^^ ,-^% ■f,-r tr , f^;^l^e.^< U-^'-X-r'^ -t^- CASE OF PROGRESSIVE PERNICIO JS ANEMIA clijsical report, BY JOHN BELL, A.M., M.D. PATHOLOGICAL REPORT, WITH REMARKS, BY WILLIAM OSLER, M.D., Professor of the Iiiatitmes of Mediciue, McGill University. leontraeU FKLNTKD BY LOVELL PillNTLVG AND PUBLISHING CO. 1877. CASE OF PROGRESSIVE PERNICIOUS ANEMIA. CLINICAL REPOHT, BY JOHN BELL, A.M., M.D. PATHOLOGICAL REPORT, WITH REMARKS, BY WILLIAM OSLEE, M.D., Professor of the Institutes of Medicine, McGill Univer«ity. fRonttati I PRINTED BY LOYELL PRINTING AND PUBLISHING CO. 1877. CX^K i)V I'ia)UliKSS[VK TKILNICIOLKS AN.KMIA. CLINICAL REPORT. BY JLHiN CELL, A.M., M.D., FATliOLOGICAL REPORT, WITH RE.MAIIK.S BY WILLIAM OSLER, M.D. rroll'ssor oi'tlio Institutes of Aledicinc, McGill I'nivorsity. J. l>.,:i^^'e(l 17, a native of Loicesstcr, England, a rubber weaver by trade, and a resident in tills country since 1S5T, came under my care in 1S75, sullering from wcakr'.ess and loss of appetite, whicJi s^'mptoms, with a})j>rupriatc treatment and dieting, disap- From the Transactions of the Canada Medical Association, 1877. tiie first ten years of residence in this country lie farmed, follow- ing at the same time the occupation of a shoemaker. Subsequently he came to Montreal, and for eight months was a conductor on the street Railwa}-, during which period lie enjoyed excellent healtii. For tlic rest of his life lie served as a felt cutter for overshoes in the Canada Ilubber factory. His general health had always been o'ood. About three years ago tlic purciiase of a piece of property some distance out of town, and the anxiety conse([uent upon making the necessary payments, caused considerable mental worry, and he suffered at the time from general debility. About the same time two of his children had a mild form of ty[)iioid fever. The chief symptoms he complains of arc excessive weakness and indisposition to exertion, together with loss of appetite. The skin is blanched ; mucous membranes pale, sclerotics pearly, and he sull\)rs from palpitation and shortness of breath on exertion. On physical examination the organs are apparently healthy ; heart sounds natural ; liver and spleen not enlarged ; no enlarge- ment of external lymphatics. No increase in the colourless blood CASK UF I'UOUUKSSIVE PKILX ICIOUS AN.KxMlA. ULIXICAL REPORT. I BY I JOHN BELL, A.M., M.D., j PATHOLOGICAL REPORT, WITH REMARKS I 'BY j WILLIAM OSLER, M.D. i I'roibssor of the Institutes of Medicine. McGill IJnivemty. j J. ]>.,a<^e(l 17, a native of Leicester, England, a rubher weaver j by trade, aiul a resident in tiiis country since 1857, came under I ray caro in 1875, suilering fi-om weakness and loss of api)etite, whicli synii>toms, with appropriate treatment and dieting, disap- peared. In May, 187(>, they recurred, and persisted more or less I throughout the year. In February of present yctiv his condition I became such as to require constant medical attention. His history ! i^i as follows : Jle is a man slightly under the medium height, but well built, complexion fair, intelligence good, flimily liistory j good; one brother suiters from dj'spepsia, another is epileptic. ! lie is married and has six children, all strong and healthy. For the first ten years of residence in this country he farmed, follow- ing at the same time the occupation of a shoemaker. Subsequently he came to Montreal, and for eight months was a conductor on the street Railway, during wiiich period he enjoyed excellent health. For the rest of his life he served as a felt cutter for overshoes in the Canada Rubber factory. His general health had always been good. About three years ago the purchase of a piece of property some distance out of town, and the anxiety consequent upon • making the necessary payments, caused considerable mental worry, and !ie suifered at the time from general debility. About tho same time two of his children had a mild form of typiioid fever. The chief symptoms he complains of are excessive weakness and indisposition to exertion, together with loss of appetite. The skin is blanched ; mucous membranes pale, sclerotics pearlj^, and he sufll^rs from palpitation and shortness of breath on exertion. On physical examination the organs are apparently healthy ; heart sounds natural ; liver and spleen not enlarged ; no enlarge- ment of external lymphatics. No increase in the colourless blood 4 CANADA MEDIUAL AiJSOCIATION. corjuiseloM, but cluingcb found in thu rod corpuscles, which will bo noticed hiter on. Ordered pill of rcd.iced iron, isi. ii., and phosplioriis 5^ t!;r. March l-lth. Has been deprosyed in spirits, and nielains of indistinctness of vision, triceps well. 27th. Has been in bed since 24:th. Hands and feet not so much swollen. Slight hacking cough. Feels too faint to sit up to have the bod made. Pulse and temperature about the same. 31st. Has had for two days vomiting and slight purgiiig, which arc no\v checked. Urine natural. Complains of numbness of left arm and hand. Vision iinpaired, sees peculiar coloured disks. Dr. Buller cxatnined the eyes to-day and reports as follows: Choroid unusually heavily pigmented, but a])purontiy every- where normal. Optic nerves pale, but not the pallor of atrophy, as there is no conspicuous absence of the smaller vessels which are alwaj's observable in the healthy optic papilla. On the surface of the right nerve the upper of the two small arteries which may generally be seen running transversely outwards towards the region of the macula lutea, present a peculiar appearance, the portion traversing the face of the nerve is much enlarged, some- what fusiform, of a dark colour, like a retinal vein, but has not sharply delined walls. Just beyond the edge of the nerve this vessel is for a short distance almost normal in appearance, but further outw^ards it is obscured by a thin, superficial, streaky-looking extravasation of blood. The macula itself is occupied by an irre- gular dark red patch about half as large as the optic papilla, ])ro- bably an extravasation of blood. There aro a number of minute blood stains in the region of nerve and macula, nearly all of them thin and streaky, and generally close to some retinal vessel of moderate size. Some appear to bo in intimate relation with the retinal veins, others with the arteries; they are all of the PETiNICIOUS AN.EMIA, 5 Hume dark venoiiH colour. There is a Blight huzliioss of the rctiiui throughout the region occupied by extravasation, but aj)i>aroiitl3' none towards the equator ol'the eyes, Tiie arteries are decidedly paler and smaller than they sliould be in a ntalo of lioalth. The patient speaks of seeing a dark spot about the size of a spectacle lens before the eye when ho looks at any ol)iect, but thiidlain8 of tight ncss in chest, and pains in the Jiead. Feels sick at stomach when he gets up. Numbness in both hands. Feeling that lie could not go on much longer, he asked to have transfusion performed, having been previously well instructed as to tlie chances of success, immediate and remote. The operation was accordingly^ performed on the 6th at 1.10 p.m., Dr. Buller kindly su})plying the necessary amount of blood. I proposed transmitting the blood into one of the veins of the foot, but it was impossible to find one prominent enough, so that the median basilic of the right arm was selected. Ten ounces of blood weie withdrawn from Dr. Buller, defibrinated by whipping with a wire egg-beater and passing through linen (lawn), the tem])erature being maintained by means of hot water. A v shaped incision was then made in the vein, and the nozzle of Aveling's transfusion ai)pa- ratus introduced, and six ounces of blood pumj)ed in without the patient exhibiting any uneasiness. The elfect of the new blood was apparent in increased fullness of the superficial veins, a pirdcer color of the lips, and increased moisture of the skin. After re- moval of the nozzle from the vein it was found impossible to check the hffismorrhagc by a compress, so that it was necessary to apply liiratures to both ends of the vein. It would have been better had these been placed in position before the vein was opened ; as it was, one or two ounces of blood were lost. The operation lasted about ten minutes. Pulse at the time wac 102, temperature 99.1°. Half an hour after he complained of feeling chilly, and the temperature began to rise ; at the end of the hour rigors w^ere well marked, accompanying every eiglith or tenth expiration, and the tempera- ture was 102°, the pulse 120, respirations 34. At the end of second I 6 CANADA MEDICAL ASSOCIATIOiT. hour the riiror« had diminished somewhat. Pulse 132, iriterinittent and feeble ; tem])cralure 10.'}. 1°. About three hours and a lialf after the operation the temperature was 104.1°, the highest it reached. Pulse and respirations about the same. He takes brandy and beef tea alternately every fifteen minutes. Passed I iii. of normal urine, eontaining no albumen. Until midnight the temperature remained about 103° and pulse between 140 and 150 ; they then gradually fell, and at 8 a.m. temperature 100°, pulse lOO, res])irations 28. He slept tolerably well through the night, passed 3 viii of normal urine, and towards morning had a hirge healthy looking liquid stool, getting out of bed for the purpose. He sa^^s he is stronger, and his mind is clearer than before the operation. April 7th. — The temperature continued to fail, and at 8 o'clock in the evening w^as 90°. Uririe was passed thi-ee times during the i\'dy, and he had one stool in the morning. The pulse is firmer, fuller, ranging from 102 to 112, and does not intermit. Takes nourishment well, only vomited once. April 8(h. — Slept at intervals througli the night, and took stimulants and nourishment well. Passed urine several times. Complained a little of ymin in the right arm, and was restless towards day break. The temjieratui'e gradually rose from 1)9° at 7. p.m. to 101° at 7 a.m., the pulse ranging from 110 to 120. Ivespi rations 25 to 30. From 7 o'clock the temperature and pulse gradually rose, till at 12 the former was 104°, the latter 130, and very feeble. Takes brandy and beef tea ever}^ ten or fifteen minutes, and dozes at intervals, llespiratioiis 140 and shallow. After 12 o'clock he became very restless, and did not care to take nourishment. The pulse rose to ncarlj^- 150, the respirations became more rajjid and very shallow, ami the temperature fell to 102°. Breathing got more and more ditficult, and he dieil at 1.40 p.m., about i'orty-eight hours after the transfusion. AUTOPSY, TWENTY-FOUR IIOUllS AFTEll DEATH. Body that of a spare man, 5 feet 5 inches in height ; com- plexion fair, hair light, whiskers red. The skin presents a yellowish tinge over the vrhole body, most marked on the face, neck, and shoulders. Rigor mortis w^ell developed. Slight oedema of lower extremities. Pour or live smooth wdiite cicatrices on outer side of rieht loi>\ Freckles abrdidant on forearnis. Panni- cuius a/iiposus thin. Brain. — Skull unusual!}' thick; marrow of diploD red. About PEIIXICIOUS ANAEMIA. 7 2 oz. of scram escapes on removal of the dura mater. Vessels of the pia mater empty. Pacchionian graniihitions numerous. Brain substance pale, of good consistence. Notliing abnox'mal in the ventricles or ganglia at the base. The remarkable pallor of the tissues is the most noticeable feature. Weight, 3 lbs. 3 oz. Thorax and Ahdomen. — The voluntary muscles exposed in the preliminary incision are of a rich dark red color. Intestines and omentum pale and bloodless ; position of abdominal viscera normal. In the thorax the rigiit pleura contains a pint of reddish serum, the left half a pint, in which a few floculi of lymph are seen. There are pigmentary (?) deposits upon parietal layer over diaphragm and bodies of the vertebne. FericarJlum is normal, a few ecchymoses on visceral layer over left ventricle. Hearty very flaccid, walls of chambers collapsed. A good deal of sub-pericardial fat, especially over right cavities. Vena3 cavae nearly empty. Kight auricle contains 3 iss. of blood, light claret coloured, and one small coagulum, partly decolourized. Eight ventricle contains a very small amount of blood ; walls thin , endocardium stained. Valves healthy. Mus. papill. pale yellow colour. Left auricle empty. Left ventricle contains very little blood ; lining membrane stained. Walls of normal thickness, muscle soft, somewhat paler than normal. Valves healthy. Aorta of normal diameter, iwnys; pigmentation moderate; slight con- gestion (post-mortem) in dependent parts, and also an excess of serosity. Structure healthy. Spleen, slightly enlarged, weighs 3X. Numerous adhesions, in- filtrated with serum, bind it to the diaphragm, stomach, and colon. On section pulp very soft, dark red in colour, almost diffluent. Left kidney (5^ inches long). Section shows a pale, coarse organ, somewhat softer than natural. Left supra-renal capsule pale, soft in the centre. Mlglit Jddney, moderately congested in the corti- cal portion and at bases of pyramids. Cones very pale. Eight capsule liQSilthy. Bladder healthy. Vesiculae seminalcs contain sper- matozoa. Stumaxh distended with gas ; contains about 4 oz. of a brownish viscid fluid. Numerous ecchymoses along the greater curvature, especially at the cardiac end. Tiic veins contain blood. Mucous membrane looks normal. Duodenum and jejunum healthy. Coats of the ileum very thin, translucent, and ansemic. The solitary glands prominent in the upper part; only one patch of Peyer found in the lower portion. Lr»rgc bowxd normal. 8 CxVNADA MEDICAL i^SSOCIATiON. Mesenteric glanrh appear even smaller than natural. Pancreas healthy. Liver, a few ecchynioses on cajjsule, a small cicatrix on upper surface of right lobe. Substance pale, in parts much softened. Weight, 3 lbs. 8 oz. Gall bladder contains normal-looking bile. HISTOLOGICAL EXAMINATION. The blood examined during life was very thin, watery, and of pale claret colour. It presented the following characteristics : — Colourless corpuscles appear perfectly natural in structure and size, and are not numerically increased. No large granular ones, such as described by Litten,^ could be found. Two forms of coloured qorpuscles : (a) ordinary forms, which are paler than natural, flattened out, less biconcave, and are very irregu- lar in outline, some ovoid, others with sinuous borders, others again with pointed processes, (li) Small red corpuscles — micro- cytes, — erroneously described by Eichorst as pathognomonic of this affection. They were numerous, 8 to 10 occurring in the field of No. 9 im. and oc. 3. The diameter ranged from 1-5000 " to 1-9000." They equalled, or even exceeded, in colouration the ordi- nary forms ; some were crenatcd, and they frequently presented a pit or cup-like depression on one side. In the repeated examin- ations of the blood, extending over three months, these forms increased but little numerically. Schultze's granular masses were not noticed. No appreciable difference could be detected in the histological appearance of the blood an hour after the transfusion. The l}£art presented signs of moderatcl}' advanced fatty degen- eration, the strisc in many fibres being obscured by molecular fat and droplets of oil. Spleen. — The normal elements, cells of the spleen pulp, and spindle-shaped corpuscles of the trabecula, together with numerous blood corpuscles, were the only structures noticeable in teased preparations. Kidneys. — In both cortical and pyramidal jDortions the cells of the tubules appear very granular, somewhat swollen, and a large number of oil droplets are seen in and about the tubules. Liver.— The cells contain oil drops in excess, and in many the nuclei are obscured- There is also some fatty infiltration. TYiQ marrow of all the bones cxam.ined, sternum, ribs, vertebrae radius, fibula, was of a violet-red colour, of good consistence, and, 1 Berliner Ivlinischo Wochenschiift; No. 19, 1877. PEllNICIOUS AN.'EMIA. 9 with the exception of that of the fibula, contained no fat. There were found the ordinary lai'go, coarsely granular, marrow cells numerous small lymphoid corpuscles, and rod blood corpuscles of both .sizes ; and, in addition, very many nucleated red blood cor- puscles, coi-responding with those described by various writers as occurring in the marrow in cases of leukaemia, and by Cohnheini ^ and myself^ as constituents of this tissue in certain cases of pernicious anaimia. They w^ere most abundant in tlie marrow of the sternum, fewest in that of tlie vertebi-a). They were considerably larger than the ordinary red blood corpuscles and of about the same intensity of colouration. The majority had only one nucleus, but cells with two, three, and four were not un- common. The position of the nucleus was usually eccentric, often, indeed, protruding luilf way from the corpuscle. The nuclei w^ere colourless. The disease which Addison was the first to recognize and de- scribe as Idiopathic Anaemia has within the past five years excited an unusual degree of interest, owing, in great part, to the publica- tion in 1S72, by Biermer, of Zurich, of a series of observations upon a form of antemia wdiicli he regarded as a new disease, and to which lie gave, as marking the chief characters of the affection, the name " Progressive Pernicious Amcmia." Lebert had previously, about the same time as Addison, under the term " Essential Ana3- mia," described similar cases. Though, no doubt, long before Addison wrote, instances of this disease had been from time to time observed, still to him is due the credit of having given the first accurate clinical picture of the affection in his own inimitable way. Judge from the following quotation, wdiich is given purposely, as his name has not received full justice in connection with this affection. He says : " For a long period I had from time to time met with a very remarkable form of ancemia, occurrinmia, shown by the pallor of the skin and mucous membranes, and the various functional symptoms of this condition, hoimic murmurs, etc. ; no emaciation; progressive increase of all those symptoms in spite of medicaments which are effective in the ordinary ana) mi as, and, lastly, the absence, post-mortem, of any changes to account for the affection, bloodlesaness and fatty degeneration of the organs being the only recognizable alterations. Our knowledge of the etiology of the disease cannot be oaid to have advanced materially since Addison wrote. The very general fatty degeneration of the internal organs, by far the most constant and marked lesion, is to be regarded as a secondar}' change. The coarse and histological changes in the spleen and lymphatic glands, where, if anywhere, we should naturally ex- pect to find alterations giving some clue to the failure in blood- making function, are not constant, sometimes they have been found slightly enlarged, at others atrophied. Indeed, so far as these organs arc concerned, the numerous and careful observations PERNICIOUS AN.EMIA. 11 of the past five years have failed to discover any definite lesion in them which would account for the symptoms, or in any way con- nect derangement of their function with the production of the disease. In one direction, however, there has been some progress, and to this we shall briefly allude. Clinically the cases present certain similarities to those of leukitmia and Hodgkin's disease, or pseudo-leukoemia. Now these latter diseases ditfer chiefly in this, viz., that in leukaemia the colourless blood corpuscles are in excess; in pseudo-leukaemia they are not. Both present three varieties : 1st the splenic, in which the chief lesion is the great enlargement of the spleen ; 2nd, the Ij'mphatic, 'n which the lymph glands throughout the body are mainly atfected ; and, 3rd, the researches of Neumann, Mosler, and others ha\:e made us acquainted with a variety known as the myelogenous or medullary, in which the marrow of the bones is the seat of disease. This tissue is now generally regarded as sharing, in the young animal at any rate, with the spleen and lymph glands in the formation of blood corpuscles. In the long bones of the adult it is in a state of atrophy, and its place, in great part, supplied by fat. In many cases of leukaemia and pseudo-leukaemia, it increases, becomes more vascular, its cellular elements multiply, nucleated red blood corpuscles, such as occur in the embryo, are formed, and the whole tissue passes into a condition of hyperplasia, strictly analo- gous to that affecting the spleen and lymphatic glands. This may be, as in a case recently reported by Mosler,^ the primary lesion in leukaemia, and the development of the marrow may produce definite symptoms, such as swelling and tenderness of certain parts of the bones ; so that the myelogenous forms of these aftec- tions are now well recognized. Clinically the myelogenous form of pseudo-leukaemia, though rarely uncomplicated, presents such a similarity to pernicious anaemia that Jaccoud,^ and Immerman ^ suggested the identity of the two affections, while Prof Pepper,* declared distinctly that pernicious anaemia was " merely the simple medullary form of pseudo-leukaemia." As I have quite recently, in commenting U2:)0n another case,'^ referred fully to the facts for and against this view, I need not 1 Berliner Klinische Wochenschrift, Nos 50, 51, 52. 1876. 2 Nouv. Diet, de Med et de Chirurg. Leucocyth6mie. 3 Ziemssen's Handbuch der Speciellen Pathologie aud Therapie, Bd. xiii. Art. Pro. Pernio. Anaemia. 4 American Journal of Medical Sciences, Oct., 1875. 5 Canada Medical and Surgical Journal, March, 1S77, 12 CANADA MEDICAL ASSOCIATION. recupitulatG them here. In the present state of our knowledge it may, I think, be reasonably affirmed that certain cases of idiopathic anaemia may be placed in the category of myelogen ous affections, and among them the one here repor'^ed. To many it may appear far-fetched to seek in the altered ccndition of the bone marrow an explanation of the extreme anaemia of this disease, but the reports of numerous easee leave no room for doubt that a serious alteration in its structure, and a return in adult life to its embryonic state, may profoundly influence the compo- sition of the blood, producing anemia and death. It must be borne in mind that the red marrow in the short bones of an adult probably equals in bulk the constituents of the spleen, and struc- turally is very similar to that organ and to the lymphatic glands. In the long bones it is largely replaced by fat, but traces of it still remain. Now, granting that the marrow is a tissue which shares in the blood-making functions, it is quite as reasonable to suppose that, if hyperplasia of the elements of the spleen can lead to serious disturbance in the composition of the blood, pro- ducing the splenic form of leukaemia or pseudo-leukaemia, accord- ing as the colourless corpuscles of the blood are increased or not, so a general increase of the constituents of the marrow may induce similar conditions. For it is to be remembered that, in a general hyperplasia of the marrow, the actual amount of lymphoid tissue in the osseous system equals or perhaps exceeds that of an enlarged spleen. Why a simple hyperplasia of this tissue should interfere with the elaboration of the blood, altering in the one case the mutual proportion of the corpuscles, and in the other simply reducing the total number, we do not know, but we are just as ignorant why an enlarged spleen and lymphatic glands should produce in the one case leukaemia and in the other not. f/