 
 chief part in haemolytic splenomegaly, and in some forms of severe 
 anaemia, as well as in some special types of cirrhosis. Chevallier 
 and Tourkine have been at much pains to insist on the dual 
 character of the haemolysing poisons, some of these having the 
 property of actually destroying the red cells, while the others only 
 cause them to become 'fragile'.
 
 42 THE SPLEEN AND ITS DISEASES 
 
 3. Poisons which excite fibrosis are very common. The process- 
 of fibrosis has been long assumed to be merely the last stage of an 
 inflammatory process ; but there is evidence to show that fibrosis 
 of the spleen may be a specific phenomenon, just as in the liver 
 biliary cirrhosis is certainly the result of active and direct stimu- 
 lation of the connective-tissue cells. 
 
 4. The poisons which excite cell-proliferation may concern the 
 cells of the Malpighian bodies, as in lymphatic leukaemia and some 
 kinds of Hodgkin's disease, or the cells of the spleen-pulp. In the 
 latter case several things may happen. The pulp-cells may assume 
 the properties usually restricted to the cells of the bone-marrow 
 concerned with the formation of white cells ; in these circumstances 
 bone-marrow cells are produced. If this should occur in a slight 
 degree, it is only revealed by microscopic examination. Instances 
 of this action are afforded by various acute specific fevers. If it 
 occurs in a greater degree, the enlargement of the so-called spleno- 
 medullary leukaemia is brought about. Sometimes the pulp-cells 
 develop enormous numbers of cells of all kinds, and so produce a 
 tissue of very complicated structure, as in lymphosarcoma or 
 Hodgkin's disease.
 
 43 
 
 CHAPTER V. 
 
 THE CLINICAL AND ASSOCIATED PHENOMENA IN 
 SPLENIC DISEASE. 
 
 THE clinical and other phenomena which occur as evidences of 
 splenic disease may now be discussed as a corollary to the various 
 matters so far considered. The list of symptoms and signs likely 
 to be encountered resolves itself into a short one when the mechani- 
 cal results which follow upon a gross enlargement of the organ, 
 or upon the obstruction to the portal circulation by a terminal 
 cirrhosis of the liver, are omitted. 
 
 1. Anaemia. Anaemia is caused by many diseases. In this 
 connection it is only necessary to consider the type of anaemia 
 which rightly directs the attention of the clinician to the spleen as 
 its cause. The preceding discussion has briefly dealt with the 
 subject of haemolysis. It may now be asserted that a disease of 
 the spleen is to be suspected when there is any evidence that 
 haemolysis is associated with anaemia. What exactly is the full 
 significance of the term ' haemolysis ' ? It may be taken to indicate 
 the occurrence in orderly succession of the following events : a 
 destruction of the red cells, the accumulation of their remains in 
 the spleen, the ingestion of these remnants by the phagocytic 
 endothelial and reticular cells, and finally the transmission of these 
 engorged cells to the liver, in whose 'sinusoids' they are dis- 
 integrated preparatory to the absorption of their particles by the 
 stellate cells of that organ. Haemolysis will be rendered an easier, 
 and therefore a more frequent process, if any diminution occurs in 
 the resistance offered by the red cells to their destruction. Such 
 a change has been described by Chauffard, who speaks of a 
 'dystrophy' of the red cells, a condition in which their vulnerability 
 is increased, and there is consequently a special ' fragility '. It has 
 been asserted that the presence of a fragility of the red cells 
 indicates that the seat of any disease in which it occurs is in the 
 spleen ; but there is evidence to controvert this opinion. Such a
 
 44 THE SPLEEN AND ITS DISEASES 
 
 fragility might be due either to an early error in the formation of 
 red cells by which there was an attenuation (through defective 
 supply of the necessary material) of their hpoid component, or 
 to the inimical effects of a substance produced by bacterial agencies 
 in some lesion, perhaps quite inconspicuous, in the mucosa of the 
 alimentary canal. 
 
 But every anaemia associated with disorders of the spleen is 
 not characterized by haemolysis. There is another important 
 group of anaemias in which the initial disorder is either in the 
 bone-marrow (and in the later changes in the spleen) or is depen- 
 dent upon the same cause as that which affects the bone-marrow. 
 In this class of case, the medulla being directly damaged, the 
 process of formation of blood-cells is inhibited, or even in some 
 cases arrested. In Hodgkin's disease, for example, the bone-marrow 
 may become involved, and the part concerned in the formation of 
 red cells then undergoes atrophy. In this instance there is from 
 the onset some agent which injures the spleen and bone-marrow 
 almost simultaneously. The train of symptoms w r hich follows 
 the anaemia may then become masked in those far more con- 
 spicuous features which present the clinical picture of the original 
 disease. 
 
 When once the process of haemolysis has developed to the 
 stage described above, the further course of events will depend on 
 the manner in which the liver-cells cope with their increased 
 burden. On the one hand, the poison (which has destroyed the 
 red cells) may pass through the liver-cells without affecting them ; 
 the extra load imposed upon them is borne without injury. On 
 the other hand, the poison may actually injure the hepatic cells, 
 so that the excess of blood-pigment is disposed of with a steadily 
 increasing difficulty. Then, at last, under a continued strain, the 
 inadequacy of the liver may become apparent, either clinically 
 in the form of jaundice, or pathologically by reason of the appear- 
 ance of urobilin in the urine. The great functional capacity of the 
 liver-cell accounts for the gradual, insidious, and tardy onset of the 
 symptoms connected with the involvement of the liver in such 
 conditions. 
 
 It is interesting to find that the clinical phenomena due to a 
 haemolysis are absent in those diseases in which the liver-cell is 
 equal to its work and does not suffer impairment. In the enlarge- 
 ment of Hodgkin's disease, of myeloid and lymphatic leukaemia,
 
 CLINICAL AND ASSOCIATED PHENOMENA 45- 
 
 of sarcoma of the spleen, of lymphogranuloma, all the phenomena 
 associated with haemolysis are characteristically absent. But none 
 the less anaemia develops. The reason is, without doubt, the 
 following : 
 
 With the exception of the leukaemias, where the energies of 
 blood-formation become overwhelmingly directed to the formation 
 of white cells instead of red, these various diseases of the spleen 
 are associated with progressive fibrosis ; there is consequently a 
 gradual interference with the normal capacity of the endothelial 
 cells to remove effete red cells. This entails a loss of iron to the 
 body. The liver-cells do not receive sufficient iron in that form 
 which is suitable for reconstruction in the next step of the cycle. 
 Even if phagocytes in other parts of the body assume the function 
 of red-cell destruction, they have not direct access to the liver, and 
 cannot therefore supply this organ with sufficient speed or adequacy. 
 It seems quite clear, from the experiments in connection with iron 
 metabolism, that the spleen is situated where it is in order to 
 enable the iron-laden endothelial cells to have a free channel for 
 their passage into the minute capillaries of the liver, through which 
 they are too large to pass. 
 
 2. Jaundice. When we consider jaundice as the result of a 
 toxic process in the spleen-liver system, it is necessary to define 
 two important factors. These are the site of action of the poison, 
 and the nature of the poison. 
 
 The site of action may be in the liver or in the spleen itselL 
 For instance, in splenic anaemia, the site of action is not in the 
 liver, for in this disease there is no primary interference with the 
 activity of the liver-cells ; these do not become affected until the 
 later stages of the disease, after cirrhosis has developed. Even 
 then the action does not begin within the liver cells, which suffer 
 only indirectly by compression from without ; disorganization 
 within the cells does not appear first. Haemolytic splenomegaly, 
 on the other hand, provides an example of a disease in which the 
 action of a toxic substance is on the liver-cells themselves, since 
 from the first they are either poisoned, or burdened beyond their 
 normal capacity for dealing with blood-pigment derived from the 
 spleen. Associated with this action, no doubt, is a passage of 
 toxic substances into the bile, for this is suggested by the remark- 
 able tendency to cholecystitis and cholelithiasis which is present
 
 46 THE SPLEEN AND ITS DISEASES 
 
 in this disease. It is possible that these toxic substances act 
 selectively upon the mucosa of the gall-bladder. 
 
 The influence of the nature of the poison is shown by its site, 
 for the locality in which such poison lodges is dependent upon the 
 kind of cell affected by it. The poison which acts directly on the 
 protoplasm of hepatic cells is necessarily of a different nature from 
 one whose energies are expended in affecting the reticular cells of 
 the spleen. The mode of production of jaundice differs in the two 
 cases, not so much in kind as in degree ; because the errors which 
 arise are developed at an earlier stage in the cycle of haemoglobin 
 metabolism when the toxin selects the spleen than in the cases in 
 which the liver-cell is primarily damaged. In the spleen, the 
 haemoglobin becomes separated from the effete red cells ; in the 
 liver this pigment becomes haematin, which, as is well known, 
 becomes bilirubin simply by hydrolysis. 
 
 In his able study of jaundice* Willcox shows very clearly that 
 the bile-pigment may occur in the blood up to a certain degree 
 of concentration without any clinical evidence of its presence 
 becoming evident. He cites Blankenhorn's recent researches on 
 the subject in which a certain ' threshold ' can be spoken of, in 
 regard to the amount of bilirubin in the blood. Jaundice does not 
 appear until that threshold has been reached. In other words, 
 a toxic process affecting the metabolism of haemoglobin may be 
 mild enough to pass away without jaundice appearing ; it may 
 indeed have existed for some time although the onset of jaundice 
 would lead the observer to assume that the toxic process was only 
 now beginning. Willcox proceeds to divide cases of toxic or 
 toxaemic jaundice into three groups : those in which the degenera- 
 tion of liver-cells predominates ; those in which destruction of red 
 cells is the chief process ; and those in which a catarrh of the finest 
 bile-ducts accounts for the phenomenon. Different toxic agents 
 act in these three ways to differing extents. Simple anaemias are 
 associated with little degeneration, but show well-marked destruc- 
 tion of the red cells ; in yellow fever, and in arsenical poisoning, 
 the liver-cells undergo degeneration, whereas in spirochaetosis 
 icterohaemorrhagica, relapsing fever, and in epidemic catarrhal 
 jaundice, the changes in the bile-passages are the most conspicuous 
 effect, 
 
 * Letlsomian Lectures, 191P,
 
 CLINICAL AND ASSOCIATED PHENOMENA 47 
 
 Thursfield & Gow* have simplified the subject by fixing 
 attention upon one type of poison disordering the functions of 
 the spleen in different ways, sometimes entailing the appearances 
 of jaundice and sometimes not. 
 
 It is now clear that the site of action and nature of the poison 
 are closely dependent upon one another. It is also clear that the 
 changes produced in the bile depend on the site of action of the 
 toxin. When its action is upon the commencement of the haemo- 
 globin cycle, that is, in the spleen, jaundice is an effect only when 
 the concentration of bile-pigment in the blood reaches a certain 
 point. When the interference with the metabolic cycle is at the 
 later stage, that is, in the liver-cell, jaundice appears only as soon 
 as there is sufficient retention in the ducts. This retention is 
 mechanical, depending on the fact that the bile ceases to be 
 sufficiently fluid because the liver-cell fails to make sufficient bile- 
 salts. The jaundice is therefore produced in this case without any 
 disturbance of the function of the cells in forming bile-pigment. 
 
 In other words, when the poison is acting in the spleen the 
 jaundice is due to active interference with the changes in the blood- 
 pigment ; when the poison is acting in the liver the jaundice is a 
 mechanical one, due to other parts of the liver-cell being disturbed 
 than those which deal with the formation of bilirubin. 
 
 On the other hand, it is not safe to argue that when a patient 
 has no jaundice his haemoglobin is therefore normal. Apart from 
 the fact, which Willcox emphasizes, that jaundice does not develop 
 until a certain amount of pigment has accumulated, there is the 
 fact that blood -pigment may fail to break up correctly and still 
 produce no jaundice. Blood-pigment, in breaking down, gives rise 
 to two portions one free from iron, the other containing iron. 
 The former, undergoing purely intramolecular change, appears in 
 the liver-cell as bilirubin, and passes out into the bile capillaries ; 
 the iron-containing portion makes its way back to the site of manu- 
 facture of the red cells. In disease, this story becomes modified, 
 either at the first stage or at the second. The division of the blood- 
 pigment molecule may not take place ; haematin is then formed, 
 and gives rise (it is supposed) to one of two substances (maleic 
 imide, maleic anhydride), either of which being colourless will 
 escape observation in the liver-cell. Or, on the other hand, the 
 
 * St. Bart.'s Hosp. Reports, 1914, i, 7.
 
 48 THE SPLEEN AND ITS DISEASES 
 
 iron-free substance formed from the blood-pigment molecule may 
 not become converted into bilirubin, but into a hsemopyrrhol r 
 which is also colourless. In this case, also, bile-pigment fails to 
 appear in the liver-cells (and in the bile in the gall-bladder ?) and 
 jaundice is not present. 
 
 These considerations provide a suggestive basis for the explana- 
 tion of the anomalies which appear from time to time in reported 
 cases of cirrhosis associated with splenomegaly. 
 
 As a rule, however, jaundice is the actual result of toxic action 
 upon some part of the spleen-liver system, however different the 
 mechanism may be in the particular types of toxin concerned. 
 Even the simplest poisons may act simultaneously upon different 
 parts of the system, so that it is difficult to describe their actions 
 according to their chemical composition. When we find that sub- 
 stances whose chemical constitution is completely known, such as 
 nitrobenzene, trinitrotoluene, toluylenediamine, do not act equally 
 upon the red blood-cells and the hepatic cells, it is not surprising 
 to find difficulties in approaching the actions of those complex 
 bodies which are associated with splenic disorders. This is why 
 it is more satisfactory to classify the poisons according to the place 
 which they select for their action than according to their nature. 
 
 When the relation between these processes and the production 
 of cirrhosis has to be considered, the old question as to whether 
 cirrhosis or liver degeneration is primary need not trouble us. The 
 view that cirrhosis begins merely as a consequence of a process 
 initiated in the spleen is much more helpful. It is clear that the 
 presence of iron which is not in a suitable condition for reconstruc- 
 tion in the liver, aided by the direct action of a poison (modified by 
 passage both through the splenic endothelium and the endothelial 
 cells of the liver sinusoids), may excite an overgrowth of the 
 fibre-cells outside the liver lobules. If it should do so, not only will 
 there be cirrhosis of the Laennec type, but there will be a special 
 form of pigmentary deposit also. A purely haemolytic poison, that 
 is to say, has modified the process of disposal of blood-pigment, in 
 spite of its own modification by the splenic products into a cirrho- 
 genic substance. It is certainly significant that in such cases the 
 pancreas not seldom shows a widespread change. 
 
 The interrelation between the pancreas and the spleen and 
 liver is not capable of sufficient discussion, because, unfortunately, 
 our information about this is slender and uncertain. A direct
 
 CLINICAL AND ASSOCIATED PHENOMENA 49 
 
 connection between pancreatic disease and hepatic cirrhosis is at 
 present clear only in one form of cirrhosis, the so-called ' pigmentary 
 cirrhosis '. If the secretion from the tail of the pancreas (where 
 the islands of Langerhans are most numerous) plays a necessary 
 part in the intravascular changes which take place between the 
 spleen and liver, attention would naturally be directed to a deter- 
 mination of the frequency with which interstitial pancreatitis, focal 
 or diffuse, is associated with splenic disease ; and this is just a 
 point upon which knowledge is lacking. Suffice it to suggest that 
 the story of the mechanism of cirrhosis is hardly complete without 
 knowledge about the part played by the pancreas. Here, as well 
 as in the subject of bile-duct infections, we find the two possible 
 channels of disease the ascending from the duodenum, and the 
 descending from the acini : the latter being intimately connected 
 with the formation of a toxaemic type of jaundice when the liver 
 is involved, whereas the possible occurrence of changes descending 
 the pancreatic ducts does not appear as yet to have been con- 
 sidered by any workers in this field of physiology. Hunter 
 elaborated the view that important changes result from a descent 
 of toxins or organisms into the duodenum,* and the French school 
 have also urged in this suggestive direction. 
 
 3. Petechial Haemorrhages. These are occasionally seen in 
 cases of splenic disease, in leukaemia, and in von Jaksch's disease. 
 They always denote damage to the endothelial cells of the capillaries 
 in various parts of the body by a particular form of poison, named 
 ' endotheliotoxin ', because its effects are known and obvious, and 
 because there is no adequate knowledge indicating its chemical 
 constitution. The minute petechial haemorrhages are scattered 
 through many organs, appear on serous surfaces, and may occur on 
 mucous surfaces, as in the nose and on the gums or in the kidneys. 
 In these cases they almost certainly denote the channel of excretion 
 of the poison by which they are caused. Such clinical phenomena, 
 as is well known, sometimes accompany the circulation of certain 
 septic organisms or of the toxins derived from them ; they here 
 signify a special property of the leukaemia and allied poisons. 
 
 4. Muscular Weakness. This may be associated with an 
 actual wasting of the muscle, which partly accounts for the 
 
 * Jour. PathoL, 1896, ii, 239.
 
 50 THE SPLEEN AND ITS DISEASES 
 
 emaciation noticeable in advanced cases of leukaemia and of splenic 
 anaemia. When we remember the intimate association between 
 the spleen and endocrine system, the question arises as to the extent 
 to which the phenomena of muscular weakness and asthenia are to 
 be attributed to a direct action upon the adrenal or thyroid glands. 
 The inter-relation of these endocrine glands with each other and 
 with the glands possessed of external secretions is only now being 
 revealed to us by the work of many observers. 
 
 5. Pyrexia. Pyrexia as a feature of splenic disease has only 
 recently attracted close attention. There is a tendency to ascribe 
 fever appearing in the course of diseases, hitherto regarded as 
 intrinsically apyrexial, to a secondary infection with septic 
 organisms, especially when the temperature curve, as is frequently 
 the case, is intermittent. In Hodgkin's disease pyrexia is almost 
 constant, is indeed regarded by some clinicians as almost essential 
 to a correct diagnosis. In pernicious anaemia pyrexia runs in waves 
 spread over three, four, or more weeks, to be followed by apyrexial 
 phases ; in leukaemia there are also pyrexial periods. The question 
 is raised at once as to whether each of these diseases may be of 
 microbic origin. In haemolytic jaundice fever occurs periodically ; 
 it is generally slight, and lasts for two or three days. In other 
 cases it is severe, but of shorter duration ; the temperature rises 
 abruptly, remains at its maximum a very brief period, and falls 
 quickly. There is the characteristic 'steeple' chart of cholangitis. 
 In such cases stones are often, but not always, present in the 
 common bile-duct. 
 
 6. Splenomegaly. When the spleen is recognized, by any 
 method of clinical examination, as being enlarged, it is certain that 
 it is at least twice the normal bulk. Any enlargement less than 
 this, and often even this, cannot be discovered by palpation or by 
 percussion. Perhaps, taking an average of all cases, the very 
 largest spleen is to be found in Gaucher's disease, the next largest 
 in leukaemia, and the next in malaria, though occasional instances 
 are found in this last disease in subtropical countries which surpass 
 all others. Then comes a series in which the spleen is large, but not 
 excessively so, and, finally, there are cases in which the spleen is not 
 enlarged at all. Thus, the spleen may be involved in Hodgkin's 
 disease without being clinically enlarged ; it is not always enlarged
 
 CLINICAL AND ASSOCIATED PHENOMENA 51 
 
 in pernicious anaemia, and its enlargement then bears no discover- 
 able relationship to the gravity of the case. These aspects of the 
 subject are so well known that this symptom is only referred to 
 for the sake of drawing attention to the fact that an absence of 
 enlargement of the spleen does not relieve this organ from the 
 suspicion of being the source of a patient's illness. 
 
 7. Leucocytosis. The significance of this phenomenon lies in 
 the fact that it affords an insight both into the nature of the agent 
 at work, and into the state of those tissues which are concerned in 
 the manufacture of the leucocytes. There are some toxic substances 
 which expend their whole baneful power upon the circulating 
 leucocytes ; others affect their formative tissues ; while a few may 
 act upon both. The action exerted may be one of stimulation, 
 so that leucocytosis results ; or it may be one of inhibition, and 
 result in leucopenia. In pernicious anaemia the poisonous action 
 on the bone-marrow affects the white cells as well as the red, 
 so that a very low white-cell count is the rule. In haemolytic 
 jaundice, on the other hand, the action on the bone-marrow 
 is one of stimulation, and leads to an increased outpouring of 
 leucocytes. 
 
 Where the poisonous substances act upon the pulp-tissue of 
 the spleen, upon the endothelium of the liver sinusoids, and upon 
 the whole reticulo-endothelial system, exciting the dormant cells 
 to form myelocytes (myeloid metaplasia), stray myelocytes can be 
 found in the blood-stream. This occurs in some forms of acute 
 splenitis, occasionally in Hodgkin's disease, notably in infantile 
 splenic anaemia, and sometimes in pernicious anaemia. The same 
 process occurs in massive fashion in leukaemia, where every part of 
 the reticulo-endothelial system competes against the rest in the 
 effort to produce and pour out these abnormal cells. The pulp- 
 tissue of the spleen then appears almost as a replica of ordinary 
 bone-marrow tissue, and the immature cells pass freely into the 
 blood-stream. In virtue of the character of these cells, which, 
 strictly speaking, are not leucocytes, such a phenomenon should 
 not be described as an extreme leucocytosis. 
 
 It is therefore not sufficient in any case of leucocytosis to 
 determine merely the presence or absence of an increase in the 
 number of white cells. It is necessary also to ascertain which 
 varieties of cells are represented in the increase, and to recall the
 
 52 THE SPLEEN AND ITS DISEASES 
 
 significance of each specific increase. An increase of the neutro- 
 philes indicates the presence of toxins of nucleoprotein form, or 
 of the products of dissolution of albuminous substances. An 
 increase of lymphocytes denotes activity of poisons of lipoid 
 character, with whose destruction these cells are especially con- 
 cerned. The large mononuclear leucocytes are increased when 
 the particles of abnormal matter are large enough to be micro- 
 scopically visible. When the eosinophils are increased, it may 
 be concluded that the poisonous substances have an affinity for 
 the sympathetic nervous system, although the relation of these 
 cells to the integrity of the nervous system is not the only one they 
 possess. Poisons may accumulate in various tissues and set up 
 local accumulations of these cells (as in Hodgkin's disease), and at 
 the same time excite the bone-marrow, the spleen, and the lymph- 
 glands to join in the over-production of these cells. 
 
 The tubercle bacillus and the spirochaete of syphilis are well 
 known to secrete lipoid substances ; the association of lympho- 
 cytosis with these diseases is to be expected. That stimulation 
 of the lymphocyte formation occurs in pernicious anaemia, splenic 
 anaemia, and Graves' disease indicates the direction of the inquiry 
 to be made into the ultimate causation of these diseases. 
 
 8. The Spleen and the Haemorrhagic Diathesis. During recent 
 years the suggestion has been made that the spleen may in some 
 degree be concerned with the life-history of blood-platelets. In a 
 patient suffering from purpura haemorrhagica there is a decided 
 diminution in the number of platelets, and the spleen is enlarged. 
 After splenectomy normal conditions are restored ; in proportion 
 as the number of platelets is increased, so the clinical symptoms 
 disappear. Cases which illustrate this experience are recorded 
 by Schmidt,* Benecke,f and Kaznelson.J The name 'splenogenic 
 thrombolytic purpura' has been given to this condition, and a 
 ' thrombocytolytic syndrome' is described. It is supposed that 
 there is an increased destruction of platelets by the cells of the 
 reticulo-endothelial system. If, however, the whole of this vast 
 system is implicated, it is not easy to understand why extirpation 
 of the spleen should cure the disease or relieve the patient of 
 
 * Wien. klin. Woch., 1918, 487, 959. f Tfierap. d. Gengenw., 1917, Dec. 
 
 %DeuL med. Woch., 1918, 5.
 
 CLINICAL AND ASSOCIATED PHENOMENA 53 
 
 symptoms. Katsch* has reported cases of thrombopenia where 
 there is no purpura ; and, conversely, cases of purpura where the 
 number of platelets is not diminished. 
 
 9. Urobilin in the Urine. Recent work shows that the 
 presence of this substance in the urine is an indication of functional 
 inadequacy of the liver-cell, which is accompanied by some degree 
 of obstruction in the minute extracellular bile canaliculi. A certain 
 quantity of bile escapes through the ducts, undergoes the usual 
 transformation into stercobilin in the intestine, re-enters the liver, 
 but cannot find a free exit through the hepatic cells. The signifi- 
 cance of this phenomenon is that there is an increased breakdown 
 of red cells and haemoglobin, and that there is a state of cirrhosis 
 in the liver ; the degree of disturbance of function is in proportion 
 to the degree of 'fragility' of the red cells. Viewed in this light, 
 the next step to be followed, after arriving at a conclusion that 
 the spleen is diseased, is to determine the degree of damage to the 
 liver, and instead of regarding cirrhosis as a collective term for 
 many distinct morbid entities, to view all cirrhoses as representative 
 of degrees of implication in the one morbid process. 
 
 * Munch, med. Woch., 1918, 33.
 
 CHAPTER VL 
 
 PERNICIOUS ANEMIA. 
 
 (ADDISON'S ANJEMIA. IDIOPATHIC ANAEMIA.) 
 (See Plate III.) 
 
 THE literature of pernicious anaemia is inexhaustible. But bulk is 
 no index of value. It is only within recent years and especially 
 since the work of W. Hunter, and of W. J. Mayo, Percy, and 
 others that some enlightenment has been thrown upon a difficult 
 and complex problem. 
 
 The first case of idiopathic anaemia was recorded in 1822 by 
 Combe, who applied this term to it. As Hunter says, the problem 
 which this disease has presented throughout its whole history was 
 never more clearly stated. Combe was recording " a well-marked 
 instance of a very peculiar disease which has been altogether over- 
 looked by any English author with whose writings I am acquainted. 
 Unfortunately, however, such is the allowable diversity of opinion 
 on most medical subjects, that it is very possible the following 
 case (disease) may be viewed in different lights, and receive different 
 appellations ; and while some may be disposed to regard this 
 anaemia as constituting a morbid state sui generis, others may 
 consider the defect in red circulatory mass (so extreme that every 
 organ in the body, with the exception of the spleen, was deprived 
 of its red blood) as an accidental and occasional circumstance 
 denoting some peculiar change in the assimilative powers, the 
 primary stages of which we have been unable to detect. Doubtful 
 myself which of the two opinions may be the most correct, I shall 
 do little more than state correctly the phenomena of the case, and 
 minutely, the appearances presented on dissection. One remark 
 only I may at present offer that if any train of symptoms may 
 be allowed to constitute anaemia a generic disease, the following 
 may be considered an example of it in its most idiopathic form ". 
 
 This description of Combe's case apparently attracted no 
 attention. In the year 1855 Addison, in his Disease of the Supra- 
 renal Capsules (pp. 2, 3), gave an account of the disease which, in
 
 PLATE III 
 
 tissue 
 
 Fattij endothelial 
 cells 
 
 SPLEEN 
 
 Malpighian bodies waste 
 
 Enlargement moderate 
 cellular pulp 
 
 'Formation of red cells 
 
 Some formation of mye/ocytes 
 
 Active phagocytosis of red cells 
 - - Phagocytes with iron pigment 
 Some fibrosis 
 
 Petechial haemorrhages euerywhere 
 
 Inf. Mesenteric Vein 
 
 Sup. Mesenteric Vein 
 
 Iron particles 
 
 fnteracinous deposit of iron-;; 
 Some formation of normoblasts 
 Wandering cells carry iron into 
 the connectiue tissue 
 
 Degeneration of liuer cell 
 
 Gall 
 Bladder 
 
 Dominant lesion. Phagocytosis; 
 unripe red cells escape into blood. 
 Free iron. Haemorrhages. 
 Hcemoglobin chemically changed. 
 
 THE CHIEF CHANGES IN PERNICIOUS AN/EAMA
 
 PERNICIOUS ANEMIA 55 
 
 fullness of detail, accuracy of statement, and clarity of language, 
 has never been surpassed. As a preface to his description of what 
 we now called 'Addison's disease', he considered that it might not 
 be without interest or unprofitable to give a brief narrative of a 
 form of anaemia the cause of which was not discoverable. It was 
 whilst seeking to throw some additional light on this form of 
 anaemia that he stumbled upon curious facts which led to his 
 discovery of the disease of the suprarenal capsules which now 
 bears his name. His account is as follows : 
 
 " For a long period I had from time to time met with a 
 very remarkable form of general anaemia, occurring without any 
 discoverable cause whatever ; cases in which there had been no 
 previous loss of blood, no exhausting diarrhoea, no chlorosis, no 
 purpura, no renal, splenic, miasmatic, glandular, strumous, or 
 malignant disease. Accordingly, in speaking of this form of anaemia 
 in clinical lecture, I, perhaps with little propriety, applied to it 
 the term 'idiopathic' to distinguish it from cases in which there 
 existed more or less evidence of some of the usual causes or con- 
 comitants of the anaemic state. 
 
 " The disease presented in every instance the same general 
 character, pursued a similar course, and, with scarcely a single 
 exception, was followed, after a variable period, by the same fatal 
 result. It occurs in both sexes, generally but not exclusively 
 beyond the middle period of life, and so far as I at present know, 
 chiefly in persons of a somewhat large and bulky frame, and with 
 a strongly-marked tendency to the formation of fat. It makes 
 its approach in so slow and insidious a manner that the patient 
 can hardly fix a date to his earliest feeling of that languor which 
 is shortly to become so extreme. The countenance gets pale, the 
 whites of the eyes become pearly, the general frame flabby rather 
 than wasted ; the pulse perhaps large, but remarkably soft and 
 compressible, and occasionally with a slight jerk, especially under 
 the slightest excitement ; there is an increasing indisposition to 
 exertion, with an uncomfortable feeling of faintness or breath- 
 lessness on attempting it ; the heart is readily made to palpitate ; 
 the whole surface of the body presents a blanched, smooth, and 
 waxy appearance ; the lips, gums, and tongue seem bloodless ; 
 the flabbiness of the solids increases ; the appetite fails ; extreme 
 languor and faintness supervene, breathlessness and palpitations 
 being produced by the most trifling exertion or emotion ; some
 
 56 THE SPLEEN AND ITS DISEASES 
 
 slight oedema is probably perceived about the ankles ; the debility 
 becomes extreme, the patient can no longer rise from his bed, the 
 mind occasionally wanders, he falls into a prostrate and half-torpid 
 state, and at length expires ; nevertheless, to the very last, and 
 after a sickness of perhaps several months' duration, the bulkiness 
 of the general frame and the amount of obesity often present a 
 most striking contrast to the failure and exhaustion observable in 
 every other respect. 
 
 " With perhaps a single exception, the disease, in my own 
 experience, resisted all remedial efforts, and sooner or later 
 terminated fatally. On examining the bodies of such patients 
 after death, I have failed to discover any organic lesion that could 
 properly or reasonably be assigned as an adequate cause of such 
 serious consequences." 
 
 In the year 1871 Biermer described cases of this disease, 
 apparently believing that it had not been observed by earlier 
 writers. His claim to be the first to recognize the disease excited 
 the wonder of the physicians in this country, especially those on 
 the staff of Guy's Hospital. His writing, however, undoubtedly 
 stimulated interest in the subject, and popularized the knowledge 
 then possessed with regard to it. He gave to it the name 
 'progressive pernicious anaemia'. The work of William Hunter 
 began in the year 1888. Between 1888 and 1890 he developed 
 his views as to the haemolytic nature of the disease, its toxic cause 
 and gastro-intestinal site ; and between 1890 and 1900 he 
 elaborated and expounded his thesis that the disease owned an 
 infective etiology. In 1907 he wrote : " Addison's anaemia is in 
 truth a very remarkable disease, of a specific infective haemolytic 
 nature, in which both clinical observations and necropsy reveal 
 definite haemolytic and infective processes as a constant feature 
 of the disease, and in which a very definite series of points can be 
 got out of the history throwing light on the mode of origin of the 
 disease, and the source of the infection in the alimentary tract, and 
 of the lesions of the tongue, stomach, and intestine connected 
 with it ". The treatment of pernicious anaemia by arsenic was 
 introduced by Byrom Bramwell. 
 
 It has long been the custom to speak of anaemia as primary 
 and secondary ; the latter being the consequence of some disease 
 or dyscrasia, one of whose manifestations is expressed in terms 
 of blood-change ; the former being a change occurring in the blood
 
 PERNICIOUS ANEMIA 57 
 
 apart from any other change in the body. The definition of an 
 anaemia as ' primary ' involves a belief in the existence of the blood 
 as an organ whose cells are capable of undergoing degeneration 
 or destruction as the consequence of a morbid process limited to 
 itself. But as Vogel points out,* the blood is not itself an organ, 
 but is the direct product of the activity of the various haemopoietic 
 organs or systems, and may in a sense be more properly regarded 
 as a secretion than as an organ. The erythrocytes having 
 relinquished their nucleus can no longer be regarded as true cells ; 
 and the leucocytes have the power of reproduction only in a very 
 limited degree, if at all. The terms 'primary' and 'secondary' 
 therefore do not hold the meaning they are intended to convey. 
 
 Within the normal blood the elements are in a state of 
 unceasing change. This change, nevertheless, maintains the blood 
 in a state of equilibrium. Cells are constantly dying, and under- 
 going destruction ; and cells are constantly being formed to replace 
 those which are lost. An anaemia may result in consequence either 
 of the diminished production of red cells or of the increased 
 destruction of red cells, or perhaps of both. The anaemias which 
 arise as a result of diminished production of red cells include those 
 seen in cachexias, wasting diseases, tumours, toxic anaemias, 
 aplastic anaemia, etc. The anaemias which arise as a result of the 
 increased destruction of red cells include those seen in cases of 
 haemorrhage, in haemolytic icterus, in the anaemias due to haemolytic 
 poisons, pyrodin, phenylhydrazin, toluylenediamine, etc., and 
 some forms of intestinal parasite, and so forth. In the latter group 
 pernicious anaemia is included. There is in this disease, as Mott 
 first showed, an abnormally great cell destruction, with a patho- 
 logically increased demand on the blood-forming tissues rather than 
 an inadequacy on the part of these to meet the normal demand. 
 But to say only this is to say no more than is true of the condition 
 hsemolytic jaundice ; yet, whatever the affinity between these 
 two diseases may be, their clinical manifestations and their destiny 
 are very dissimilar. In pernicious anaemia the red-cell-forming 
 tissue in the bone-marrow is also profoundly affected by the 
 haemolytic poison, and is subject to a double stress ; it is stimulated 
 to over-production at a time when it is fighting to ward off the 
 attack of a poison attempting its destruction. So great is the 
 
 * Jour. Amer. Med. Assoc., 1916, Ixvi, 1012.
 
 58 THE SPLEEN AND ITS DISEASES 
 
 effort of the bone-marrow to meet the demand made upon it that 
 the parent cells of the erythrocyte are liberated before their 
 offspring daughter and granddaughter cells are created. The 
 greater the urgency of the demand made upon the bone-marrow, 
 the earlier is the type of cell liberated and set adrift in the circula- 
 tion. The character of the nucleated cell set free may therefore 
 be an index of the gravity of the disease. Death occurs in 
 pernicious anaemia because of the persistence of the increased 
 destruction of red cells at a time when the efforts of the medulla 
 to form blood break down under the ceaseless heavy strain imposed 
 upon it. It will be recognized at once that the conditions existing 
 in this disease, in so far as the changes in the blood and in the 
 organs producing blood are concerned, resemble those seen in the 
 embryo ; a " reversion to the embryonal type of haematopoiesis " 
 is spoken of as a characteristic of the disease. 
 
 If, then, the disease is primarily a haemolytic process, a process 
 in which red-cell destruction is the outstanding feature, what is the 
 nature of the poison, and whence does it come ? Haemolysins of 
 definite origin are known. In the haemolytic anaemia of pregnancy 
 a definite haemolysin has been found in the placenta. In the 
 anaemia due to bothriocephalus, cholesteryl oleate, set free by the 
 decomposing segments of the worm, affords the poison for the red 
 cells, although every harbourer of this parasite is not equally 
 susceptible to the action of this substance. In some forms of 
 cancer, especially of the stomach and ascending colon, poisons 
 appear to be liberated which cause a blood-picture hardly dis- 
 tinguishable from that of pernicious anaemia. Chronic carbon- 
 monoxide poisoning among charcoal workers, industrial lead, and 
 perhaps also arsenic poisoning, appear to operate in the same 
 manner. It is suggested that haemolytic substances formed by 
 pathological bacteria in the intestine may gain access by this route, 
 as first suggested by Hunter.* J. H. King,f after careful study 
 of three cases of pernicious anaemia treated by splenectomy, and 
 after conducting a series of experiments upon dogs, concludes : 
 " In pernicious anaemia, haemolytic jaundice, and cirrhosis of the 
 liver, the hyperactive spleen influences unfavourably the anaemia 
 through its regulation of the highly haemolytic unsaturated fatty 
 acids of the blood. The removal, therefore, appears to be 
 
 * Brit Med. Jour., 1907, ii, 1299. f Arc h- of Internal Med., 1914, xiv, 145.
 
 PERNICIOUS ANAEMIA 59 
 
 indicated. Splenectomy of itself, besides influencing the produc- 
 tion of haemolytic, unsaturated fatty acids, raises the percentage 
 of antihaemolytic substances in the blood ; that is, the total 
 fats and cholesterins ". 
 
 The work of the surgeons in the last few years has afforded 
 some evidence, if not as to causation at least as to associated con- 
 ditions, in cases of pernicious anaemia. N. M. Percy, whose work 
 on this difficult disease has been marked by a most earnest devotion 
 and remarkable success, has pointed out that since his attention 
 was especially directed to the testing of Hunter's view of the 
 infective origin of pernicious anaemia, he has found evidence of 
 infective foci in 95 per cent of cases. In a consecutive series of 
 nine operations for pernicious anaemia, all specimens removed 
 (spleen, gall-bladder, appendix) were sent at once for pathological 
 examination. Bacteria were grown from 3 of the 9 spleens, from 
 4 of the 7 gall-bladders, and from 6 of the 7 appendices. The only 
 case not giving a bacterial growth was one in which pyorrhoea had 
 long been present. The chief organism found was the haemolytic 
 streptococcus 7 cases ; in 5 the Bacillus coli was found ; in 4 
 Streptococcus viridans. Smithies, of Chicago, has grown bacilli and 
 cocci of the haemolytic type from infected areas about the teeth, 
 tonsils, and accessory sinuses. In a series of 24 cases, preceding 
 the 9 just mentioned, Percy records the following gross lesions. 
 In 20 there was chronic cholecystitis with or without gall-stones ; 
 in 17 of these there was evidence of old disease in the appendix ; 
 in 6 there were infective foci in connection with the teeth ; and in 
 1 in connection with the tonsil. 
 
 A detailed description of the symptoms and the diagnosis of 
 pernicious anaemia is not necessary. But I may be allowed to 
 quote from a description kindly sent to me by Dr. N. M. Percy, of 
 Chicago, whose experience of the surgical treatment of this disease 
 is unsurpassed. Dr. Percy has been impressed with the importance 
 and constancy of the following conditions, and believes them to 
 be of such importance that their presence or absence may well 
 decide the diagnosis in a difficult case : 
 
 " 1. Achlorhydria. In all cases where a test was made, with 
 one exception, no trace of free hydrochloric acid was found in the 
 fasting contents and in the specimens of test meal. The exception 
 was a very early case, and showed a very low hydrochloric acid 
 content. A few cases were in such an extreme condition that it
 
 60 THE SPLEEN AND ITS DISEASES 
 
 was not deemed advisable to subject them to the strain of passing 
 the stomach tube. In all other cases the gastric analysis was part 
 of our routine in making the diagnosis. The absence of free hydro- 
 chloric acid occurred with such regularity that I would hesitate 
 to make a diagnosis of pernicious anaemia in any case showing the 
 presence of free hydrochloric acid in the stomach unless it be a 
 very early case and the acid content very low. 
 
 " 2. Tongue. The appearance of the tongue was noted in every 
 case, which revealed a peculiar smooth, glossy surface. In some 
 this was present only on the sides of the tongue, in others its whole 
 surface was involved. This appearance of the tongue, which was 
 always present but in varying degrees, is due to an atrophy of 
 the mucous membrane and sometimes to a hyperplasia of the 
 tongue muscle-bundles. A glossitis was present in a large per cent 
 of our cases. Hunter lays particular emphasis upon the lesions 
 in the mouth, and claims there is no other anaemia in which glossitis 
 is so constant and persistent. The appearance of the tongue is so 
 constant that it may be considered the most important external 
 sign of pernicious anaemia. 
 
 " 3. Pigmentation. Pigmentation was found to be present in 
 the majority of cases, especially on the backs of the hands. In 
 some this may be diffuse, in others freckle-like. 
 
 " 4. Hypertension (chronic nephritis}. It is noted that hyper- 
 tension (chronic nephritis) frequently co-exists with pernicious 
 anaemia, both probably being due to chronic infection, but they 
 have no definite connection with each other. The cases having high 
 blood-pressure were of middle age or beyond. Strange as it may 
 seem, the hypertension persists through periods of severe weakness 
 and with a blood-count as low as one million or under, only letting 
 down when the patient becomes extremely ill in the terminal state 
 of the disease. 
 
 " The disturbance of renal function which accompanies marked 
 cases of pernicious anaemia as pointed out by Christian was noted 
 in many of our cases. The disturbance is similar to that found in 
 patients with advanced nephritis, but is not accompanied by hyper- 
 tension or any other evidence of chronic nephritis. The disturbance 
 seems to be due to the anaemia, and subsides as this improves. 
 It is important from the standpoint of prognosis to determine in 
 each case whether the disturbance of renal function is due to the 
 anaemia or to chronic nephritis.
 
 PERNICIOUS ANEMIA 61 
 
 " 5. Diarrhoea and Vomiting (intermittent}. Attacks of 
 diarrhoea and vomiting, especially the former, were frequently 
 noted, and were found difficult to control by medical means. These 
 cases yielded readily to blood transfusions, followed by adminis- 
 tration of large doses of hydrochloric acid. Vomiting invariably 
 stopped immediately after transfusion, and the diarrhoea usually 
 subsided within a few days. In a number of instances an attack 
 of diarrhoea was the first symptom of the disease noted by the 
 patient. 
 
 " 6. Nerve Manifestations. The nerve symptoms noted were 
 many and varied, ranging from the most common, that of tingling 
 in the fingers and toes, to those simulating tabes and multiple 
 sclerosis. The tingling sensation in the fingers, the presence of 
 which varies from time to time, was noted in practically every 
 case. Marked psychical disturbances were noted in some cases. 
 
 " The characteristic appearance of the tongue, the pigmenta- 
 tion, and the achlorhydria occurred with such constancy that 
 their presence may often be the deciding factors in the diagnosis.'* 
 
 Splenectomy in Pernicious Anaemia, In the year 1913 three 
 observers independently, and for different reasons, suggested the 
 performance of splenectomy in cases of pernicious anaemia. 
 Eppinger* advocated the operation because he had observed a 
 diminished output of urobilin, and other evidences of diminished 
 haemolysis, after the spleen had been removed for other conditions ; 
 and he assumed that in pernicious anaemia, a disease of exaggerated 
 haemolysis, the removal of the spleen would control or counteract 
 this tendency. De Castello| was guided by the observations of 
 himself and others as to the great benefits resulting from the 
 operation in the related conditions splenic anaemia and haemolytic 
 jaundice. KlempererJ was influenced by the clinical observation 
 that splenectomy for such simple conditions as laceration was, in 
 some instances at least, followed by polycythaemia. Advocacy by 
 all of these men of great repute soon led to a wide adoption of the 
 practice in Germany, and an adoption, not so general, in America.. 
 In England very little was done. The results, which were not long 
 in coming, showed that the mortality of the operation was high, 
 
 * Berl. klin. Woch., 1913, xxix, 2409. ] Deul. med. Woch., 1914, xl, 639. 
 
 J Therap. d. Gegenw., 1913, liv, 385.
 
 2 THE SPLEEN AND ITS DISEASES 
 
 that the immediate benefit which not seldom followed was transient, 
 that post-operative complications were frequent, and that, with 
 few exceptions, the general course of the disease was not materially 
 altered. That splenectomy alone might offer help seemed probable 
 from the work of Robertson,* who found, in cases studied by him- 
 self, that the rate and degree of haemolysis in pernicious anaemia 
 underwent a constant and marked decrease after removal of the 
 organ. Largely owing to the work of W. J. Mayo and his most 
 able band of colleagues, and of N. M. Percy, a wider view of the 
 necessities of these cases was taken, with a great improvement in 
 results. The anaemic condition of the patients was improved by 
 transfusion of whole blood ; and foci of infection, possibly ' primary ', 
 but certainly co-existent, in the mouth or accessory sinuses, or 
 in organs laid bare by the abdominal operation, were removed. 
 The purpose of the extended operations consisted, as Percy said, 
 of three main factors : (1) An attempt to stimulate the production 
 of new blood by massive 'step-ladder' transfusions of whole 
 blood ; (2) An attempt to overcome the absorption of haemolytic 
 bacteria or their toxins by the radical removal of local foci of 
 infection ; and (3) An attempt to protect the newly-formed and 
 older red cells by removing the spleen. Each of these steps is 
 important. The 'step-ladder' transfusions bring about an eleva- 
 tion, step by step, of the quality of the patient's blood in respect 
 of red cells, haemoglobin content, etc. ; they supply blood which 
 is not only useful in itself, but acts also in a manner stimulating 
 and nourishing to the bone-marrow, encouraging it to still further 
 efforts. The eradication of active foci of infection relieves the 
 patient of a chronic toxaemia which is possibly an etiological factor. 
 The removal of the spleen reduces the abnormal amount of blood 
 destruction. Discussion has recently ranged around the question 
 .as to whether transfusions frequently repeated are competent of 
 themselves to produce an improvement in the patient's condition 
 equal to that seen when both transfusion and splenectomy, or 
 these two with the addition of the eradication of infective foci, are 
 undertaken. Under what circumstances may these steps of treat- 
 ment be taken ? They are useless in the ' aplastic type ', and 
 they are of little value, if any, in cases where cerebral or spinal 
 symptoms are already present, unless the anaemia is profound, 
 
 * Arch, of Internal Med., 1915, xvi, 429.
 
 PERNICIOUS ANEMIA 63 
 
 when transfusion alone may give some degree of transient benefit. 
 In all other cases the repetition of a blood transfusion about every 
 eight or ten days gives very striking results. They are briefly 
 stated by Percy : 
 
 " The red blood-count is increased, often doubling immediately 
 if the count is very low. The haemoglobin percentage rises and the 
 number of platelets is increased. The blast-cells become more 
 numerous, and occasionally HowelPs particles will appear in the 
 blood, indicating a stimulation of the bone-marrow. The general 
 appearance and the appetite of the patients improve at once, the 
 condition of the mouth (glossitis is not infrequent) clears up, and 
 sleep returns. It is not only that new blood is given ; it appears 
 certain that a great stimulation of the (under-nourished ?) bone- 
 marrow occurs. In those patients who are much improved by 
 transfusions the question of splenectomy should be considered ; 
 it should not be countenanced unless such improvement has been 
 unmistakable. Before it is performed, a search for foci of infection 
 outside the abdomen will have been made, and all accessible disease 
 removed. When an abdominal operation is undertaken its scope 
 must be comprehensive." 
 
 Percy's work has shown how necessary a wide inspection is, 
 and how safe the extended procedure may be made. In a private 
 communication he tells me that in 77 laparotomies performed by 
 him, the spleen, gall-bladder, and appendix were removed in 54 
 cases ; the spleen and gall-bladder in 11 ; the gall-bladder and 
 appendix in 4 ; the spleen alone in 4. There were 8 deaths. In 
 74 of these patients one or more transfusions had been per- 
 formed before operation ; in 40 a transfusion was undertaken 
 immediately after operation ; in 10 cases a later transfusion was 
 performed. 
 
 " Of the 69 cases that left the hospital, 5 had recurrence of 
 symptoms at the end of four months, and died at intervals of eight 
 to twelve months ; 10 had recurrence at end of six to eight months 
 and followed about the same course. Forty-eight were in good 
 condition at the end of twelve months. Of these, 12 are alive at 
 the end of two years, 9 at the end of three years, 4 at the end of 
 four years, 5 living nearly five years after operation, and 1 a little 
 over six years. Two of the five-year cases have been retransfused, 
 one several times, the other only twice. The one living six years 
 since operation has had no transfusion since operation. Two of
 
 64 THE SPLEEN AND ITS DISEASES 
 
 the four-year cases have been back for transfusions, as have also 
 4 of the three-year cases, 5 of the two-year cases, and 8 of the one- 
 year cases. 
 
 " The progress of the 4 cases in which gall-bladder and appendix 
 were removed without the spleen was not so good, in any instance, 
 as was the average of other cases. They did not experience the 
 immediate remission of the average case of the other group, and 
 all of them had an early recurrence of their anaemia, which had 
 been temporarily improved by the transfusions. The spleen was 
 not removed in these patients because it was not enlarged and 
 there were no adhesions to indicate that there had existed a 
 splenitis or perisplenitis. It is evident that some of our patients 
 should not have been operated upon, as undoubtedly just as good 
 or better results would have followed transfusion alone. 
 
 " There were 45 cases treated by transfusions without surgical 
 procedures other than those for the eradication of local foci of 
 infection when present. In 10 of these, most of which were of the 
 aplastic type, no marked improvement resulted. In 12 cases, all of 
 which presented evidence of cerebral or cord involvement, some 
 improvement was noted in the blood-picture and general condition, 
 but the nerve destruction progressed without interruption. In 2B 
 cases the transfusions brought about a marked improvement, and 
 in some a very rapid remission of the disease resulted. In no 
 instance was the remission as complete as it was in several of the 
 cases which were operated. The longest remission noted following 
 a series of transfusions was eleven months ; the majority, how- 
 ever, required transfusions at much shorter intervals. There are 
 still 2 patients enjoying fair health after the lapse of nearly two 
 years since their first transfusion." 
 
 The evidence as to the efficacy of the newer methods of treat- 
 ment now outlined is not all on the one side, and is certainly not 
 yet sufficient to enable final conclusions to be drawn. Two further 
 series of cases may be here contrasted and compared. Bloomfield* 
 analyzed a series of 57 cases treated during a period of five years 
 at Johns Hopkins Hospital. In order to allow of an informed judge- 
 ment upon the effect of treatment in cases of pernicious anaemia, 
 regard being paid to the well-known variations and spontaneous 
 remissions which occur, the following points were considered : 
 
 * Johns Hop. Hosp. Bull, 1918, xxix, 101.
 
 PERNICIOUS ANEMIA 65 
 
 (1) The effect of treatment on the total duration of the disease ; 
 
 (2) The readiness with which remissions are induced ; (3) The 
 length of the remissions ; (4) The effect of a particular form of 
 treatment on special symptoms ; (5) The death-rate in hospital ; 
 and (6) The blood picture. 
 
 Twenty-eight cases treated by the older method of rest, diet, 
 and arsenic in the forms of Fowler's solution, cacodylate of sodium, 
 and salvarsan, served as controls to the other and more modern 
 methods. 
 
 The reputation of arsenic is said to rest entirely on general 
 impressions : analysis of the cases yielding no reliable data as to 
 its efficacy. In twelve cases a thorough investigation of the nose, 
 throat, sinuses, teeth, gastro-intestinal canal, and lower urinary 
 tract was made for foci of infection, and when found these were 
 eliminated. In none of them was there any feature in their subse- 
 quent course to distinguish them from the group in which such 
 foci were not found, or, if found, were not treated, either as to 
 total duration of life, or extent and degree of remissions. It was 
 considered unlikely, therefore, that such foci were the cause of 
 pernicious anaemia. Twenty-six patients received transfusions of 
 blood, varying in number from one to seventeen, and from a total 
 of 300 to 8700 c.c. of blood. In patients who were not in a stage 
 of the disease refractory to all forms of treatment, remissions came 
 on more often when transfusion had been performed, but the 
 artificial plethora thus induced did not increase the duration of the 
 remission, though the patients felt better while the red count was 
 high. At the Johns Hopkins Hospital splenectomy for pernicious 
 anaemia has now been given up ; out of 8 cases so treated, 6 are 
 dead, and in no instance was the clinical picture essentially altered 
 or life unusually prolonged. In 5 of the cases transfusion of blood 
 was performed during the period following splenectomy, but in the 
 4 cases in which the duration of the remission could be accurately 
 determined there was no evidence that transfusions are ' held ' better 
 after than before splenectomy. The central nervous symptoms 
 were as little benefited by transfusion and splenectomy as by other 
 means of treatment. 
 
 The result of Bloomfield's report is to suggest that no suffi- 
 cient evidence has been given to the value of the three procedures 
 above mentioned elimination of septic foci, transfusion of blood, 
 and removal of the spleen. 
 
 5
 
 66 THE SPLEEN AND ITS DISEASES 
 
 A more recent review of a series of cases is published by Giffin 
 and Szlapka.f Fifty cases are reviewed in which splenectomy had 
 been performed more than three years previously. The effect on 
 the total duration of the disease was found to be that life was pro- 
 longed in 20 per cent ; 10 patients had survived more than three 
 years (the furthest limit of expectation of life under ordinary circum- 
 stances), and 5 of them had lived four and a half years after the 
 operation and are still living. As regards the readiness with which 
 remissions are induced, it was found that the anaemia improved 
 for at least three to six months and the haemolytic activity 
 diminished. The blood did not approximate to the normal, but 
 remained at a fairly satisfactory level for a long tine. Recurrences 
 were liable to follow an acute infection such as a severe cold. Trans- 
 fusions were found to be more lasting in effect in splenectomized 
 cases. 
 
 The special symptoms of the disease appeared to be less evident 
 after splenectomy : 13 patients without spinal cord lesions con- 
 tinued without them ; 14 with such lesions remained as before ; 
 12 showed an advance in nervous symptoms ; 11 who had numb- 
 ness and tingling of the extremities were definitely improved after 
 operation. Estimation of bile pigments in the duodenal contents 
 suggested that haemolysis was less after than before operation. 
 
 The bone-marrow showed signs of stimulation, large showers 
 of monoblasts and megaloblasts appearing in the blood. This state 
 continued for four years in some cases. Leucocytosis persisted 
 much longer than ordinarily. The neutrophile leucocytes tend to 
 preponderate. The blood-count does not infallibly indicate the 
 progress of the patient, because several of the most successful cases 
 show few nucleated red cells and only slight leucocytosis. 
 
 The immediate operative mortality was 3 in 50 cases (6 per 
 cent). The deaths occurred in the first 19 cases, after which pre- 
 operative treatment was very carefully handled and more acute 
 forms were rejected. There are no post-operative complications. 
 Preference in respect of operation was given to persons between 
 the ages of 35 and 45, with only one year's history and a favourable 
 type of blood picture, and no sign of spinal-cord involvement. 
 
 Favourable indications were absence of marked leucopenia, 
 with neutrophils dominant rather than lymphocytes, marked 
 
 f Jour. Amer. Med. Assoc., 1921, Ixxvi, 290.
 
 PERNICIOUS ANAEMIA 67 
 
 hsemolytic activity shown by examination of the duodenal contents, 
 a competent bone-marrow, and a moderately enlarged spleen. 
 
 The following is the summary given by Giffin and Szlapka : 
 
 1. This review concerns fifty patients with pernicious ansemia 
 for whom splenectomy was performed. All were operated on more 
 than three years ago. 
 
 2. The operative mortality was 6 per cent. 
 
 3. Ten patients (21-3 per cent) of those who recovered from 
 operation survived splenectomy three years or longer. 
 
 4. Five patients (10-6 per cent) of those who recovered from 
 operation have survived splenectomy more than four and one-half 
 years, and are still living. The total length of history of these five 
 patients averages almost six years. 
 
 5. It may be stated with reasonable accuracy that, in addition 
 to the immediate remissions which occurred constantly following 
 splenectomy, splenectomy prolonged life in at least 20 per cent of 
 our cases. 
 
 6. We cannot satisfy ourselves that any particular pre-operative 
 characteristics of the disease are indicative of favourable results 
 following splenectomy. However, in the type of case in which 
 there is evidence of active haemolysis, the patient shows a more 
 marked immediate improvement. 
 
 7. Splenectomy may be recommended in pernicious anaemia 
 when, in view of all the circumstances, personal as well as medical, 
 the possibility of the prolongation of life appeals to the family and 
 to the patients. Occasionally the operation may be performed in 
 order to bring about an immediate remission. 
 
 What may be said, then, of the efficacy of splenectomy in this 
 disease ? In the first place it cannot be claimed, and is not claimed, 
 that any patient has been cured of his disease. The risks run in 
 undergoing the operation are small, but not so insignificant that 
 they can be ignored. A few lives are sacrificed. All the patients 
 who survive are not benefited, but in the majority a degree of 
 improvement results, and a prolongation of life, in greater comfort 
 and with increased zest, can be recorded. The truth is approxi- 
 mately this, that as a result of repeated transfusions of blood, 
 removal of the spleen, and eradication of all foci of infection, one- 
 quarter of the patients are greatly improved, living happier and 
 more useful lives, prolonged beyond the expectation by a period of
 
 68 THE SPLEEN AND ITS DISEASES 
 
 two or three years ; one-half of the patients are improved in some 
 degree, they feel better, take nourishment better, sleep better, 
 and live perhaps a few months, or even a couple of years, longer than 
 the average ; the remaining one-quarter of the cases do not receive 
 any help greater than that which could be derived from careful 
 medical treatment, which may include the 'step-ladder' trans- 
 fusions of blood if these are found to be helpful, and the treatment 
 of such foci' of infection as can be found in the mouth, nose, or 
 accessory sinuses. When the position is accurately stated to 
 patients who suffer from this disease, they are likely to decide the 
 matter according to their temperaments. Surgeons should rarely, 
 or never, urge operations, for they should rarely, or never, find it 
 necessary to do so if the problem to be decided is fully and honestly 
 stated to a patient or his relatives. In cases of pernicious anaemia 
 an operation is indicated for those patients who are found by such 
 tests as I have mentioned to be likely to do well, and who are eager 
 to get the most out of the remainder of their days and to prolong 
 them.
 
 PLATE IV 
 
 SPLEEN 
 
 
 
 Dilated capillaries; white- 
 cell formation vigorous; 
 nodules of this, enlarge- 
 ment of organ. 
 
 Massive Spleen; thick capsule 
 & adhesions; big vessels. 
 Centres of formation of the 
 leuhaemic cells everywhere. 
 Normoblasts; phagocytosis 
 Attenuated reticulum 
 
 WASTING. 
 HXEMORRHAGES. 
 
 Inf. Mesenteric Vein 
 
 Excessive activity. Immature 
 Sup.Mes. cells liberated. Giant cells 
 
 increase. Unripe red cells escape. 
 
 BONE MARROW 
 
 LIVER 
 
 THE CHIEF CHANGES IN
 
 69 
 
 CHAPTER Vll. 
 
 LEUKAEMIA. 
 
 (See Plate IV.} 
 
 To turn over the pages of the history of leukaemia is to see 
 recorded in orderly succession many of the chief features in the 
 growth of our knowledge concerning human pathology and 
 hsematology. A case of this disease was first recorded in 1845 by 
 Hughes Bennett, of Edinburgh. The spleen was greatly enlarged, 
 and the blood, examined after death, was seen to contain a large 
 number of cells similar to those found in the ordinary purulent 
 discharges from wounds. Hughes Bennett described the con- 
 dition as one of " suppuration of the blood ". One month later 
 Virchow described a similar case. A rather acrimonious contest 
 for priority arose, and different views were expressed as to the 
 nature of the white bodies found in the blood. Virchow asserted 
 that they were not to be distinguished from the colourless cor- 
 puscles or leucocytes of the blood. Hughes Bennett had regarded 
 them as pus-cells. But the discussion lost all its significance when 
 it was recognized that pus-cells and leucocytes were identical. 
 Virchow, we may well suppose, was interested, not so much in the 
 purely clinical phenomena which his case displayed, as in the 
 question of its intrinsic nature. He regarded " the blood as a 
 transitory tissue with a fluid matrix, constantly changing because 
 constantly developing ", and he showed that the cells of the blood 
 are continually perishing and continually being replaced. The 
 occurrence of a disease such as this was for him the confirmation 
 of his opinion as to the nature and constitution of the blood, for 
 he had, as it were, foreseen that such a disease as this would be 
 likely to exist. When once his prediction that there was a 'white 
 blood' was confirmed by the examination of the blood in this 
 disease, the problem at once arose as to the nature of the process 
 involved in the excessive production of leucocytes, and as to the 
 nature of the tissue changes present in this disorder. 
 
 The study of these questions led to an intensive study of the
 
 70 THE SPLEEN AND ITS DISEASES 
 
 cellular processes occurring in suppuration. Neumann, in 1878, 
 showed the active part played therein by the bone-marrow, and 
 Ehrlich (1898) demonstrated that it was possible by using aniline 
 dyes as stains to differentiate between the various types of cell 
 activity awakened by this process. From this time, the know- 
 ledge of the floating cells of the body has advanced with great 
 rapidity ; and the intimate relationships which exist between the 
 cells circulating in the blood, the cells in the blood-forming organs, 
 and the cells met with in inflammatory infiltrations of all kinds, 
 have by degrees been brought to light. The changes in the blood 
 of living patients were first described in 1846 by Dr. Fuller, of 
 St. George's Hospital, and Dr. Walshe, of University College 
 Hospital. 
 
 Virchow sought to place the primary seat of this disease in the 
 spleen and in the lymphatic glands. He believed that the changes 
 in the blood arose from the liberation into it of chemical substances 
 which were normally retained within these organs. The cells of 
 the blood were stirred to a greater activity by these substances, 
 and ultimately the cells of the various organs also showed evidence 
 of hyperplasia. 
 
 The original belief of the great pathologist received corrobora- 
 tion from Neumann's discovery of the state of the bone-marrow in 
 this disease. As a result of this, leukaemia was then regarded as a 
 disease of the spleen, lymph-glands, and bone-marrow, an interpre- 
 tation not essentially different from that held to-day. But the 
 subsequent history of this disease shows many vicissitudes. Diffi- 
 culties were continually arising in the interpretation of details ; 
 and in spite of most assiduous research by many observers, no 
 real advance was made in our knowledge of the disease until the 
 work of Pappenheim. 
 
 As a result of the investigations of this worker and his school, 
 the origin and fate of every type of cell found not only in leukaemia 
 but in every 'blood' disease, and in every inflammatory process, 
 were thoroughly investigated by special staining methods applied 
 to all manner of tissues : to those removed by operation as well as 
 to those obtained by post-mortem examination, in man as well as 
 in animals. 
 
 The modern science of haematology received immense impetus 
 from all this work, and a host of earnest students in all lands were 
 eager to lend their help. The question in this disease resolved
 
 LEUKAEMIA 71 
 
 itself into an inquiry as to whether the abnormal blood-cells were 
 formed in one organ or in many, thence to be distributed to all 
 parts of the body ; or whether the cells were formed ' locally ', 
 that is, in the parts where they were found. It was an old problem 
 re-stated, the problem as to whether the exudates occurring in 
 inflammation are due to chemiotaxis and the migration of leuco- 
 cytes from afar ; or whether (as was the original view) these cells 
 are developed at the seat of the disease. The general opinion of 
 those most competent to express one, now appears to be that the 
 origin, both of these inflammatory cells and of the leukaemic cell- 
 infiltration, is local. This is a matter of great interest, and the 
 historian will recall that in the year 1863, Beale, a solitary voice 
 heard only to be opposed and derided, stoutly defended his 
 opinion that the phenomena of tissue infiltration were the result 
 of the irritation of the endothelial cells of the smallest local 
 capillaries. 
 
 Leukaemia may therefore be considered as a morbid process 
 manifesting itself diffusely, and consisting of hyperplasia of various 
 leucocytes sometimes of the lymphocytes, sometimes of the 
 myeloid cells scattered throughout the body. The severity of 
 the degree of hyperplasia may be so great, and the type of cells 
 produced may be such, that what is called a 'sarcoid' process 
 results. There are cases in which, however, the newly-formed 
 cells are found in the spleen, lymph-glands, and bone-marrow, but 
 do not enter the blood-stream ; the blood on examination is normal. 
 'Leukaemia' therefore may be regarded as having two relationships : 
 on the one side to the disease known as lymphosarcoma ; on the 
 other to Hodgkin's disease. 
 
 The search for the cause of this disease would be fruitless 
 without the clear conception that leukaemia is a disorder in the 
 process of the formation of white blood-cells, whose birthplace 
 is the endothelium of the reticulo-endothelial system. We have 
 not, therefore, to search a particular organ to find the cause of 
 the disease ; we have to discover the type of agent likely to affect 
 so diffusely distributed a system of cells. We should be able to 
 explain why in some cases the proliferative process goes on outside 
 the blood-vessel and produces a massive deposit of new tissue 
 without altering the appearance of the blood (resulting in 
 Hodgkin's disease), whereas in other cases the proliferating process 
 extends into the lumen of the vessel and allows the myriads of
 
 72 THE SPLEEN AND ITS DISEASES 
 
 newly-formed cells to enter the circulation and produce a typical 
 condition known as leukaemia. 
 
 It was Pappenheim who elaborated the thesis that the virus at 
 work may travel either by the lymphatic channels (producing a 
 'lymphatic leukaemia') or in the blood-channels (producing a 
 'myeloid leukaemia'), and that the purpose of an inquiry should 
 be to ascertain the nature of the stimuli or irritants capable of 
 exerting such effects. 
 
 SYMPTOMS. The first and striking clinical feature is that the 
 disease does not always run the same course. On the one hand, 
 there are acute forms in which a fatal issue ensues within a few 
 weeks ; on the other, the disease may last for many months, or, 
 usually from two to four years, or even as in a case recorded by 
 Grawitz for ten years. The duration of the chronic cases depends 
 to a certain extent upon the circumstances of the patient. The 
 necessity for earning a livelihood, even though the work is not 
 heavy, has a very harmful influence upon the course of the disease. 
 
 Acute Leukaemia is no doubt commoner than appears from 
 the literature, owing to the non-recognition of cases. It begins 
 very suddenly, and is characterized by the severity of its sym- 
 ptoms, which follow acute tonsillitis or stomatitis. Haemorrhages, 
 as in scurvy, especially from the gums or nose, form an important 
 feature, and in a few cases general glandular enlargement is 
 noticed. The remainder of the clinical course strongly simulates 
 that of typhoid fever, with rapid wasting, and a degree of mental 
 disturbance which sometimes ends in delirium. Jaundice, when 
 present, is attributed to enlargement of the glands in the hilum 
 of the liver, which cause pressure upon the hepatic duct. An 
 exfoliative dermatitis has been noted. The blood-picture may be 
 either 'lymphatic' or 'myeloid'. 
 
 Chronic Leukaemia is usually of very insidious onset. A slow 
 progressive wasting becomes noticeable, and carries with it 
 increasing lassitude, asthenia, and loss of mental activity. In 
 this case also there is a tendency to haemorrhages, usually from 
 the nose, sometimes from the intestine, or under the skin ; 
 infrequently from the gums, from haemorrhoids, from the stomach, 
 uterus, or urinary passages. Ulceration of the lips and mucous 
 membrane of the mouth is not seldom seen, and may suggest an 
 examination of the blood to conform a tentative diagnosis. Periods
 
 LEUKEMIA 73 
 
 of fever are usual. Physical examination reveals a massive 
 enlargement of the spleen ; less massive enlargement of the liver ; 
 in the ' lymphatic ' cases there is enlargement of the lymph-glands 
 in various places. Every system of the body may show changes, 
 so that patients in respect of their most troublesome symptom 
 may come before ophthalmologists, dermatologists, gynaecologists, 
 urologists, and surgeons, as well as physicians. 
 
 Studies in the metabolism of this disease have been extensively 
 made. Perhaps the chief change in this respect has reference to 
 the metabolism of the purin bodies. Uric-acid excretion is high ; 
 indeed, uric acid calculi may form. Charcot-Leyden crystals 
 have been found in the blood and tissue-juices after death. 
 
 When a patient suffers from an added infection, the enlarge- 
 ment of the spleen and lymph-glands may diminish, and return 
 almost to the normal ; the blood-picture alters, the myelocytes 
 disappear, and the polynuclear leucocytes greatly increase. The 
 change, however, lasts only so long as the infection is present. As 
 that fades away the conditions of the disease return. The injec- 
 tions of normal splenic extract, or of spermin, or of cinnamic acid, 
 have restored the blood-count to normal for a time. As men- 
 tioned later, the administration of benzol produces a profound 
 change in the state of the blood. Some cases have been reported 
 in which a concurrent tuberculous lesion led to shrinkage of the 
 spleen. 
 
 Neither age nor heredity appears to have any influence upon 
 the disease. It does not occur in epidemics. Injuries have some- 
 times been considered a cause. Animals, cows, horses, dogs, cats, 
 and fowls are said to suffer from the disease. So far no bacterial 
 cause for it has been discovered, in spite of arduous and protracted 
 search. Many of the clinical features could be easily explained 
 as the result of a microbic infection ; the acute form is clinically 
 very similar to one of the acute specific fevers. It is true that 
 many organisms have been found associated with the disease : 
 micrococci, staphylococci, in lymph-glands ; streptococci in the 
 acute cases seen in America ; and other organisms. These are 
 instances, almost certainly, rather of chance secondary contami- 
 nations than of causative agencies. Attempts have been made to 
 transmit the disease experimentally by the injection, intraperi- 
 toneally or intravenously, of leukaemic blood, but no success has 
 followed. Transmission has occurred from one fowl to another.
 
 74 THE SPLEEN AND ITS DISEASES 
 
 An examination of the abnormal leucocytes has shown peculiar 
 cell-inclusions, but no evidence exists that these are to be regarded 
 as parasites. So many of the features of the disease are 'toxic' 
 that a further research for a biological cause is worth while. It 
 has been suggested that the 'toxic' features are due to secondary 
 infections occurring in patients whose normal protective neutro- 
 phile leucocytes are gravely diminished in numbers and in efficiency, 
 being overwhelmed by the abnormal cells. It is possible that the 
 absence of the normal leucocytes may account for the wasting 
 seen in this disease, for many of the processes enacted in the tissues 
 are deprived of the help which it is the part of these cells to give. 
 
 TREATMENT. Until recent years no treatment seemed to have 
 any considerable effect in cases of leukaemia. In the year 1909, 
 Selling, of Johns Hopkins Hospital*, reported three cases of 
 poisoning by benzol, two being fatal. The patients suffered from 
 purpura haemorrhagica with aplastic anaemia, and the bone-marrow 
 was found aplastic. The red cells showed no changes other than 
 slight pallor and anisocytosis. No regeneration forms of the red 
 cells and no normoblasts were found. Platelets were few. There 
 was a diminution in the granular type of leucocytes, and a relative 
 increase in mononuclear types. Leucopenia was present. 
 
 In 1912, Koranyif observed the effects of benzol poisoning in 
 girls working in a factory where benzol was used as a solvent for 
 rubber. The symptoms produced by this drug suggested to him 
 the possibility of its use in the treatment of leukaemia. In 
 reporting his experience, he states that there were no failures with 
 benzol in cases of chronic leukaemia ; that the spleen and lymph- 
 nodes were little affected ; that benzol given alone was of benefit, 
 and, although more gradual in its effect than x rays, it succeeded 
 where these failed ; but that patients responded better to benzol 
 treatment after the spleen had been exposed to x rays. No serious 
 ill-effects were observed to follow the treatment, but certain dis- 
 agreeable symptoms were noticed : a sense of burning in the 
 stomach, and the eructation of offensive gas, with transient catarrh 
 of the trachea and bronchi, and giddiness. In one case the white 
 cells were reduced from 220,000 to 8000 within three months ; 
 and the general health improved considerably. Dr. Frank 
 
 * Johns Hop. Hosp. Bull., 1910, xxi, 33. f Ber l- M- Woch., 1912, xlix, 1857.
 
 LEUKEMIA 75 
 
 Billings,* who reports a series of five cases treated by this drug, 
 was impressed with it as a very powerful agent, and as one 
 apparently of great promise in the treatment of leukaemia ; but it 
 was 'a two-edged sword' which, used carelessly, might defeat the 
 purpose of its use and produce an equally serious condition, 
 namely aplastic grave anaemia, with a hypoplastic bone-marrow, 
 and result in a fatal issue. He noted a diminution in the size of 
 the spleen, a rapid fall in the number of the leucocytes, and, in all 
 the cases of a myelogenous type, an improvement of the red-cell 
 count and haemoglobin. Later experiences have confirmed many 
 of these opinions ; but it was soon found that there were cases 
 resistant to treatment by benzol, and that in others a short period 
 of improvement was followed by a rapidly fatal termination. Such 
 dramatic endings to the disease occur both without treatment and 
 with other forms of treatment, but benzol seemed often to be a 
 factor in causing an earlier death than had been anticipated. The 
 pure drug is administered in capsules containing about 1 grm., and 
 olive oil is given simultaneously to diminish the irritating local 
 effect. A dose of 5 grm. daily is gradually reached. When the 
 leucocyte count is reduced to 20,000 the administration is stopped. 
 Boardmanf states that 16 out of 100 cases failed to show improve- 
 ment, and that another 8 cases, although reacting favourably at 
 first, died during or soon after the discontinuance of treatment. 
 
 The application of radium produces the most astonishing 
 effects in reducing the size of the spleen. Within eight or ten 
 weeks a spleen which appears to occupy almost the whole of an 
 enlarged abdominal cavity shrinks until it is only just palpable 
 beneath the costal margin. If the abdomen is marked week by 
 week to indicate the size and shape of the tumour, the evidences of 
 rapid shrinkage are very remarkable. As the spleen diminishes, 
 the general condition of the patient steadily improves, and the 
 blood-count approximates to the normal. In a very interesting 
 paper OrdwayJ discusses the whole question of radium therapy 
 very fully, and illustrates the improvement seen in cases under 
 his care by photographs. He draws the following conclusions : 
 
 1. Surface applications of radium in leukaemia produce striking, 
 indeed remarkable, improvement in : (a) The blood-picture, which 
 
 * Jour. Amer. Med. Assoc., 1913, Ix, 595. 
 t Quoted by ORDWAY, Boston Med. and Surg. Jour., 1917, clxxvi, 490. J Ibid.
 
 76 THE SPLEEN AND ITS DISEASES 
 
 becomes almost normal ; (b) The size of the spleen and glands, 
 which are reduced almost to normal ; (c) The general condition of 
 the patient, who, from being emaciated and weak, may become 
 plump and strong. 
 
 2. The duration of the remission is variable ; it may last from 
 months to years. 
 
 3. The results of radium treatment are not regarded as cura- 
 tive. It is believed to be, however, the safest as well as the most 
 prompt palliative measure in cases of chronic leukaemia, whether 
 refractory or not to benzol or x-ray treatment. 
 
 From the results of radium therapy in leukaemia it is believed 
 to be the best form of treatment now at our disposal. 
 
 The facts which were clearly established by this work and by 
 similar experiences at the Radium Institute in London in cases 
 under the care of Hayward Pinch, led to the inference that the 
 spleen might possibly be a factor of greater significance in the 
 etiology of the disease than had been supposed. This view was 
 strengthened by the further experience that the exposure of the 
 long bones, or other parts, as well as the spleen, to the action of 
 radium, did not produce results in any degree better than those in 
 which the spleen alone was treated. As a result of the work at 
 the Mayo clinic, by W. J. Mayo, Balfour, Giffin, and others, it 
 seemed not improbable that if the spleen were a factor of causal 
 significance, its removal, when it had been greatly reduced in size 
 by the application of radium, and when the patient's condition 
 was at its best, might be of benefit to the patient. In the old days 
 removal of the spleen has been undertaken because the organ was 
 grossly enlarged ; the new view was that the smaller the spleen 
 the safer its removal would be. 
 
 The first case in which the spleen was excised in myelogenous 
 leukaemia is recorded by T. Bryant, in 1866,* and the second by 
 the same author in 1867. Both patients died as a direct conse- 
 quence of the operation ; in both the spleen was very large. After 
 this, splenectomy was performed on many occasions in this disease, 
 and by no means all of the cases found their way into surgical 
 literature. The condition in most of these was profoundly 
 unfavourable ; the patient was in grave ill-health, and the spleen 
 was of very large size ; indeed, only those patients appear to have 
 
 * Guy's Hasp. Rep., 1866, xii, 444.
 
 LEUKEMIA 77 
 
 been selected for surgical treatment in whom the mammoth spleen 
 was a serious and burdensome discomfort. The mortality up to 
 the year 1900 is said to have been just under 90 per cent. Bessel 
 Hagen* gave the records of 42 cases, with 38 deaths, and ' temporary 
 improvement' in 4. I know of a few cases, all fatal, occurring 
 before this date, which never found their way into the literature. 
 In 1908, J. B. Johnstonf recorded a further 7 cases, of whom 
 2 lived to show slight improvement after the operation. 
 
 H. Z. GiffinJ reports that the total number of cases appearing 
 in the literature up to Jan. 1, 1918, is 51. Of these, 43 died at 
 once : 8 showed a temporary improvement ; but of these, 4 died 
 within so short a period of the operation that their death should 
 count as a fatality from it. If this is done, the mortality is to be 
 reckoned as 93 per cent. It is not surprising to find that all voices 
 speaking with authority, such as Bland-Sutton's, were raised 
 against a continuance of such surgical work. The record was a 
 martyrology. 
 
 The experience of the Mayo clinic is epitomized in the following 
 summary by Dr. Giffin : 
 
 "1. Twenty patients with myelocytic leukaemia have been 
 splenectomized 18 of them after preliminary treatment by means 
 of radium exposures over the spleen. The spleen and the leuco- 
 cyte count were very much reduced by means of radium, and the 
 general condition of the patients was greatly improved. 
 
 " 2. One patient died an operative mortality of 5 per cent. 
 The operative mortality of cases reported in the literature in which 
 little or no preliminary medical treatment had been given was 86- 
 per cent. 
 
 " 3. Ten of the 20 patients are living in good general condition 
 from nine months to one year and seven months following splen- 
 ectomy. However, these patients have not yet outlived the life 
 expectancy for the disease. 
 
 "4. Of 7 patients operated on within six months of the onset 
 of the disease, 6 are alive. 
 
 "5. It is probable that, at least in certain chronic types of 
 myelocytic leuktemia with fibrous spleens and relatively low leuco- 
 cyte counts, splenectomy may be justifiable for the comfort of 
 the patient. 
 
 * Arch. f. klin. Chir., 1900, Ixii, 188. f ^nn. of Surg., 1908, xlviii, 50. 
 
 J Med. Record, 1918, xciv, 1020.
 
 78 THE SPLEEN AND ITS DISEASES 
 
 " 6. A review of the cases at this time reveals no evidence that 
 the duration of the disease is altered in any definite way by 
 splenectomy." 
 
 The statistics of the Mayo clinic up to Sept. 20, 1920, which 
 Dr. W. J. Mayo has kindly given to me, show a total of 26 cases 
 with 1 death, a mortality of 3'8 per cent. The immediate mortality 
 is therefore strikingly different from that which occurred when the 
 cumbersome size of the spleen was the chief indication for the 
 removal of the organ. The last report shows, too, that 5 patients 
 are in good condition and 2 in fair condition after periods of time 
 beyond the life expectancy of the disease. It is interesting to 
 learn that two cases, supposed to be early examples of myelogenous 
 leukaemia (not included in this list) have been cured, or at least 
 have lived many years after the operation. Dr. Mayo writes : 
 " The operation is not difficult after radium treatment, and in 
 selected cases should be further considered ".
 
 PLATE V 
 
 Coeliac 
 Axis 
 
 SPLEEN 
 
 Not necessarily uery large 
 Proliferation in and round 
 Malpighian bodies. 
 Nodules of granulation 
 
 tissue. 
 Fibroid sinuses. 
 
 the nodules: giant cells, plasma cells, 
 eosinopfiiles, fit ob/asts etc. 
 
 Inf. Mes 
 
 Vein 
 
 Liuer: Nodules as aboue. Press on 
 ueins and bile ducts (occasionally) 
 
 No nodules in pancreas or intestine 
 
 No haemorrhages (.'. endothelium 
 escapes). 
 
 Bone marrow: nodules. White cell 
 manufacture accelerated. 
 
 Gall Bladder 
 
 BONE MARROW 
 
 THE CHIEF CHANGES IN HODGKIN'5 DISEASE
 
 79 
 
 CHAPTER VIII. 
 
 HODGKIN'S DISEASE. 
 
 (See Plate F.) 
 
 IN the year 1831, Hodgkin, Lecturer on Pathology at Guy's 
 Hospital, observed a series of cases in which the spleen and the 
 lymphatic glands were enlarged.* Among these were four examples 
 of the condition now known as 'Hodgkin's disease'. All remem- 
 brance of this paper seems to have been lost, for in the year 1862 
 Wilks, then Lecturer on Pathology at the same Hospital, described 
 the same disease under the title 'anaemia lymphatica'. By the 
 year 1865 Wilks had, however, discovered the previous description 
 by Hodgkin, and though his own observations were entirely 
 original, he suggested, as a title for the disease, the name it has 
 ever since borne, 'Hodgkin's disease'. 
 
 The morbid anatomy of the condition has been investigated 
 since by a great number of observers, among whom Reed, Long- 
 cope, and Andrewes deserve special mention. A number of diverse 
 views have been held as to the nature and causation of the 
 condition. 
 
 One of the most recent writers, Mellon, f considers that the 
 disease has not any relationship with tuberculosis as Sternberg 
 asserted , with lymphosarcoma, or with pseudoleukaemia. The 
 prevailing view of most of those who have recently investigated 
 the condition appears to be that all these diseases should be 
 regarded as disorders of the reticulo-endothelial system, probably 
 infective in origin, and therefore to be classified as infective granu- 
 lomata or " lymphomatosis with granulation-tissue formation ". 
 In his review of recorded cases Mellon found only two in which it 
 seemed possible that the spleen was the primary focus of the 
 disease ; in neither was an autopsy obtained, yet the necessity 
 for this could not be better shown than in a case recorded by Mellon 
 as coming under his own care. In this there was no evidence of 
 glandular enlargement, and a primary splenic origin of the disease 
 
 
 
 * Trans, Roy. Med. Chir. Soc., 1832. f Amer. Jour. Med. Sci., 1016, cli, 704.
 
 80 THE SPLEEN AND ITS DISEASES 
 
 seemed most probable. After death the inguinal, bronchial, and 
 retroperitoneal glands all showed hyperplasia of the lymphoid 
 cells, and endothelium with multinucleated giant cells. The spleen 
 showed advanced changes ; the lymphoid tissue of the splenic 
 pulp was practically obliterated by the intense proliferation of 
 the hyaline connective tissue. There were many areas of anaemic 
 necrosis which indicated that the disease in the spleen was of long 
 standing. A similar case was recorded by Wilks in 1856 : the 
 patient was a man who died in Guy's Hospital in an extremely 
 debilitated and anaemic state, with an enlarged spleen. The 
 autopsy showed that the mediastinal and lumbar glands were very 
 much enlarged, although the superficial glands were quite healthy. 
 
 The true nature of the disease has baffled inquiry. It may be 
 regarded as a separate and distinct disorder having no ostensible 
 attachment to any other. Or, alternatively, it may be regarded 
 as a special form of a certain type of morbid process which exists 
 also in other conditions tuberculosis, pseudoleukaemia, and 
 lymphosarcoma. The latter opinion has the advantage of corre- 
 lating various morbid states as to the nature of which there has 
 long been confusion, and attributing them all to one common 
 underlying cause. 
 
 Hodgkin's disease has, as its essential anatomical feature, the 
 presence of tumours made up of granulation tissue. The lesions 
 diffej from those of tuberculosis partly in the heterogeneous 
 character of the inflammatory cells concerned in the formation of 
 the nodules, and partly in the fact that the original cells of the 
 affected tissues undergo active multiplication. The ordinary struc- 
 ture of the glands or spleen becomes lost in the abundance of 
 lymphocytes, which appear intermingled with those epithelial 
 cells, giant cells, fibre cells, and eosinophil leucocytes, all of which 
 together help to build up the masses found in Hodgkin's disease. 
 
 In the reticulo-endothelial system there are the following 
 two types of disease. There is that in which the cells undergo an 
 intense proliferation and are liberated into the blood, as in the 
 leukaemias. And there is that in which the proliferation goes on 
 outside the vessels without the entry of any of the new cells into 
 the blood. The microscopist, studying the spleen and allied organs, 
 might well believe that he had an ordinary leukaemia tissue under 
 examination, although the clinical phenomena might make such 
 a diagnosis impossible. For him, the nature both of Hodgkin's
 
 HODGKIN'S DISEASE 81 
 
 disease and of leukaemia is essentially the same, and the state of 
 the blood (upon which the clinician lays so much stress) is a mere 
 incident. 
 
 The histological study of these diseases of the reticulo- 
 endothelial system suggests a similarity, if not an identity, of 
 causation, both for the widely disseminated lesions, and for those 
 in which a definite 'tumour', as, for example, lymphosarcoma, 
 occurs. 
 
 The following classification, for help in the preparation of 
 which I am indebted to Dr. Gruner, embraces all the disorders 
 of the reticulo-endothelial system, and shows, as well as our present 
 knowledge allows, their relationship to each other : 
 
 DISORDERS OF THE RETICULO-ENDOTHELIAL SYSTEM. 
 
 I. Those in which there is an excessive formation of specific tissue elements. 
 
 A. With the appearance of cells which are normal to blood-forming tissues : 
 
 1. The cells grow away from the vascular channel : 
 
 i. The disorder is disseminated throughout all parts of the system : 
 
 (Disseminated) PSEUDOLEUK^MIA. 
 ii. The disorder is focal: 
 
 a. In the lymph-glands : LYMPHOMATOSIS ; also in TYPHOID 
 
 lesions. 
 
 6. In the bone-marrow : 'MEDULLARY PSEUDOLEUK^EMIA'. 
 c. In the spleen (and liver) : 'LIENAL PSEUDOLEUIOEMIA'. 
 
 2. The cells grow partly into the vascular channel, so that myelocytes 
 
 appear in the blood : ACUTE SPECIFIC FEVERS ; VON JAKSCH'S 
 ANEMIA. 
 
 3. The cells grow mainly in the vascular channel. Therefore large 
 
 numbers of myelocytes (or lymphocytes) appear in the blood : 
 a. Disorder in the lymph-glands or lymphatic tissues : .Clinically 
 
 acute or chronic LYMPHATIC LEUKEMIA. 
 6. Disorder in the bone-marrow, spleen-pulp, or any 'myeloid' 
 
 tissue : Clinically acute or chronic MYELOID LEUKAEMIA. 
 
 B. With the appearance of entirely new cells : 
 
 1. Definite tumour- formation : 
 
 a. Widely disseminated through the body : LYMPHOSARCOMA. 
 
 b. Only local masses : in the spleen : LYMPHOSARCOMA. 
 
 in the bone-marrow : MYELOMA. 
 in the lymph-glands : CHLOROMA. 
 
 2. Definite tumour formation not present, but tumour cells are inter- 
 
 mingled with myelocytes or lymphocytes of large size : 'SARCOID' 
 LEUKAEMIA. 
 
 (Each of these may also show 'leukzemic' blood.) 
 
 6
 
 S2 
 
 II. Those in which there is excessive formation of the stroma cells : 
 
 A. One kind of cell is noticeably predominant in the tissues : 
 
 1. Fibre cells : PASSIVE CONGESTION OF THE SPLEEN ; SYPHILITIC 
 
 SPLENOMEGALY ; MALARIA ; KALA-AZAR ; CIRRHOSIS with SPLENO- 
 MEGALY. 
 
 2. Epithelioid cells : GAUCHER'S SPLENOMEGALY. 
 
 B. Many cell-types involved, so that a granulation-tissue tumour is formed : 
 
 1. Disseminated through the whole system : HODGKIN'S DISEASE ; 
 
 LYMPHOGRANULOMA. 
 
 2. Local, e.g., in the spleen only (very rare) : primary HODGKIN'S 
 
 DISEASE ; TUBERCULOSIS OF SPLEEN ; GUMMATA OF SPLEEN. 
 
 III. Those in which there is an excessive formation of stroma cells, with disturb- 
 ance of the formation of the specific tissue cells : PERNICIOUS ANAEMIA ; 
 SPLENIC ANAEMIA ; ELEMOLYTIC JAUNDICE ; SPLENOMEGALY IN RICKETS. 
 
 The clinical symptoms of Hodgkin's disease are very familiar. 
 They are largely mechanical in origin, and are due to the presence 
 of widespread glandular enlargements which may press upon 
 important structures. The periodic pyrexia of this disease may be 
 regarded as a specific and typical feature. It is uncertain as to 
 whether it is sometimes, or often, the result of secondary infections. 
 
 The symptoms certainly suggest the existence of a definite 
 infection. There is a latent period, with occasionally slight swellings 
 of the glands. A stage of declared disease may then begin quite 
 abruptly. There may be a sudden general enlargement of the 
 lymphatic glands, which themselves cause pressure symptoms, 
 recurring attacks of fever, with increased heart action, and pro- 
 gressive wasting. It is said that the blood often shows no change, 
 but it is very probable that an increase of the large mononuclear 
 leucocytes and transitional cells is generally to be expected. 
 
 TREATMENT. It is only very rarely that an operation upon 
 the spleen is necessary in a case of Hodgkin's disease. I have 
 performed one such operation. The case occurred in a man, 44 
 years of age, who had a colossal enlargement of the spleen with no 
 discoverable change in any of the lymph-glands. Under radium 
 the spleen diminished rapidly in size, but after two months again 
 began to increase and became as large as ever. A second and 
 third application of radium caused an equal reduction, and when 
 the spleen was small I removed it. It showed the typical evidences 
 of Hodgkin's disease, and this diagnosis was confirmed by the later
 
 HODGKIN'S DISEASE 83 
 
 enlargements of the cervical glands on both sides, which receded 
 after the application of radium. The original operation was per- 
 formed twenty-two months ago, and the patient is still in good 
 health and at work. It is very doubtful if the removal of the spleen 
 has had any effect, good or ill, upon the progress of the disease. 
 The general treatment of the disease needs no mention here.
 
 CHAPTER IX. 
 
 SPLENIC ANAEMIA. BANTI'S DISEASE. 
 
 (See Plate VI.} 
 
 HISTORICAL. 'Banti's disease' is the name given to the con- 
 dition described in 1883,* and again in 1894,f by Guido Banti, of 
 Florence. In 1866 GretzelJ described a clinical condition of 
 anaemia associated with splenomegaly to which Griessinger applied 
 the name 'splenic anaemia'. The case occurred in a child ten 
 months old who suffered from dysentery and severe anaemia, with 
 considerable enlargement of the spleen, and enlargement, less con- 
 siderable, of the liver and lymphatic glands. Examination of 
 the blood showed that the proportion of white to red cells was 
 not increased ; the condition was therefore not leukaemic. In 1871 
 Wood described a 'splenic form' of pseudoleukaemia, and reported 
 a case in which the spleen was greatly enlarged, and there was 
 severe anaemia without leucocytosis. Banti, in his later descrip- 
 tion mentioned above, considered the disease as possessing clinically 
 three stages, merging gradually into each other. These stages 
 were : (1) One in which there was enlargement of the spleen and a 
 secondary anaemia the duration being three to twelve years ; 
 
 (2) One in which the liver gradually enlarged, and the amount of 
 urine underwent progressive diminution the duration was brief; 
 
 (3) One in which the liver gradually shrank in size and ascites 
 appeared, the symptoms being those of an ordinary atrophic 
 cirrhosis the duration of this stage was between one and two 
 years. The disease was invariably fatal, and death occurred either 
 from haemorrhage, or from auto-intoxication from cirrhosis. 
 
 In a third publication, Bantij] asserts that the disease is also 
 characterized by the following definite pathological changes : 
 (1) The chief change noted in the spleen is a fibrosis of the 
 
 * " Dell' anaemia splenica," Arch. L. Schula Anat. palhol., Firenze, 1883, ii, 53. 
 
 t Sperimenlale, xlviii, 407. $ Berl. klin. Woch., 1866, ci, 212. 
 
 Amer. Jour. Mcd. Sci., 1871, Ixii, 373. || Folia hcematol., 1910, x, 1.
 
 PLATE VI 
 
 Coeliac 
 Axis 
 
 Enlargement of the Spleen. 
 
 Perisplenitis 
 
 Fibrosis of Malpighian bodies & 
 
 throughout pulp. Thick capsule 
 Swelling of endothelial cells. 
 Pressure on uasa breuia. 
 Patches of sclerosis in Splenic Vein. 
 
 ~ Inf. Mesenteric Vein 
 
 UVER 
 
 HEPATIC ARTERY 
 
 Fibrosis round liuer acini 
 compressing the liuer-cells,but 
 not the bileducts.( Portal type) 
 
 BONE 
 MARROW 
 
 Activity of bone marrow normal in 
 type but fewer cells liberated. 
 
 THE CHIEF CHANGES IN SfLENIC AN/E/AIA
 
 SPLENIC ANEMIA. BANTI'S DISEASE 85 
 
 Malpighian follicles, spreading outwards from the central artery, 
 which often shows a hyaline degeneration ; (2) There is fibrosis of 
 the splenic reticulum, with narrowing of the splenic veins, a 
 thickening of the splenic capsule, and of the trabeculae, larger and 
 smaller, running through the organ ; (3) Endophlebitis, with calci- 
 fication of the splenic veins, extending up to, and even into, the 
 portal vein; (4) Cirrhosis of the liver, of the 'Laennec type'; 
 (5) The characteristic red marrow of a secondary anaemia ; (6) There 
 is no general glandular involvement. 
 
 Banti's hypothesis is that there is a primary splenomegaly due 
 to an infective agent. The splenic enlargement itself produces 
 another toxin which, acting on the liver and on the splenic veins, 
 produces the changes just described. The anaemia is the result 
 partly of the toxaemia and partly of the haemorrhages. The hypo- 
 thesis is unnecessarily complex, for there is no reason why a single 
 infective agent should not produce effects alike in the liver and in 
 the spleen. The production by a sclerosing organ of a toxin 
 destined to cause sclerosis in another organ is unknown elsewhere. 
 
 The difficulty in the strict recognition of Banti's disease, as 
 he describes it, is great ; for there are many conditions with sym- 
 ptoms very closely resembling those described by him, and the 
 chances of obtaining a pathological examination of the spleen and 
 its vessels, and of inspection of the liver, are so remote, in view of 
 the restriction of operative treatment, that an accurate diagnosis 
 is only then obtainable after death. The etiology in Banti's 
 disease is held to be unknown. If, therefore, a case clinically and 
 pathologically resembling Banti's disease has a known causation, 
 it cannot be accepted as an example of this disease. 
 
 Again, both clinically and pathologically the conditions in 
 certain cases may so closely resemble those of Laennec's cirrhosis 
 that many authors have considered that there are not two diseases, 
 but one disease with different names.* If the ordinary clinical 
 course is followed, there is no doubt that in Banti's disease the 
 splenic enlargement precedes the affection of the liver, whereas in 
 Laennec's cirrhosis the liver is first attacked ; though in some 
 cases the splenic enlargement may be so considerable as to distract 
 attention from the less obvious change in the liver. 
 
 The truth appears to be that a large clinical group of cases, 
 
 * Krull, Mitteil. a, d. Grenzgeb. d. Med. u. Chir., 1915, xxviii, 718.
 
 86 THE SPLEEN AND ITS DISEASES 
 
 distinguished by enlargement of the spleen and anaemia, is being 
 gradually encroached upon by keener distinctions, pathological 
 and etiological, than formerly existed. Griessinger's original 
 description of splenic anaemia included, for example, the condition 
 we know now as Gaucher's disease, the disease now called 
 'haemolytic jaundice', and that form of infantile pseudoleukaemia 
 called von Jaksch's disease. In connection with the latter, the 
 view is taken by some observers that it is an infantile form of 
 Banti's disease in which " a moderate leucocytosis, due to the 
 higher values of leucocytes in the normal blood of infants, is 
 to be found " (Mayo). 
 
 Splenomegaly associated with anaemia may have its etiology 
 determined, and so be withdrawn from the group of 'splenic 
 anaemia '. This has happened, for example, in connection with 
 chronic syphilitic enlargements, with the enlargements due to 
 kala-azar, to malaria, and so on. The group is raided from every 
 side. What remains ? Only the forms of * splenic anaemia ' the 
 cause of which is unknown. Or, as Mayo wisely and wittily says, 
 " Put in the form of an Hibernianism, incomplete knowledge is 
 essential to the diagnosis. If we know the cause of splenic anaemia 
 it is not splenic anaemia". 'Banti's disease' and 'splenic anaemia' 
 are therefore synonyms for the same condition, the former title 
 indicating especially the later, the latter the earlier, stages. 
 
 CLINICAL HISTORY. Splenic anaemia was defined by Osier as 
 " an intoxication of unknown nature characterized by great 
 chronicity, primary progressive enlargement of the spleen which 
 cannot be correlated with any known cause, anaemia of a secondary 
 type, with leukopenia, a marked tendency to haemorrhage 
 particularly from the stomach, and in many cases a terminal 
 stage with cirrhosis of the liver and jaundice ". The clinical 
 features of the disease, then, are the following : 
 
 1. A very chronic course in which the symptoms progressively 
 and steadily increase in severity, without amendment, and without 
 any hope of spontaneous recovery. 
 
 2. A slowly progressive enlargement of the spleen. This is the 
 first of all evidences of disease ; the bulk of the organ undergoes 
 an increase, at first apparently slight, but later more rapid. The 
 ratio of increase probably remains unaltered throughout. The 
 enlargement may finally be very considerable, though it is rare
 
 SPLENIC ANEMIA. BANTI'S DISEASE 87 
 
 for the spleen to become as large as in myeloid leukaemia, or in 
 some cases of Hodgkin's disease, or in malaria, or in Gaucher's 
 disease. The spleen is not altered except in bulk, so far as physical 
 examination shows : the surface is smooth, the notches are 
 apparent ; there is no tenderness, nor is a friction rub felt or heard. 
 It is said that a ' bruit de diable ' has been heard (Sippy, Rolleston) 
 " due to eddies produced by slight torsion of the dilated veins in the 
 gastro-splenic omentum or of the splenic vein ". Seeing that 
 clinical recognition of splenic enlargement is not possible until the 
 spleen is at least double the normal size, it is more than probable 
 that the inaugural and early symptoms of splenic anaemia are 
 quite unrecognized. 
 
 3. Changes in the blood are of the type found in 'secondary' 
 anaemia. The red cells may drop to less than 2,000,000 per c.mm. ; 
 the average number is one-half of the normal. The colour-index 
 is low. In a series of fifteen cases Osier found the number of red 
 cells to be 3,425,000 per c.mm. and the haemoglobin 47 per cent. 
 A recent haemorrhage will of course affect the count very con- 
 siderably ; though it has often been observed that recovery after 
 a haemorrhage is rapid, and that within two or three weeks the 
 blood-count may so improve as almost to reach the normal. The 
 white cells are never above the normal unless there has been a 
 recent haemorrhage, or an inflammatory complication is developing. 
 Leukopenia is the rule. In Osier's case the average count was 
 4520. 
 
 4. The tendency to hcemorrhages is remarkable. Haematemesis 
 especially is seen, occasionally with copious melasna. Other forms 
 of bleeding are also mentioned in recorded cases ; epistaxis, 
 purpura, and haematuria are the most commonly seen. The amount 
 of blood lost, especially from the stomach, may be enormous. I 
 have seen two cases in which the apparently pure blood vomited 
 within a couple of hours measured over three pints. Osier records 
 a case in which three quarts of blood were lost within thirty-six 
 hours. Recurrence of the haemorrhage is frequent. A remarkable 
 case is related by Hutchison and Ledingham* of a woman who 
 was admitted to the London Hospital for severe haematemesis 
 no fewer than thirteen times within a period of fifteen years. 
 The blood comes in such cases, it is believed, from oesophageal 
 
 * Allbutt's System of Medicine, v, 759.
 
 88 THE SPLEEN AND ITS DISEASES 
 
 varices and dilated vasa brevia, both of which are found in a large 
 proportion of the cases. 
 
 5. Affection of the liver. In the later stages of the disease the 
 liver enlarges, and presents the clinical picture of Laennec's 
 cirrhosis. Ascites is present with the hepatic enlargement, or in 
 some cases without it. This terminal condition, in which the liver 
 is enlarged and dropsy is present together with the earlier con- 
 ditions described, is often spoken of as ' Banti's disease ' ; but if 
 this latter term is retained, it is perhaps wiser to use it only as a 
 synonym of 'splenic anaemia'. 
 
 6. An unknown causation. The discovery of a cause for the 
 splenic condition removes the case from the category of splenic 
 anaemia. As I have said, the term 'splenic anaemia' as originally 
 used included a group of diseases characterized by certain clinical 
 features common to them all. Upon this group encroachments 
 have steadily been made, and may well continue to be made, as our 
 knowledge of the etiology of special diseases becomes by degrees 
 more accurate. 
 
 7. Other phenomena of less importance may briefly be 
 enumerated. A general enlargement of lymph-glands is not 
 present. Until the latest stage there is no alteration of the urinary 
 function. Occasional attacks of heaviness in the epigastrium, 
 flatulence, and indigestion are observed, which lead, when haemor- 
 rhage occurs, to a diagnosis of 'gastric ulcer'. Such dyspepsias are 
 less frequently seen than might be supposed. Rarely there may be 
 slight pigmentation of the skin. If jaundice is present the case 
 is not one of splenic anaemia. 
 
 THE DIFFERENTIAL DIAGNOSIS. This as a rule is not difficult. 
 The mistake I have most commonly seen is the making of a diagnosis 
 of gastric or duodenal ulcer. I have now seen five cases in which 
 a patient suffering from splenic anaemia was referred to me as an 
 example of these diseases. The absence of a clear history of 
 dyspepsia, the presence of an easily palpable spleen, and the blood 
 changes, soon revealed the true condition. The contrary mistake 
 may be made. Rolleston relates the following case* : 
 
 " Some years ago a middle-aged man was under my care in 
 St. George's Hospital. He was very anaemic, and with a history 
 
 * Practitioner, 1914, April, 480.
 
 SPLENIC ANEMIA. BANTI'S DISEASE 89 
 
 of recurrent haematemesis. There was a tumour which appeared 
 to be an enlarged spleen, and the condition was regarded as splenic 
 anaemia. The necropsy showed that the tumour was a large 
 hydatid cyst in the left kidney, and that a chronic gastric ulcer 
 was responsible for the repeated haematemesis." 
 
 In any doubtful case an #-ray examination would almost 
 certainly clear away the uncertainty and demonstrate the presence 
 of a chronic gastric ulcer. 
 
 Cirrhosis of the liver has occasionally presented difficulties in 
 diagnosis. The number of cases in which the splenic enlargement 
 is considerable, and the hepatic enlargement slight, must be exces- 
 sively small. That the spleen may be much enlarged in cases of 
 Laennec's cirrhosis is certain ; and in such a condition a copious 
 haematemesis might well raise a doubt as to the true diagnosis. 
 Naunyn and others consider that splenic anaemia is merely a type 
 of hepatic cirrhosis in which the liver changes are relatively slight, 
 at least until the final stages are approaching. If a patient is 
 first seen when the spleen is grossly enlarged, the liver cirrhotic, 
 ascites abundant, haemorrhages recurrent, and ill health and 
 emaciation advanced, it is not certainly possible to say whether 
 the case is one of advanced Laennec's cirrhosis, or is in the ter- 
 minal stages of Banti's disease. The accurate diagnosis is, how- 
 ever, made without difficulty if the earlier stages of the disease 
 are carefully sought. 
 
 Syphilitic enlargement of the spleen and liver may be associated 
 with a moderate degree of anaemia. In such cases the symptoms of 
 splenic anaemia are reproduced with remarkable accuracy. The 
 differential diagnosis is achieved by a close study of the history, 
 by a discovery of a positive Wassermann reaction, and by a recog- 
 nition of the effects of antisyphilitic treatment. The latter, 
 however, is not always successful. W. J. Mayo records five cases* 
 in which he removed enlarged spleens in conditions of chronic 
 intractable syphilis with severe anaemia, when the patients had been 
 resistant to careful treatment for syphilis, carried out during a 
 period of several months. After removal of the spleen the anaemia 
 rapidly disappeared and the syphilis was cured with comparatively 
 mild antiluetic treatment such as had previously failed to affect 
 either the syphilitic condition or the spleen. Coupland records a 
 
 * Trans. Amer. Surg. Assoc. 1919, xxxvii, 483.
 
 90 THE SPLEEN AND ITS DISEASES 
 
 case in which the spleen was removed for 'splenic anaemia' with 
 much benefit ; the patient died two years later, and syphilitic 
 disease of the liver was found.* 
 
 Chronic obstruction of the splenic vein. Many years ago Dock 
 and Warthinf called attention to the occurrence of phlebitis and 
 calcification in the splenic vein, in cases in which the group of 
 symptoms and signs associated with splenic anaemia was present. 
 Other changes in the splenic vein in similar cases have been 
 recorded by various observers. These are summarized by 
 RollestonJ as follows : 
 
 The splenic vein may be : 
 
 1. Reduced to a fibrous cord. 
 
 2. Represented only by a plexus of veins, as in a case in 
 
 which haematemesis occurred at intervals of ten 
 months for twenty years. 
 
 3. Thrombosed as the result of extensive endophlebitis.|| 
 
 4. Occluded by an organized thrombus at its proximal 
 
 end.** 
 
 These various morbid changes may be different stages of the 
 same process, but the sequence of events may vary : thus endo- 
 phlebitis may undoubtedly cause thrombosis, and it is quite possible 
 that organization of a primary thrombosis may be followed by 
 endophlebitis and calcification. ff 
 
 In cases such as these the differential diagnosis is impossible. 
 The view that all cases of splenic anaemia are the result of changes 
 such as these in the splenic or portal vein cannot be sustained. 
 In some cases of splenectomy for splenic anaemia, it is true, these 
 changes may be found, in greater or less degree, and at times they 
 have been known to embarrass the operator by causing a difficulty 
 with the ligation of the pedicle, and troublesome haemorrhage. But 
 in the great majority of instances no such changes are discoverable, 
 though recently search has been carefully made for them. 
 
 " The influence of trauma in exciting phlebitis and thrombosis 
 
 * Brit. Med. Jour., 1896, i, 1445. 
 
 t Amer. Jour. Med. Sci., 1904, cxxvii, 24. J Practitioner, 1914, xcii, 479. 
 
 Langdon Brown, St. Barfs. Hosp. Rep., 1901, xxxvii, 155. 
 
 || Oettinger et Fiessinger, Rev. de Med., 1907, xxvii, 1109, etc. 
 ** Bland-Sutton, Proc. Roy. Soc. Med., 1913, vi, 239. 
 ff Thompson and Turnbull, Quart. Jour. Med., 1911, v, 291.
 
 SPLENIC ANAEMIA. BANTl'S DISEASE 91 
 
 in the splenic or portal vein must be remembered. Ledingham * 
 writes that " many cases which showed symptoms of splenic 
 anaemia or Banti's disease have presented a history of previous 
 severe abdominal injury, and that thrombosis of the portal vein, 
 with consequent splenomegaly, anaemia, and moderate cirrhosis of 
 the liver, has been proved on several occasions to follow injury ". 
 A recent case in my own experience confirms this association of 
 early and severe trauma with the symptom-complex of splenic 
 anaemia. 
 
 Moschowitz, in an admirable summary and discussion of the 
 subject of Banti's disease,f calls attention to the simulation of 
 this disease by cases in which there is persistence of the umbilical 
 vein. In recent years four such cases have been described in which 
 the clinical symptoms were closely similar to, or identical with, 
 those of Banti's syndrome. There was also a hypoplasia of the 
 liver attributed to persistence of the vein, which on post-mortem 
 examination was found enormously dilated in all cases, and com- 
 municated in some with the deep hypogastric or deep epigastric 
 veins. The unusual and excessive amount of blood carried in this 
 vein caused a damming back of blood in the splenic vein, which in 
 turn was responsible for the gigantic overgrowth of the spleen. 
 
 THE PATHOGENESIS OF BANTI'S DISEASE. The fact of utmost 
 significance in connection with the causation of this disease is that 
 it is cured or arrested by removal of the spleen. This fact may be 
 accounted for either by assuming that the disease is primarily and 
 essentially located in the spleen, or by assigning to the organ the 
 role of modifying the action of some agent situated elsewhere in 
 the body. 
 
 If the disease is primarily splenic, a search for a specific 
 microbic infecting agent should ultimately be successful. Hitherto 
 no convincing evidence of this has been found, although Hollins 
 has argued strongly in favour of incriminating the colon bacillus. 
 There is scope for further research in this direction ; and the organ 
 removed during life, if straightway examined, should provide 
 profitable material for routine bacteriological investigation. 
 
 The enlargement of the spleen has been attributed to excessive 
 
 * Allbutt's System of Medicine, v, 759. 
 
 t Jour. Amer. Med. Assoc., 1917, Ixix, 1045.
 
 92 THE SPLEEN AND ITS DISEASES 
 
 haemolytic activity by those who consider the disease to begin in 
 some other part of the body. But such a view does not sufficiently 
 explain the fibrosis which is the outstanding histological feature 
 of the disease. A chronic infective process would account for the 
 enlargement as well as the fibrosis, and accord better with the 
 absence of undue haemolysis of the red blood-cells. In splenic 
 anaemia the red cells never show 'fragility'. If there is a change, 
 the corpuscles may exhibit increased rather than diminished 
 resistance. 
 
 The anaemia, in like manner, may be regarded as an incident, 
 or as an essential part of the disease. Rolleston, a very dis- 
 tinguished authority, does not regard the anaemia as primary ; he 
 believes it to be secondary to attacks of very severe haemorrhage, 
 chiefly because he finds that regeneration of blood takes place after 
 these events. This view, however, is, I think, subject to the 
 criticism that such severe haemorrhage is not invariable, and that 
 the substance elaborated in the spleen need not be capable of 
 affecting the bone-marrow until after it has left the liver, where it 
 has undergone modification. Further, whatever the poisonous 
 substance may be, it need not completely arrest blood-cell develop- 
 ment. A parallel case is, I think, sometimes furnished by subjects 
 of leukaemia in which an intercurrent infection supervenes, with a 
 temporary restoration of the normal blood-picture. 
 
 Hollins regards the disease as being due to an active 
 'intoxication' produced by the colon bacillus, whose 'colilysin' 
 brings about the anaemia, whilst its actual presence in both spleen 
 and liver accounts for the fibrosis of each organ. This view would 
 put every kind of cirrhosis of the liver on the same level, because 
 'colilysins' could not be expected to vary radically in their action. 
 The facts would be better met were it suggested that the spleen 
 harbours various organisms, some of which only excite a local 
 fibrosis, others induce a simple cirrhosis of the liver, and still others 
 produce that form of cirrhosis associated with Banti's disease, 
 with a toxic anaemia and other specific symptoms. 
 
 In respect of the haemorrhage which is so conspicuous and 
 alarming a feature of some cases, Rolleston considers that the 
 enormously distended vasa brevia rupture into the stomach as a 
 result of the torsion of the splenic vein caused by the great bulk 
 of the organ. This opinion is certainly correct in many cases. 
 The haemorrhage is so profuse and so swiftly escapes from the
 
 SPLENIC ANAEMIA. BANTl'S DISEASE 95 
 
 stomach that large vessels must be implicated. Such vessels as 
 Rolleston describes are often seen in operations upon cases of 
 splenic anaemia when abundant haematemesis has occurred. But 
 this cannot, I think, be the whole explanation. The relationship 
 between enlargement of the spleen and gastric haemorrhage is 
 cryptic, but certain ; for, as Balfour was the first to show, removal 
 of the spleen may cure a patient whose life has been jeopardized 
 by severe and recurrent haemorrhages from the stomach. Gastric 
 haemorrhage is known to be toxic in origin in certain cases as, for 
 example, those in which there is a lesion in the appendix, intestine,, 
 or gall-bladder ; and those also in which the lesion lies in the spleen 
 or liver, or both. 
 
 TREATMENT. The only treatment for splenic anaemia is- 
 splenectomy. The appropriate moment for the removal of the 
 organ is chosen. It is inadvisable to operate soon after a grave 
 haemorrhage, or when the spleen is extremely large. In the latter 
 case the effect of radium on the tumour should be tried ; almost 
 certainly it will cause a rapid and considerable shrinkage in the 
 organ. If this should happily be the case, splenectomy is done 
 when the spleen is at its smallest, and before it has begun to enlarge 
 afresh, as it will certainly do after a few weeks. It is imperative 
 to operate upon cases of this disease as early as possible. No other 
 form of treatment needs consideration ; the dangers and difficulties 
 of the operation increase with the lapse of time ; early operation 
 means a more certain chance of recovery and a quicker con- 
 valescence. In the later stages the mortality of operation is 
 higher, amounting to 25 per cent as compared with an average of 
 about 10 per cent. In the terminal stages operation becomes 
 so dangerous that only the inevitably fatal outcome of the unhealed 
 disease justifies its performance. 
 
 The degree of improvement that may take place is astonishing, 
 even in the late stages of the disease with advanced involvement 
 of the liver. It is, as W. J. Mayo says, an evidence that the great 
 power of the liver to regenerate its specific cells is utilized to the 
 full. 
 
 The difficulties of the operation are greater in splenic anaemia 
 than in any other disease. In almost all cases adhesions binding 
 the organ especially to the under surface of the diaphragm are 
 present. They may be numerous and exceedingly dense, and
 
 *4 THE SPLEEN AND ITS DISEASES 
 
 their separation may cause a copious and grave hremorrhage. But 
 they are never so dense nor so strong as to prevent the completion 
 of the operation. The details of the operation in other respects 
 are the same here as elsewhere. At the Mayo clinic up to Sept. 20, 
 1920, 73 operations had been performed, with 9 deaths, equal to 
 12-3 per cent. The after-results are excellent ; the rather high 
 operative mortality is due to the technical difficulties of the late 
 eases, which, apart from operation, would all be fatal.
 
 PLATE VII 
 
 (Occasionally sclerosed) 
 SPLENIC 
 
 u 
 
 SPLEEN 
 
 Cceliac 
 Axis 
 
 AORTA 
 
 R 
 
 ^ i >X 
 
 \SCLEROSIS 
 
 1 OF k 
 PANCREAS 
 
 (Especially 
 round the 
 
 'ATROPHIC 
 ADRENAL 
 
 LIVER 
 
 Pigment- bearing cells 
 choke the sinusoids. 
 Pigment passes as 
 shown. 
 
 ~*^ ti | _ _ _ . _ L ^ 
 
 HEPATIC 
 Extensiue Fibrosis 
 
 Lymphocytes 
 
 Perisplenitis in 
 patches 
 
 Progressive enlargement 
 Fibrosis of pulp 
 Phagocytes containing pigment 
 Free pigment in the fibrous tissue 
 Splenic uein wide 
 
 Jnf. Mesenteric Vein 
 
 Gall Bladder 
 
 Calculi 
 INTESTINE 
 
 **j' '_' Iron particles 
 Biliary Cirrhosis 
 
 Bile 
 
 ;MJffipyr* Leucocytes 
 BONE MARROW lnct ' eased 
 
 THE CHIEF CHANGES IN H/EttOLYTIC JAUNDICE
 
 95 
 
 CHAPTER X. 
 
 H^MOLYTIC JAUNDICE. 
 
 (See Plate VII.} 
 
 IN his work, Diseases of the Liver, Murchison, a well of wisdom, 
 describes cases of chronic slight jaundice occurring in several mem- 
 bers of the same family : an association with splenic enlargement 
 is not mentioned. Cases of congenital jaundice and splenomegaly 
 occurring together were first recorded by Claude Wilson in 1890 
 and in 1893.* Hay em, in 1898, described five cases of icterusf 
 similar in character to these, though acquired and not congenital, 
 and presenting certain features in common. There were in all 
 a slight chronic jaundice, and normal stools and urine. The 
 absence of such conditions as pale stools, mahogany-coloured urine, 
 and tormenting itching of the skin was especially noted. The 
 spleen in all was large and hard, and the liver a little increased in 
 size. In all anaemia was present, the erythrocytes numbering 
 between one and three millions ; and in all there was a history of 
 acute exacerbations. In none was there any family history of 
 similar conditions ; in three the first appearance of jaundice 
 occurred in adult life. 
 
 In 1900 Minkowski described the occurrence of chronic 
 jaundice in eight members of one family, extending over three 
 generations ; in these the symptoms and signs were similar to 
 those described by Hayem, but in addition urobilin was noticed in 
 the urine ; there were pigment deposits in the kidney ; there was 
 enlargement of the spleen as the result of hypertrophy and vascular 
 engorgement ; there was no cirrhosis of the liver. 
 
 Two types of disease were thus recognized : the acquired form 
 of Hayem, and the congenital or familial form of Wilson and 
 Minkowski. The former type was more fully described, and its 
 clinical history and blood condition more critically examined, by 
 Widal. The latter type in respect of its haematology was especially 
 
 * Trans. Clin. Soc., 1890, 162, and 1893, 165. 
 f Bull, et Mem. Soc. Med. de Paris, xxv, 122.
 
 96 THE SPLEEN AND ITS DISEASES 
 
 studied by Chauffard, who first pointed out that the resistance of 
 the red blood-cells to hypotonic salt solutions was greatly 
 diminished. This increased 'fragility' constitutes the factor of 
 chief importance in the disease. Of the two, the acquired form 
 (the ' Hayem-Widal type') is the more serious, and apart from 
 surgical treatment appears to be inevitably fatal. 
 
 THE SYMPTOMS in the two types are very similar. There are 
 acholuric jaundice that is, jaundice with unaltered stools and 
 urine enlargement of the spleen, and anaemia. There is no 
 itching of the skin, and there is not that degree of rapid wasting so 
 often seen in cases of obstruction to the common duct. The blood 
 changes show a reduction in the number of red cells, an increased 
 number of reticulated cells, and a lessened resistance to hypotonic 
 salt solution. In two of the cases of the acquired type which I 
 have seen, the symptoms have very closely resembled those of 
 obstruction of the common duct by calculus. In both there were 
 exacerbations of jaundice preceded and accompanied by fever, and 
 by pain and tenderness in the epigastrium. In one of these my 
 diagnosis would certainly have been confidently given as 'cholan- 
 gitis due to calculus', but that a surgeon of great experience had 
 explored the duct and discovered no stone. The diagnosis may 
 be very difficult in cases in which gall-stones also are present. In 
 about 60 per cent of recorded cases stones have been found in the 
 gall-bladder or in the ducts at the time that operation for removal 
 of the spleen was undertaken. 
 
 These acute exacerbations during the otherwise tranquil course 
 of the disease were first described by Widal as ' crises of deglobuli- 
 zation'. They are acholuric crises, and are due, it is supposed, to 
 massive haemolytic activity, an activity which Eppinger estimates 
 as being competent to destroy the whole of the red blood-cells in 
 the body within a period of twenty-four hours, with the result of 
 throwing an immense strain upon all the organs of the body con- 
 cerned in blood production. In these crises there are great 
 malaise ; an elevation of temperature to 101 or 102 ; increase in 
 the size of the spleen, which may become very tender ; a deepening 
 in the tinge of jaundice ; acute anaemia, intense haemolysis with, 
 in the graver cases, a temporary haemoglobinaemia ; and urobilin 
 is found in the urine. More rarely the liver also is enlarged, and 
 the epigastrium is often tender. There is no itching of the skin,
 
 H^EMOLYTIC JAUNDICE 97 
 
 and there are no petechial haemorrhages. It will be seen how close 
 is the mimicry of the symptoms caused by a comparatively small 
 gall-stone floating in a comparatively wide common duct ; and 
 remembrance must always be given to the fact that in so large 
 a proportion of cases gall-stones, whether in the gall-bladder or in 
 the common duct, are found at operation. Probably the very 
 worst forms of crises are often, if not always, due to impaction of 
 calculi in the common duct, and the evidences of biliary obstruc- 
 tion in the urine and faeces may then be found. Elliott and 
 Kanavel,* in an admirable paper, say that in the crises " one 
 can always find evidence of excessive regeneration, i.e., polychro- 
 matophilia, nucleated red cells, and certain reticulated bodies 
 in the red cells stained by vital stains as first recorded by 
 Vaughan ". 
 
 The distinction between the congenital and acquired forms 
 is real. The congenital form is exceedingly chronic in its duration 
 and quiescent in its manifestations. Chauffard said of patients 
 suffering from this form, that they were " more jaundiced than ill ". 
 I have more than once been consulted by patients on account of 
 other diseases (loose cartilage in the knee, and carcinoma of the 
 breast) who were suffering from the congenital form of this disease ; 
 the jaundice was regarded with as little interest as the colour of 
 the hair. In the familial type of the disease several observers have 
 noted that the condition is of a graver type in the parent ; the 
 jaundice is deeper, the crises are severer and more frequent, and 
 complications are more prone to develop. Not a few of the 
 patients, affected though not afflicted by the disease, live their 
 days out in comfort, and die, at advanced ages perhaps, of maladies 
 unconnected with this condition. A few patients have lived to the 
 age of 80, and one at least to the age of 90. 
 
 The acquired form may begin abruptly, and run an eager rapid 
 course from the first. Anaemia quickly becomes profound, the red 
 cells falling to one million within a few weeks. The crises of pain, 
 temperature, and deepened jaundice are more frequent than in the 
 congenital type. In one direction the disease, whether congenital 
 or acquired (generally the latter), may wander away into the 
 neighbourhood of pernicious anaemia. Chauffard describes an 
 " icteric form of pernicious anaemia which, when accompanied by 
 
 * Surg. Gynecol. and Obst., 1915, xxi, 21.
 
 98 THE SPLEEN AND ITS DISEASES 
 
 diminished resistance and reticulated red cells, represents the 
 least compensated form of haemolytic icterus ". Weissenbach 
 records a case of this type also. 
 
 PATHOGENESIS. The older views that this disease is primarily 
 hepatic in origin are for ever set aside by our surgical experiences ; 
 for it is known beyond dispute that removal of the spleen 'cures' 
 the patient, who, if the operation has been done in stages earlier 
 than the terminal, remains entirely free from symptoms at all 
 subsequent periods. The spleen, if not the exclusive cause or 
 seat of the disease, exerts the profoundest influence upon its 
 pathogeny. 
 
 Several views as to the ultimate causation have been held. 
 Chauffard at first, and Widal later, believed the essential factor to 
 be a dystrophy, an increased fragility of the red cells. This view 
 is held by the great majority of those who have studied the question 
 in recent years. Other authorities, led by Minkowski, hold the 
 opinion that the primary change is an increased haemolytic activity, 
 probably restricted to the spleen. Widal, the most earnest sup- 
 porter of the former view, considers that the red cells which are 
 congenitally infirm are destroyed in the general circulation ; their 
 remnants are taken up by the spleen which undergoes enlarge- 
 ment, forming a tumour for which Ponfick introduced the term 
 ' spodogenous ' and also by the bone-marrow, kidney, and liver, all 
 of which are found on post-mortem examination to be deeply 
 pigmented. This opinion has lost ground since the many good 
 results following splenectomy have been witnessed, though, as I 
 shall mention, it does not appear from the very late examination 
 of Sir Spencer Wells's case that the dystrophy of the red cells is 
 always altered, even after many years of perfect health following 
 splenectomy. Consequently the altered character of the red cells 
 may be sometimes evidence of faulty manufacture, their lipoid 
 component being deficient, as I have already suggested. This does 
 not nullify the opinion that the spleen has much to say in the 
 subsequent treatment of such defective cells. In my own cases 
 fragility of the red cells disappeared soon after splenectomy, and 
 has not returned. The experience in Spencer Wells's case is, I 
 think, exceptional. 
 
 Minkowski's view is held by a few later writers, including Banti, 
 who consider that the spleen is not only enlarged as a consequence
 
 ILEMOLYTIC JAUNDICE 99 
 
 of the retention within it of cell remnants, but that within the 
 spleen cells are prepared for destruction and are there actively 
 destroyed. An examination of the spleens removed during life or 
 obtained at autopsy shows no specific change. The deep con- 
 gestion of the splenic pulp and of the sinusoids, constantly found, 
 is common to many other forms of splenic disease. Occasionally 
 biliary cirrhosis is found at autopsy. 
 
 TREATMENT. Treatment of this condition is by no means 
 always necessary. The symptoms may be very slight, or may 
 even be absent. If crises occur they may be so infrequent and so 
 speedily pass away that the patient, having suffered from them 
 for years, may pay no serious heed to them. In cases rather more 
 severe, general medical treatment and the use of radium therapy 
 have proved to be valueless. Where the symptoms are trouble- 
 some to the patient, and especially so in the acquired form, recourse 
 to operation should be had in as early a stage as possible. It is 
 better not to operate in, or near, a time of crisis, and if the spleen 
 is unduly large its size may be reduced temporarily by the applica- 
 tion of radium. Splenectomy has proved to be a specific in this 
 disease. Its dangers are slight : in Kanavel's collection of 48 
 cases there were 2 deaths ; in Mayo's series of 32 cases there was 
 1 death. And the results are excellent. Within a few days the 
 patient loses the tinge of jaundice entirely, all symptoms disappear, 
 and there is never any recurrence. No operation in surgery gives 
 such swift and striking results. It is very remarkable to witness 
 the change in a patient who has been jaundiced for years or from 
 birth ; the skin becomes clear and white, sometimes within forty- 
 eight hours. The first case submitted to operation was recorded 
 by Sir Spencer Wells.* The patient was a young unmarried lady, 
 age 22, who had an abdominal tumour " the size of a young child's 
 head ". The tumour was 'below the umbilicus, central, elastic, 
 but without fluctuation. Its movements were closely associated 
 with those of the uterus, and its lower border was felt behind and 
 to the left of the uterus. Sir Spencer Wells was doubtful as to the 
 precise seat and character of the tumour, but thought that it must 
 be either uterine or ovarian. The patient's very florid complexion 
 inclined him to the former view. Since the age of nine the patient 
 
 * Med. Chir. Trans., 1888, Ixxi, 255.
 
 100 THE SPLEEN AND ITS DISEASES 
 
 had been subject to frequent attacks of jaundice, and the mother 
 said the urine had " always been dark in colour ". The operation 
 was performed on Dec. 5, 1887, was followed by a good recovery, 
 and six weeks later the patient's medical man wrote : "I question 
 whether she has for many years past been six weeks without an 
 icteric tinge ". It is interesting to note that the patient was alive 
 and well in the year 1914, and Lord Dawson then reported* " that 
 the red cells still showed increased fragility ". Two. similar cases, 
 in which the symptoms have been completely relieved by splen- 
 ectomy but the increased fragility remains unchanged, are recorded 
 by Kahrf and Roth, but, as I have remarked, this experience is 
 probably unusual. The matter needs further inquiry. 
 
 The second case of haemoly tic jaundice to be treated surgically 
 was operated upon, in 1895, by Bland-Sutton ; the result was 
 excellent, and the patient was reported alive and well five years 
 later. Sir John Bland-Sutton tells me that he has not seen the 
 patient for five years, but that she was then quite well, and the 
 fragility of the red cells was normal. In my own cases the fragility, 
 tested two months and over after the operations, was normal. 
 There can therefore be no hesitation in advising operation in all 
 appropriate cases. 
 
 Giffini reports that the result of the examination of patients 
 in the Mayo clinic, by the method of Schneider, shows that the 
 quantity of the bile pigments found in the duodenum, always in 
 excess of the normal in this disease, steadily declines after removal 
 of the spleen. 
 
 In all operations the condition of other abdominal organs will 
 of course be examined as a part of the usual routine. The associa- 
 tion in so many cases of cholelithiasis, and of a greatly-thickened 
 bile, in stages earlier than those of calculous deposit, will involve 
 the removal or the drainage of the gall-bladder, and possibly an 
 exploration of the common bile-duct. No operation for haemo- 
 lytic jaundice is complete until the bile-passages have been 
 thoroughly explored. The removal of the appendix will be per- 
 formed in all cases in which the condition of the patient does not 
 prohibit the very slight additional manipulation. 
 
 * Proc. Roy. Soc. Med. (Clin. Sect.), 1914, vii, 86. 
 t Verh. d. deul. Kong. /. inn. Med., 1913, xxx, 326. 
 j Surg. Gynecol. and Obsl., 1917, xxv, 152.
 
 HJSMOLYTIC JAUNDICE 101 
 
 The results at the Mayo clinic up to Sept. 20, 1920, showed 32 
 cases with 1 death, a mortality of 3-2 per cent. Like all other 
 statistics of this clinic they represent the results obtained by a 
 group of men of the highest technical skill, working under con- 
 ditions unsurpassed elsewhere. They show the level which highly 
 organized surgical endeavours can attain, and are an example and 
 an encouragement to all.
 
 102 
 
 CHAPTER XL 
 
 GAUCHER S DISEASE. VON JAKSCH S DISEASE. 
 POLYCYTH.EMIA. 
 
 GAUCHER'S DISEASE. 
 
 OUR knowledge of Gaucher's disease has become much more 
 definite as a result of the work of F. S. Mandelbaum,* who has 
 shown its essential difference from Banti's disease. The following 
 are the salient clinical features : 
 
 The appearance of a greatly enlarged ('colossal') spleen in 
 childhood ; a chronic course without disturbance of the health 
 until late in the history of the case ; a family tendency ; and a 
 frequency seven times as great in girls as in boys. There is a 
 uniform discoloration of the skin of the face, neck, and hands, and 
 a wedge-shaped thickening of the conjunctiva on either side of the 
 cornea. There may be a tendency to bleeding from the nose, the 
 gums, or under the skin after slight injuries. Glands are not 
 enlarged. There is no jaundice, and no ascites. The liver is 
 much enlarged. The blood shows a diminution of the number 
 of white cells, but no anaemia until late in the disease ; the urine 
 contains urobilin but no bile. The disease generally begins 
 during childhood, before the twelfth year, and may last over a 
 quarter of a century. 
 
 Interest in the pathology of the disease centres round the 
 so-called 'Gaucher cell', which occurs in masses in the Malpighian 
 bodies and in the venous sinuses of the spleen, as well as in the 
 bone-marrow and in the sinusoids of the liver. The cells are very 
 large (at least five times the diameter of a red cell), and contain 
 usually from one to four nuclei. The protoplasm is streaked or 
 wrinkled, and can be traced into the reticulum, according to 
 Downey (1916). This observer concludes, after a very careful 
 study, that the cell is a modified reticular cell a view which 
 
 * Jour. Exper. Med. 1912, p. 697.
 
 PLATE VI 11 
 
 CceliacJ 
 >X 
 
 LIVER 
 
 
 
 SPLEEN 
 
 Blurring of Malpighian bodies 
 Sinuses conspicuous, walls fibrosed, 
 swollen endothelium, numerous red 
 & white cells. No phagocytosis 
 
 Inf. Mesenteric Vein 
 
 Sup. Me&enteric Vein 
 
 V^_" MEPATlC ARTERY 
 
 Hypertrophy of endothelium 
 
 Nucleated red cells 
 
 Myelocytes 
 
 Foamy degeneration 
 of liuer cell 
 
 -p-WlAIWin.1. - -" -- " 
 
 Inspissated bile 
 
 BONE MARROW 
 
 Gall 
 Bladder 
 
 ,Normoblasts 
 
 Myelocytes 
 
 THE CHIEF CHANGES IN VON 
 
 DISEASE
 
 VON JAKSCH'S DISEASE 103 
 
 is not essentially at variance with that which looks on it as a 
 modified endothelial cell. 
 
 As the disease progresses, cirrhosis of the liver develops, but 
 this produces clinical features which are different from those of 
 biliary cirrhosis and the cirrhosis of acholuric jaundice. The 
 difference lies chiefly in the absence of much disturbance of 
 health. 
 
 In biliary cirrhosis there are jaundice, fever, and leucocytosis. 
 In this form, where there is also leucocytosis, there are marked 
 changes in the state of the red blood-cells. It seems as if the 
 presence of the large endothelioid cells in the interstitial tissue of 
 the liver produces merely a passive deposition of fibrous material, 
 without the liberation of poisonous substances. But when the 
 fibrosis has advanced, the liver-cells undergo pressure atrophy, and 
 emaciation becomes a symptom. 
 
 VON JAKSCH'S DISEASE. 
 
 (ANAEMIA PSEUDOLEUK^EMIA INFANTUM.) 
 (See Plate VIII.) 
 
 The disease to which von Jaksch first drew attention was 
 considered by him to be a form of leukaemia occurring in infants. 
 The cases which he gathered together resembled each other chiefly 
 in the fact that the blood showed a very high degree of leuco- 
 cytosis. This feature came to be regarded as the chief criterion 
 of the diagnosis, and consequently confusion arose ; many various 
 conditions being classified as instances of this one disease. When 
 Hayem, and subsequently Luzet, directed attention to this disease 
 and came to analyze the material at their disposal, they found 
 that the important features were the presence of numerous 
 nucleated red cells in the blood, and the appearance of centres of 
 formation of red cells in the spleen and liver. 
 
 The discussion of the relation between this form of anaemia 
 and pernicious anaemia and leukaemia is almost a thing of the 
 past. No one, I think, regards von Jaksch's anaemia to-day as 
 a form of pernicious anaemia, and it is quite clear that it is not a 
 variant of leukaemia. 
 
 The salient features of the disease are : that the infant is 
 strikingly anaemic, and develops cedema, haemic murmurs, dilata- 
 tion of the heart, shortness of breath, and bleeding from the nose,
 
 104 THE SPLEEN AND ITS DISEASES 
 
 gums, and bowel. Examination shows the presence of a much 
 enlarged spleen, a moderately enlarged and flexible liver, and 
 possibly some enlarged glands. The pathologist finds a diminu- 
 tion of the red cells even to 2 million per c.mm., with a colour 
 index of 0-5 to 0-7. The white cells number from 20,000 to 
 100,000 per c.mm., and the differential count shows a decided 
 increase of the lymphocytes, with not a few myelocytes. Normo- 
 blasts are found in all cases ; megaloblasts are sometimes noted. 
 There is considerable variation in the size and shape of the red 
 cells. 
 
 It is especially noteworthy that this blood picture remains 
 constant over long periods of time. The outlook is not often 
 serious. After a chronic lingering course, recovery slowly takes 
 place. Arsenic sometimes brings about a rapid recovery. If 
 death occurs it is usually the result of pneumonia or some acute 
 infection. 
 
 W. K. Hunter* records ten cases which he describes as instances 
 of infantile splenic anaemia. He states that the two criteria of 
 diagnosis are : the presence of anaemia, and decided enlargement 
 of the spleen. The cases fall into three types : (1) That in which 
 there is a fall in the number of leucocytes, the lymphocytes pre- 
 ponderating ; (2) That in which there is a moderate leucocytosis 
 (up to 20,000 per cm.) and a few myelocytes appear in the 
 blood ; and (3) That in which there is a great increase of the 
 leucocytes. The last-named class conforms to the condition 
 generally known as von Jaksch's disease. 
 
 His diagnosis leads him to regard all forms as secondary to 
 other conditions lack of fresh air, lack of suitable food, presence 
 of syphilis, rickets, and previous infectious disease, notably 
 measles. 
 
 Both Naegelif and GrawitzJ have expressed this view very 
 clearly, showing that the disease is merely an unusual type of 
 secondary anaemia. It is because the blood-forming organs are 
 still unstable that the abnormal stimuli (rickets, gastro-enteritis, 
 syphilis) bring about the appearance of megaloblasts and myelo- 
 cytes in the blood, whereas in an older child the ' reversion to the 
 embryonic type ' would not be possible. The increased activity 
 of the blood-forming organs accounts for the enlargement of the 
 
 * Lancet, 1909, i, 230. f Text-book, 1908. J Text-book, 4th ed., 1911.
 
 PLATE IX 
 
 SPLEEN 
 
 Tendency 
 
 to 
 Haemorrhages 
 
 May be uery 
 painful. 
 
 Sometimes 
 Massive. 
 
 Very full 
 
 of Blood, v^ 
 
 Centres of 
 red & white 
 
 cell 
 formation. 
 
 Stroma not 
 changed. 
 
 Sometimes arteriosclerosis 
 Engorged Portal System 
 Blood; 7 - 10 mill, red cells 
 
 120-140 Hb. 
 
 12-20,000 white cells 
 
 Excessive 
 thropoiesis 
 
 THE CHIEF CHANGES IN POLYCYTH/EttIA VERA (VAQUEZ' DISEASE)
 
 PLATE II 
 
 -M Gastric 
 
 Malpighian Body 
 
 SPLEEN 
 
 Spleen pulp 
 
 HEPATIC ARTERY 
 
 . Inf. Mesen teric Vein 
 
 'Sup. Mesenteric Vein 
 
 ;' One liuer cell 
 BILE DUCT 
 
 LIVER 
 
 BONE MARROW 
 
 TO SHOW THE RELATIONS BETWEEN LIVER, SPLEEN, AND BONE AARROW
 
 POLYCYTELEMIA. VAQUEZ' DISEASE 105 
 
 spleen (a merely transient hypertrophy), of the liver (which resumes 
 its previous blood-forming activity) and the bone-marrow (which 
 is now very red and plentiful). If the lymphatic glands enlarge, 
 it is the result of the formation of myelocytes in them that is, of 
 the resumption of functions of blood formation. 
 
 Hunter has questioned whether the rachitic cases may not 
 owe their existence to the fact that the bone changes of the 
 epiphyses extend into the marrow. The whole bone is engorged. 
 In this case the increased activity of red-cell formation would be 
 the inevitable outcome of the congestion of all parts of the bones. 
 He found that the cases with leucocytosis were rachitic, those 
 without leucocytosis were not. The associated changes in other 
 parts of the body would be explained by the fact that rickets is a 
 general disease. 
 
 It is evident that the most satisfactory view of this disease is 
 that which regards it as a symptom of some other disorder. It is 
 accordingly desirable to remove it from the list of separate disorders 
 of the spleen, and its introduction here is merely for the purpose 
 of emphasizing this view. 
 
 POLYCYTHiEMIA. VAQUEZ' DISEASE. 
 
 (See Plate IX.) 
 
 A person is said to be suffering from polycythaemia when his 
 red-cell count has risen to 6 million per c.mm. and upwards. 
 Such a condition has been found to occur for short periods of time 
 in association with the profuse sweating, diarrhoea, or diuresis 
 which various diseases produce. It is characteristic of the new- 
 born child, and it appears in adults visiting tropical countries or 
 ascending high mountains. An increase in the number of red 
 cells which persists during a much longer time is also a feature of 
 congenital cyanosis due to malformations of the heart, and of some 
 cases of acquired heart disease in which there is marked cyanosis. 
 It is met with in cases of fibrosis of the lung, emphysema, and 
 similar conditions in which there is respiratory difficulty. Such 
 poisonous substances as arsenic, phosphorus, and haemolysins 
 associated with haemoglobinuria are capable of producing this 
 change in the blood. 
 
 Polycythsemia may occur also in the course of recognized 
 diseases of the spleen. Widal and Lefas noticed it to be present
 
 106 THE SPLEEN AND ITS DISEASES 
 
 in cases of primary tuberculosis of the spleen, and believed it 
 formed part of the syndrome. Rist, Kindberge and Parvu found 
 it in a case of hydatid cyst of the spleen, the blood-count returning 
 to the normal after excision. Schupfer noticed that a case of 
 Banti's disease developed polycythaemia after splenectomy, and 
 Renon and Richet observed a similar change in a case of hsemolytic 
 jaundice. 
 
 In addition to all these forms of polycythaemia there is the 
 true polycythaemia, the so-called polycythaemia vera, Vaquez' 
 disease, the 'malady of Vaquez-Osler ', which possesses certain 
 features that raise it into a clinical entity. It begins in adult 
 life, in males, and runs a progressive and fatal course lasting a 
 few years. 
 
 The skin becomes a deep purple colour, with dilated venules. 
 The spleen becomes greatly enlarged, though it never reaches the 
 size of some leukaemic spleens. The ordinary causes of cyanosis 
 are absent. There is a tendency to haemorrhage, but this is due to 
 the engorgement of all vessels, not to changes in coagulability. 
 
 The red-cell count is usually at least 7 million per c.mm. ; it 
 has reached 13 million (Aubertin) ; and it is always progressive. 
 The individual corpuscles are not altered in size. There is 
 generally a considerable increase of the leucocytes also, up to 
 15,000 or 20,000 a point which serves to distinguish these cases 
 from splenic anaemia. The haemoglobin rises concurrently with 
 the number of red cells, and estimations of the volume of blood 
 have shown that there is a definite increase of this (true plethora 
 of Parkes Weber). 
 
 The nature of the disease is not clear. Vaquez himself 
 believed it represented a functional over-activity of the haemo- 
 poietic organs. Menetrier and Aubertin, writing in 1906, placed 
 the disease in the group of myelomatoses, according to which there 
 is a tumour-like over-formation of red cells, as in leukaemia there 
 is a similar formation of white cells. French writers seem disposed 
 to accept this view, and therefore speak of 'myelogenic poly- 
 globulism'. An important objection would seem to lie in the 
 fact that in this case the red cells which are turned into the circu- 
 lation are quite normal, whereas in leukaemia the excess of cells 
 are all immature, and entirely abnormal. On the other hand, 
 cases are described (as ' subleukaemic erythraemia') in which 
 transitions to true leukaemia appear to develop.
 
 POLYCYTH^MIA. VAQUEZ' DISEASE 107 
 
 It is possible that the disease may not be due to direct stimu- 
 lation of the red-cell-forming tissues, but may be a collateral effect 
 of some deeper and more general disturbance of metabolism. 
 
 In consequence of the uncertainty as to the etiology, it is 
 only as a tentative measure that the spleen has been removed. 
 This was done in 1905 by Blad, with a fatal result. In 1907 it 
 was performed by Schneider without fatal result, but without 
 altering the state of the patient either way. Other forms of treat- 
 ment have been equally ineffective. The enlargement of the spleen 
 is in the nature of a work hypertrophy. It is the spleen which 
 keeps the disease in check ; removal of the organ is therefore 
 theoretically unsound and practically most dangerous, and should 
 never be performed. The warning is necessary, for I have had one 
 case of this disease submitted to me for splenectomy, the examina- 
 tion of a specimen of blood sent by post to a distinguished laboratory 
 worker having shown the characteristic count of splenic anaemia.
 
 108 
 
 CHAPTER XII. 
 DIFFERENTIAL DIAGNOSIS. 
 
 THE differential diagnosis of the several diseases I have now 
 described is often a matter of grave difficulty. The table which 
 follows, adapted from Krumbhaar, presents the points of similarity 
 and of difference in a form that can be quickly seen : 
 
 
 GAUCHER'S 
 DISEASE 
 
 SPLENIC 
 ANEMIA 
 
 ACQUIRED 
 H.SMOLYTIC 
 JAUNDICE 
 
 FAMILIAL 
 H.SMOLYTIO 
 JAUNDICE 
 
 PERNICIOUS 
 ANAEMIA 
 
 Etiology 
 
 Toxin T 
 Tumour ? 
 Tumour 7 
 
 Toxin T 
 
 1. Primary t 
 2. Secondary 
 to infection 
 
 Hereditary 
 
 Enterogenous 
 
 Pathology of 
 Spleen 
 
 Peculiar cell 
 hyperplasia 
 
 Hyperplasia. 
 Fibrosis 
 
 Congestion 
 and pigment- 
 ation 
 
 Congestion 
 and pigment- 
 ation 
 
 Fibrosis. 
 Toxin ? 
 
 Family 
 History 
 
 Occasionally 
 positive 
 
 Negative 
 
 Negative 
 
 Positive 
 
 Negative 
 
 Time of Onset 
 
 Childhood 
 
 Adult life 
 
 Any age 
 
 Congenital 
 or child- 
 hood 
 
 Adult life 
 
 Duration 
 
 Many years 
 
 Few years 
 
 Many years 
 
 Many years 
 
 Few years, 
 with remis- 
 sions 
 
 Icterus 
 
 Rare 
 
 Rare 
 
 Present 
 
 Present 
 
 Very rare 
 
 Splenomegaly 
 
 + + + 
 
 + 
 
 + + 
 
 + + 
 
 Slight or 
 diminished 
 
 Hcemorrhagea 
 
 Occasionally 
 
 Occasionally 
 
 Rare 
 
 None 
 
 Rare 
 
 Anaemia 
 
 Slight 
 
 Slight to severe 
 
 Severe 
 
 Slight 
 
 Severe 
 
 Resistance 
 of Red 
 Blood-cells 
 
 ? 
 
 Normal 
 
 Diminished 
 
 Diminished 
 
 Increased 
 
 Reticulated 
 Red Blood-cells 
 
 ? 
 
 Normal 
 
 Increased 
 
 Increased 
 
 Increased 
 
 Urobilinuria 
 
 ? 
 
 + 
 
 + 
 
 + 
 
 + 
 
 Leucocytes 
 \ in Blood 
 
 
 
 
 
 
 
 
 
 or + 
 
 Liver 
 
 + 
 
 First + 
 Later 
 
 + 
 or normal 
 
 + 
 
 Normal 
 
 Treatment 
 
 Splenectomy ? 
 
 Splenectomy 
 
 Splenectomy 
 
 Splenectomy 
 
 Iron, arsenic, 
 etc. (splen- 
 ectomy and 
 transfusion)
 
 109 
 
 CHAPTER XIII. 
 
 ON THE LIVER IN SOME OF ITS RELATIONS 
 TO THE SPLEEN. 
 
 THE diseases of the liver of special interest to the surgeon in 
 this connection are those in which 'cirrhosis' develops. 
 
 Clinical medicine recognizes two main forms of cirrhosis the 
 portal type first clearly described by Laennec, and the biliary type 
 to which the name of Hanot is often attached. Pathology recog- 
 nizes many forms of cirrhosis, which are named either according to 
 the distribution of the fibrous tissue in the liver, or according to 
 the supposed channel of infection. A study of the literature shows, 
 clearly enough that these different modes of classification have 
 always been a source of great confusion, escape from which is. 
 possible only by conceiving of a single disease which may affect 
 now this, now that, anatomical portion of the liver-tissue. The 
 real question at issue, therefore, comes to be : Is there any essential 
 difference between the two clinical types of cirrhosis ? If this 
 question can be answered negatively, it will be found that the 
 multiple classifications of pathology are needlessly complex and 
 may be disregarded. 
 
 In the preceding descriptions of the hepatic aspect of diseases 
 of the spleen, the anatomical basis (as represented in the diagrams) 
 consisted of a vascular channel and a single liver-cell with the 
 bile-duct issuing from it. The position of the various post-mortem 
 types of cirrhosis can be diagrammatically represented on this 
 scheme, it is true ; but it is necessary to modify the picture a little, 
 for the purpose of moving the central theme from the spleen to 
 the liver. Instead of regarding the changes which occur in a 
 single cell, a whole column of cells must now be depicted and con- 
 sidered, and the outflowing bile-channels may be regarded as 
 issuing from a few only of the components of the cell-columns. It 
 will be necessary also to introduce a part of the lymphatic system 
 as intervening (in the case of the ultimate radicles) between some- 
 part of the vascular walls and the corresponding hepatic cells.
 
 110 THE SPLEEN AND ITS DISEASES 
 
 In this way we are able to survey a scheme which is midway 
 between the purely diagrammatic form hitherto used, and the 
 histological appearances actually found in sections of the liver, 
 wherein the columns of cells occur in large numbers and radiate 
 from the centre to the periphery of innumerable hexagons, or 
 lobules. The advantage of concentrating attention upon a single 
 hepatic cell (the only satisfactory way of discussing the diseases 
 which affect the liver as a whole, and one adopted in the celebrated 
 hand-book of Castaigne and Chiray*) is now supplemented and 
 extended in order that the various strictly anatomical problems 
 of cirrhosis, which affects cell masses, may be discussed. It will 
 be realized that the clinical types necessarily overlap the histologi- 
 cal varieties. 
 
 The blood in the portal vein is usually described as passing 
 from the periphery of a lobule of the liver inwards to the centre of 
 the lobule, and thence into the radicles of the hepatic vein. In 
 its course, the blood bathes the columns of liver-cells, which are 
 commonly regarded as uniform in function. No discrimination in 
 the activity of the cells in respect of their relationship to one or 
 other of these veins is recognized. This method of description is 
 the result of the study of ordinary histological preparations in 
 which the vascular channels are quite conspicuous when the 
 healthy organ is examined, and the interlobular fibrous tissue is 
 conspicuous when the cirrhotic liver is investigated. 
 
 The bile-ducts, with the exception of the larger channels in the 
 * portal canals', are not made visible without arduous preparation. 
 The part played by them in disease is therefore learnt by deduction 
 rather than by observation ; indeed, but for the existence of the 
 bile-ducts and the gall-bladder, this aspect of the whole problem 
 might possibly escape scrutiny altogether. 
 
 A new scheme is here suggested for consideration in which a 
 single column of liver-cells may be regarded as forming a glandular 
 acinus, with a fundus and an outlet (Plate X). At the fundus the cells 
 are massed together ; they are sometimes several layers deep. At a 
 little distance from the fundus the origin of the bile canaliculus is 
 seen ; it runs downwards as a channel lined only by a single layer 
 of cells which gradually give place to the endothelial lining of the 
 efferent bile-duct. The bile-duct from the one acinus joins that of 
 
 * Maladies du Foie, Paris, 1910.
 
 LIVER IN RELATION TO SPLEEN 111 
 
 its neighbours, and the fused channels become progressively larger, 
 still situate in the so-called 'portal connective tissue', until they 
 are easily visible to the naked eye. 
 
 The portal blood first bathes that portion of the glandular 
 acinus in which the duct is formed, and then courses towards the 
 fundal end of the gland, where the blood-vessel containing it under- 
 goes a change of name, and becomes the 'hepatic vein'. What- 
 ever the physiological action may be that is accomplished in the 
 'portal' blood, it has therefore to be achieved within a short length 
 of vascular channel. The capillary suddenly becomes larger at the 
 fundal end of the gland, as several similar capillaries all meet at 
 this point ; the volume of blood to be carried away from that 
 moment becomes suddenly greatly augmented. An obstruction of 
 the flow from this larger channel is apt to make the capillaries 
 distend, especially around the fundal portion of the gland. In 
 order to produce a distention of the capillaries round the portion 
 of the gland acinus nearest to the portal vein, there must be an 
 excessive inflow of blood in that vein, not an obstruction to the 
 outflow from the hepatic vein. 
 
 If now we consider the gland loop itself more closely, we shall 
 find that the character of the cells is not the same throughout. 
 The fundal portion, as I have stated, is a solid cord or mass ; the 
 tubular portion consists of cells arranged round a lumen. The 
 tubular portion connected with the duct is excretory ; the fundal 
 portion is secretory. The flow of material from the cells is into the 
 bile-channel in the tubular portion of the loop, and is into the blood 
 in the fundal portion. In other words, the portion of the loop 
 which is first in contact with the portal blood separates out from 
 it the biliary constituents ; so, in consequence, a great accession 
 of pressure in the portal vein may influence the biliary portion of 
 the hepatic physiology and lead to the development of jaundice. 
 The portion of the loop last touched by portal blood (no doubt 
 already purified to a not inconsiderable extent) is concerned with 
 the foodstuffs brought in to the liver, and pours out into the blood 
 the 'internal' secretion of the liver. Stagnation of blood in this 
 part of the system means disturbance of this aspect of the liver 
 function in the first instance, and consequently does not entail any 
 icteric manifestations until the disease has so far progressed that 
 the biliary end of the gland-loop is implicated also. It is clear, 
 then, that the story of the function of the liver can be read
 
 112 THE SPLEEN AND ITS DISEASES 
 
 accurately and more easily if we discard the traditional conception 
 of liver 'lobules'. Instead of making the hepatic venule the pivot 
 of the anatomy, with cell-columns radiating from it, and directing 
 the attention to a blood-current converging as it were along the 
 spokes of a wheel, the present scheme makes the point of origin 
 and the direction of the secretions the centre of attention, the 
 liver-cells being grouped into acini exactly comparable to the acini 
 of any other racemose gland. 
 
 The reason for this will presently be obvious, in that the 
 unification of all the forms of cirrhosis into mere variants of one 
 single process thereby becomes possible. 
 
 So far the gland acinus has been regarded as a finished struc- 
 ture. In life, however, it is not stationary. It grows or it withers. 
 The growing point is in the solid portion of the acinus, the fundal 
 portion. When there is more food-supply the hepatic cells 
 multiply. They cannot do so where they abut upon the lumen 
 of the excretory duct, but easily grow in a direction away from the 
 excretory duct ; that is, in the fundal portion. Should there be 
 interference with the activity of some of the fundal cells, portions 
 of the column of cells around the duct tend to multiply, to form a 
 new fundus, and a new or 'regenerated bile-duct' then arises. 
 What was originally that part of the gland connected with the 
 duct now becomes the new solid column, the original column having 
 withered. Irregular slender double lines of cells which have been 
 'newly formed' come to lie amongst the connective tissue of the 
 portal canal, and form the new tubular portion of the gland acinus. 
 
 The blood-vessel and the secretory cell in most parts of the 
 body are separated by a lymphatic space. In the case of the liver 
 acinus the same arrangement is to be expected. As already 
 suggested, however, there is not a continuous lymphatic sheath to 
 the acinus, but the liver-cells are in direct contact with the blood 
 in some situations. To complete the diagrammatic scheme, there- 
 fore, it is necessary to picture a lymphatic sheath only between 
 the cells of that portion of the acinus in proximity to the duct, 
 no sheath being present over the fundal portion. Lymphatics thus 
 emerge in common with the bile-channels and the tributaries of 
 the portal vein. 
 
 The hepatic artery must also be considered, and a place for 
 this is found at the part of the liver acinus lying nearest to the 
 bile-duct. The arterial blood meets the venous blood in close
 
 LIVER IN RELATION TO SPLEEN 113 
 
 relation to the bile-secreting portion, not in relation to those fundal 
 cells which deal primarily with digestive products. The hepatic 
 artery supplies, not the liver-cells, but the network of biliary 
 channels in the liver. When the hepatic artery of a cirrhosed 
 liver is injected it is seen to supply the newly-formed fibrous tissue. 
 The branches into which the portal vein breaks up are with 
 difficulty distinguished, and may appear to be almost obliterated. 
 
 The fundamental components of the liver have now been 
 introduced and arranged into their appropriate positions. Hence 
 it becomes possible to discuss what cirrhosis is and how it is pro- 
 duced, our attention for the time being fixed upon these few micro- 
 scopic elements rather than upon the liver as a whole. 
 
 It has been found very easy to induce a cirrhosis experi- 
 mentally ; the mere ligature of the bile-channel always produces 
 this effect. The histological picture is that of a 'biliary' cirrhosis, 
 which has long been supposed to be the result of stagnation of bile 
 in the small ducts. The extensive recent experiments of Rous 
 and Larimore upon this subject appear to contribute all that can 
 bear upon this conception of biliary cirrhosis. These authors 
 found* that ligature of the main ducts in rabbits caused rapid 
 distention of the minute bile-channels, then pericholangitis, and 
 finally a stellate cirrhosis within three weeks. Death occurred in 
 five weeks. 
 
 When the ducts were ligated at a higher level, so as to involve 
 only one lobe of the liver, leaving a passage free for the bile from 
 the other lobe, it was found that the liver parenchyma of the 
 unligated side was capable of compensating completely for the 
 biliary inactivity of the mutilated lobe. In consequence, the 
 pathological changes in the liver were not nearly so marked, and 
 the cirrhosis which developed on the ligated side appeared much 
 more slowly than when the main duct was tied. 
 
 The other experiments by Rous and Larimore are best under- 
 stood after the preliminary explanation that the rabbit's liver con- 
 sists of two distinct portions, each provided not only with its own 
 duct, but also with its own distinct branch of the portal vein. If 
 the bile-duct of one lobe and the portal vein supplying the other 
 lobe were tied, it was found that very little change occurred in the 
 side with the ligated bile-duct. This shows that the liver-cells can 
 
 * Jour, of Exper. Med. 1920, July, 249. 
 
 8
 
 114 THE SPLEEN AND ITS DISEASES 
 
 continue to excrete even though they do not receive a direct blood- 
 supply. It also shows that the state of the portal circulation has 
 something to do with the vulnerability of the liver-cells to inter- 
 ference with their excretory channels. 
 
 The most drastic interference with the liver is exemplified by 
 their fifth experiment. In this case the one bile-duct was tied, 
 and after the animal had recovered the other bile-duct was also 
 tied, and the gall-bladder (which belongs to the larger portion of 
 liver) removed. The portal vein to the second (the main) lobe 
 was also tied, later. The result was that there was no outlet for 
 bile at all, and only one lobe the smaller was furnished with 
 blood. The changes produced were : swelling of the bile-channels 
 of the smaller lobe, with accumulation of bile between the liver- 
 cells ; the whole lobe became infiltrated with bile, and the liver- 
 cells finally died. But the main lobe of the liver did not become 
 jaundiced, and kept alive. The nutrition of the animal suffered 
 greatly, however. 
 
 The explanation of the various phenomena is supposed by 
 these authors to lie in the presence or absence of interference with 
 the portal circulation. Swelling of the bile-ducts interferes with 
 the flow of blood in the portal veins, and brings about a passive 
 congestion followed by 'an orderly atrophy' of the excretory cells. 
 This atrophy carries with it a steadily diminishing output of bile 
 until, when the last cell has disappeared, the last drop of bile has 
 been formed. Cirrhosis appears round the lobules, but does not 
 penetrate between the cell-cords. 
 
 It is believed that mere inspissation of the bile, as it occurred 
 in these experiments, exerts no ill effect on the liver. Nevertheless, 
 rabbit's bile is a powerful irritant to tissues. Therefore, when the 
 common duct is blocked, and the bile is dammed back so much that 
 it ruptures the finest channels for the liver-cells appear to continue 
 to secrete bile despite the ever-increasing pressure it sets up 
 parenchymal necroses, the so-called 'biliary infarcts and necroses'. 
 Cirrhosis begins, progresses, and finally occludes the blood-vessels 
 and interferes with the nutrition of the tissue to a still greater 
 degree. Consequently the injury to the liver is due not so much 
 to the bile, even in the rabbit, as it is to the mechanical inter- 
 ference with the vascular supply. 
 
 The type of cirrhosis is different according to the position of 
 the obstruction in the ducts (Plates XI, XII). When the finest
 
 PLATE XI 
 
 PORTAL CIRRHOSIS. 
 
 A low-power view showing the essential changes in ]>ortal cirrhosis 
 of the liver with splenomegaly. The amount of fibrous tissue between 
 the lobules is considerably increased, and there is some round-celled 
 infiltration especially in the immediate neighbourhood of the liver-cells.
 
 PLATE XII 
 
 *3& J iQ8^P%F&?Z, 
 
 &^$^C? 
 
 \&M*2* *& 
 
 BILIARY CIIMJHOSIS. 
 
 A low-power view of the liver in which the cirrhosis has extended 
 widely, causing the atrophy of the two lohules shoun in the middle of 
 the drawing. The cells show fatty degeneration. The con ne<-tive tissue 
 between them is coarsely fibrous. A collection of small round cells is seen 
 close to the_lar<*er lobule. The vessels in the portal tract at the foot 
 of the drawinu are sclerosed. 
 
 The numerous small fragments of tubules are regenerated bile-ducts. 
 This is a biliary cirrhosis of the tj pe occurring in haiinolytic jaundice.
 
 LIVER IN RELATION TO SPLEEN 115 
 
 canaliculi are obstructed, a diffuse intralobular cirrhosis develops ; 
 when larger ones are involved, the cirrhosis is of a pure mono- 
 lobular form ; when the largest channels are involved, stellate 
 lesions result. In all cases an obstruction to the hepatic veins 
 ultimately occurs, and the changes of chronic passive congestion 
 supervene, with the usual clinical phenomena aroused by such a 
 condition. 
 
 The work of these two investigators indicates that the problem 
 of cirrhosis is rather one of vascular supply than of biliary outflow. 
 They conclude that the character of the bile does not play a notable 
 part in the production of cirrhosis ; that stagnation of bile is 
 secondary to changes in the liver-cells ; and that infection of the 
 stagnated bile an event very prone to occur is the last step in 
 the history of biliary cirrhosis. In other words, biliary cirrhosis 
 develops in increasing amount during the progress of the following 
 four steps : first an interference with vascular supply ; then 
 derangement of function of liver cells ; then modification of the 
 character of the bile ; and finally infection of the bile. 
 
 These conclusions bring the portal and biliary types of cirrhosis 
 together, and do not exclude the type associated with passive 
 congestion due to cardiac disease. In this respect they accord 
 with the views expressed by W. J. Mayo*, whose studies have led 
 him to believe that there is no essential difference between the 
 Laennec type and the biliary type of cirrhosis. In the case of the 
 former, however, he places much weight on the importance of the 
 circulatory disturbances ; in the Hanot type, on infectious agents. 
 The associated enlargement of the spleen may be mechanical in 
 the one, by introducing circulatory distress to an organ already 
 hampered by stagnant blood; and causative in the other, by 
 harbouring micro-organisms which are passed on to the liver. In 
 either case the response by the liver is in the form of cirrhosis. 
 Its anatomical form is simply the outcome of a combination of 
 the two factors in varying proportions. The more extensive the 
 infection, the more mixed the type of cirrhosis. 
 
 The view that the source of biliary cirrhosis is an infection 
 ascending the bile-ducts is supported by Rosenow's observation! 
 that streptococci occur, not in the bile, but in the walls of the gall- 
 
 * Jour. Amer. Med. Assoc. 1918, May, Ixx, 1361. 
 t Jour, of Infect. Dis. 1916, 19, 527.
 
 116 THE SPLEEN AND ITS DISEASES 
 
 bladder and larger ducts. It is also supported by the fact that the 
 glands near the pelvis of the gall-bladder and the cystic duct are 
 enlarged, because they drain the lymphatic spaces in the sub- 
 stance of the wall of the gall-bladder. Further support is afforded 
 by the observation that the pancreatic ducts may become exces- 
 sively sclerosed in these cases, for the infective agent would be 
 liable to travel up the pancreatic ducts as much as the biliary 
 passages*. McCarty and Corkery* report a series of histological 
 changes in the gall-bladder wall, found in 4998 gall-bladder speci- 
 mens, which might be held to show equally either that the process 
 is a descending one, infected bile passing into the bladder from the 
 liver, or that infection is due to the ascent of organisms from the 
 intestine. Lyon,f experimenting with an Einhorn tube in order to 
 study the duodenal contents and the character of the bile from the 
 common duct as distinct from that in the gall-bladder, concluded 
 that the latter is germ-free, whereas the former is liable to contain 
 streptococci. 
 
 The hypothesis that the source of infection of the bile-passages 
 is in the spleen, whereby both portal and biliary cirrhosis are 
 regarded as different forms of the same process, has been especially 
 mentioned by Mayo.J The mechanism by which cholangitis and 
 cholecystitis are produced necessarily implies a descending infection 
 in such cases ; the organisms carried by the blood-stream pass 
 through the excretory epithelium of the liver acinus. 
 
 It would almost seem, then, as if the question of biliary 
 cirrhosis centres in the process of bile-secretion. That this is not 
 really so is shown by a consideration of haemolytic jaundice, where 
 the liver is as greatly enlarged as it is in biliary or * hypertrophie 
 cirrhosis'. In each case there is a development of 'new bile-ducts', 
 which is another way of expressing the statement that the secretory 
 tissue of the liver is hypertrophying. As Mayo points out (loc. 
 cit.), the enormous amount of blood destruction compels the liver 
 to dispose of a much greater quantity of bile constituents than the 
 organ can deal with in the ordinary manner. There is therefore a 
 'work hypertrophy', without any increase of fibrous tissue neces- 
 sarily appearing. On the other hand, the spleen being a strainer 
 for typhoid bacilli, for protozoa, and other organisms, which 
 
 * Amer. Jour. Med. Sci. 1920, i, 646. f lbid - 1920 > ' 509 - 
 
 % Jour. Amer. Med. Assoc. 1918, May, xi, 70, 1361.
 
 LIVER IN RELATION TO SPLEEN 117 
 
 ultimately pass on to the liver, disease of the spleen of this kind 
 obliges the liver to dispose of the poisons brought to it by the 
 portal blood. Whatever the liver-cells cannot absorb and eliminate 
 accumulates in the pericellular spaces, and evokes the deposition 
 of fibrous tissue in this situation. 
 
 As has been shown, in haemolytic jaundice the poisonous sub- 
 stances may pass through the liver-cell satisfactorily and yet 
 irritate the bile-channels and apparently be absorbed by the lining 
 epithelium, and thence pass into the connective tissue of the portal 
 canals and excite fibrosis of the biliary type. 
 
 It is in this supposition that the basis of splenectomy as an 
 appropriate treatment for cirrhosis lies. Evidently the experi- 
 mental work already detailed does not furnish a clue to the cause 
 of the circulatory changes which are regarded there as initiating 
 the whole process of cirrhosis. 
 
 An important feature brought out by the schema remains to 
 be considered. It will be noticed that the fundal portion of the 
 hepatic loop is a solid column of cells, and it has been stated that 
 the cells of this portion are concerned with the secretion of food 
 material into the blood. The portal blood, bringing carbohydrates, 
 proteins, fats, and toxic substances from the intestine (and 
 probably colon bacilli), is caused to linger round the fundal por- 
 tions of the glandular loops owing to the narrowing of the channels 
 towards the centres of the lobules, and also, no doubt, on account 
 of the junction of several currents in the sublobular vein. The 
 splenic blood is therefore of greater interest to the tubular portions 
 of the acini, while the intestinal component of the portal blood is 
 sought after by the solid fundal portions. This conception enables 
 the nutritional factor in cirrhosis of the liver to receive its due 
 and proper place in the consideration of this subject. Interference 
 with the vascular supply within the liver will cause more serious 
 disturbance of health when the fundal cells begin to atrophy ; and 
 such a change is evidently not likely to occur till a late stage. 
 These cells are spared in virtue of their position, because the dis- 
 tention of the portal vessels begins, as far as the liver acinus is 
 concerned, at the tubular portion, and the fundal cells are left 
 undisturbed both in the discharge of their nutritive functions and 
 in their powers of reproduction. As cirrhosis extends, the tubular 
 portions atrophy, and the fundal portions are stimulated to 
 regenerate and consequently bring about the appearance of
 
 118 THE SPLEEN AND ITS DISEASES 
 
 increasing numbers of tortuous slender 'bile-ducts' amongst the 
 fibrous tissue. 
 
 This sharp demarcation between solid and tubular portions of 
 a liver acinus is of course largely descriptive, being introduced in 
 order to clarify the conceptions concerning a subject which is 
 admittedly intricate. It does not follow that some cells secrete no 
 bile, and that others pour out no glycogen or urea into the blood- 
 stream, although it is not necessarily true that every cell does all 
 this work. On the other hand, this kind of demarcation is met 
 with in salivary glands, in the pancreas, and in other glandular 
 structures, and accounts for the multiplicity of functions which 
 evidently belongs to such organs. The advantage of such a con- 
 ception is not confined to its provision of an easy explanation of 
 the phenomena of cirrhosis, but helps to bring out a fact of very 
 great importance namely, that the amount of active tissue of 
 the liver is constantly varying, even during a single day. Where 
 there is a great afflux of portal blood, as after a meal, the increased 
 volume is naturally due to the amount of blood in the viscus. But 
 the presence of an increased amount of food also causes a hyper- 
 trophy of the secreting tissue. In the schema which has been used 
 as the basis of this account of the liver, the fundal portion of the 
 acinus may be regarded as variable in size and in the number of 
 its constituent cells. Increase of the size of the cells is frequently 
 noticed in post-mortem material, and many changes which are 
 regarded as pathological are now being recognized as indicating 
 only transient variations of a purely physiological activity. In 
 the early stages of hypertrophic cirrhosis, where the liver-cells are 
 excessively active, there is room for difference of opinion as to 
 whether the microscopic characters are to be regarded as intrinsi- 
 cally morbid or not. 
 
 If we translate the term 'fundal cells' into 'the portion of the 
 liver cells concerned with the absorption of food material and with 
 the output of glucose and urea', the description of the nature of the 
 liver tissue would be more accurate without being so easy to grasp. 
 It may confidently be hoped that some of the difficulties in the 
 subject of cirrhosis will be removed by a careful study of the dis- 
 position of the parts furnished by this simple schema. When 
 read in conjunction with the abridged representation which occurs 
 in the diagrams of the spleen, the part played by diseases of that 
 organ in inducing cirrhosis of the liver will become increasingly
 
 PLATE XIII 
 
 SUP. VENA CAVA 
 
 CAPUT 
 
 -VASA BREVIA 
 -PANCREATIC 
 
 INF, VENA CAVA 
 
 INT. ILIAC 
 
 CIRCUMFLE 
 
 To SHOW THK AxAsroMoTir CUNNKCTIONS BKTWKKX TDK VOIIT.U/ (HIIKKX) .\xi> THK SVSTKMK: (IJLUK) VEIXS 
 
 Al'l'KAKINt; IX CASKS OF POKTAL OBSTISl'i TluN
 
 LIVER IN RELATION TO SPLEEN 119 
 
 clear, and make the contention increasingly reasonable that 
 surgical interference might do something to give effective relief to 
 diseases hitherto regarded as only within the scope of expectant 
 therapy. 
 
 The two types of cirrhosis, which are now seen to be patho- 
 logical variants of a single type, are clinically distinguished as 
 portal and biliary. They depend upon the development within 
 certain parts of the liver of connective tissue laid down in de- 
 fensive response to irritation. 
 
 Portal cirrhosis results from the admission to the portal vein 
 through one of its tributaries of substances capable of causing 
 irritation. Clinically the condition is recognized by a change in 
 the size of the liver, by a tendency to haemorrhages, and by other 
 changes due to obstruction in a vascular system devoid of valves 
 (Plate XIII), by ascites in the later stages, and rarely by jaundice. 
 The disease is not seldom latent, for examples of it are occasionally 
 found on the operation table when no disturbance of health has 
 resulted. If death occurs from the disease it is due to circulatory 
 changes. 
 
 Biliary cirrhosis results from infection, which may be ascending 
 or descending, gaining access, that is, either by the splenic vein or 
 by the common bile-duct. Clinically it is recognized by an enlarge- 
 ment of the liver, by jaundice, which is the predominant feature, 
 and very rarely, and only finally, by ascites. If death occurs it 
 is due to toxaemia caused by jaundice. 
 
 Portal cirrhosis is often associated with the name of Laennec. 
 The disease was well known before his time, but the application 
 by him of the distinctive name 'cirrhosis' to the disease gave it 
 prominence, and led to its closer investigation. Laennec chose 
 the name because of the yellow (ppde) colour of the granular 
 tissue of the liver. He believed that the coloured masses were 
 neoplastic ; they are, of course, portions of the liver substance 
 enclosed by new-formed connective tissue. Biliary cirrhosis has 
 been confused with other diseases, notably with haemolytic jaundice. 
 In Hanot's description we cannot recognize a specific type of 
 disease separable from other types. The title of the thesis, pub- 
 lished in 1875, in which he first described the disease, is " A Form 
 of Hypertrophic Cirrhosis with Chronic Jaundice ", and he asserted 
 his intention to be to describe " a variety of hypertrophic cirrhosis, 
 meaning by this an hepatic affection which had only distant
 
 120 THE SPLEEN AND ITS DISEASES 
 
 relationships with Laennec's cirrhosis ". As Castaigne defines it, 
 " this disease is one in which the patients are markedly jaundiced, 
 but have no acholic stools, whose liver and spleen are hyper- 
 trophied, but without ascites or development of a vicarious venous 
 circulation, or even any urinary evidence of hepatic insufficiency ". 
 Such a group of symptoms do not constitute the indications of a 
 separate and distinct disease. They are merely symptoms com- 
 mon to several disorders, hsemolytic jaundice, biliary cirrhosis, or 
 some cases of cholelithiasis. 
 
 This is also the opinion of W. J. Mayo, who says, " This type 
 of cirrhosis has no pathologic basis, and little clinical evidence to 
 support its existence. The large majority of cases that have 
 taken the term Hanot's cirrhosis are either haemolytic icterus, 
 or the ordinary type of biliary cirrhosis ". The mistake can be 
 condoned when we remember the frequent association of gall- 
 stones with haemolytic jaundice. If the term Hanot's disease is 
 to be retained, it would be best to range it as a synonym for biliary 
 cirrhosis. 
 
 In both forms of cirrhosis the spleen may be enlarged. The 
 frequency of the association has been very variously estimated. 
 Frerichs and Lange assert that it is found in one-half of the cases ; 
 Bamberger in nine-tenths of them. No estimate is reliable unless 
 it is based upon post-mortem evidence, for, as I have said, the 
 spleen cannot be palpated until it is more than double its normal 
 size. If the enlargement of the spleen were due merely to portal 
 obstruction it would be similar in all its details to that form which 
 follows upon cardiac disease ; yet it is well known that there is a 
 great difference. In portal cirrhosis of the liver, according to 
 Quincke and Hoppe-Seyler*, swelling of the spleen appears very 
 early, before other symptoms of stasis, and a hyperplastic con- 
 dition of the pulp followed by a connective-tissue increase is noted. 
 It would appear, therefore, that active processes occur also in the 
 spleen, and vary with the primary cause of the disease. 
 
 If the original source of disease in a case of * biliary cirrhosis ' 
 has ascended along the bile-passages, the nature of the infecting 
 organism may have an important word to say in regard to the 
 exact clinical and anatomical form of the cirrhosis produced. 
 Should streptococci or other haemolysin-secreting organisms be 
 
 * NothnagePs Encyclopedia, 702.
 
 LIVER IN RELATION TO SPLEEN 121 
 
 the active agents, it is likely that the blood will become changed 
 as it passes the foci in which the substances are made. The spleen 
 will then be set into increased activity, and the cycle of phenomena 
 associated with a primary disorder of the spleen would be super- 
 added to the existing clinical picture. Transition or mixed forms 
 which are not typical examples of haemolytic jaundice would then 
 occur. 
 
 It would appear to be exceedingly probable that forms of 
 biliary cirrhosis due both to ascending and to descending infections 
 come under the care of the surgeon dealing with cases of gall- 
 stones. It is a common experience in cases of cholelithiasis with 
 a, typical early history ending in an obstruction of the common 
 duct by stone, to find the duct grossly dilated, and the gall-bladder 
 thick and shrunken by cicatricial tissue. When such a duct is 
 opened, many large stones, and much thick and perhaps offensive 
 mud, are emptied away. A stone or stones may be found also in the 
 common hepatic duct, whose walls also are thickened. But beyond 
 this stones are not often found ; when the hepatic duct is cleared 
 by gauze strips the bile flows freely, and is generally almost or 
 quite clear. The duct being drained, the patient recovers easily 
 and normally. There are also cases of a different type in which 
 jaundice has been a precocious and almost constant symptom 
 from the earliest recognizable onset of the disease. Operations 
 upon them disclose the presence of stones in the common duct, in 
 the common hepatic duct, in the right and left hepatic ducts, and 
 in their branches within the liver. The higher one goes the smaller 
 are the stones, and the stones are always polished, smooth, and 
 well made. There is little or none of the mud seen in the other 
 type. No matter how careful one may be in extracting stones, 
 the end of them seems never to be reached. Small shiny pebbles 
 and beads still keep coming down into the operative field, and 
 are discharged through the tube which is left in the duct at the 
 completion of the operation. It appears to me very possible that 
 the former type is associated with a biliary cirrhosis due to an 
 ascending infection, and that the latter is due to a descending 
 infection. In the former, stones form first in the gall-bladder, 
 escape into the common duct, and thence migrate upwards into 
 the hepatic ducts. Stagnation and infection there may lead to a 
 further deposit of calculi. In the latter type tiny calculi are 
 formed in the finest ducts, and migrate downwards to the larger
 
 122 THE SPLEEN AND ITS DISEASES 
 
 and still larger ducts. The affected lobe of the liver is filled with 
 tiny stones in the minute ducts and with larger stones in the larger 
 ducts. The condition is incurable by operation, and 'recurrence' 
 will always take place, no matter how carefully the ducts are 
 cleared. Biliary abscess is often the terminal stage in each 
 condition. 
 
 The surgical treatment of cirrhosis of the liver is concerned 
 with two problems : (1) The diminution of the vascular burden 
 carried by the liver ; (2) The destruction, or the diversion from 
 the direct path to the liver, of the poisons carried to this organ 
 from the spleen. 
 
 1. The diminution of the vascular burden of the liver may be 
 effected : 
 
 a. By the creation of new channels of anastomosis between 
 the portal and systemic circulation. Many such channels exist 
 normally, communicating on the one hand with the portal system 
 and on the other with the inferior vena cava (see Plate XIII}. But 
 new vessels can be created by causing adhesions to form between 
 the liver and diaphragm, or between the omentum and the anterior 
 abdominal wall. The first operation intended to secure this result was 
 performed in 1889 by von der Meule ; the patient died shortly after 
 it. Talma also suggested this operation and practised it. The 
 first successful case was performed by Rutherford Morison at the 
 suggestion of Drummond, who had also conceived it independently, 
 in 1895. The method is one that has been widely adopted : at 
 times with much success, at times with disappointment. I have 
 performed the operation on seven occasions : one result has been 
 perfect, the patient living seven years and having no further 
 trouble referable to the cirrhotic liver or from ascites ; one patient 
 was decidedly improved, and required only two tappings of the 
 abdomen in the first twelve months ; the remaining cases were 
 not appreciably benefited by the operation. In one case nervous 
 phenomena, the result probably of auto-intoxication, were observed ; 
 they have been recorded by Morison as occurring in the third 
 patient upon whom he operated. 
 
 The direct anastomosis of the portal vein to the inferior vena 
 cava, by the establishment of ' Eck's fistula ', has very rarely been 
 practised upon the human being, and will never enjoy the approval 
 of surgeons. 
 
 b. By the obliteration of tributaries of the portal vein, which
 
 LIVER IN RELATION TO SPLEEN 123 
 
 will compel the formation of new anastomoses, or the dilatation 
 of normal ones, between the portal and systemic circulation. For 
 example, the inferior mesenteric vein may be ligatured, or the 
 spleen may be removed. 
 
 2. The purpose of splenectomy in cases of cirrhosis of the 
 liver may therefore be either the relief of the vascular turgescence 
 of the liver, or the removal of the poisons sent direct to the liver. 
 The proportion of the portal blood derived from the spleen is usually 
 assessed at about one-seventh of the total volume ; but if the 
 spleen is grossly enlarged it is likely that the quantity of blood 
 passed through the splenic vein will equal that of all the other 
 portal tributaries. When this vast quantity of blood is turned 
 aside from the liver, the relief to the hepatic cells must be very 
 considerable : these will be given full opportunity for that capacity 
 for repair which they possess to so remarkable a degree. 
 
 Ligature of the splenic artery has been adopted rather than 
 splenectomy in a few cases. Consequent upon it there is an 
 atrophy not necrosis of the spleen. The operation was first 
 suggested by J. Gerster, and cases are related by Hartmann and 
 others. The mortality has been large.
 
 124 
 
 CHAPTER XIV. 
 CONCLUSION. 
 
 It is evident that a consideration of the whole subject of 
 diseases of the spleen must take a very wide view. A number of 
 symptoms may direct attention to the spleen, even when clinical 
 examination does not reveal the presence of splenomegaly. It is 
 through the correct insight into the significance of the clinical 
 symptoms and other morbid phenomena that the real understanding 
 of any supposed case of splenic disease becomes possible. Instead 
 of searching only for the existence of this or that splenic disease, 
 an inquiry should be directed to the determination of the functional 
 capacity of all the various organs likely to be deranged. The 
 symptoms already referred to may be looked upon as evidence of 
 some disorder in the particular systems here considered. This 
 derangement must be regarded not merely as a restriction of the 
 morbid changes to the spleen, but as a disturbance of wide ramifi- 
 cation throughout the whole body, affecting one or other, or 
 perhaps even all, of the four systems in which the spleen plays a 
 part. The focus, at the moment, may in truth be in the pulp of 
 the spleen ; but even so, the general picture presented by the 
 patient is the outcome of the participation of the other systems 
 in the process which started in the spleen. It may be that 
 splenectomy in any of these diseases will remove the obvious 
 culmination of the morbid process, and thus bring about a 'cure' 
 of the disease or an arrest of its development ; but it does not by 
 any means follow that all the other related parts are thereby 
 caused to return to their normal states. Absence of symptoms 
 does not imply the restitution of normal functions. The case of 
 Sir Spencer Wells and Lord Dawson (see p. 99) discloses this truth 
 unequivocally. In this case fragility of the red cells was found 
 twenty-seven years after the removal of the spleen for haemolytic 
 jaundice. 
 
 A further step in the investigation of the clinical condition 
 of the patient should aim at the exact discovery of the site of the 
 lesion in certain particular cell-types : (a) In the spleen-pulp ;
 
 CONCLUSION 125 
 
 (b) In the bone-marrow and in any part where reticulo-endothelial 
 cells may exist in specially congregated or active masses ; (c) In 
 the liver ; (d) In the endocrine organs, including the pancreas- 
 This lesion being predicted, or recognized, the question will arise 
 as to whether it consists in, or entails, the elaboration of poisons 
 capable of causing haemolysis, cirrhosis, or asthenia. 
 
 The tissue affected, and the changes therein resulting, being 
 recognized, further research must be directed to the discovery of 
 the type of infective agent at work, whether bacillary, spirochaetal,. 
 or other. In other words, the patient is no longer to be regarded 
 merely as the victim of some type of 'disease', but as the victim 
 of disorders of a certain character in certain parts of certain 
 anatomical or functional systems of the body. It is the form of 
 the disorder, the form of distribution (determined by an assessment 
 of the functional capacity of the several organs concerned or likely 
 to be concerned), which, when correctly studied, will inevitably 
 lead to the source and cause of the morbid state, and ultimately 
 to the prospect of the 'cure ' of the patient.
 
 126 
 
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