Columbia ^nitiersfttp intljeCitpoflmgork €oUege of ^ijpgitians anb ^urgeonjf Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/lecturesonrenaluOOsaun LECTURES ON RENAL AND URINARY DISEASES. 0^ \ v^ Vlectures ^KAL & URINARY DISEASES. ROBERT SAUNDBY, M.D. Edin, KELLOW OF THE ROYAL COLLEGE OF PHYSICIANS, LONDON ; EMERITUS SENIOR PRESIDENT OF THK ROYAL MEDICAL SOCIETY; FELLOW OF THE ROYAL MEDICO-CHIRURGICAL SOCIETY; MEMBER OF THE PATHOLOGICAL SOCIETY OF LONDON ; PHYSICIAN TO THE GENERAL hospital; CONSULTING PHYSICIAN TO THE EYE HOSPITAL; CONSULTING PHYSICIAN TO THE HOSPITAL FOR DISEASES OF WOMEN ; PROFESSOR OF MEDICINE IN MASON COLLEGE, BIRMINGHAM ; LATE EXAMINER IN MEDICINE TO THE EXAMINING BOARD FOR ENGLAND. WITH NUMEROUS ILLUSTRATIONS, SECOND EDITION. ipbUaOelpbia : W. B. SAUNDERS, 925, WALNUT STREET. 1897. I Sin PRE FAC E. The favour accorded to these lectures has induced me to re-publish them in a single volume. They have been carefully revised, much new matter has been added to them, and I have included a fourth section on miscellaneous affections of the kidney, which makes the book more complete as a work of reference. R. S. Birmingham, September, iSg6. PREFACE TO THE FIRST EDITION OF THE LECTURES ON BRIGHT'S DISEASE. In presenting this work for the indulgent consider- ation of my professional readers, I would disclaim all pretension to have said the last word on the many vexed questions with which its subject matter is encumbered. I have endeavoured to explain, within a modest compass, the present state of con- temporary knowledge, making such additions and suggestions as have resulted from thirteen years' clinical and pathological study of Bright's Disease. Some of the material for this book has been previously published, but every chapter has been re -written, every point has been thought out again, and I need offer no apology for such alterations of opinion as may be perceptible in these pages. Except v;here the source is acknowledged, all the figures have been drawn by myself from preparations in my possession. I desire to express my indebted- ness to Dr. G. F. Crooke, Patholoo-ist to the General .Hospital, for many beautiful microscopical prepara- tions; to Dr. MacMunn, and Mr. Kales, for kindly overlooking portions of the proof-sheets ; to the publishers of Landois and Stirling's Physiology for PREFACE. vii permission to use certain illustrations of the Anatomy of the Kidney ; and to all preceding writers on Urinary Disease, among whom I desire to mention Sir William Roberts, whose work on Urinary and Renal Diseases must remain for all time a never-failing source of sound clinical information. R. S. Birmingham, February^ iSSq. PREFACE TO THE FIRST EDITION OF THE LECTURES ON DIABETES. The very kind reception accorded to my " Lectures on Bright's Disease," has encouraged me to publish the present volume. These Lectures have, in great part, appeared already in print, but, with the exception of the Bradshaw Lecture, which is reproduced verbatim, they have undergone considerable modifications. I desire to express my grateful thanks to the Right Hon. Lord Knutsford, G.C, M.G., Her Majesty's Secretary of State for the Colonies, for the valuable assistance he has afforded me by ob- taining for me a return showing the incidence of Diabetes Mellitus in the British Colonies. I wish to acknowledge my indebtedness to many successive pathologists, resident medical officers and viii , PREFACE. clinical clerks at the General Hospital, for their indispensable co-operation in these pathological and clinical studies, and I desire to thank my friend, Mr. Gilbert Barling, for his kindness in helping me to see this book through the press. R. S. Birmingham, /anuary, iSgi. CONTENTS. Section /.— BRIGHT'S DISEASE. CHAP. PAGES I. GENERAL ANATOMY OF THE KIDNEY - - . i — 7 II. THE PATHOLOGY OF ALBUMINURIA - - - 8 — 24 III. THE PATHOLOGY OF DROPSY - - . - 25 — 35 IV. PATHOLOGICAL RELATIONS OF TUBE CASTS - - 36 — 42 V. CARDIO-VASCULAR CHANGES - - - - 43— 57 VI. PATHOLOGY OF POLYURIA- - . - 58— 61 VII. PATHOLOGY OF UR.EMIA .... 62 — 69 VIII. RETINAL CHANGES - - . - 70 — 82 IX. HISTORY — CLASSIFICATION — ETIOLOGY - - - 83 — 96 X. INFECTIVE NEPHRITIS . - - - 97 — 116 XI. LITH/EMIC NEPHRITIS . . - - 117 — ijg XII. OBSTRUCTIVE NEPHRITIS - - - - I40 — 147 XIII. COMPLICATIONS OF CHRONIC BRIGHT's DISEASE - r I4S — 166 XIV. TREATMENT OF BRIGHT's DISEASE - - - 167 — 178 Section //.—THE URINE. XV. CLINICAL EXAMINATION OF THE URINE - - - I79 — 217 Section ///.—DIABETES. XVI. DIABETES MELLITUS - - . - - 2lS — 236 XVII. ETIOLOGY ------ 237 — 261 XVIII. MORBID ANATOMY — THE BRADSHAW LECTURE - 262— 2S3 XIX. CLINICAL HISTORY ----- 284 — 329 XX. DIABETIC COMA - . . . 330 — 356 XXI. TREATMENT ----- 357 — 373 XXII. DIABETES INSIPIDUS - . - - 376 — 389 Section /F.— MISCELLANEOUS RENAL DISEASES. XXIII. STONE IN THE KIDNEY . . . _ 3^0 — 399 XXIV. HYDRONEPHROSIS, PYONEPHROSIS, PYELITIS- - 4OO — 4O7 XXV. HEMATURIA, H.EMOGLOBINURIA - - . ^08 — 420 GENERAL INDEX .... ^21 — 434 B LIST OF ILLUSTRATIONS. COLOURED PLATES. I'ACiE Plate I. — Retinitis albuminurica - - - - - 7° Plate II. — Neuro-retinitis albuminurica hsemorrhagica - - 72 Plate III. — Retinitis hasmorrhagica diabetica . . . - 307 Pl.ate IV. — Retinitis centralis punctata diabetica ... 312 WOOD ENGRAVINGS. fk;. pace I. — Diagram of course of two urinary tubules - - - - 3 2. — Arrangement of blood vessels in renal cortex - . . ^ 3, — Pyramid of Malpighi with corresponding cortex - - - 5 4. — Varieties of tube casts ...... 37 5. - Deposit from acute catarrhal nephritis - - - - 38 6. — Convoluted tubule, catarrhal nephritis - - - - 40 7. — Normal pulse tracing - - - - - - - 45 8. — Pulse tracing, acute nephritis - .... ^^ 9 — Pulse tracing, chronic nephritis - - - - - 45 10. — Pulse tracing, contracting kidney - - - - 47 II. — Renal arteriole, showing endarteritis obliterans - - - 48 12.— Atrophic retinal patch, showing fatty degeneration of exudation- 73 13. — Convoluted tubule in acute nephritis - - - - 98 14. — Convoluted tubule in acute nephritis - - - - - 99 15. — High tension pulse tracing of acute nephritis - - - 100 16. — Deposit in acute nephritis, showing slender hyaline cast - - loi 17.— Malpighian body in subacute nephritis of ulcerative endocarditis 106 iS. — Malpighian body, showing marked peri and endo-capsulitis - 109 19. — Atrophy and fatty degeneration of the epithelium of the con- voluted tubules --.-... log 20. — Chronic infective nephritis, showing the thickened stroma - no 21. — High tension pulse tracing of chronic febrile nephritis - - in 22. — Capsulitis of Malpighian body with hyaline degeneration of glomerular tuft - . - - - - -122 23.-- Concentric hypertrophy of wall of capillary vessel - - - 122 24.— Renal arteriole, showing endarteritis obliterans - - - 123 25. — Convoluted tubule, showing epithelium, granular protoplasm and nuclei - - - - - - - 123 26. — Convoluted tubule, with proliferated epithelium and casts in lumen --...... 123 27. — Dilated convoluted tubule, with atrophied epithelium - - 124 28. — Pulse tracing from case of lithaemic kidney ... 130 xii LIST OF ILLUSTRATIONS. FIG. PAGE 29. — Crystals of triple phosphate - - - - - ' - 186 30 — Crystalline phosphate of lime - . . - - - . 187 31. — Amorphous phosphate of lime - _ . . . 187 32. — Crystalline carbonate of lime - - . - _ 1S7 33. — Crystals of nitrate of urea ------ igo 34. — Apparatus for estimating urea ----- igo 35.— Urinometer - - - , - . - - igo 36. — Crystals of uric acid ------ iga 37. — Amorphous urate of soda - • - - - - 193 38. — Hedgehog crystals of urate of soda - _ . . ig3 39. — Urate of ammonia crystals - - - - - - '93 40. — Crystals of hippuric acid - - - - - - 193 41. — Crystals of oxalate of lime ------ ig^ 42. — Hexagonal plates of crystals ----- ig^ 43.— Balls of leucin and sheaves of tyrosin . - . . ig^ 44. — Crystals of cholesterin ------ 203 45. — Esbach's test tube ------- 206 46. — Blood discs ------•• 208 47. — Pus corpuscles - - - - - - - - . 09 48. — Blood, hyaline and epithelial casts - . _ . 210 49 and 50. — Casts and cells of acute Bright's disease - . - 211 51. — Micro-organisms in various forms - - - . 213 52. — Pulse tracing in D. mellitus following enteric fever - - 251 53. — Right median nerve, showing interstitial and parenchymatous neuritis -------- 266 54. — Heart muscle of fatty and fibroid degeneration - - - 268 55. — Heart muscle, showing granules of glycogen - - - 269 56. — Section of liver, showing interstitial hepatitis in a portal canal - 272 57. — Section of atrophic cirrhiotic pancreas . - - - 275 58. — Group of pancreatic acini ------ 276 59. — Enlarged pancreas, showing commencing cirrhosis, etc. - - 277 60. — Hyaline degeneration of Henle's tubes - . - - 279 61. — Renal tubule, showing masses of glycogen - - - 279 62. — Fat droplets in portion of renal tubule ... - 280 63. — Pulse tracing, showing full tidal \Aave . - - _ 286 64.— Pulse tracing, showing failing heart ----- 286 65. — Right median nerve, showmg advanced interstitial and paren- chymatous nephritis ------ 302 66. — Pulse tracing in D. mellitus, following inflaenza - - - 305 67. — Temperature chart in D. mellitus, resembling typhoid relapse - 323 lectures on Renal and Urinary Diseases. Section I.— BRIGHT'S DISEASE. ClIAl'TER I. GENERAL ANATOxMY OF THE KIDNEY. THE shape of the kidney, in health, is a flattened ovoid, larger and rounded above, flattened and pointed below. Its colour is dark-red with a smooth surface. The average length is 4*4 inches, the breadth two inches, and the thickness one inch. The usual weight is about five and a half ounces in the male, and five ounces in the female. At the end of this chapter a table of weights at different ages is appended. The outer border is convex and rounded, while the inner is concave and traversed by a longitudinal fissure, — the Jiiluvi, in which are situated the renal vein, ureter, and renal arter}^ The hilum leads into a hollow in the kidney called the sinus, in which the vessels lie before penetrating the renal substance. The kidney is enveloped by a thin tough fibrous capsule, which is continuous with the outer fibrous coat of the ureter. This capsule is attached to the renal substance by fine pro- cesses of connective tissue and by blood vessels. Under the capsule there is a laj-er of un-striped muscular fibres. On section the kidney is seen to be made up of two portions: (i,) an outer light brown portion, the co/tical layer, of friable consistence and fairly homogeneous appearance ; and, (2,) an inner darker portion composed of a series of cones, the pyramids of Malpighi, whose apices are turned towards the sinus, the mednllaiy layer. This inner layer is di\-ided by I 2 B RIGHT'S DISEASE. anatomists into two parts, — a bo7i7idary zone consisting of the broader portions of the pyramids, and a papillary portion, constituted by the projecting apices. The relative proportions of these three divisions are, accord- ■ingto Klein, Cortical Layer - - - - - 3'5 Boundary Zone ----- 2'5 Papillary Portion .... - 4-0 The structure of the cortex is slightly granular from the presence of the Malpighian bodies, while it is marked by lighter lines at right angles to its surface. The Diedullary rays, or pyramids of Ferrein, are conical bundles of straight tubules running from the cortex into the medulla. Between the medullary rays are the interlobular vessels, the Malpighian bodies, and the convoluted tubules, together form- ing the labyrinth. The medulla is distinctly striated by alternating light and dark lines arranged fan-wise, the handles of the fans being at the apices of the pyramids. The whitish lines are bundles of straight tubes, the darker lines blood vessels. In the foetus the kidney is distinctly lobulated, each lobule consisting of a pyramid of Malpighi with its corresponding cortical portion. In the adult this lobulated condition persists only rarely, but the connection between each pyramid and the uriniferous tubules and blood vessels of its cortical portion always remains (yFig. 3). The icriniferous tubitles take origin in Bowman's capsules, membranous expansions of their extremities, measuring 050 of an inch in diameter. They pursue a tortuous course, effect junctions with one another, and ultimately form large collect- ing tubes which open on the apices of the papillae. Each tubule is formed of a homogeneous basement membrane lined by epithelial cells, with an axial space or lumen for the passage of urine. Fig. I represents the course of a uriniferous tubule. Con- nected by a narrow neck (2) with Bowman's capsule (i) is the proximal convoluted tubule (3), which ultimately leaves the labyrinth and passes down the medullary ray into a pyramid. Before leaving the labyrinth its convoluted appearance be- comes less pronounced, and it is called a spiral tubule (4) ; descending, it narrows very much, finally turning at Henle's loop (6), the descending and ascending portions being called ANA'IOMY OF THE KIDNEY. 3 the desccndti/g- and ascending limbs of HciUes looped lube. The ascending Hmb is at first spiral, then wavy, and on reachinj^ the cortex it re-enters the labyrinth as an irregular tubule (10), — a short irrci^ular portion, which soon becomes wide and n, SuD-capsular layer with- ut Slalpigliiaii Licdies. 11. Bistal convoluted tubule. 10. Irregular tubule. 13. Straight part of <;ollecting Tube. 9. Wavy part of as- cending limb of Hen- le's loop. a. Inner s'ratum of <;ortex without JVIai- pighian liodies. 7&«. Ascending limb 4)f Ilenle's loop. convoluted n. Wavy part of ascending 2. Constriction of neck, 4. Spiral tubule. 1. Malpighian tuft sur- rou! ded by liowman's cap- sule. 8. Spiral part ol ascending limb of Henle's loop. 3 B. Boundary zone. 5. Descending limb of Hcnles loop. 6 Henle'B loop. \-^ C. Papillary zone. Tig, 1. — Diagram of course of two urinary tubules (after Landois and Stirling). convoluted, forming the distal convoluted tubule (11), v/hich after pursuing a tortuous course again enters a medullary ray -as a collecting tube (12) ; this collecting tube passes down into BRIGHT' S DISEASE. a pyramid, is joined by others and opens on the surface of the apex of a papilla. The convoluted tubules are lined by a large granular epi- thelium arranged in a single layer. The cells are composed of two parts, an inner containing a spherical nucleus, and an outer part which has a fibrillated appearance from the rods placed at right angles to the axis of the of presence tube. The cells appear continuous, no separation between them being ordinarily visible, adjacent cells interlocking by tooth- like projections on their surfaces. Similar epithelium is found in the spiral tubule, and the ascending limb of Henle's loop. In the descending limb the epithelium is clear and flattened with a bulging nucleus. In the irregular tubule the cells somewhat resemble those of the convoluted tubes, but they are shorter, the nuclei are oval and the rods are coarser and better defined. The collecting tubes are lined by large clear cubical or columnar epithelium with distinct nuclei. MalpigJiian bodies are small spherical structures composed of Bowman's capsules, already alluded to, which enclose capillary tufts, and are pierced by affej-ent and efferent vessels. They are situated upon the extremities of horizontal branches of the interlobular arteries, and are about 250 of an inch in diameter. Within the capsule each afferent vessel breaks up to form a capillary tuft, an arrangement of vascular loops supported by connective tissue and covered by a layer of endothelium {^Fig. 2, GL). The inner surface of the cap- sule is likewise covered by a lining of flattened cells, which are continuous with and prob- Tu,. 2.--Diagram of arrangement ot blood Vfs- ably mOcHficationS of thctubular sels in the renal cortex (after Tyson). )?i, region / of the medullary ray ; b.regionof the convoluted pnitllpllllTTl tubules; VI, interlobular vein ; AI, interlobular '-1^^'-^^^^^ "^^^• artery; VA.vas afEerens; VE, vas efferens ; GL. T^Jnnrl ■7;/?er/?/<' Thp- rpnpl Bowman's capsule containing capillary tuft; VZ, J-JLUULV ai^ctot-l-J. J. lli„ iv^iidi venous radicle of interlobular vein. artcry as it cHters the hllum divides into four or five branches, which are invested by sheaths derived from the fibrous capsule. They pass in- ANATOMY OF THE KIDNEY. wards between the bases of the papillae to form arches with one another in the boundary zone. From these arches the interlobular arteries arise ; they ascend towards the surface of the cortex between the medul- lary rays, furnishing lateral horizontal branches, — the afferent twigs to the Malpighian bodies {Fig. 2, A I). Other branches are supplied to the matrix of the kidney and to the capsule, the latter anastomosing with branches of the supra- renal, phrenic, and lumbar arteries. On leaving the Malpighian body the efferent vessel, which in structure resembles an artery, breaks up into a capillary Boundaiy zone. Papillary zone. riff. S" — Diagram of a pyramid of Malpighi with corresponding cortex (after Landois and Stirling!. PF, Pyramids of Ferrein or medullary rays : R.\. Branch of renal artery ; RV, Branch of renal vein joined by interlobular vein ; VR, Vasa recta ; P.\, Papilla ; b, b embrace the bases of renal lobules. meshwork surrounding the tubules ; from this meshwork venous trunks arise, which terminate in the interlobular veins (Fig. 2, VI). The interlobular veins originate just below the capsule as the vencs stellatce. They anastomose freely in the boundary zone, and accompany the arteries to the sinus, where they finally unite to form the renal vein. 6 BRIGHT'S DISEASE. From the same arches in the boundary zone, formed by the branches of the renal artery after their entrance into the kid- ney, other vessels arise called the vasa recta {Fig. 3, VR), which enter the pyramids and pass between the tubules towards the apices. Some vasa recta are said to arise from efferent vessels which lie near the medulla, or even from the union of the capillaries of the medullary rays (HUSCKE). In their course through the pyramids they form capillary meshworks around the tubules. From these capillaries venous radicles arise, the vencs rectcB, which open into the venous trunks in this region. The connective tissue of the kidney consists mainly of an intertubular stroma, which in the papillae is broad and fibrous, but in the cortex is more delicate, and is said to be composed almost entirely of branching and anastomosing connective tissue corpuscles (Goodsir). Around Bowman's capsules, and continuous with the adven- titial coats of the blood vessels, is also a small quantity of white fibrous tissue. The ureter is the duct by which the urine is conveyed to the bladder. It takes origin from the kidney in a number of cup-shaped tubes, called calices or infundibula, each of which embraces the apex of a pyramid, or of more than one. The several calices become united to form two or three larger tubes which unite again in the dilated chamber called the pelvis, which is a funnel-shaped expansion of the upper end of the ureter. Its coats are three in number. An outer fibrous coat con- tinuous with the capsule of the kidney and the sheaths of the renal blood vessels. A muscular coat composed of an outer longitudinal and an inner circular layer. A mucous lining consisting of several layers of epithelial cells, round and cylindrical. Lymphatics of the kidney originate in wide meshed plexuses in the capsule and in large spaces which are more numerous between the convoluted tubules of the cortex, but are also present between the straight tubules. Large lymphatics provided with valves pass out of the kidney at the hilum, while others emerge through the capsule. The nerves are derived from the renal ganglia and lesser splanchnic nerve- They are gangliated, and contain both ANA TO A/ V OF THE KIDNEY medullated and non-medullated fibres. Their mode of ter- mination is unknown. Table of weii^hts of the kidneys at different ages (taken from Boyd's tables). Average weight 1 Average weight Age. Sex. both kidneys. 1 Age. Sex. both kidneys. 0.^. oz. I to 2 Male 2-55 30 to 40 Male ii"35 Female 2-4 Female 10-34 2 to 4 M. 3'33 40 to 50 M. 10-89 F. 3-14 F. 8-8 4 to 7 M. 4-05 50 to 60 M. 9-1 F. 4"26 F. 8-5S 7 to 14 M. 6-58 60 to 70 M. 8-83 F. 575 F. 8-28 14 to no M. 9"34 70 to 80 M. IO-68 F. 9-09 F. 7-63 20 to 30 M. 11-57 Upwards M. 8-25 F. 10-17 of 80 F. 6-86 Chapter II. THE PATHOLOGY OF ALBUMINURIA. By Albuminuria we mean the presence in the urine of an albuminous body which is coagulated by heat or precipitated by neutralisation. Serum albiunen is the substance ordinarily found in albu- minous urine. It is soluble in water, coagulable by heat at from 73° to 75° C, and precipitated by acids ; it is readily soluble in strong nitric acid, and not precipitated by common salt, carbonates of the alkalies or very dilute acids. , Syntonin, or acid albumen, is formed from serum albumen in the presence of a free acid ; alkali-albumen is a similar modification caused by the presence of a free alkali ; these bodies are not coagulated by heat, but are precipitated by neutralisation. Syntonin may be formed by the careless use of a test tube containing traces of nitric acid. Alkali-albumen is often present in putrid urine. Serum globulin is insoluble in distilled water, but dis- solves readily in the presence of common salt, and is then coagulable like serum albumen at 73° to 75° C. It may be precipitated from its solutions by carbonic acid gas, or by saturation with common salt or magnesium sulphate. It differs moreover from serum albumen in its more ready diffusibility through animal membranes. It is always present in albuminous urine. In the blood the proportion of serum globulin to serum albumen is as 2 to 3 ; but in urine, owing to its higher rate of diffusion, this proportion may be reversed. It has been more than once suggested that it is the body present in functional albuminuria or after paroxysmal hsemo- globinuria (GULL, Ralfe) ; but this does not appear to be the case. Out of 16 cases of functional albuminuria examined for this purpose, the albuminous body was pure globulin in only one case, and on a second examination serum albumen was present with it ; these results have been confirmed by the more recent observations of Noel Baton and Douelas. It has THE PATHOLOGY OF ALBUMINURIA. 9 been noted to be in excess in cantharidcs poisoning, in chronic nephritis with waxy de^^eneration, in the early stage of scarla- tinal nephritis, in the albuminuria associated with dyspepsia, in phthisis, etc. Werner found globulin alone present in a case of acute nephritis, and attributed it (following SENATOR) to the destruction of the renal epithelium which contains seven or eight times more globulin than serum albumen. Hermann found globulin to be chiefly present in a case of eclampsia of pregnancy with albuminuria. Retractile albumen (BOUCHARD) was the name given to albumen which, on boiling, falls down in dense flakes ; it was held to be characteristic of Bright's disease. It is worth mentioning in order to note that this has been abundantly proved to be a mistake, this peculiar behaviour being dependent upon the acidity of the urine (LfiPlNE). Formerly all albuminates not precipitated by ferro-cyanide were regarded as peptone, until Kiihne showed that part of this residue is thrown down by ammonium sulphate, part not. The former is now recognised as albumose, and only the latter called peptone ; recent observations have shown that what used to be called peptone in the urine is always albumose (SCHULTER, SENZ, StOFFREGEN, DeVOTO, THOMSON). Albumose is characterized by not being thrown down by heat or by being more easily soluble by heat than in the cold, by being precipitated by am.monium sulphate, and by giving the biuret reaction with solution of copper sulphate. It has been observed to be present in the urine in many acute and chronic diseases, generally in association with serum albu- minuria. It must not be assumed that it is necessarily a product of digestion excreted by the kidneys ; it is said on good authority (Grutzner) that digestive ferments are present in the urine. According to Mya and Belfanti, trypsin, the normal proteolytic ferment of the urine, is replaced by pepsin in Bright's disease ; but either would be capable of effecting the conversion of albumen into albumose, — a process which is probably favoured by elevation of the body temperature in fever, and by the retention of the urine for a certain time in the bladder. Albumose is not coagulable by heat or precipitated by neutralisation ; it is thrown down by several of the tests recommended of late years for albumen, e.g., picric acid, metaphosphoric acid, Tanret's test (potassio- mercuric iodide), etc. Bence Jones's albumen or hemi-albumose, as Salkowski lo BRIGHT'S DISEASE called it, is a body of doubtful position. According to Salkowski, it remains clear on boiling ; it is precipitated on adding acetic acid and common salt solution, but clears up on heating, to be thrown down again on cooling. With pure nitric acid it is precipitated ; on heating it dissolves, with the development of an intense yellow colour, and on cooling comes down again. Treated with caustic soda and cautiously with copper sulphate, it gives a purple violet which is lost if excess of copper sulphate is used. With phosphoro-tungstic acid, tannic acid, acetic acid and ferro-cyanide of potassium it is precipitated ; but the last reaction does not occur in the presence of ammonia. Heated with a drop of Millon's reagent (acid nitrate of mercury), it gives a deep red colour and precipitate, but this reaction fails when much common salt is present Bence Jones described the albuminous body in his case as affording the following reactions ; he wrote, " The urine that contained it did not give a precipitate immediately by nitric acid, and when heated it did not coagulate, and nitric acid when added to the boiling urine did not give a precipitate. If, after boiling, the urine was cooled, then the precipitate fell, but was immediately redissolved by heat." The difference between this and the reactions given above is that it was not precipitated by nitric acid. Thormahlen has described a form of albumen in which the precipitate caused by nitric acid did not re-dissolve on heating, and the solution when cleared by heating, remained clear on cooling. The urine of Joseph B , a patient in the General Hospital, gave a similar reaction on one occasion. In the urine of a case of pernicious anaemia I found an albuminous body which presented most of these reactions, but on boiling there was a dense cloud which on adding acetic acid disappeared, while the whole fluid became gelatinised, so that the test tube could be turned upside down. Nitric acid gave a precipitate, but it dissolved on heating without any yellow coloration. Acetic acid and ferro-cyanide of potassium gave no reaction, but this may have been due to the presence of salts of ammonia. Posner has found hemi-albumose in human semen, as well as in the urine ot spermatorrhoea and after pollutions. It has been noticed in many diseases, mollities ossium (Bence Jones) syphilitic cachexia, diphtheria, cancer of oesophagus, muscular atrophy (SENATOR), petroleum inunction (LasSx\R), chronic THE PATHOLOGY OF ALBUMINURIA. ii nephritis (Hoppe-Sevler), and therefore has no special clinical significance. Albuminuria once regarded as diagnostic of Bright's disease has lost this primitive meaning. The number and variety of the pathological relations under which albumen may appear in the urine compel us to regard it as dependent not only upon inflammation, grave congestions and other coarse organic changes, but upon slight variations in the mechanical conditions of the circulation in the kidney. Excluding accidental admixtures of blood or pus from the bladder or urethra, albuminuria is met with not only in acute and chronic Bright's disease, but in diseases of the heart, lungs, and liver, in peritonitis, pregnancy, abdominal tumours, in most febrile and inflammatory diseases, in many cases of poisoning, in cancer, tubercle and syphilis, in lardaceous disease, in anaemia, debility, dyspepsia, purpura, scurvy, after paroxysmal heemoglobinuria, in gout, in delirium tremens, in various diseases of the brain and spinal cord, in epilepsy, in certain skin diseases, as well as in apparently healthy persons after bathing, exercise, etc. All these states are capable of being arranged under the following groups. I. — Congestions of the kidney. Active or arterial congestion may result from a chill to the skin as in bathing (MAHOMED, Jopinson) ; from exposure to cold ; from elimination of some irritant through the kidneys such as alcohol, uric acid, phosphorus, lead, cantharides, etc. ; from the direct action on the kidneys of a morbid poison derived from the blood, such as the toxins of scarlatina, diph- theria, typhoid, etc., a condition very liable to pass on to acute nephritis ; or finally from vaso-motor paralysis after injuries to the spinal cord, and in some other nervous affections. Passive or venous congestion may result from cardiac, pul- monary or liver disease, peritonitis, pregnancy, abdominal tumours, the hypostatic congest!^ n of prolonged illness, failure of the circulation from enfeebled heart, in fever, in anaemia, in exophthalmic goitre, in fatigue, after violent exertion, e.g., epilepsy. 2. — Inflammation, acute or chronic, in many infective diseases, in gout, in chronic lead poisoning, etc. 3. — New GrozutJis. Cancer, tubercle or syphilitic deposits in the kidney. 12 BRIGHT S DISEASE. 4. — Degeneratio7is. Lardaceous degeneration of the renal arterioles. 5. — Alterations in the composition of the blood, as in purpura, or scurvy, and after attacks of paroxysmal hsemoglobinuria. Looked at in this way the difficulties which have beset the discussion of the significance of albuminuria melt away; this result is attained by the absolute surrender of the doctrine that albuminuria signifies Bright's disease, and the acceptance of the view that it is simply the admixture of albumen derived from the blood serum with the urine. It is a fact beyond dispute that albumen may be present in the urine of persons apparently in good health. I do not care to contend that there is not some departure in these cases from the normal mechanism of the renal circulation ; but it is certain that neither this lesion nor the loss of albumen gives rise to any derangement of health which impairs the working capacity of the individual or tends to shorten his life ; in other words, there are cases of albuminuria which not only do not require medical treatment, but may be safely accepted by life assurance companies. In these cases the urine is normal in every other respect, there are no tube casts, the amount of solid matter excreted is sufficient, and there are no signs of cardiac hypertrophy, of high arterial tension, no retinal changes and no oedema. Leube examined the morning urine of 119 healthy soldiers, of ninety once, of twenty-three twice, and of six three times. Albumen was found six times in the urine of five different soldiers, five times only a trace, once a distinct cloud. The last urine was that of a soldier whose morning urine was examined twice and contained once a distinct cloud, the other time only a trace. The mid-day urine of 119 soldiers was examined, especially that passed after a five hours' march or many hours' parade, in the months of June, July, and August. The five soldiers whose morning urine contained albumen also had albumien in their mid-day urine, three times a trace, three times more distinctly. Moreover, in 148 observations, albumen was found eighteen times in the urine of soldiers whose morning urine was quite free from albumen, in eight distinctly, in ten only a faint trace. The results were that 4'2 per cent, of the soldiers had albumen in their morning urine, and sixteen per cent, had albumen in their mid-day urine. No casts or blood cor- puscles were found. All the cases in which albuminuria appeared were carefully examined, and urethral discharges. THE PATHOLOGY OF ALBUMINURIA. 13 as well as signs of Bright's disease, were carefully noted to be absent. The test used was boiling and acetic acid ; but the albuminous body was separated and tested by Millon's reagent, sulphate of copper, ferro-C}'anide of potassium, etc. Grainger Stewart examined the urine of 505 presumably healthy individuals, comprising 205 soldiers. of the Seaforth Highlanders, 100 healthy male adults in civil employment, 150 healthy inmates of Craiglockhart Poorhouse (100 adults, over sixty, and 50 children), and 50 children in the Orphan hospital; of these 166 or 32-8 had albuminuria. Of the 205 soldiers yj, or 37'56 per cent, had albuminuria ; of lOO healthy male adults 10 only ; of 100 inmates of Craiglockhart, about or above sixty years of age, 62 had albuminuria, and of 100 children it was present in 17. Dr. Stirling examined 461 healthy persons of whom 369 were boys, and of these 118 had albuminuria, of whom JJ were boys, giving for adults 44 per cent., for boys 20 per cent. In Leube's cases the albu- minuria was found in the mid-day urine four times more frequently than in the morning urine, that is the urine passed immediately on rising. Stirling found the erect posture was the great determining factor in the production of albuminuria in his cases. The same fact is attested by Senator's experience, who found that the urine of himself and three clinical assistants at the Augusta hospital in Berlin repeatedly contained albumen between 11 a.m. and 12.30. Bull has pub- lished a case in which the albumen was always absent when the patient was in bed. Marcacci could produce albuminuria in himself by making rotatory movements with his arms for fifteen minutes. It therefore may be accepted that this form of albuminuria in healthy persons depends essentially upon some mechanical condition connected with the erect position and exercise. Grainger Stewart concludes that albuminuria is more common in healtJi as life advances ; but this is doubtful. His elderly people show a high percentage, but there is no evidence that care was taken to eliminate prostatic and vesical catarrh or even latent Bright's disease, — all very common conditions at that age. Other observers have met with functional albuminuria most commonly in young men. But there are other cases in which some departure from health is present, for example, atonic dyspepsia, with oxaluria or lithuria, anzemia, perhaps not very marked ; or the patient 14 BRIGHT' S DISEASE. is an overgrown weakly person, with a tendency to varicose veins in the lower extremities. In 1876 Moxon described two forms of latent albuminuria. One he called the albuiniimria of adolescence. It occurs in youths and young men ; the patients are languid, perhaps have headache ; some slight derangement of the digestive system is often present ; there is no evidence of organic disease, and if the urine were not examined the cases would be regarded as debility without any tangible signs of lesion. Albumen is usually found in the urine passed after breakfast, and is nearly surely present in some specimen of the urine collected for a period of forty-eight hours. A few hyaline casts and oxalates are often to be found. In the other form, which he called remittent albuminuria, the albumen is present in greater quantity, usually after breakfast, but there is a remission at some period of the day, nearly always in the early morning, so that no albumen is present in the urine passed on rising after a night's rest. These cases have been re-named cyclical albuminuria by Dr. Pavy, but it is conceded that the condition depends upon debility and the erect position. It must be admitted that all our knowledge of these benign forms of albuminuria is recent, and in the face of authorities who maintain that even the smallest trace of albumen in the urine is always pathological, indicating, if not actual disease, a condition of renal stress which sooner or later tends to organic change, it is necessary to state what we know about their subsequent life history. Dr. Moxon mentions that all his cases ended in complete recovery. A medical man has pub- lished his own history, showing that from the age of seventeen to thirty-six he had had albuminuria, which was present during the day, but absent when in bed and on first rising ; he had ■enjoyed good general health in spite of hard work of body and mind. Most of my cases have passed out of sight with per- sisting albuminuria, but some, like the case just related, have lost the symptom and appeared quite well. One of my medical friends at the age of 16 suffered from well-marked remittent albuminuria ; he lost it in four or five years, and has never had any trace of kidney disease, though it is now twenty-one years since the albuminuria was first noticed. I see him almost daily, and have often examined his urine. A gentleman was sent to me to be examined for life assurance ; he was 46 years of age, and in every respect strong and sound THE PATHOLOGY OF ALBU.VINURIA. 15 except that his urine was albuminous ; he told me that he was rejected for life assurance for this cause eighteen years before, and that on two subsequent occasions his urine had been examined and found to be in the same state. There was no urethral discharge, and no other evidence of kidney disease. I may also refer to a young gentleman who was sent down from a public school in 1879 with albuminuria, and who was ordered by a London physician to wnnter in a warm climate as a case of Bright's disease, actually or potentially. This advice was not taken ; he has continued to enjoy excellent health, and has always been a very active athlete. If he is going to have Bright's disease he has not yet shown any sign of it. Although I often see him I have not had an opportunity of examining his urine for some years ; it formerly contained oxalates, but no casts. These cases are of practical interest in relation to the question of life assurance. There is great unwillingness to admit that under any circumstances albuminuria can be dis- regarded. We are told by authority that it is always " a danger signal," and this may be granted readily enough if this is only meant to imply that it calls for the greatest care in the ■examination of the case, but the time has come to declare that only ignorance of the facts can justify the continued refusal to accept cases where the albuminuria is clearly depen- dent only on the erect position or on exercise, and the applicant in all other respects satisfies the required standards. What is the mechanism by which albumen passes into the urinary secretion ? Since the time of Bright there have been two rival theories of this process, and of late years a third has been added ; these three theories may be called : (i), the Ha^matogenous ; (2,) the Parenchymatous ; and (3,) the Vas- cular. There always has been a school which attributed albuminuria not to changes in the kidney but to changes in the blood, and even in Bright's own day he was told that the structural alterations described by him were only the results of the elimination of albumen by the kidneys : this doctrine still survives and finds a persistent defender in Semmola, of Naples. His argument is especially directed to the etiology of Bright's disease, where he contends that the blood contains albuminoids of an abnormal diffusibility, so that they are found in the saliva, sweat and bile, — a fact in which he is .supported by Vulpian and others. Tizzoni, however, found that albumen from the urine of a case of Bright's disease did i6 BRIG NT'S DISEASE. not cause albuminuria when injected into the circulation of animals. Semmola entirely overlooks all that has been recently- observed with regard to albuminuria apart from Bright's disease. Nothing can be farther from the truth than to suppose that the elimination of albumen by the kidney is liable to set up inflammatory action, for we know that it may go on for many }'ears without any such result. But variations in the diffusibility of the albuminoids of the blood may yet account for albuminuria in certain cases, and there is a great tendency on the part of authorities to accept such a view. Globulin diffuses more rapidly than serum albu- men, and it has been stated by Lepine that albumen found in the urine after food diffused more rapidly than that passed fasting. The truth of the doctrine of haematogenous albu- minuria is by no means bound up with food albuminuria, so that it is perfectly allowable to doubt the occurrence of the latter, while admitting the general probability that changes in the blood account for a certain number of cases of albu- minuria ; for example in purpura, scurvy, profound anaemia, after hsemoglobinuria, etc. With respect to food albuminuria we have Christison's case of the young man whose urine was always albuminous after eating cheese, and the experiments of Brown-Sequard, Barres- wil, and others, in which the urine became albuminous on a diet largely composed of eggs. But in the first case the albu- men excreted was not shown to be casein, nor in the second to be Q.^'g albumen, while more recent experiments have proved that it is not egg albumen* (GRAINGER Stewart), and that it is only when the digestive powers are overtaxed, as by swallowing many raw eggs together, that albuminuria occurs (Lauder Brunton). Parkes was one of the first to notice that there was an apparent increase of albumen after food. He stated that the albumen was increased after food in two cases of chronic Bright's disease, although it was diminished after food in a case of heart disease. He inclined to the view that the increase after food was due to the passage of imperfectly digested albu- men, analogous to that which occurs when albumen is injected into the veins, or to the albumen undergoing some modifica- tion in the digestive process, such as its conversion into * When egg albumen is injected into the veins^ egg albumen is ex- creted by the kidneys. THE PATHOLOGY OF ALBUMINURIA. 17 an acid albuminate, by which its cliffusibihty would be increased. Parkes's facts do not seem to warrant this conclusion ; for, while the albumen was increased after food in the two cases of Bright's disease, it was diminished under similar circumstances in the case of heart disease, so that it is necessary to postulate a peculiar inability to digest albumen in the former cases, which did not exist in the latter. On the other hand, if we regard albuminuria as a result of congestion of the kidney, we can easily understand why, in the cases of chronic Bright's disease, the stimulus to the circulation increased the albu- minuria in already inflamed organs, while it diminished it in the case of heart disease, where the transudation was due to passive engorgement of the renal capillaries and veins. 'But Parkes's views have been adopted by many writers. Pavy sup- ports Parkes by giving a table of the amounts of albumen excreted before and after breakfast in six experiments, all showing a marked increase. Pavy further adopted Parkes's view that this might be due to the increased diffusibility of the albumen, and supported it by showing that in some urines it is highly diffusible ; but he did not attempt to prove that the albumen passed after food was more diffusible than that passed before food, or to indicate to what circumstances this increased diffusibility might be due. Most physiologists deny that unchanged albumen is absorbed into the blood, and the only piece of direct evidence I know to the contrary is the statement of Brlicke, that he has found coagulable albumen in the lacteals. I endeavoured in the first place to determine whether this apparent increase of albumen after food really took place, and the following observations were made on a case of Bright's disease in the Queen's Hospital under the care of Dr. Carter. The patient had been on milk diet previous to this experi- ment, but on March loth, 1880, he was put on the following diet : — Breakfast, 5 a.m., two slices of bread and butter with tea. Lunch, 10 a.m., two slices of bread and butter with one pint of milk. Dinner, i p.m., four ounces of cooked meat, eight ounces of potatoes, bread and water. Tea, 6 p.m., the same as breakfast. Supper, 7 p.m., half-pint of milk. He took walking exercise twice daily for half an hour at 12.20 and ■z.so. BRIGHT'S DISEASE. Quantity of Albumen in 40 Date. Period. Urine. ccms. Total Alb umen. March lo 7 P.M. to 5 A.M. 1620 CC. •008 grms. ■1296 grm. 5 A.M. to I P.M. 150 CC. •or6 „ •06 )) I P.InI. to 5 P.M. 180 CC. •01 „ •045 !> 5 P.M. to 7 P.M. 120 CC. •008 „ •024 )> „ 12 7 P.M. to 5 A.M. 870 CC. •0069 „ •1479 )5 5 A.M. to I P.M. 180 CC. ■017 „ •0756 )) I P.M. to 5 P.M. 180 CC. •0141 „ •0630 11 5 P.M. to 7 P.M. 150 CC. •009 „ •0330 11 » 13 7 P.M. to 5 A.M. 14 10 CC. •OIS5 „ •5358 11 5 A.M. to I P.M. 180 CC. •020 „ •090 11 I P.M. to 5 P.M. 180 CC. •0166 „ •0738 11 5 P.M. to 7 P.M. 120 CC. ■015 „ •0444 11 On each day, the relatively greatest quantity of albumen was excreted between breakfast and dinner. The quantity each day fell as the day advanced, in spite of the meat eaten at dinner, and the exercise taken in the afternoon. The total quantity of albumen excreted rose steadily under the influence of meat diet, being three times greater on the fourth day than on the first. One bottle containing the urine of part of March nth got broken, so that day's record was incomplete. The analyses were performed by Dr. MacMunn. This observation is opposed to the doctrine of Parkes that unassimilated albumen is excreted by the kidneys. But it has been suggested that after food there may be a more rapidly diffusible albumen present in the blood. That there should be such differences is quite probable, as Graham long ago pointed out that an acid solution of albumen diffuses readily, while an alkaline solution scarcely diffuses at all ; so that differences in the alkalinity of the blood serum may determine variations in the amount of albumen excreted. Pavy showed, using peri- cardium as a membrane, that Q.gg albumen diffuses more readily than serum albumen, and Lepine has filled up the gap left by Pavy by observing that albumen in the urine after food diffused more rapidly than that passed fasting. The following experiments appear to show that the results may depend upon variations in acidity, etc., and not upon any primary difference in the albumen itself The septum used was vegetable parchment ; and the time allowed was twenty-four hours in each case. THE PATHOLOGY OF ALBUMINURIA. 19 The following experiments were made on the urine of the same case : — Experiment I. — Before breakfast : In bed. Urine faintly acid ; one-third of a column of albumen ; no albumen in diffu- sate. — After breakfist : In bed. Urine acid; four-fifths of a column of albumen ; a trace of albumen in diffusate. Experiment II. — Before breakfast : In bed. Urine neutral ; a trace of albumen in diffusate. — After breakfast : In bed. Urine acid ; a trace in diffusate. Experiment III. — Before breakfast: In bed. Urine faintly- acid ; one third of a column of albumen ; a faint trace in diffusate. — After breakfast : In bed. Urine acid ; two-thirds •of a column ; a trace in diffusate. Experiment IV. — Before breakfast : In bed. Urine faintly acid ; one-third of a column of albumen ; a trace in diffu- sate. — After breakfast : In bed. Urine acid ; two-thirds of a ■column of albumen ; a trace in diffusate. Experiment V. — Befoi'e dinner : Up. Urine neutral ; a dis- tinct cloud in diffusate. — After dinner: Up. Urine acid; a ■distinct cloud in diffusate, but less than before dinner. Experiment VI. — Before dinner : Up. Urine acid ; half a •column of albumen ; a cloud in diffusate. — After dinner : Up. Urine strongly acid ; a whole column of albumen ; a dense ■cloud in diffusate. Experiment Nil. — Before dinner: Up. Urine acid ; half a ■column of albumen ; a faint trace in diffusate. — After dinner : Up. Urine faintly acid ; one-third of a column of albumen ; a faint trace in diffusate. As a rule, the albumen appeared to diffuse in proportion to the acidity of the urine. The diffusate bore no relation to the quantity of albumen present in the urine. While it is fully admitted that more carefully conducted ■experiments might determine differences in diffusibility due as suggested to alterations in the salts of the blood or the alkalinity of the blood serum, there is no evidence that un- digested albumen is ever excreted by the kidneys ; and in this shape the doctrine of food albuminuria must be abandoned. The parenchymatous theory ascribes the albuminuria to the ■destruction of the epithelial lining of the renal tubules, but there are several hypotheses which are strongly opposed to one another. One of the most interesting, that of Von Wittich, .adopted by Ludwig, and lately revived in Glasgow, is that .albumen is physiologically transuded through the Malpighian 20 BRIGHT' S DISEASE. tufts, but reabsorbed by the epithelium of the tubules. When the parenchyma is diseased this reabsorption is more or less hindered and albuminuria results. This theory, attractive as it is, is disposed of by the experiments of Posner and Ribbert, who proved by boiling freshly excised kidneys and hardening them in alcohol that there is no albumen present in the cap- sular space around the Malpighian tuft in healthy kidneys, though it can be easily demonstrated in albuminuric kidneys even when the epithelium is intact. Another form of the parenchymatous hypothesis is that when the parenchyma has been shed from the tubules the basement membrane permits the transudation of albumen. This theory has never been disproved ; and it is in its favour that kidneys prepared by the boiling and alcohol method showed albumen in the straight tubes ten minutes after ligature of the renal vein. A third suggestion made by Senator is that the destruction of the renal epithelium, itself furnishes a sensible amount ot albumen. In the early stage of nephritis the epithelial cells shed their protoplasmic contents into the lumina of the tubules. This would only apply to cases of irritative or in- flammatory albuminuria. Lastly, there is the vascular theory. The ordinary seat of the transudation of albumen has been shown by Posner to be the Malpighian tufts ; as was suggested by an experiment of Nussbaum's. In frogs the veins of the posterior extremities divide in the pelvis into two branches, one of which passes to the kidney like a portal vein, while the other joins its fellow ol the opposite side to form the vena abdominalis anterior. The blood in the other branch passes through the kidneys and the liver into the vena cava inferior to reach the right side ot the heart. The renal glomeruli receive their blood from the renal arteries, and the vasa efferentia pass into the same capillary network as that supplied by the renal portal veins, so that by tying the renal arteries in frogs the renal circulation is not brought to a stand-still as it is in mammalia. Taking advantage of this anatomical fact, Nussbaum tied the renal arteries, and then injected a five per cent, solution of o.^^ albu- men or a ten per cent, solution of peptone into the anterior abdominal vein without causing albuminuria, although when the renal arteries were not tied a smaller quantity sufficed to> produce albuminuria. It is therefore proved that in frogs an albuminuric dyscrasia causes transudation of albumen only" THE PATHOLOGY OF ALBUMINURIA. 21 through the glomeruli, and it is probable that this is also true in man ; taken together with Posner's observations we may- regard the point as practically determined in that sense. The question is, What causes the transudation ? Is there a physical change in the membrane, or is there some alteration in the blood pressure or the rapidity of the blood current ? These questions have given rise to much discussion. Thoma showed that in contracting kidney the walls of the glomeruli are actually abnormally permeable, permitting the passage, not only of thin fluids and colloids, but of small solids such as crystals of cinnabar, and this, too, in parts of the kidney pre- senting no recognisable structural alteration ; but observations are wanting to enable us to extend this to other conditions under which albuminuria occurs. We know that very slight alterations in the coats of the vessels, such as may be induced by temporarily clamping or ligaturing the renal artery, give rise to albuminuria, and this may follow simple persistent blocking of the ureter. The action of certain poisons, for example, carbolic acid, has been proved by boiling, and harden- ing the kidneys in alcohol, to cause albumen to transude through the glomerular wall without any visible structural alteration taking place (RiBBERT). It must therefore be allowed that such changes may account for certain forms of albuminuria. But there are other impor- tant factors in this vascular theory, especially the pressure and rapidity of the circulation. Since Robinson experimented by tying the abdominal aorta below the origin of the renal arteries, the influence of increased blood pressure in determin- ing albuminuria has been generally recognised ; but of late years it has been called in question. It is fully admitted that the amount of urinary secretion varies directly with the pressure ; but Runeberg has contended that the amount of albumen varies inversely. Lepine supports this in the following table : — Pressure. Albumen. 100 c.c. 1*3, I '077, o'66 40 c.c. 0-95, 1-5 100 c.c. I, 07, o'6 40 c.c. 0-8, 1-3, 1-4, 1-5 Senator accepts this view, and holds that the higher the pressure the more water but the less albumen. Bamberger also believes the albumen to be diminished as the pressure rises. Lobisch and Rokitansky caused albuminuria in healthy 22 B RIGHT'S DISEASE. persons by lowering the blood pressure with pilocarpine. There can be no doubt that increased venous pressure leads to albuminuria as is seen clinically in cases of heart, lung, and liver disease, pregnancy, abdominal tumour, and probably too in many cases of debility, anaemia, and in the hypostatic con- gestion of fevers, pneumonia, etc. In ligature of the renal vein albuminuria occurs rapidly, and has been proved by Senator to take place by direct transudation into the tubules^ probably from the lymphatics. Charcot and Bamberger attach much importance to the influence of slowing the current^ which is shown by physical experiment to favour the filtration of albumen. Ischsemia of the kidney, by experimental narrowing of the renal artery, leads to albuminuria, probably by slowing the current and reducing the pressure. Claude Bernard's puncture and experimental lesions of the spinal cord give rise to albu- minuria by vaso-motor paralysis, the kidneys being deeply congested (SCHIFF). Many of the cases which have been regarded as neurotic albuminuria are susceptible of a more simple explanation, as has been already suggested for epilepsy and tetanus ; and it will be admitted that other conditions are present in exophthalmic goitre, besides the nervous distur- bance, sufficient to account for albuminuria, though this may be due in part to altered vascular innervation. We may usefully summarise the teachings of this lecture in the following conclusions : — I. — Albuminuria is defined as the presence in the urine of serum albumen, or serum globulin, or their modifications, syntonin and alkali albumen. 2. — Albuminuria may be present in healthy persons and persist for long periods without causing any derangement of the general health, or of the structure of the kidneys. 3. — Albuminuria per se should not be regarded as an in- superable objection to life insurance. 4. — -Albuminuria may occur in dyspeptic people, and in weakly over-grown persons, without being an indication of actual or potential renal disease. 5. — Albuminuria may depend upon many causes, grouped under three headings: (1), Haematogenous : due to alterations in the diffusibi-lity of the blood albuminoids, owing to changes in the salts of the blood or the alkalinity of the blood serum ; but albuminuria is never due, as has been .asserted, to the excretion of undigested or partly digested albumen taken as THE PATHOLOGY OF ALBbWINURIA. 23 food. (2), Parench}'matous : inflammatory changes in the epitheHum give rise in the first instance to an albuminous exudate which must be present in the urine, and secondly by destroying the cell layer and altering the basement membrane, allow direct transudation from the lymphatic vessels into the tubules. (3), Vascular : the walls of the glomeruli probably undergo alterations of their permeability from the effects ot poisons, inflammation and vaso-motor paralysis, while lower- ing of the blood pressure and slowing of the blood current favour filtration of albumen through them. In venous obstruction there is oedema of the whole organ and transuda- tion of albuminous fluid direct from the lymphatic spaces into the tubules ; in inflammation and vaso-motor paralysis a similar cedema is likely to occur with identical results. BIBLIOGRAPHY. Adami (J. G.). On the Functions of the glomeruhof the Kidney. A contri- bution to the study of Albuminuria. " The Practitioner," April, 1S89. Bamberger (Von). Ueber hjimatogene iVlbuminurie. "Wiener Med. Woch.," 18S1, Nos. 6 and 7. Bull. Albuminuri — latent skrumpnyre ? " Nord. Med. Arkiv," 18S5, Bd. XVII., No. 25. Charcot (J. M.). Conditions pathogeniques de I'albuminurie. " Le Progres Med.," Tome IX., iS8i,p. 55. Devoto. Ueber den Nachweis des Peptons und eine neue Art der quanti- tativen Eiweissbestimmung. " Zeitschr, f. phys. Chemile," XV., 465. Jones (Bence). Animal Chemistry in its Application to Stomach and Renal Diseases. London, 1850. Lepine (R. ). Quelques travaux relatifs a I'albuminurie et a la pathologie renale. " Revue de Med.," Tome II., 1882. Leube (W.). Ueber die Ausscheidung von Eiweiss im Harn des gesunden Menschen. " Virchow's Archiv," Bd. LXXII. , Heft 2. Marcacci (G.). Di un nuovo caso di albuminuria fisiologica. "Comment. Clin. d. Mai. d. Org. Gen.-urin." Pisa, 18S4, I. MoxoN (W.). On Chronic Intermittent Albuminuria. " Guy's Hosp. Reports," 3rd S., vol. XXIII. NooRDEN (C. Von). Ueber neue Arbeiten zur Peptonurie. " Berl. Klin. Woch.," 1893, p. 72. NussBAUM (M.j. Fortgesetzte Untersuchungen ueber die Secretion der Niere. " Pfluger's Archiv," Bd. XVII., 187S, p. 5S0. Paton (D. Noel). Observations on the proportions of the chief proteids occurring in the urine in various forms of albuminuria. " Brit. Med. Journ.," 1S90, Vol. II. Pavy (F. W.). Gulstonian Lectures. On the Assimilation, and the influ- ence of its defects on the Urine. " Lancet," 1S62, II., p. 613 ; 1S63, I., p. 461. PosNER (C). Studien ueber pathologischen Exudatsbildungen. "Virchow's Archiv," Bd. LXXIX., p. 311. Ueber pathologische Albuminurie. "Berl. Klin. Woch.," Bd. XXII., 18S5, p. 654. 24 BRIGHT' S DISEASE. RiBBERT (H.). Ueber die Eiweissauscheidung durch die Nieren. "Cent, f. d. Med. \Viss.," iSyg, p. 47 and 1881, p. 17. Robinson (G.). Researches into the connection existing between an unnatural degree of compression of the blood contained in the renal vessels and the presence of certain abnormal matters in the urine. " Med. Chir. Trans.," 2nd S., Vol. VIII., 1843, p. 51. RuNEBERis (J. W.). Ueber die pathologischen Bedingungen der Albu- minurie. " D. Arch, fiir Klin. Med.," Bd. XXIII., p. 41. ScHULTER. Over het opsporen van Peptoon in de Urine. " Dissert. Groningen," 1886. Semmola. Nuove contribuzioni alia patologia ed alia cura del morbo di Bright. " Med. Contemp. Napoli," 1886, III., pp. 449 to 467. .\lso see " Le Progres Medical," 1883, Tome XL, p. 471. Senator (H.). Die Albuminuric im gesunden und kranken Zustande. Berlin : A. Hirschwald, 1882. Senz. Ueber Albumosurie und Peptonurie. " Dissert, Berlin," 1891. Stewart (Grainger). Clinical Lectures on important symptoms. Fasc. II. Albuminuria. Edinburgh, 188S. Stirling (A. W.). Albuminuria in the apparently healthy. "Lancet," 18S7, II., p. 1157. Stoffregen. Ueber das Vorkommen von Pepton im Harn, Sputum und Eiter. "Dissert. Dorpat.," 1891. Thoma (R.). Zur Kenntniss der Circulationsstorung in den Nieren bei chronischer interstitieller Nephritis. " Virchow's Archiv," Bd. LXXL, Heft. I and 2. Thomson. Ueber Peptonurie in der Schwangerschaft und im Wochenbett. "Deutsche Med. Woch.," 1889, No. 44. Thormahlen (J.). Ueber eine eigenthiimliche Eiweissart im menschlichen Urin. " Virchow's Archiv," Bd. CVIIL, p. 322. Tizzoni (G.). Alcuni esperimenti intorno alia patogensi dell' albuminuria. " Gaz. deg. Ospit. Milano," 1885, VI. 12. Wittich. Ueber Harnsecretion und Albuminurie. " Virchow's Archiv," Bd. X., p. 325. Chapter III. THE PATHOLOGY OF DROPSY. Dropsy is certainly the most striking symptom of Bright's disease, and the one that commonly first attracts the patient's attention, but the proportion varies in the different forms of Bright's disease. It is usually present in acute nephritis, but it may be very slight or altogether absent. Thus it is commonly absent in cases of acute nephritis supervening in the course of pneumonia, diphtheria, typhoid fever, etc., though the state of the urine proves incontestably that acute nephritis exists. In subacute nephritis and in large white kidney, dropsy is very coinmon, being absent in only eight or ten per cent. In the contracting form it is much less common ; in the earlier stages it is generally absent, but later on it is more frequent. Thus, out of a hundred cases seen in the out-patient department, I found dropsy present in ten per cent, only, while in the bodies of persons who had died with contracting kidney, I found the proportion as high as twenty-five per cent. This variation is fully explained by the cause of the dropsy, which in con- tracting kidney must for the most part be attributed to heart failure. So long as the hypertrophied heart can do its work all goes on fairly well ; but when this organ at last breaks down, dropsy appears along with other signs of collapse of the whole system. Like ordinary cardiac dropsy, it is first seen in the legs and ankles, increasing after rising or getting about, and must be regarded as of grave prognosis, indicating failure of the heart to maintain the struggle any longer. The fluid in renal dropsy varies in different situations, being poorer in albumen and solids in the subcutaneous tissue than in the serous sacs. The following table taken from Bartels gives the composition in the various seats of dropsy. j Sp. g. . Water. S°'"^^- Salts. Albumen. Blood Serum: 11015-58 957-656 41-402 21-38 1 15-58 15-69 ; i4"48 11-70 11-69 30-39 ? 2-55 Pericardial fluid ! 1009-69 978-622 Peritoneal „ 11009-63 984-31 Subcutaneous,, 1007-65 9S8-30 26 BRIGHT S DISEASE. Schmidt gives the following figures : — Subcutaneous tissue, 0"36% albumen ; Meninges, 0'6 to 0'8 %; Peritoneum, 1-13 % ; and Pleura, 2-85 %. Urea has been found in it by many observers, and Bartels quotes the following figures from Edlefsen : — Subcutaneous tissue, o"359 % ; Peritoneum, 0"28 to 0*30 %; Pericardium, i °/q. What is dropsy ? Dropsy consists in an accumulation of watery fluid in the lymph spaces of the subcutaneous cellular tissue and in the serous cavities of the body. This fluid or lymph is derived from the capillaries, and under normal cir- cumstances is poured out into these spaces, but taken up again by the venous and lymphatic radicles as fast as it is poured out. For the production of dropsy, the equilibrium of this arrangement must be upset by either {a) an increase in the outflow of fluid, or {b) a failure on the part of the veins and lymphatics to take up the effused fluid. An increase in the outflow of lymph from the capillaries is caused experimentally by section of the vaso-motor nerves^ and occurs in disease when their function is paralysed ; it may also be due theoretically to increased permeability of the vascular walls, and to changes in the blood serum. We shall afterwards see what share to assign to each of these factors. The principal source of power in pumping these lymph spaces dry is the heart ; it is assisted by the aspiratory action of the thorax in respiration, and the contractions of the muscles in the limbs. When the heart fails to maintain a negative pressure in the veins oedema sets in. Localised venous obstruction acts with less certainty in the same way, as the lymphatics which open into the venous circulation beyond the obstruction may carry on the work ; if, however, their task is added to by cutting the vaso-motor nerves, and so leading to a greater influx of blood to the capillaries and increase in the outflow of lymph, dropsy sets in. Section of the nerves probably has more than this simple effect, but it need not concern us at present. There are no difficulties in the way of understanding dropsy due to heart failure ; it is a break down in the central pumping apparatus, and need not detain us longer. The dropsy of acute nephritis presents problems of greater difficulty. In most cases there can be no question of heart failure, and its explanation must be sought for in the factors that determine an excessive outpouring of lymph from the THE PATHOLOGY OF DROPSY. 27 blood vessels. In acute Bright's disease the urinary secretion is very scanty, and as patients continue to swallow fluids the total quantity of blood must increase absolutely in volume while suffering" a relative diminution of its solids ; that is to say, the water is absolutely increased and the solids relatively decreased, inducing a state of hydraemic plethora. A watery condition of the blood has long been regarded as a cause of dropsy, some authors seeing in it a predis- posing factor, others ascribing to it still greater importance. Briicke's experiment of cutting one sciatic nerve of a frog and putting the animal on a piece of moist blotting paper in a large glass vessel, showed that after some weeks oedema occurred in the palsied limb, which disappeared on food being administered, reappeared in inanition, and disappeared again when nutrition was restored. But there is considerable difficulty in ascertaining what are the circumstances under which hydrsemia will produce dropsy, for authorities certainly differ as they are wont to do. One of our earliest experimenters. Hales, succeeded in producing " both the ascites and the anasarca " in a dog by pouring water into the jugular vein, but when we read the description it appears that the dog died during the pro- gress of the experiment, and we are not told whether these phenomena preceded death or not ; this is an important point, as the retentive power of the vascular walls alters altogether after death. Magendie in his " Lecons sur les Phenomenes Physiques de la Vie " alludes to this matter in several lectures ; he certainly tells us that he succeeded in pro- ducing general dropsy by defibrinating the blood of a dog, and in another experiment he produced analogous results by pouring water into the veins, as Hales had done. But he performed a much more remarkable experiment by intro- ducing no less than ten litres of water into the veins of a patient suffering from hydrophobia ; he had observed the wonderful calmative influence which similar injections had upon ferocious dogs, and he hoped by this means to combat this fatal disease. His patient lived several days, and died presenting the phenomena of several " pseudarthroses " or dropsical swellings of joints. We are not told that oedema was absent, but from the relation the story bears to the main point of the lecture, we may feel justified in concluding that had there been any anasarca, the lecturer would not have failed to mention it. 28 BRIGHT' S DISEASE. Niemeyer states — -I know not on whose authority — that " if we abstract blood from an animal and inject a corresponding quantity of water into its veins in its stead, the animal does not become dropsical " ; on the other hand, Jaccoud says " the artificial dyscrasia created by the injection of water is rapidly and constantly followed by temporary dropsy." Wagner quotes Bonders, Kierulf and Hermann in proof that dropsy may be caused by the injection of abundance of water into the circulation ; but to this is opposed the experiment of Cohnheim, which showed that a solution of salt might be passed under low pressure through a limited vascular area, such as the ear of a rabbit, without causing oedema. It is obvious that all these experiments do not fulfil the conditions necessary to throw light upon the influence which hydraemia may have in producing dropsy in certain diseases. Injections of pure water destroy the blood corpuscles, and paralyse the heart, as well as, in all probability, the walls of the blood-vessels ; while the pressure employed by some of the observers was probably greater than the normal blood pressure of the animal. Bartels ranged himself very unreservedly on the side of those who regard the hydraemia of Bright's disease as the efficient cause of the dropsy, but he thought there had been much confusion in the minds of many physicians who sup- ported this view, as to the cause of the watery state of the blood. He admitted that in renal diseases a large quantity of serum albumen is lost by the blood, and he believed that this must render the blood serum more watery ; still, he was of opinion that this is neither the sole nor the essential cause of the hydraemia, for renal disease may lead to most extensive dropsy before any quantity of albumen worth mentioning has been eliminated ; and he regarded the occurrence of dropsy as dependent less upon the loss of albumen than upon the diminution of the amount of water secreted by the kidney. Even in cardiac disease, he said, we see the influence of the quantity of the renal secretion on the presence of oedema, and he denied that the malnutrition existing has anything considerable to do with the matter. On the other hand, in renal disease a considerable daily loss of albumen may take place without any dropsy resulting if only the quantity of water passed is sufficiently copious, while dropsy may ensue during an insignificant loss of albumen directly the daily urinary secretion falls below a certain minimum quantity. THE PATHOLOGY OF DROPSY. 29 He quoted the observations of Rchder, who, with the view of estabHshing the proportion borne by the quantity of water taken in drink and food towards that which afterwards appears in the urine, instituted a series of experiments upon healthy persons Hving under identical external conditions and then compared the results with a series of analogous observations made on dropsical subjects. Rehder subjected five healthy persons to experiment, and the average of the daily results, extending over thirty-two days, was, that of every hundred parts of fluid ingested, 76"4 parts were excreted in the urine ; the lowest mean in one individual was 68 per cent, the highest 88 per cent. Very contrary results were obtained by the observations on persons suffering from cardiac and renal dropsy. A man aged fifty, with cardiac disease, excreted quantities of water varying from 297 to 49'2 per cent. ; a youth with chronic parenchymatous nephritis excreted i8"6 to 33-5 percent, only; in a woman with the same disease the excreted water averaged 16 per cent, and never exceeded 24-4 per cent ; a man with the same gave an average of 28 per cent In another case the exact correspondence between the increase and subsidence of the anasarca and the diminution and increase of the urinary secretion was perfectly established. Bartels held that these experiments show that the dropsy of renal disease is due to the relative insufficiency of the kidneys to eliminate water ; but some time must elapse before anasarca occurs ; in one case, in which stoppage of both ureters was present, one hundred and twenty-two hours elapsed without a trace of oedema showing itself, but this patient vomited large quantities of liquid. The cases given by Trousseau of two patients suffering from general anasarca due simply to retention of urine, and whose symptoms were completely relieved by emptying the bladder, are, if any be needed, additional clinical illustrations of the dependence of dropsy on a free exit of water by the kidneys. Cohnheim and Lichtheim directly oppose Bartels' view, and they have endeavoured to show that hydrsemia per se cannot produce subcutaneous oedema. Their experiments were made by injecting, with a syringe or under very low constant pres- sure, large quantities of a blood-warm 0'6 per cent solution of common salt into the circulation of dogs, rabbits, and other animals ; rabbits were used without any preparation, but dogs and the larger animals were soothed with morphia or curarised. 30 BRIGHT' S DISEASE. As a preliminary proceeding they endeavoured to gain some idea of the quantity of fluid which might be injected without kilHng the animal, and they i'ound that dogs could stand much more than rabbits ; the latter generally could support an injection of 46 per cent, of their body weight before they died, but dogs withstood a much greater quantity, especially if the abdominal cavity were opened, 92 per cent, of his body weight being introduced into one dog before he died. In one case the dog died of acute oedema of the lung, but they were unable to account for this exceptional occurrence ; in general the animals died with symptoms of deoxygenation of the blood, paralysis of the heart, and in some cases con- vulsions. . In none of these experiments — and they were very numerous — was any subcutaneous oedema or anasarca pro- duced ; even after the largest injections the subcutaneous tissue was quite free from water, and as this is the earliest and principal seat of the so-called hydraemic oedema, it appeared from these observations that hydraemic plethora had nothing to do with hydraemic oedema. The following figures show the amount of hydraemia they produced : — They found the normal dried residue of a dog's blood to be about 20 per cent, the highest being 24*09 per cent. ; Andral and Gavarret found the dried residue of the blood of a case of kidney disease to be I3'23 per cent. ; in their experiments the percentage fell from 22*05 percent, to ir64inone case; in another from 2076 to ii'33; in a third, with the abdomen open, from 22* 16 to 8'29 per cent. A still greater degree of hydraemia was produced by ligaturing the whole portal circu- lation ; for example, in one case in which the coeliac, superior and inferior mesenteric arteries and the portal vein were ligatured, the percentage fell from 24*09 to 4*87. Many authors have considered the hydraemia of renal dropsy as it affects not the; entire solids of the blood but those of the blood serum. Christison found these to be 6"i per cent, and-Frerichs, in three cases of commencing nephritis, found them 9*19 per cent In one of their cases, after injecting ■64 per cent, of the body weight of common salt solution the serum residue was only 2 per cent, so that there can be no •doubt that the thinning of the blood produced in these experi- ments not only equalled but exceeded that which occurs in disease, and the absence of anasarca cannot be thus explained. THE PATHOLOGY OF DROPSY. 31 In the next place they proceeded to enquire what influence hydraemic plethora had upon the pressure and rapidity of the blood current; this is of especial interest with reference to the views of Traube, who regarded the increased arterial tension and the hypertrophy of the left ventricle as the result of the diminished secretion of water, and the resulting hydraemic plethora. They could not succeed in raising the pressure above the normal except momentarily, and they found impor- tant increase of pressure to occur only when it had previously been below normal. The shape of the curve of the blood- pressure underwent remarkable changes during the experi- ments ; at first the respiratory wave disappeared and only the pulse wave remained, but got much larger ; after a time the -curve resumed its original outline. A similar negative result followed experiments on the venous pressure; a slight increase was produced temporarily, and was accompanied by a venous pulse proved to originate by back-stroke from the heart. The blood current was quickened ; this was directly observed in the mesentery and tongue of frogs, but it did not last long. They observed the same in the mesentery of dogs and rabbits, and also by counting the blood drops from the vein of the anterior extremity of a dog ; although this method cannot be exact, the increase was too enormous to leave any •doubt. The most obvious appearance was transudation of water from the blood, not only through the glandular organs, but into their tissues themselves. The first point seems to indi- cate that all glandular organs secrete a very large quantity of water. The animals passed a very large quantity of pale limpid urine, which in some rare cases contained a small quantity of albumen, and more frequently but not constantly, sugar, which had been previously recorded by Bock and Hoffmann. The saliva and the secretions of the glands of ,the mouth were increased enormously, also the secretions of the gastric and intestinal glands ; the bile was richly secreted, but the pancreatic fluid was not increased. The secretion of the conjunctiva, lachrymal glands and mucous membrane of the nose was greater than normal, and the perspiration in two experiments on a goat and on a horse was very profuse. In order to estimate the part played by the absorbents, a cannula was placed in the thoracic duct and an enormous acceleration of the lymph stream was demonstrated, but it is remarkable that when the cannula was placed in the lymphatic 32 BRTGHT'S DISEASE. trunk of an extremity no acceleration of the lymph stream could be produced ; between these two extremes the lym- phatics of the neck showed a definite increase, but not nearly equal to what was observed in the thoracic duct. These differences correspond to the differences produced by hydraemic plethora in different parts ; for although no oedema of the subcutaneous connective tissue was ever observed, there was a special localisation of the dropsy which the authors believed to be characteristic of the dropsy of hydraemic plethora. The bodies of the animals swelled very much, and the peritoneal cavity was always full of fluid, as were the intes- tines, while their mucous and submucous coats were oedema- tous ; the coats of the stomach presented a still higher grade of oedematous swelling. The lymphatics and chyle ducts of the mesentery were distended and the mesenteric lymph glands were swollen and oedematous. The pancreas pre- sented the most extreme degree of dropsical distension ; the kidneys were both enlarged, pale, and extremely moist on section ; the liver was distended, of doughy consistence, and on section discharged a large quantity of thin watery blood ; the gall bladder was very oedematous, its wall being more than a millimetre thick. The vesiculae seminales and the retroperi- toneal tissue were also oedematous. The spleen was somewhat swollen and tight to the feel, but frequently scarcely at all enlarged. The thoracic cavities and viscera presented a striking contrast ; neither pericardium nor pleural cavities contained a drop of fluid ; the lungs (except in one case, in which they were oedematous) were quite dry, or at most there was only slight oedema of the connective tissue bands radiating from the hilus. The sub-maxillary, salivary and lymphatic glands were swollen, as were the sublingual glands and the lymphatic glands of the neck. The conjunctivae and lach- rymal glands were oedematous. All other organs, such as those of the central nervous system, were free from oedema. These results were uniformly the same in all their numerous experiments. In order to exclude the possible objection that by injection into the jugular vein, the fluid was driven directly into the inferior cava and the veins of the liver so as to cause a special obstruction of the portal circulation, they injected fluid into the femoral vein or into an artery, and got the same results. They varied their experiments by using other fluids ; THE PATHOLOGY OF DROPSY. 33 distilled water killed the animals too soon by destroying the blood corpuscles, but solutions of sugar, various salts, albumen and blood scrum gave the same results as the solution of common salt. They also used defibrinated dog's blood in a few cases, and, except that the resulting oedema was much less, often somewhat sanguineous, and complicated by puncti- form haemorrhages, the results were the same as before. Again, they bled dogs and injected an equal quantity of salt solution, without causing anything at all except slight oedema around the operation wound. But, as it might be questioned whether the skin of dogs and rabbits is analogous to that of man, more especially as the important sweat function of the latter is absent in these animals, they per- formed experiments on a horse and a goat. Both animals died of oedema of the lung ; before death there was copious perspiration, but no subcutaneous oedema. The following circumstance appeared to throw some light upon the occurrence of oedema. In fixing their dogs for experiment they used to place an iron ring between their toes and fasten this to their noses by a loop ; they noticed that the snouts of the animals became oedematous ; they repeated the experiments on animals with wounds, and found that oedema occurred around the wound. Painting with iodine always produced slight subcutaneous oedema, but animals so treated showed marked oedema after hydraemic plethora was induced. They produced the most superficial dermatitis by shaving animals and exposing them to the sun's rays for an hour or two, and the slight oedema resulting was greatly increased by hydrsemic plethora. Tying the femoral vein of a dog produces no oedema of the corresponding foot, but this occurred frequently when the blood was thinned. They argue from these facts that some change in the state of the vessels is the necessary factor for the occurrence of oedema in hydraemia ; and while they admit that it is not easy to explain renal dropsy by any demonstrated changes in the cutaneous vessels, the combination in scarlatina is very note- worthy. In this disease along with the skin affection there is often slight oedema, which becomes very pronounced on the supervention of suppression of urinary secretion by renal disease and the consequent hydrsemic plethora ; occasionally the changes in the skin vessels are sufficiently great to cause oedema, apart from renal mischief, forming the long recog- nised hydi'ops scarlatinosus without albuminuria. 3 34 BRIGHT' S DISEASE. The frequent absence of dropsy in the acute nephritis of pneumonia, diphtheria and other non-eruptive infective diseases already alluded to, supports this explanation. In the hydraimic dropsies of cachectic diseases they suppose that the prolonged hydraemia injures the walls of the vessels. Although it is competent to deny the parallelism of these experimental conditions with those of disease, we must admit that they corroborate the previously alluded to experioient of Cohnheim, that watery solutions of common salt at the temperature of the body do not readily pass through the walls of the subcutaneous vessels ; and there seems reason to doubt whether, volume and pressure remaining the same, simple hydra^mia can by itself induce oedema. We know that inanition rarely produces dropsy in the human subject ; patients suffering from malignant stricture of the oesophagus often present the most extreme degree of emaciation without any or with the slightest possible dropsical swelling. Virchow noticed no dropsy in the famine in the provinces of Upper Silesia and Spessart ; individuals who suffer from most pro- found anaemia from haemorrhages rarely show corresponding oedema. Many cases of total suppression of urine from calculous obstruction have been observed without oedema, but there is frequently constant vomiting which would tend to prevent an increase in the volume of fluid in the circulation. In hysterical oliguria there may be an extreme reduction of the urinary secretion without oedema or vomiting. In a case seen by me with Mr. Lawson Tait in September, 1885, a lady passed only 16 ounces of urine in a week, without dropsy, vomiting, or ursemic symptoms. She was under close obser- vation in Mr. Tait's private hospital, so that there can be no room for doubt as to the facts. We are therefore driven to look to a third factor, increased permeability of the vessels, to fully explain the dropsy of acute nephritis. What the exact nature of the physical change is, remains obscure. Cohnheim, perceiving its analogy with what occurs in inflammation, calls it an " inflammatory " change ; he believes that it may be brought about when hydraemia has persisted for a long time. It is probably influenced by the innervation of the blood vessels. Landois says it occurs when the blood contains dissolved haemoglobin or too little oxygen or albumen. Lauder Brunton has found that the permeability of the vessels after death is increased THE PATHOLOGY OF DROPSY. 35 by the presence of acids in the blood, and suggests that acids or substances acting in the same way may accumulate in the blood in Bright's disease. He quotes from an inauguration thesis by Feitelberg, who shows that a number of poisons, among them arsenic, have the power of increasing the acidity of the blood ; and he recalls the edematous condition of the eyelids induced by arsenic as an illustration to the point. This is all that is at present known on the subject. Suvimary. — i. Dropsy is an accumulation of lymph or watery fluid in the lymph spaces of the body as a conse- quence of — {a) defective pumping arrangements, by which the fluid is allowed to accumulate ; {U) changes in the blood and capillaries by which the outflow of fluid is increased. 2. Dropsy is generally present in acute and sub-acute nephritis, and in about 90 per cent, of cases of large white kidney ; but in uncomplicated contracting kidney it is absent in at least 90 per cent, of those able to get about. In the later stages of contracting kidney it is more frequent, being present in 25 per cent. 3. In uncomplicated contracting kidney dropsy is due to heart failure ; but in acute nephritis and its sequelae it is due to more obscure causes in which a watery state of the blood is accompanied by increased permeability of the capillaries, caused possibly by the presence of an acid or other toxic substance in the blood. BIBLIOGRAPHY. Bartels (C). Art. Dropsy. " Ziemssen's Cyclopjedia of the Practice of Medicine," Vol. XV. Brunton (Lauder). Pathology of Dropsy. "Practitioner," Vol. XXXI., 1883, p. 177. CoHNHEiM (J.). Embolische Prozesse. CoHNHEiM AND LiCHTHEiM. Ueber Hydramie und hydramisches Oedem. "Virchow's Archiv," Bd. LXIX., 1877, p. 106. Dickinson (W. H.). On Renal Dropsy with especial relation to the Circu- lation, together with some considerations relating to pulmonary apoplexy in Renal Disease. "Med. Chir. Soc. Trans.," 1892, p. 317. Hales (S.). Statical Essays. Vol. II., p. no. Jaccoud (S.). Pathologic interne. Tome I., p. 53. Laxdois (L.). A Text-book of Human Physiology. Stirling's translation. Vol. I., p. 420. NiEMEYER (F. von). Text-book of Practical Medicine. Vol. II., p. 29. Wagner (E.). Manual of General Pathology. Amer. Edition, 1876, pp. 234 and 542. 36 Chapter IV. PATHOLOGICAL RELATIONS OF TUBE CASTS. Since it has been shown beyond dispute that albuminuria may be present not only in acute diseases, but in various chronic maladies, apart from renal inflammation, and even under certain circumstances in healthy men, it has lost its former significance as evidence of Bright's disease. Moreover, we know that Bright's disease may be present, and progress to its termination (Bartels) without the occur- rence of albuminuria ; so that we stand greatly in need of some more trustworthy sign. If in recent years the discovery of tube casts in the urine of patients suffering from jaundice, diabetes and secondary con- gestions of the kidneys, or even in more transitory conditions, as in the urine of the famous pedestrian Weston, during his prolonged walk, may have appeared to throw a little doubt on their diagnostic value, it is certain that they afford us the best and clearest indications of the changes that are taking place in the renal epithelium, — changes which rightly interpreted afford the safest grounds for diagnosis and prognosis. Varieties of Casts. Casts of the renal tubules are of three kinds : (i,) Blood Casts ; (2,) Epithelial Casts ; (3,) Hyaline Casts. There are also mixed varieties, blood or epithelium adhering to or forming part of a hyaline cast ; and the term " granular " is frequently used to describe either epithelial or hyaline casts, which have become opaque and granular from infiltration with fat granules or micro-organisms. Blood Casts. Casts composed of blood clot, i.e., blood corpuscles matted together with fibrin {Fig. 4, a^ indicate as may be supposed, the entrance of blood into the tubules of the kidney. The source of the haemorrhage is for the most part the capillary tufts of the Malpighian bodies. The blood in its passage down the tubes becomes coagulated, and passes into the urine in the shape of cylindrical casts of the tubules. The presence of such casts affords important evidence in hsema- PATHOLOGICAL RELATIONS OF TUBE CASTS. yj turia, proving that the blood comes from the glandular substance of the kidney, and not from the renal pelvis as in calculus of the kidney, or from any lower part of the urinary tract. These casts are seen in the early stages of acute nephritis, so long as h?ematuria persists, or when it occurs in any form of Bright's disease, as well as in haemorrhage from congestion. They must therefore be regarded as evidences only of rupture of blood vessels in the glandular part of the kidney, and not as signs of any stage or form of Bright'? disease. EpitJielial Casts. There are two main types under which the renal epithelium appears in the urine under the form ol Fiq. 4. Varieties o( tube casts: a, Elood cast; h. Epithelial cast oot>'"' ed of small round cells; c, Epithelial cast formed of desquamated and fatty epithelium; rf ^y&,nular hyaline cast; Hyalo- epithelial cast. C/ casts of the tubules of the kidney. In one th^ cast is made up of distinct small round granular cells, like leucocytes, but of smaller size, and which are, as their appearance suggests, pro- liferated renal epithelium {Fig. 4, b). These are met with in acute and sub-acute nephritis, and always indicate an active degree of inflammation, with pro- liferation of the renal epithelium. In the second type the cast is composed of a mass of epithelial cells, crowded together so as to obscure their 38 BRIGHT S DISEASE. individual outlines, and more or less opaque from fatty degeneration {Fig. 4, c). These are formed by the desquamation of the epithelium, which is pushed off the basement membrane by the inflamma- tory exudation from the venous plexuses surrounding the tubule ; they are usually of large diameter, being moulded in tubes denuded of epithelium, and they witness to severe diffuse inflammation of the kidney. They are met with in cases of recent inflammation in healthy kidneys, in sub- acute nephritis, and in the acute and sub-acute attacks which so frequently supervene in the course of the contracting kidney. Hyaline or Colloid Casts. These are by far the most common casts ; they are met with in all forms of Bright's disease, in venous congestion, and in many conditions where the kidney is undergoing slight or temporary irritation. They occur in jaundice, diabetes, heart disease, and pregnancy ; they were found in the urine of Weston during his famous walk, and are occasionally seen in the urine of dyspeptic patients, especially when oxaluria or lithuria is present. They are usually slender homogeneous transparent cyl- inders {^Fig. 5, a), but are often more or less opaque from fatty degeneration, and are then called " granular " casts (^Fig. 4, d). Various origins are assigned to them, and they are probably formed in three different ways. Langhans has described a colloid metamorphosis of epithelial casts by which they Tit,. 5. Deposit from - .ite catarrhal nephritis bccomewhollyor partly hyalinc showing: a, slender hyai.ne cast ; i, Mucous cylin- r 1 ■! ■ T der; c Hyaline and epithelial cast; d, Pear-shaped Or glaSS-llKe m appCaraUCC \ II epithelial cells from pelvis of kidney; e, Epithelium ,", . .'- '^ .•1,1 from tubules. thc changc IS only partial they would be called hyalo-epithelial casts {Fig. 4, e) ; if complete they form one kind of hyaline cast, which, like the epithelial cast it originally was, is distinguished by its large diameter. In some instances, these transformed casts give the character- istic colour reactions of lardaceous material, turning mahogany- brown with iodine and rose-violet with methyl bhie ; but not PATHOLOGICAL RELATIONS OF TUBE CASTS. 39 necessarily in association with or dependent upon lardaceous changes in the blood vessels of the kidney. The second mode of origin is by coagulation of transuded plasma. Salkowski and Leube suggest that fibrin is formed by the action of the dead epithelium on the fibrinogen of the blood serum. This doctrine has been warmly opposed by the French school, who have pointed out that hyaline casts are physically and chemically differentiated from fibrin ; they are non-fibrillated, they do not swell upon the addition of acetic acid, and they are soluble in distilled water, especially when warmed. Fibrin cylinders are sometimes met with, but supporters of the doctrine that hyaline casts, or some variety of them are derived from the blood, ascribe them now to a modification of albumen, effected in some such way as acidu- lation by the renal epithelium. Ribbert tied the renal artery of a rabbit for i^ hours and then injected a weak 2^ per cent, solution of acetic acid into the jugular vein. After boiling the excised kidney he found Bowman's capsules filled with a hyaline mass, and after hardening in alcohol this mass was granular. He also boiled an albuminuric kidney in acidulated water, with the result that beautiful hyaline masses were formed in it ; uric and phos- phoric acid and hydrochloric acid gave equally good results ; but urea did as well, so that acidulation per se appears not to be the essential condition. As these casts have been found in kidneys whose epithelium was quite intact, it must be admitted that congestion alone may give rise to them. Ernst has more recently revived the argument in favour of the fibrinous nature of hyaline casts by showing that they give Weigert's characteristic fibrine staining, but Lubarsch contends that there are many non-fibrinous substances in the body which take up Weigert's stain and in addition hyaline casts may be coloured by agents that will not stain fibrine. Ribbert admits that fibrine cylinders occur under certain conditions, but still believcb in the usual origin of these casts from a modified albuminous transudation. A third theory ascribes them to an exudation or secretion from the tubular epithelium. Aufrecht found after ligature of the ureter in rabbits, if the kidneys were examined within the first three days, the tubules contained many hyaline cylinders, although the epithelium was intact and the interstitial tissue and blood vessels did not show the slightest change ; more- over, he once saw a cylinder made up of single irregular pieces. 40 BRIGHT S DISEASE. separated by fine bright lines, and some of the epithelial cells had fine bright rounded structures projecting firom them. Strauss and Germont have recently confirmed this observa- tion by researches made with a degree of care that leaves nothing to be desired. In thin sections of pieces of kidney hardened in osmic acid, it is seen that even in the first few hours after the ligature the clear protoplasm of the epithelium of the convoluted tubes, and of Henle's loops disappears, and only the striated basal portions with the nuclei remain. This change is closely connected with the formation of these casts, which three or four days after the ligature are present in great numbers in the convoluted tubules, as well as in the medulla and pyramids. Other tubules may be seen liot yet filled by casts, in which the granular contents of the epithelial cells are projecting into the lumen, in the shape of spherical processes of the same colour and consistence as the casts. The following stages in the formation of casts from the exuded droplets can be noted : some are already exuded from the cells and lie free in the lumen of the tube {Fig. 6) ; others project half-way or more and remain still in connection with the cell matrix. Where the change is further advanced, a Tiq. G. Convolaled tubule, catarrhal nephritis. Epithelium represented bj' only basal portion. Cavity of tubule filled with protoplasmic droplets from which casts are formed (osmic acid). number of droplets may be seen to group themselves so as to form a cylindrical mass, the centre of which is homogeneous while the exterior is scalloped by the want of coalescence of its spherical components. It is said by Kelsch that casts formed in this way are com- posed of a colloid material which differs from that of the PATHOLOGICAL RELATIONS OF TUBE CASTS. 41 ordinary hyaline cast, by coagulating into a harder and more brittle substance, having a feebly yellow colour, which stains dark brown with osmic acid, and rose-pink with picro-carmine. There appears to be good reason for accepting the view that hyaline casts originate in each of these ways. It has been already stated that those formed, by metamorphosis from epithelial casts, can generally be recognised by their larger size, or by the change being incomplete. Of the other two kinds it is a question which is the more common. On a priori grounds we should expect that where there is only congestion the casts should be formed by transudation ; but where in- flammatory conditions are present, by secretion. If this is really so, the staining reactions given by Kelsch would afford valuable indications. I believe that casts are very rarely formed by transudation, and my opinion is based on their rarity in so-called functional albuminuria. As a' clinical fact we know that casts are only few and far between, unless inflammation is present. We know that in diabetes, when casts are present, there is apt to be structural kidney change ; and their presence in jaundice is explained by the observations of Mobius, who found that per- sistent excretion of bile by the kidneys destroyed the renal epithelium. So, too, in old standing heart disease, the kidneys are liable to more or less change of a chronic inflammatory nature. It is also quite probable that there are transient con- ditions of renal irritation, comparable with that produced by. temporary constriction of the renal artery, in which the epithelium 'may secrete casts, and that this explains their occurrence in the case of Weston, and in attacks of gout. Practically, therefore, we ought to attach very high importance to the recognition of epithelial and hyaline casts as evidences of irritation or inflammation of the renal epithelium. We can measure the intensity of this process by their number, and watch its progress by their persistence. Epithelial casts bear witness to severe inflammation, such as occurs in acute and sub-acute Bright's disease ; broad hyaline casts have the same meaning, being formed from the epithelial variety as already explained, but slender hyaline casts testify only to a mild inflammatory process, such as occurs in the contracting kidney, or during the subsidence of an acute attack. Stcimiiary. — i. Casts of the renal tubules are of three kinds — blood, epithelial, and hyaline. 42 BRIGHT S DISEASE. 2. Blood casts are evidence of haemorrhage from the gland- ular substance of the kidney. 3. Epithelial and broad hyaline casts are evidence of acute and sub-acute inflammation of the kidney. 4. Slender hyaline casts are evidence only of a mild inflam- matory process, which rnay be the result of a transient irritation. BIBLIOGRAPHY. AuFRECHT. Die diffuse Nephritis und die Entziindung in allgemeine. " Cent. f. d. Med. Wiss.," 1878, p. 337. CoRNiL and Brault. Etudes sur la Pathologic du Rein. Paris: Felix Alcan, 1884. Ernst (P.). Ueber das Vorkommen von Fibrin in Nierencylindern. " Beitr. z. allg. Path. u. path. Anat.," XII., p. 553, 1893. Langhans (T.). Ueber die Veranderungen der Glomeruli bei der Nephritis nebst einigen Bemerkungen iiber die Entstehung der Fibrincylinder. " Vir- chow'sArchiv," Bd. LXXVL, p. 85. LuBARSCH (O.). Ueber die Natur und Entstehung der Nierencylinder. " Centrlblt. f. allg. Path.," 1893, IV., 6. MoBius. Beitrage der Niere beim Icterus. "Arch. d. Heilkunde," Bd. XVIII., p. 83. PosNER (C). Studien liber pathologischen Exudatsbildungen. " Virchow's Archiv," Bd. LXXIX., p. 311. RiBBERT (H.). Ueber die Eiweissausscheidung durch die Nieren. "Cent. f. d. Med. Wiss.," 1S79, p. 47, and 1881, p. 17. Zur Bildung der hyalinen Harncylinder. Ihid. XI. Strauss and Germont. Des Lesions histologiques du Rein, chez le Cobaye, a la suite de la Ligature de I'Uretere. " Arch, de Phys.," Tome IX., 1882, p. 3S6. 43 CHArTER V. CARDIO-VASCULAR CHANGES. Next to dropsy and the state of the urine, the alterations in the circulatory system are the most striking clinical and pathological facts met with in Bright's disease. Clinically, they are present in the shape of physical evidences of cardiac hypertrophy, with increased arterial tension ; pathologically, the changes described are hypertrophy of the heart, and thickening of the small arteries. The h}'pertrophy of the heart may be a genuine hyperplasia of the muscular substance, but evidences of interstitial myo- carditis, such as thickening of the inter-muscular fibrous tissue, and pigmentary or fatty degeneration of the muscular fibre are often present. The heart may enlarge very rapidly even in acute nephritis, but it is in association with the chronic forms, especially the contracting kidney, that hypertrophy is most commonly met with. Bartels asserted that he had " never failed to obtain the objective signs of hypertrophy of the left ventricle in any of his cases of genuine contracting kidney, or to confirm the fact in every post vioTtein made upon their bodies, and therefore he can never hold that a diagnosis of this renal disease is made certain when no enlargement of the left ventricle is recognised." This statement would be of the utmost value if true, for we should then have a most important confirmatory sign. Dickinson says that an analysis of 250 cases of granular degeneration, drawn from St. George's Hospital books, gave 48 per cent, as the proportion of cardiac enlargement, and that since his attention was directed to the subject he has scarcely seen an instance in which, if the renal disease was distinctly recognised, whether after death or in life, some degree of cardiac hypertrophy was not also present. He re- gards simple cardiac hypertrophy as one of the most important diagnostic signs of this form of renal disease. Ewald found hypertrophy of the heart in 20 out of 21 cases of granular kidney. On the other hand Grainger St: wart 44 BRIGHT S DISEASE. speaks of nearl}- one half of a series of cases he examined post mortem having had enlarged heart simply from renal disease, while many others had enlargement connected with valvular or vascular lesions. Gull and Sutton state that they have particulars of nine cases in which the kidneys were very contracted and the heart was free from hypertrophy. I found that out of lOO typical cases examined /^j-^ mortem at the General Hospital, 44 had simple cardiac hypertrophy, and 16 hypertrophy with valvular disease, the proportion being 60 per cent, of hypertrophy with and without valvular disease. In addition, out of 87 carefully selected living" cases in which the state of the heart was noted, and in which the coincidence of symptoms fully justified the diagnosis of con- tracting kidney, there was evidence of cardiac hypertrophy, with or without valvular disease, in 52, — also as nearly as possible 60 per cent, of the cases. The following table gives the state of the heart in 807 cases of all forms of Bright's disease collected by Bamberger. I I g.^jj )-i (U . S^i '^' a Form of 'Z 0^ TS^'i: < Bright's Disease. Excentrl trophy whole Excentri trophy left ver Simple trophy whole III til III a5 — H Acute - 3 4 2 2 4 15 Chronic 51 38 3 24 5 I 122 Contracting 88 142 65 6 39 7 2 207 Total 107 II 65 16 3 344 Senator has endeavoured to show that in contracting kidney the heart undergoes concentric hypertrophy, while in fatty kidney the hypertrophy is accompanied by dilatation, causing cxcentric hypertrophy. Hanot has supported these views. While every pathologist will admit the frequency with which hypertrophy with very little dilatation accompanies contracting kidney, all pathological records disprove such an arbitrary division. Grawitz and Israel found in artificial nephritis, that while the small red or large white kidney resulted indifferently, concentric and excentric cardiac hypertrophy occurred also without any relation to the type of the accompanying change in the kidney, and this is equally true in human pathology. Traube has the merit of being the first to draw attention to the CA RDIO- VASC ULA R CHA NGES. 45 hard radial pulse so frequently present in contracting kidney ;• and this fact, together with the accentuation of the second sound of the heart, has been particularly insisted on by Johnson. Sibson drew attention to the doubling of the first sound often accompanying these two phenomena, and explained all three as evidences of increased blood pressure in the aortic system. Galabin has shown that the high tension pulse occurs in all forms of renal disease, but is most constant in cases of con- tracting kidney. Our present purpose is to enquire into the nature and causes of these changes. This pulse of high tension can be readily recognised. In some cases the radial artery is hard and prominent, feeling, as has been said, like the spermatic cord, but without any un- evenness to suggest calcareous deposit ; in other cases there is nothing noteworthy about the feel of the vessel. The com- pressibility of the pulse can be best estimated by placing the forefingers of both hands side by side upon the artery, gradual pressure being made with the proximal finger, while the distal finger notes the effect upon the pulse. The sphygmographic tracing of the high tension pulse is characteristic. Fig. 7 represents a tracing from a normal pulse. The letter a is placed at the summit of the percus- sion up-stroke, which is caused by the sudden impulseof the ventricular systole, and corresponds in height to the force of the left ventricle. The letter b marks the dicrotic notch ; the little fall is due to the termination of the systole and the little rise to the recoil of the Fig. 7. Normal pulse tracing mit of percussion up-stroke; notch; a to 6, Tidal wave. Fi<7. 8. Pulse tracing, acute nephritis, showing high tension with a relatively feeble ventricle (myocarditis ?). Fiij. 9. Pulse tracing; chronic nephritis, with heart failure. High tension with a relatively feeble ventricle (brown atrophy and incompetent aortic valves). vessels and the closure of the aortic valves. From a \.o b is the curve of the tidal wave, which lies below the straight hne drawn from a to b. The position of this tidal wave line is the 46 BRIGHT S DISEASE. index of tension ; it rises with the tension until in high tension pulse tracings it lies above the line a b. Figs. 8, 9 and lo are tracings of pulses from three typical cases of Bright's disease. Fig. 8 is from acute catarrhal nephritis after sore throat ; Fig. g is from a case of large white kidney which died from heart failure ; and Fig. lo is from a well marked case of contracting kidney which led to complete blindness from albuminuric retinitis. In Figs. 8 and g the short up- stroke is due to the relatively feeble left ventricle. In the acute case there were signs of cardiac dilatation probably caused by acute softening (myocarditis) ; and in the Fio.lO. Pulse tracing; contracting kidney. SCCOnd CaSe We ha.Q. J>OSt IllOrteVl High tension, with cardiac hypertrophy. g^idence of thc State of the heart. Bright, in recording the various organic changes in a hundred cases of renal disease, says, " The obvious structural changes in the heart have consisted chiefly of hypertrophy, with or without valvular disease ; and what is most striking, out of fifty-two cases of hypertrophy, no valvular disease whatsoever could be detected in thirty-four ; but in eleven of these thirty-four, more or less disease existed in the coats of the aorta ; still, however, leaving twenty-two without any probable organic cause for the marked hypertrophy generally affecting the left ventricle. This naturally leads us to look for some local cause for the unusual efforts to which the heart has been impelled ; and the two most ready solutions appear to be, either that the altered quality of the blood affords irregular and unwonted stimulus to the organ immediately, or, that it so affects the minute and capillary circulation as to render greater action necessary to force the blood through the distant sub-divisions of the vascular system." It will be found that the pendulum of modern opinion is now again oscillating between these two explanations in spite of fort)^ years of discussion and observation with the aid which the modern use of the microscope has lent to pathological re- searches. Thus Senator suggests that in chronic parenchyma- tous nephritis the hypertrophy is probably attributable to the increased capillary resistance ; while, in interstitial nephritis, the hypertrophy is due to direct irritation of the heart, either from some nervous disorder, as in Graves' disease, or, as is more likely, from the blood dyscrasia. CARDIO-VASCULAR CHANGES. 47 Since the time of Bright there have been four original explanations brought forward and all other writers have adopted some one, or a combination, of these four theories. Traube, to whom we owe the observation of the hard pulse of Bright's disease, regarded the destruction of a large capillary area in the kidneys as necessarily causing so much obstruction to the circulation that, aided by the imperfect elimination of water, the blood pressure in the aortic system must rise and cardiac hypertrophy follow. Bamberger objected to this that the hypertrophy begins in the earlier stages of Bright's disease ; moreover it is present in chronic parenchy- matous nephritis in which no destruction of capillaries has occurred. Ludwig and his pupils have shown that ligature of both renal arteries, or of even larger arteries, does not raise the blood pressure in the aorta; while it is well known that in contracting kidney the elimination of water is rather in excess of the normal, yet it is specially in this affection that cardiac hypertrophy occurs. It is, therefore, not without reason that this hypothesis has been generally abandoned, although in recent times it received thesupportof so eminent an authority as Bartels. The next original explanation was that given by Johnson, which has undergone at least two modifications. In the first place Johnson pointed out the excessive thickening of the muscular walls of the renal arterioles, and suggested that the obstruction to the circulation offered by a state of tonic spasm in these vessels would explain their own alterations, the rise of blood pressure and the cardiac hypertrophy. But having been able to discover similar changes in the vessels of the pia mater and mesentery, he enlarged his hypothesis and imagined a state of tonic spasm of the whole systemic arterioles which he attributed at first to direct irritation by the impure blood, and later on to stimulation of the vaso-motor centre. According to his latest views he regards the condition as analogous to asphyxia, in which unoxygenated blood going to the brain stimulates the vaso-motor centre in the medulla, and causes contraction of the arterioles throughout the body with conse- quent increase of the arterial blood pressure. A great objection to this theory of general constriction of the vascular system is that, under such circumstances, the urinary secretion would be diminished or suppressed, as happens in asphyxia (Eichhorst) ; whereas in contracting kidney, as is well known, the rise in blood pressure is accompanied by an in- crease in the flow of urine. Griitzner has shown that the 48 B RIGHTS DISEASE. diuresis excited by the intravascular injection of salts, such as nitrate of potash, is arrested during suspension of the respiration, unless the nerves to the kidney are divided. There is, however, good clinical evidence that vascular contraction occurs in the skin, as shown by the remarkable grey complexion, cold hands and feet, and " dead fingers " so often observed in the subjects of chronic Bright's disease, and it may be fairly allowed that the constant recurrence of this phenomenon would not be without effect upon the heart in the course of time. The third original explanation is that of Gull and Sutton. They rediscovered the vascular changes described by Johnson, but drew special attention to the thickening of the inner and outer coats, and asserted that the muscular coat was atrophied. They regarded these vascular changes as primary and essential ; of which the increased blood pressure and cardiac hypertrophy are results, while the kidney disease is a mere local expression of a generalised degeneration of the arterioles and capillaries, attended by atrophy of adjacent tissues. With regard to these assertions we owe to Thoma the careful measurements which demonstrate that the arterioles of the kidney are absolutely dilated, in spite of the increased thickness of their walls. He showed, too, by careful injections, that while fluids run well into the Malpighian bodies, the efferent artery is often destroyed, and the capillary plexus on the tubules is to a large extent obliterated. , / Moreover, an unprejudiced / investigation of sufficient extent will convince any one that many vessels show great hypertrophy of the muscular coat, and that not a few present an appearance of a concentric arrangement of spindle cells lined by swollen elastic tissue {Fig. 1 1 ). In others, however, the inner coat is much thickened, forming a broad layer of lowly organised connective tissue ; the muscular coat may be atrophied, and the adventitia passes inseparably into the sur- rounding connective tissue. I have looked for the changes in pia mater, peritoneum, skin and other tissues. In the pia mater, thickened vessels are often seen, in other situations very rarely. But the pia mater Fig. 11. Eenal arteriole showing Endarteritis obliterans, a. Swollen elastic lamina, its fibres separated and oedematous ; b, Broad growth ot connective tissue from the endothelial layer; c, Swollen muscular coat with large distinct nuclei {contracting liidney). CARDIO-VASCULAR CHANGES. 49 itself is often altered in chronic Bright's disease, looking opaque, and more or less milky. It is in this condition that the thickened vessels are found, and the true interpretation seems to be that it is a chronic endo- and peri-arteritis associ- ated with sub-inflammatory changes in the perivascular tissues. But, apart from this, the changes are not constant. Ewald found out of twenty cases of contracting kidney with hyper- trophied heart, the vessels were not thickened in four, while in a similar examination I found them not thickened in two cases out of ten, so that this disposes of the assertion that the vascular lesion is primary and essential. As, too, in chronic nephritis following an acute infective attack, cardiac hypertrophy is common while the vascular changes are exceptional, they cannot be regarded as standing in any important relation to one another. Finally, we know that both cardiac hyper- trophy and high tension pulse occur in acute nephritis and even in " surgical kidney," in which there is no question of " arterio-capillary fibrosis." The last explanation is that of Buhl. He believes the cardiac and renal changes proceed pari passu, the hypertrophy being attributed to the increased activity of the heart. Myo- carditis occurs very early, and may lead to no alteration, or to atrophy or hypertrophy of the organ, according to circum- stances. Most frequently it causes hypertrophy. As the inflammatory process comes to an end the cardiac muscle hypertrophies from excess of nutrition, and to overcome the increased work of the dilated ventricle. In addition he asserts that a relative stenosis of the aorta is present. The rise of blood pressure in the aortic system is therefore due to the hypertrophy of the ventricle and the narrowing of the aorta. The relative frequency of myocarditis in renal disease is an undoubted fact, and this process plays an important part in many cases, but there is no warrant for the assumption that it has occurred in all cases. Buhl is not at all clear as to the cause upon which the increased activity of the heart or the myocarditis depends. He cannot claim novelty for the fact that the aorta is in some cases relatively stenosed, for Bamberger adduced it as opposed to Traube's hypothesis. With regard to its frequency in granular kidney Ewald has measured the circumference of the aorta above the valves in twelve cases, and found it to vary between I2'i and 57 cm., 4 50 BRIGHT S DISEASE. the average being y6 cm., while the normal circumference according to Bouillaud is 6'3 cm., so that very much im- portance cannot be attached to it as a cause of cardiac hyper- trophy. Having failed to find any of these explanations quite satisfactory, let us return to Bright's suggestions, either that the altered quality of the blood affords irregular and unwonted stimulus to the heart immediately ; or, that it so affects the capillary circulation as to render greater action necessary to force the blood through the distant subdivisions of the vascular system. Both these explanations rest upon the supposed im- pure state of the blood. In the acute and chronic stages of parenchymatous nephritis the condition of the blood was investigated many years ago by Bostock, Gregory, and Christison. According to the latter, urea was always found in considerable quantity in the blood whenever the excretion of urine was diminished ; the density of the blood serum was always less, and the fibrine was frequently increased. Nothing of importance has been added to this observation in modern times ; but experiments with animals have shown that urea, extractive matters of the blood, creatine and leucin accumulate in large quantities in the blood and tissues after nephrotomy ; and it cannot require much argument to convince anyone that during the abeyance of the renal function the blood depurating process must be more or less incomplete. In contracting kidney the density of the serum is diminished (Rees, Rayer) ; the proportion of salts and albumen is lowered ; and there is a rapid reduction of the blood pigment or hsemoglobin (Leichtenstein). Bartels published some observations, but none of them bearing on the state of the blood in the earlier stages ; in the later stages, when dropsy v/as present, the density of the blood serum was low ; a certain amount of urea was found in many cases, in others it was absent. There are other reasons for believing that blood impurities are early and important phenomena in contracting kidney. Todd first pointed out the frequent co-existence of this form of renal disease with gout, hence the name gouty kidney ; Ollivier has drawn attention to its common occurrence among workers in lead. Johnson states that the disease is common in persons who " eat and drink to excess, or who, not being intemperate in food or drink suffer from certain forms of dyspepsia, without the complication of gouty paroxysms." He says that "renal CARDIO-VASCULAR CHANGES. 51 degeneration is probably a consequence of the long-continued elimination of products of faulty digestion through the kid- neys." Murchison was persuaded of the relation borne by contracted kidney to persistent lithaimia. Semmola, of Naples, maintained the view that Bright's disease is a conse- quence of the blood dyscrasia resulting from suppression of the respiratory function of the skin. Therefore, although during the greater part of its course this affection does not lead to any diminution of the renal secre- tion, there is ground for believing in a blood dyscrasia depending upon other causes. The next point for inquiry is whether such blood impurity as may arise from defective elimination or perverted digestive functions can be shown under any conditions to obstruct the capillary circulation. Heidenhain speaks of copious diuresis occurring after the injection of urea in spite of the blood pressure remaining below normal, or not being proportionately increased. Ustimowitsch and Grlitzner after injecting urea into the blood observed a certain constant rise in blood pressure accompanied by increased flow of urine. Rendu in his inaugural thesis quotes Potain as having noticed that although injections of urea into the blood do not modify the mechanical conditions of the circulation, yet if a mixture of urea and blood serum be allowed to stand some hours, and be then injected, the arterial tension rises to an un- expected degree. Haig finds that retention of uric acid in the blood causes in- creased vascular tension, but he considers that the effect is produced by the intervention of some modified albumens re- sulting from the dyscrasia. Gravvitz and Israel found that neither unilateral artificial nephritis nor extirpation of one kidney, although followed by hypertrophy of the heart, effected any rise in the blood pres- sure. By taking strict antiseptic precautions they were able to clamp either of the renal arteries of a rabbit without any unfavourable surgical result. One and a half to two hours afterwards the clamp was removed. In half an hour after the operation the urine became bloody, and in from one to two hours the organ if examined was found to be greyish red and opaque. If the clamp was allowed to remain on longer the kidney became of a dirty yellowish grey colour, indicating commencing gangrene. The effect of this operation was t® 52 BRIGHTS DISEASE. cause intense acute parenchymatous nephritis with fatty degen- eration of the epitheHum of the tubules. This passed into either granular atrophy or the large white kidney. In the former, microscopical examination showed no trace of nuclear prolification, the substance of the organ consisting simply of wasted tubules. In another series of experiments they extir- pated one kidney altogether. They found that the results of these conditions varied accordingly as the animals operated on were young and growing, or old, strong, and fully grown. In you7ig animals, after two or three days, the intact kidney began to increase in size to 20 or 30 per cent, more than its normal weight. As the contraction of the other kidney went on, the intact organ continued to increase until it equalled the weight of the two kidneys of an animal of the same size. At the same time they ascertained by abdominal section that the other kidney still secreted a watery urine of low specific gravity, but in small quantity. In old animals the intact kidney also increased a little, the greatest being in one case of nephrotomy, where the extir- pated right kidney weighed 77 grms., and the left, after 82 days, weighed 1 1 "3 grms. The hypertrophy of the kidney consisted in a true hyperplasia of the renal elements, at least the enlargement was certainly not due to increase in the diameters of the tubules. The consequence of the imperfect compensation by hypertrophy of the other kidney caused in some cases death by acute or chronic uraemia ; in others the animals continued to live, but were ill nourished until the deficit was covered by hypertrophy of the left ventricle. By careful estimations of the relative normal weights of the heart and kidneys, and comparison of these data with the weights of the altered organs, they were able to determine that the cardiac hypertrophy bore a definite proportion to the loss of renal substance, and therefore was truly compensatory for the renal defect. As a rule the heart was not dilated, in many cases the ventricle was in a state of spasmodic contraction, and they were unable to obtain any confirmation of Senator's views already quoted relative to the pathogenesis of excentric and concentric hypertrophy. In those cases where cardiac dilatation occurred, the symp- toms during life indicated that compensation was either primarily defective or later destroyed, and the animals died with acute or chronic dropsy. In the case of a large black CARDIO-VASCULAR CHANGES. 53 doe, which died with dropsy of all the serous cavities ten days after the operation, the cardiac muscle was intensely granular, even after the addition of soda solution. They regard this as evidence of the occasional occurrence of primary myocarditis. Much more frequently the myocarditis was secondary, but whichever it was it produced the appearance of " excentric hypertrophy." They were never able to obtain evidence of any increased blood pressure, but by careful measurements they determined a constant increase in the velocity of the circulation. Injections of urea also failed to produce a rise of blood pressure, but stintulated tJie heart's action and quickened the blood stream. More recently Grawitz has shown that cardiac hypertrophy may be induced by loading the blood with urea by giving it to rabbits in their food. Here we have the explanation of the " self increased activity " of the heart, to which Buhl refers, and also of the myocarditis. The impure state of the blood acts as Bright suggested, by affording an unwonted stimulus to the heart im- mediately, and this leads to a hypertrophy proportionately compensating for the loss of renal secreting substance. Myocarditis is the cause of dilatation and the subsequent hypertrophy takes place as Buhl indicates, from over nutrition and increased work due to the greater capacity of the ventricle. The rise in blood pressure is not a cause of the cardiac hyper- trophy, but a consequence ; yet in these experiments the state of the heart, the renal condition, and the blood impurity com- bined, were unable to effect any increase in the tension of the aortic system. But the high pressure pulse of Bright's disease is a constant and now universally admitted fact. Traube asserted, not without reason, that he could diagnose contracting kidney by the pulse alone, and Galabin has shown that the same con- dition is present in the other forms of Bright's disease. A great step was taken when Mahomed proved that this rise in blood pressure precedes the occurrence of albuminuria, the development of which he watched at the termination of scarla- tina. Here there is no question of structural change in the heart or arterioles ; the sole condition present is that of faulty elimination due to the morbid state of the skin. When constipation occurs the blood pressure rises, and if not averted by a sharp purge, albuminuria follows. Moreo\'er, Mahomed recorded cases of high arterial tension, sometimes accom- 54 BRIGHT S DISEASE. panied by albuminuria, in young dyspeptic patients free from cardiac hypertrophy. If the rise in pressure precedes all structural change it must be due to increased energy in the cardiac contractions, or to obstruction in the distant parts of the vascular system, or to both combined. Most modern writers, Grainger Stewart, Broadbent, Mahomed, Ewald, and others, regard the obstruc- tion as seated in the capillaries, and the cardiac hypertrophy as the consequence of this impediment to the circulation. But we have seen that the cardiac hypertrophy must be regarded as directly dependent on the state of the blood, and therefore is rather to be regarded as a cause than an effect of the rise in blood pressure. Grawitz and Israel appear to have proved that the cardiac hypertrophy /^r se does not raise the blood pressure, nor does the state of the blood which manifests itself by the stimulus to the heart's action seem to suffice to produce any peripheral obstruction great enough to cause this result. We are com- pelled therefore to seek some other factor, or to believe that in some respect the conditions of these experiments differ from those of patients suffering from Bright's disease. Such a difference plainly existed in the intact state of one kidney, and it may be that the rise of blood pressure, with which we are clinically familiar, is the result of a dyscrasia differing in some respects from that present in these experiments. Hamilton has suggested that the increased capillary resist- ance may be explained by alterations in the specific gravity of the blood serum, and gives the following ingenious explanation of the way in which obstruction would be effected by this change. Any one who has watched the circulation of the blood in a frog's web or mesentery, has noticed the way in which the corpuscles run in a central core in the blood vessels. " This is due to their being of almost exactly the same specific gravity as the serum. If a body of the same specific gravity as the liquid in which it is suspended is made to travel through either a straight or bent tube, it runs in the axial stream, while, if it is lighter or heavier than the liquid it runs respectively on the upper or lower surface of the tube. The coloured blood cor- puscles are almost of exactly the same specific gravity as the living plasma in which they are suspended, while the colourless are markedly lighter. Now the whole essence of the blood as a circulating fluid, is that the coloured corpuscles suspended in CARDIO-VASCULAR CHANGES. 55 it never touch the wall of the smaller vessels, even of the minutest capillaries. They glide along in the axial stream without any sign of impediment. A body of the same specific gravity as the liquid in which it is suspended further turns round a curve in the tube with ease, while one lighter or heavier experiences the greatest difficulty in doing so and continually tends to catch at the bends. " Hence from the great mass of the solid particulate matter of the blood being practically of like specific gravity with the living plasma, undue friction is avoided, and the blood as a whole circulates with very much the same facility as pure plasma would. When a light substance such as oil or milk is introduced into the circulation it will not circulate, because the particles catch in the curves of the vessels, more especially in parts like the lung, where the vessels are particularly tortuous. Blood circulates through a capillary glass tube exactly as it does through a small vein or capillary vessel. The coloured corpuscles occup}' the axial stream, the colourless the peri- pheral. Hence the phenomenon must be a purely physical one. Further, the position in the stream occupied by bodies thus suspended in a liquid may be altered at will, not only by altering the specific gravity of the bodies themselves, but also by clianging that of the suspending liquid. " Thus by substituting a very light liquid or a very heavy one, the suspended blood corpuscles may be made at will to course along either the lower or the upper surface of the vessel. They come in contact with it, and by rubbing against the wall are made to roll instead of to glide. The friction thus caused retards their progress ; they tend like oil globules to catch in the curves of the vessels and thus to cause obstruc- tion to the ever continuous flow of the blood stream. The difficulty that may thus be caused by this apparently trivial cause in moving the blood onwards, comes to be very great when estimated all over the body ; and were it the case that a marked difference in the relative specific gravities of the blood plasma and the coloured corpuscles prevailed, the continuance of the even onflow of the blood with the usual propelling power would become a physical impossibility." I have made this long quotation in order to secure the advantage of the author's own words, as the explanation is exceedingly interesting and ingenious, and has not received the attention it deserves. Sumviary. — i. Cardiac hypertrophy is met with in all forms 56 BRIGHT S DISEASE. of Bright's disease, including acute nephritis, but is most com- mon in contracting kidney. 2. It is due to : {a) stimulation of the heart to increased activity by the presence of non-eliminated poisonous matter, e.g., urea, in the blood ; {I)) increased capillary resistance. 3. Increased capillary resistance may be ascribed to altera- tions in the density of the blood plasma. 4. The high tension pulse is due to the same causes : viz., increased energy of the heart and greater capillary resistance. BIBLIOGRAPHY. Bright (R.). Tabular view of the morbid appearances occurring in one hundred cases with the secretion of albuminous urine. " Guy's Hosp. Reports," Vol. I., p. 380. Buhl. Ueber Bright's Granularschwund der Nieren und die damit zusammenhangende Herzhypertrophie. " Mitt, aus dem path. Ins. zu Miinchen," 1878, p. 38. Dickinson (W. H.). The pathology and treatment of Albuminuria. 2nd edition. London, 1877, p. 178. EiCHHORST (H.). Der Einfluss des behinderten Lungengaswechsels beim Menschen auf den Stickstoffgehalt des Harns. " Virchow's Archiv," Bd. LXX. . p. 56. EwALD (C. A.). Ueber die Veranderungen kleiner Gefiisse bei Moibus Brightii und die darauf beziiglichen Theorien. "Virchow's Archiv," Bd. LXXL.p. 453. Galabin (A. L.). The state of the circulation in acute diseases. " Guy's Hosp Reports," 3rd series, Vol. XIX., 1873-4, p. 61. Grawitz (P.) and Israel (O.), Experimentelle Untersuchungen ueber den Zusammenhang zwischen Nierenerkrankung und Herzhypertrophie. " Vir- chow's Archiv," Bd. LXXVIL, p. 315. Grutzner. Beitriige zur Physiologic der Harnsecretion. " Pfliiger's Archiv," Bd. XL, p. 370 Gull and Sutton. On the pathology of the morbid state commonly called chronic Bright's disease with contracted kidney. " Med. Chir. Trans.," 1872, Vol. LV. , p. 273. Haig (A.). The connecting link between the high pressure pulse and albuminuria. " Brit. Med. Journ.," 1890. Vol. I. Hamilton (D. J.). Discussion on Albuminuria. " Glasgow Med. Journal," Vol. XXL, 1884, p. 211. Hanot (V.). Contribution a I'etude de I'hypertrophie concentrique du ventricule gauche dans la nephrite interstitielle. "Arch. Gen. de Med.," 1878, Vol. XL, p. 172. Johnson (G,). Diseases of the Kidney. London, 1852. Lectures on Bright's disease. London, 1873. '■ Lumleian lectures on the Muscular Arterioles, London, 1877. Mahomed (F. A.). Clinical aspects of chronic Bright's disease. "Guy's Hosp. Reports," 3rd Series, Vol. XXIV., p. 363. The Etiology of Bright's disease and the pre-albuminuric stage. " Med. Chir. Trans.," 2nd series, Vol. XXXIX., p. 197. CARDIO-VASCULAR CHANGES. 57 Rendu. Etudes comparatives des Nephrites chroniques, " These de Paris," 187S. Senator (H.). Ueber die Beziehungen der Herzhypertrophie zu Nieren- leiden. " Virchovv's Archiv," Bd. LXXIIL, p. 313 SiBSON (F.). Harveian lectures on Bright's disease and its treatment. " Brit Med. Jour.," 1877, Vol. I., p. 33. Stewart (Grainger). A practical treatise on Bright's disease of the Kidneys. 2nd edition, 1871, p. 233. Thoma (R.) Zur Kenntniss der Circulationsstorung in den Nieren bei chronischer interstitieller Nephritis. " Virchow's Archiv," Bd. LXXI. Heft. I and 2. Traube. Ueber den Zusammenhang von Herz und Nierenkrankheiten. Berlin, 1856. UsTiMowiTscH. Beitrage zur Theorie der Harnabsonderung, " Arbeit, aus der physio. Anstalt zu Leipzig," 1S71, p. igS. 58 Chapter VI. PATHOLOGY OF POLYURIA. In the later stages of acute Bright's disease the urinary- secretion, which is greatly diminished at the commencement of the attack, often rises to more than the normal amount ; in chronic parenchymatous nephritis the daily quantity of urine is generally excessive, while in the contracting kidney Christi- son wrote truly " No single symptom has appeared to be so invariable or of so much service for indicating the commence- ment of the disease as the fact of the patient being awakened once or oftener in the night time by the necessity of passing urine. I have scarcely ever known it wanting when any other local symptom existed ; frequently it has been present without any other for a great length of time, and it is so remarkable a deviation from the ordinary rule of health that, although it may have been neglected, no individual can fail to recall it when his memory is tasked on the subject by his physician." This copious urine is after all a poor secretion, often con- taining less than the normal total solids, and represents solely an increase in urinary water. The question how this increased outflow of water is caused may not appear at first sight a very practical one, but it has an important bearing on prognosis and treatment, and its theoretical interest is evidenced by the attempts of most authors to give some satisfactory account of it. Thus Bartels gave the following explanation : — " Observation teaches us that contracting kidneys which have dwindled down to more or less considerable remnants of secreting glandular tissue, do not merely continue to secrete urine, but in the large proportion of cases actually furnish, in- the same interval of time, a larger quantity of urine than healthy kidneys would supply. This, however, takes place only so long as the condition of the hypertrophied left ventricle is capable of maintaining the blood pressure in the aortic system at its abnormal height. That the secretory perform- ances of the kidneys depend upon the elevation of the pressure PATHOLOGY OF POLYURIA. 59 in the arterial system, is proved as distinctly as is possible by physiological experimentation. If the arterial pressure ex- ceeds its normal bounds, it follows of necessity that, (csteris paribus, a larger quantity of urinary fluid must be forced through the renal apparatus during the same interval of time than would take place under normal pressure." .... " The greater rapidity with which the secretion of the urine is conducted is, at the same time, the cause of its possessing so invariably low a specific gravit}% i.e., of its remaining so relatively poor in solid constituents." . . . . " But so soon as the propulsive power of the hypertrophied heart is reduced, in consequence either of some temporary or permanent in- fluence, the abnormally large amount of urine falls off" and the abnormally low specific gravity rises." On the other hand, Johnson takes a different view ; he says, " There is no reason to suppose that high arterial tension has any direct tendency to cause an increased secretion of urine. In cases of contracted kidney the two conditions are associa- ted, but in the early stages of lardaceous kidney the copious secretion of urine occurs without arterial tension. It is probable that in both classes of cases the copious flow of urine is caused by the diuretic influence upon the kidney of some abnormal products in the circulation, — an influence analogous to that of sugar in diabetes." But it is also part of Johnson's theory that the renal arterioles are contracted ; in his own words, "The contraction of the hypertrophied renal arterioles counter- acts the injecting force of the strong left ventricle, and thus prevents an afifiux of blood in the capillaries of the kidney." GrUtzner found that when he injected saltpetre into the blood, the renal nerves on one side only being divided, the urinary secretion was copious, and equal from both kidneys, when there was only a slight rise in the blood pressure ; but when the latter was artificially raised by suspension of respira- tion, the secretion of urine sank in the kidney with its nerves undivided. That is to say, the saltpetre produced its diuretic influence on both kidneys so long as the flow of blood to them was unimpeded, and without the aid of a general rise in the blood pressure ; but the moment the arterioles were contracted under the influence of the vaso-motor nerves stimulated into action by the poisonous effect of the carbonic acid upon their centre in the medulla oblongata, the urinary secretion continued only from that kidney whose arterioles, by division of their nerves, were beyond the reach of vaso-motor action. 6o BRIGHT'S DISEASE. Newman has suggested that the polyuria of contracting kidney is due to obstruction of the lymphatics. Physiologists are now agreed that the amount of urine depends for the most part upon the blood pressure in the area of the renal artery ; this may in turn depend upon [a) Systemic causes, by which the general blood pressure is raised ; {U) Local causes, determining the afflux of blood to the glomeruli. The last chapter was devoted to the subject of the high arterial tension of Bright's disease, and to proving that this is due to two factors — (i,) The over activity of the heart stimu- lated by the presence of excrementitious matters (urea, urates, etc.,) in the blood, and (2,) Impeded capillary circulation from alterations in the blood serum. It is unnecessary to repeat the facts and arguments of that chapter. In the general rise of blood pressure there is the first and most important factor in the causation of polyuria, for nothing can be more certain than the clinical fact already alluded to by Bartels, that as in the later stages the heart fails, the polyuria disappears and dropsy sets in. Temporary plethora produced by abundant drinking is rapidly followed by polyuria. In the large white kidney, the renal vessels are dilated from inflammation, so as to favour the access of a large amount ot blood to the Malpighian bodies ; this in part accounts for the polyuria in this form of Bright's disease. In early cases of contracting kidney there is nothing to oppose the free afflux of blood to the glomeruli, while the pro- gressive destruction of capillary areas beyond them must tend to raise their blood pressure and favour filtration. But in the advanced stages of contracting kidney the renal ai'tery is, according to Thoma, narrower than normal ; this is probably counterbalanced by the reduced number of glomeruli to be supplied, and we know from the same observ^er that the arterioles are dilated, so that the afflux of blood to the glomer- uli is very free. We may therefore conclude that there are local conditions which favour the occurrence of high pressure within the glomeruli. But hydrostatic pressure alone is not concerned ; the epi- thelial cells covering the glomeruli participate in the process of secretion. It is to this factor that Johnson ascribes the polyuria. Heidenhain found that a copious flow of urine followed the injection of urates into the blood, while the blood PATHOLOGY OF POLYURIA. 6i pressure remained low ; and urea is said (Landois) to owe its diuretic action to its influence on the epithelium, though Ustimowitsch and Griitzner observed the polyuria produced by it to be accompanied by increased arterial tension, — a result we should expect from what we have learnt previously of its action in stimulating the heart's energy. Munk says that all ordinary diuretics, except digitalis {e.g., common salt, sugar, caffeine, saltpetre, glycerine, pilocarpine) cause diuresis by their direct effect on the renal epithelium, as they widen the renal arteries and slow the blood current. Finally, differences in the permeability of the glomerular walls must also be held accountable for changes in the amount of urine. Thoma found that in \'ery early stages of the contracting kidney, before the microscope shows any changes in the glomerular wall, this structure becomes abnormally permeable. We may assume a similar increased permeability as being probably present, though this has not been proved, in the large white kidne}^ Sumviaiy. Polyuria is due to the co-operation of these four factors : — {a) Increased general blood pressure ; explained in the last chapter. {[}) Increased local blood pressure ; due to dilatation of afferent vessels and destruction of capillary areas bej'ond the glomeruli. (c) Increased activity of the glomerular epithelium, stimu- lated by the presence of urea, urates, etc., in the blood. (<^) Increased permeability of the glomerular walls. BIBLIOGRAPHY. Bartels (C). Diseases of the Kidney. " Ziemssen's Cyclopaedia of the Practice of Medicine. " Vol. XV. London, 1877. Grutzner. Beitrage zur Physiologie der Harnsecretion. " Pflijger's Archiv," Bd. XL, p. 370. Johnson (G. ). Lumleian Lectures on the Muscular Arterioles. "Brit. Med. Journal," 1887, I. Landois (L.). A Text Book of Human Phj'siology. "Stirling's Transla- tion," p. 572. Munk (J.). Neuere Arbeiten auf dem Gebiete der Nierenph3rsiologie. " Deutsche Med. Woch.," 1889, No. i. Newman (D.). Discussion on Albuminuria. " Glasgow Med. Journal," 1884. Thoma (R.). Zur Kenntniss der Circulationsstorung in den Nieren bei chronischer interstitieller Nephritis. " Virchow's Archiv," Bd. LXXL, pp. 42 and 227. UsTrMOWiTSCH. Beitrage zur Theorie der Harnabsonderung. " Ludwig's Arbeiten," 1871, p. 198. 62 Chapter VII. PATHOLOGY OF UREMIA. Uremia is the name usually given to certain disturbances of the nervous system arising in the course of Bright's disease and in other serious renal disorders. There are three types under which these phenomena may be grouped. In one the patient lies in a typhoid condition with a dry tongue and feeble pulse, often vomiting, but show- ing no disturbance of intelligence or special sense, without convulsions or any loss of consciousness that could be called coma. Such cases are met with in bladder diseases and in obstructive suppression of urine. In the more common type there are a moist tongue, headache, sometimes loss of vision, sometimes sudden deafness, or persistent hiccough, vomiting and diarrhoea, persistent dyspnoea, skin eruptions, hyper- aesthesia of skin, tremor, twitchings, Jacksonian epilepsy, convulsions and coma. This is the classical type of uraemia associated with Bright's disease. In yet a third type there may be convulsions and coma, preceded by epigastric pain, with rapid pulse and deep sighing respiration. This resembles that form of coma met with in diabetes, called " Kussmaul's coma," but it has been described by Riess in eight cases of pure anaemia, in five cases of anaemia with renal disease, and in four cases of gastric and hepatic cancer. Senator has observed it in chronic cystitis, gastric cancer, anaemia and atropine poisoning. Roberts gives " slow panting and laborious breathing " among the symptoms of obstructive suppression of urine. As this type is little known the following case is of interest. Case i. Harriet B., aged twenty, was admitted into the General Hospital, on Sept. 6th, 1884, complaining of severe pain in the left hypochondrium, which came on suddenly fourteen days before and had continued ever since. This was attended by vomiting and purging". On the night of admission there was some epistaxis, which did not recur. Ten months ago she had typhoid fever, for which she was an in-patient at the Queen's Hospital, and she stated that she had never been well since. When she was five or six years of age she had scarlatina, but PATHOLOGY OF URAEMIA. 63 could remember no other illness. On admission she appeared an anaemic girl with an anxious expression of face. She complained of lancinating pains in the region ot the spleen. On examination the tenderness was too exquisite to permit of very exact exploration ; but there was evidently a resistant mass occupying the whole of the lelt hypochondrium. The heart, lungs and liver were apparently normal. Her tongue was moist, streaked with brown and white paste, but clean in the centre. Her bowels were relaxed, with about three motions in twenty-four hours. She vomited two or three times daily. Her urine amounted to about twenty ounces daily, it was albuminous, and contained a little pus, but no sugar. The needle of an aspirator passed into the swelling failed to withdraw any fluid. The day after admission the quantity of pus in the urine increased very much, so as to constitute nearly half a column of deposit in the urine glass. September 9th, at 8.0 a.m., she had a convulsive attack which lasted five minutes, and she afterwards passed into a semi-comatose condition. When seen at 10.-25 a.m., she was lying apparently insensible, but on being shouted to opened her eyes and turned her head. Her eyelids were partially open ; there were sordes on the teeth and lips. Her pupils die} not react to light, but the conjunctivae were sensitive to touch. Pulse 120. Respirations 24, deep attd sighing. On auscultation, air could be heard entering freely into the thorax. The nurse said that just before the con- vulsions she complained of pain in the stomach. 4.0 p.m. — Pulse 132. Respirations 28 ; noisy ; slightly delirious, crying out occasionally. At 6.30 p.m., the house surgeon. Dr. Morrison, saw her, at the request of the house physician's assistant, with the idea of performing venesection. He found her with sighing respiration, pulse small and scarcely perceptible. Every now and then she moaned " Let me die." Temperature 97". At 6.45 p.m. she was pulseless, and apparently in artiado 7nortis. A vein at the bend of the right elbow was opened and 24 ounces of a solution of sulphate of soda in distilled water injected. The fluid was neutral, sp. gr. 1018, at a temperature of about 100° F. The apparatus consisted of a glass funnel connected with a fine pointed pipette by rubber tubing. This was first filled with fluid, and the pipette was then inserted into the vein and the funnel raised. Ey this means a steady flow into the venous system took place. Within a few minutes the pulse returned at the wrist and the breathing became deeper. After 24 ounces were injected, the fluid in the end of the pipette was reddened from the blood and fluid mingling ; the flow was then stopped and the arm bound up. The patient revived, became conscious and spoke ; said she was thirsty and drank some milk. Temperature 98'6°. At 7.45 p.m. about a drachm of foul urinous pus was drawn off by the catheter. She died at 10.25 P-m-, about fourteen hours after the convulsion. During the last thirty-six hours of her life her tempei-ature was taken every hour. Before the convulsive attack it ranged between 98° and 99-5°. At the time of the attack it was 98'5'', it then rose steadily, till at lo.oa.m. it had reached ioo'6'^, falling again by 12 noon to 98°, and, as mentioned above, when Dr. Morrison saw her at 6.30 p.m. the temperature was only 97^. After the operation it rose to 98"6"^, and this was maintained at the last recorded time, 9.0 p.m. At noon on the day of her death, as she had passed no urine since the night, a catheter was introduced into the bladder and about six ounces were drawn off. It was examined the following day by myself. My note 64 BRIGHT' S DISEASE. taken at the time says : Colour reddish brovv^n, putrid, alkah'ne, deposits one-third column of pus ; sp. gr. loii. Gives a deep brown colour with ferric chloride not diminished by heating. Albumen about one-third column. No sugar. Deposit under the microscope consisted of granular cells, squamous and pyriform epithelium, bacteria and blood corpuscles. On the following day a careful post-mortem examination was made by Ur. C. E. Purslow, who kindly favoured me with the following notes : — External appea-^ances. — The body was that of a young woman. Post- viorteni rigidity was well marked in the lower extremities. There was a small incision in the fold of the left elbow, and the mark of a puncture in the left lumbar region. Head. — There was slight increase of the sub-arachnoid fluid, but otherwise the cranial contents were normal. Jho7'ax. — The heart weighed gi oz. The left ventricle was slightly hypertrophied. Both lungs were congested and cedematous, and the lung tissue was friable. The blood was very watery, with no disposition to clot. (The result of the intra-venous injection resorted to just before death.) Abdomen. — The liver weighed 43 oz., and appeared normal. The spleeft weighed 65 oz., but was otherwise normal. The stomacli showed signs of chronic catarrh. The right kidney weighed i^ oz. only ; its ureter was patent; its pelvis was dilated and contained a calculus the size of a pea. The medullary and cortical substances were indistinguish- able, and together measured only a quarter of an inch in breadth. The capsule stripped off readily. In the left hypochondrium there was a large mass, on the upper surface of which, and adherent to it, were the duodenum, pancreas, and descending colon. The surface of the mass was purple coloured, and the colon ov^er it also appeared to have blood extravasated under its mesentery and peritonseal investment. On removing the entire mass it weighed 38 oz. At the upper part there was a cyst the size of an orange, containing purulent fluid, which was accidentally ruptured. On section it was com- posed of an external cyst wall within which was a mass of recent blood clot ; inside this was the left kidney in a condition of saccular dilatation. All normal kidney structure was absent. The pelvis contained an irregularly shaped calculus the size of a bean, and another smaller calculus lay in one of the saccules. The ureter was dilated but patent. The bladder was not enlarged, or its walls hypertrophied. Its mucous membrane was dark coloured, and presented sevei'al wart-like outgrowths about one line in height, with rounded surfaces. The uterus and ovaries were quite normal. It is very hard to explain these differences in the clinical phenomena of ursemia on the assumption that the simple retention of urea in the blood is the cause of all of them. When we go a step further and enquire into the various theories that have been propounded to explain these phe- nomena, we find our difficulties increase. These theories may be divided into two groups : ia) Mechanical, {b) Chemical. In the first group, Owen Rees, Traube, and Rilliet attributed the nervous phenomena to oedema of the brain, dependent upon the watery condition of the blood and the increased blood pres.sure ; this has been PATHOLOGY OF URAL Ml A. 65 supplemented by Rosenstcin, who has suggested that the initial change is spasm of the cerebral blood vessels leading to convulsions by cutting off the blood supply, and followed by effusion of serum into the lymph spaces of the brain. Plainly such a hypothesis involves the necessity for some toxic agent to stimulate the vaso-motor centre, so that it brings us ultimately to some sort of chemical theory ; but the fact that the brain is oedematous is disputed by many. Carter, of Liverpool, in the Eradshawe Lecture for \\ gives the results of his actual determination of the amount of Avater present in the brains of two patients dying of uraemia. In one case twenty grammes of partly white and partly grey matter were taken from the middle lobe, carefully dried for forty-eight hours at 82^ C. over sulphuric acid, then pulverised and dried again in a similar manner until weight was no longer lost. The weight when the drying was complete was 4" 1 5 grammes. The fluid part therefore equalled 15 '83 grammes ; the percentage proportions being 79*25 water to 2075 solids, or almost exactly those of normal brain substance, namely, 80 water and 20 solids. In the second case the brain was examined in exactly the same way, and the percentages were 74"55 liquid and 2 5 '45 solids, the water being actually less than in normal brain. The value of these figures is per- haps lessened by the fact that fluid leaves the tissues and drains into the lymph spaces after death, so that fluid which may have been in the brain substance during life may have drained into the ventricles before the examination was made. But Bartels reported several cases of uraemia in which he had noticed absence of cerebral cedema, hypertrophy of the heart, and variations in the density of the blood serum. The chief chemical theories are : — (i,) That it is due to urea in the blood, hence the name uraemia, originally given by Piorry, and accepted by Christison. This theory is the one which has managed to hold its ground, although numerous experimenters have failed to produce any toxic phenomena by the injection of urea into the blood of animals or by making them ingest quantities of urea with their food. Peabody has calculated on data obtained by experiments on dogs that at least \\ lbs. of urea would be required to prove fatal, whereas in the body of a man dying of uraemia only '009 lb. could be recovered. According to Grehant and Quinquaud the quantity of urea required to produce convulsions in dogs is from luoth to s'oth of their body weight, confirming Peabody 's estimate. A 66 BRIGHT'S DISEASE. In uraemia the amount of urea found in the blood has varied from "2 to I per cent. Vierordt estimates the total quantity of blood in man to be 5o62"5 grammes or about i^sLh of the body weight, so that even the highest estimate, i per cent, would only give about ih oz. instead of the requisite minimum of U lbs. Snyers found that he could inject into a dog doses of urea equivalent to the amount it would eliminate in three days without producing any ill effects. Cases have been described by Owen Rees, Christison, Bright, and Frerichs, in which the blood contained large quantities of urea without giving rise to any symptoms of uraemia. Biermer has published a case of anuria lasting 1 18 days without uraemic phenomena These appeared after the urine began to flow. Moreover, uraemic symptoms may supervene in spite of the elimination of a normal quantity of urea ; such cases have been reported by Rosenstein, Christison, and Liebermeister. Case 2. Emily M , aged 28, was admitted August 7th, 1888, with headache, vomiting, and hsematuria. She had no dropsy, but her urine, which was persistently albuminous, contained numerous epithelial and hyaline casts. She suffered constantly from frontal headache, and had frequent cramps and vomiting. The urine generally averaged 35 oz. daily. On a diet of fish, chicken, milk, bread, butter and tea, she still complained of these ursemic symptoms, but the quantity of urea elimi- nated was 450 grains in 24 hours, the percentage being as high as 3'2. (2,) This urea theory was slightly modified by Frerichs and Treitz, who suggested that the urea, itself innocuous, became converted, under the influence of a peculiar organised ferment, into carbonate of ammonia. This theory is based upon («,) The facility with which this transformation is effected ; {b,) The resemblance of the symptoms produced by the intravenous injection of carbonate of ammonia to those of uraemia ; (<:,) The presence of carbon- ate of ammonia in the blood of uraemic patients. Researches made to determine the point whether carbonate of ammonia is really present in the blood in uraemia have attained very contradictory results. Snyers states that the blood of dogs some days after the ligature of both ureters con- tains only traces of ammonia. Rommelaere concludes that the quantity of ammonia in the blood is increased after nephrectomy ; that the quantity is too small to explain the occurrence of uraemia ; but that in a few hours after death a large quantity of ammonia is formed in the blood. PATHOLOGY OF UR.^MIA. 67 (3,) Schottin in 1853 suggested that the extractives of the blood, — creatin, creatinin, leucin and tyrosin were the real poisons. In support of this Oppler found a great excess of creatin in the blood of nephrectomised animals, and Hoppe-Seyler found a great accumulation of extractive matter in the blood of a patient who had presented uraimic symptoms in the course of an attack of cholera. (4,) Gauthier has suggested that ptomaines may be the poisonous substances. (5,) Feltz and Ritter in 1881 commenced a new series of researches which led to unexpected results. They determined (^,) That the intravenous injection of fresh urine causes con- vulsions, coma and death ; {b^ That their results were independent of the increased pressure produced by the injec- tion or of the organic constituents ; (^,) That the inorganic constituents injected separately produced the same symptoms as the urine itself, and that of these the potassium salts showed the most powerful toxic action. Astaschewsky published about the same time experiments supporting these conclusions. There is no doubt of the toxic properties of potassium salts, but Bouchard and Snyers believe that they do not play so ex- clusive and preponderating a part as Feltz and Ritter affirm. In the blood of two eclamptic women in Braun's wards at Vienna, Snyers found in one Toy parts of potash per thousand, and in the other 2'o6 per thousand, a quantity rather less than the normal amount. On the other hand, Lepine found in some experiments on animals by temporary compression of the renal artery, that the urine secreted by the injured kidney showed diminution of its solids chiefly in phosphoric acid and potash, while the chlorides were not diminished, but rather increased. (6,) Bouchard accepts the position that the urine is itself poisonous, but attributes this to various sources : (<«,) Food derivatives, especially potash salts ; (^,) Products of intestinal putrefaction absorbed with the blood ; (c,) Admixture of bile, saliva, and other secretions ; (^,) Products of tissue metamor- phosis. Voit says, " Symptoms of disease originate wherever any substance which does not belong to the economy accumulates within the body and is not eliminated from it ;" and he shows that even sulphate of soda may be deleterious under such cir- 68 BRIGHT S DISEASE. cumstances. The toxic effects are the result of interference with the normal exchanges which take place between the blood and the tissues, and upon which the vital phenomena of the latter depend. (7,) Lepine has shown that febrile urine is very much more poisonous than non-febrile urine ; and Bouchard observed that the day urine is more poisonous than that of the night. The urine in certain diseases is especially poisonous, e.g., pernicious anaemia, jaundice, cancerous cachexia, chronic Bright's disease, etc. (8,) Rademaker has found urethane in albuminous urine and suggests that this powerful narcotic may be the cause of ura^mic coma. We are not in a position at present to explain precisely the pathogenesis of so-called Uraemia. It is plain that the clinical phenomena vary, and that there are many poisons to which these symptoms may be due. Since the case of Harriet B. was published (1884), the doctrine that Kussmaul's coma is due to the presence of an acid in the blood has gained ground ; it is extremely probable that some cases of uraemia are due to this cause, although the acid has not yet been identified. Carter, in his Bradshawe lecture, relates a case of coma with sighing respiration and " decidedly acid " blood. The acid is probably formed in the intestine, and thence absorbed into the blood. If we are to get a nearer knowledge of these problems, it must be by differentiating the clinical types, and by recog- nising the probability that different agencies may be at work in each ; moreover in one we may see the effects of a sudden large dose, in another of chronic intoxication. Summary. — (i,) Uraemia is a convenient generic name given to a large series of nervous accidents which occurs in Bright's disease. (2,) Its causes must be looked for in certain toxic agencies arising in the blood, in the tissues, or in the intestines, which have not at present been identified with certainty. (3,) Normal urine contains a certain proportion of some of these poisons, so that its retention is liable to cause them to accumulate in the blood. In disease, these or other poisons may be present in greater quantities with proportionately more serious results. (4,) Poisons are known to be formed in the intestines ; when constipation is present this process is facilitated, and PATHOLOGY OF URAEMIA. 69 opportunity is given for their absorption into the blood. Moreover, the intestine forms a channel by which elimination may take place when the renal function is depressed, so that failure of intestinal action is a grave additional danger in Bricjht's disease. BIBLIOGRAPHY. AsTASCHEWSKY. Zur Frage von der Uramie. " St. Petersburger Med. Woch.," 1881, No. 27. BiERMER. Ein ungewohnlicher Fall von Scharlach. " Virchow's Archiv," Bd. XIX., p. 537. Bouchard. Poisons de I'organisme et toxicite urinaire. " Compt. Rend.," 6 Juillet, 1885. Bright (R.). Renal disease accompanied with the secretion of albuminous urine. Case ig. — Urea in the serous fluids. " Guy's Hosp. Reports," Vol. V., 1840, p. 138. Carter (W.). The Bradshawe Lecture on Uraemia. "Lancet," 1888, II. , P- 355- Christison (R.). On granular degeneration of the Kidneys. Edinb., 1839. Feltz and Ritter. De I'uremie experimentale. Paris, 1881. Frerichs (F. T.). Die Bright'sche Nierenkrankheiten und deren Behand- lung. Braunschweig, 1851. Gauthier (A.). Sur les ptomaines. " Le Progres Medical," 1886, p. 69. Bull, de la Soc. de Medecine, Jan., 1886. Grehant and Quinquaud. L'uree est un poison ; mesure de la dose toxique dans le sang. " Comp. Rend.," Vol. XCIX., 1884, p. 383. LipiNE and Aubert. Sur la toxicite des matieres organiques et salines de I'urine normale et febrile. " Lyon Med.," 1885, I., p. loi. Oppler. Zur Lehre von der Uramie. "Virchow's Archiv," Bd. XXI., p. 260. Peabody (G. L.). The relation existing between retention of urea and uraemia. " New York Med. Rec," Vol. XXVII. , 1885, p. 22. Rademaker. "The Lancet," 1891, Vol. II., p. 139. Rees (Owen). On the nature and treatment of diseases of the Kidney. London, 1850. RiEss (L.). Ueber das Vorkommen eines dem sogenannten Coma diabeti- cum gleichen symptomencomplexes ohne Diabetes. " Zeitsch. fiir Klin. Med.." Vol. VII., 1883, Supp. Heft., p. 34. Rilliet and Barthez. Maladies des Enfants, Vol. I. Paris, 1843, p. 777. Roberts (W.). A practical treatise on Urinary and Renal Diseases. Fourth Ed., p. 34. London: Smith, Elder and Co. Rommelaere , quoted by Snyers, op. cit. , p. 143. Rosenstein (A.). Die Pathologie und Therapie der Nierenkrankheiten. 3rd Ed., Berlin, 1886. Schottin. Beitrage zur Characteristik der Uramie. " Vierordt's Archiv," 1853, Heft I. "Archiv der Heilkunde," i860. Senator (H.). Ueber Selbstinfection durch abnorme zersetzungsvorgange und ein dadurch bedingtes (dyscrasisches) Coma Kiissmaul'scher symptomen- complex des " diabetischen Coma." "Zeitsch. fiir Klin. Med.," Bd. VII., 1883, Heft 3, p. 235. Snyers (P.). Pathologie des Nephrites chroniques. Bruxelles, 1886. Traube (L.). Gesamellte Beitrage zur Pathologie und Physiologie. Bd. XL, 1871, p. 551. Treitz. Ueber uramische Darmaffectionen. "Prag. Viertel.," 1859, Bd. 4. 70 Chapter VIII. RETINAL CHANGES. Amaurosis, or defect of vision in association with dropsy, was noticed by Wells, in 1812 ; but the first actual observation of retinal change in connection with Bright's disease was made post mortem by Tiirck, in 1850. The visual defects associated with Bright's disease are divided into two classes : (i,) Those due to uraemic poisoning, in which the visual centres in the brain are chiefly at fault ; and (2,) Those due to structural changes in the optic nerve and its retinal expansion. The so-called uraemic blindness of the former class is generally unattended by any changes in the fundi ; but Dobrowolsky has observed transitory oedema of the discs, while Litten has noticed that in uraemic attacks there is swelling and cloudiness about the disc. In the second class the changes observed in the retina may be enumerated as follow : (i,) Diffused opacity from oedema ; (2,) White patches, of which there are two kinds — {a^ rounded soft-edged areas of exudation ; and {b^ smaller bright radiat- ing streaks or specks; (3,) Haemorrhages ; (4,) Optic papillitis; (5,) Diffused retinitis, in which many of these may be com- bined ; (6,) Atrophic changes secondary to inflammation ; and (7,) General retinal periarteritis. Apart from the slight changes which occur in acute uraemic poisoning, no retinal affections are met with in primary acute nephritis, though they are liable to supervene rapidly in the acute attacks which so commonly occur in the course of chronic Bright's disease. They are most frequent and characteristic in the contracting form, and it is to this that most of the recorded observations refer. It has been disputed whether they ever occur in the lardaceous kidney, and this point has been settled in the affirmative ; but as what is often called lardaceous disease is merely chronic Bright's disease — plus lardaceous degeneration — it is doubtful if the observations recorded are of much pi 05 ?^ » S S o" CD V s= o 3 Cf=3 RETINAL CHANGES. 71 value. The existence of retinal changes, in a pure case of primary lardaceous degeneration, has yet to be placed on record. Some years ago I collected a hundred cases of contracting kidney from among my out-patients, and these were examined by Mr. Eales, who published the result of his observations in the Birmingham Medical Review for January, 1880. Out of the hundred cases, retinal changes were present in twenty- eight, rather less than the number recorded by Galezowski (fifty out of a hundred and fifty) ; but decidedly greater than the nine per cent, found by Wagner. In sixteen of these twenty-eight cases, changes were found in one eye only ; probably because they are apt to begin in one eye before the other ; thus in one case at the first examination no ophthalmoscopic changes were found ; two months later several white specks were observed in one eye along a branch of the retinal artery, but there was no evidence of inflammation. In these sixteen cases the lesions were as follow : In' six, several round white patches ; in five, one or two spots only ; in one, a single recent haemorrhage near the disc ; in two, black specks, associated in one instance with white specks ; in one, two large, round, soft-edged, whitish patches close to the disc. In the twelve cases in which both eyes were affected the following lesions were noted : In four, difiuse retinitis in both eyes ; in one, diffuse retinitis in one eye, with a single haemorrhage in the other ; in five, many whitish round patches ; in two, a few white patches. In addition to these twenty-eight cases, there were three in which the disc was abnormal, this structure being abnormally pink (hyperaemic) in one, and abnormally pale (atrophic), with blurred edges, in two. The first was probably a case of incipient neuritis, and the others were very likely atrophy secondary to a slight neuritis ; so that if we include them we obtain thirty-one cases out of a hundred, a number very close to the thirty-three per cent, recorded by Galezowski. Although there is no evidence that these retinal changes ever occur in acute infective nephritis supervening in healthy kidneys, they are very common in connection with the albu- minuria of pregnancy. But the albuminuria of pregnancy is preceded and caused by chronic blood poisoning, of which the retinal changes are only another local expression. Doubtless 72 BRIGHT'S DISEASE. when the kidneys begin to fail in their function, the blood poisoning rapidly gets worse ; but it is a condition which must be dated back some time anterior to the earliest expression of renal trouble. Pathology. — With the exception of the slight opacity and cloudiness of the retina which may occur in the course of an acute uraemic attack, all these conditions are met with only when the primary disease is of some duration, and the pathological causes at work are at least three in number : — 1. The dyscrasia, or altered condition of the blood. 2. Secondary degenerative changes in the small blood vessels. 3. Excessive pressure of blood within the vessels. The first is by far the most important, and is probably the starting point of the other two. The dyscrasia is caused by the failure of the kidneys to eliminate the products of disassimilation, and this leads to imperfect nutrition of the tissues, especially to inflammatory and degenerative changes in and around the walls of the small arteries, and also to obstruction to the course of the circulation. Denissenko denies the existence of an inflammatory exudation, and regards the retinal changes as merely oede- matous ; in accordance with this view he proposes to substitute the name of ophthalmia Brightica or oedematosa for that of albuminuric retinitis ; this opinion appears, however, to be based on a partial view of the facts. Holstoi, who has recently investigated the subject, comes to the conclusion that the affection originates in inflammation of the coats of the smaller arteries, and describes them as having their walls converted into a shining homogeneous mass, recalling the "colloid" change of the vessels of the choroid described by Poncet. Maguire has expressed the opinion that the lesions are the result of degeneration and not of inflammation ; he thinks excessive intravascular tension is the sole cause, and that this alone sufficiently accounts for the haemorrhages and the nutritive disturbance, but, in view of the positive evidence of inflammatory changes, the explanation is not very satisfactory. Weeks ascribes the alterations to primary vascular changes of a hyaline and fibroid character. Duke Charles, of Bavaria, describes a general arteritis as the essential lesion in the retinal affections of Bright's disease, the chief changes being in the vascular layer of the choroid and the retina, but more in the former than in the papilla or the ffl E, £ !B 5 »£. RETINAL CHANGES. retina. The coats of the larger vessels in the retina and papilla present in parts a wavy structure, in other parts they are homogeneous; numerous dissecting aneurysms occur, as well as haemorrhages into the sheath of the vessel. The inflammatory process is most marked in the capillary area between the small arteries and the veins. He states that the choroidal capillaries possess an actual perivascular sheath, and in some places fibres are present, lying at right angles to the axis of the vessel, between the endothelium and the perithelium. The thickening of the vessels is caused by oedematous swelling of their walls, and by the degeneration of masses of red and white blood corpuscles. In places the lumina are narrowed, and thromboses occur. Near the arteries the capillaries show ampulla-like diverticula and dilatations of their walls. These changes are situated chiefly in the peripapillary zone. He describes an infiltration of the rods and cones by small cells, and the formation of hyaline masses in the granular layer. He found nowhere any trace of sclerosis of nerve fibres. Haemorrhages occur in the pia-matral sheath of the optic nerve, and its vessels show thickening of their walls. The arteritis is seen also in the vessels of the sclerotic, ciliary body, iris, and conjunctiva. If we examine a section through a soft-edged white patch we find that the nerve fibre layer is greatly thickened, and contains granular masses formed by the fusiform en- largement of the nerve fibres ; these fusiform enlargements often reach a great size, become filled with fatty gran- ules, and ultimately become isolated, so to form spheroidal bodies (/^z^'. 12). Areas may also be infiltrated with a finely fibrillated material, which may be fairly regarded as coagulable lymph. Such an exudation may occur in the outer molecular layer, where large cavities, separated goweSI).' by the remains of the vertical fibres, are filled by this substance. Capillary dilatation, with ampulla-like diverticula of the vascular walls, are also seen in this section. W'--\::r^ O ''^. ■00 Tig. 12. Section through atrophic ret'nal patch showing fatty degeneration ol exudation, x 250 (after 74 B RIGHT'S DISEASE, But in the other form of white patches, so commonly seei» radiating from the 5^ellow spot, the lesion is different. Here the round corpuscles and vertical fibres of Miiller are affected. The latter become swollen and filled with minute oil globules, and in this condition they possess an undue refractive power, hence their glistening appearance ; while the radiated arrange- ment of the specks is due to the fact that these fibres radiate from the yellow spot. Diffuse opacity of the retina is mainly due to oedema, the lymph spaces around the ganglion cells of the nerve fibre layer being distended with clear fluid, so that these drop out of the section, leaving large spaces. But there may also be an effusion of coagulable lymph, especially in the outer molecular layer, where it may occupy large cavities separated by the remains of the vertical fibres, or such an exudation may separate the membrana limitans interna and bases of Muller's fibres from the rest of the nerve fibre layer, while the layer of rods and cones may show remarkable thickening. Of less importance are the small grey angular spots of pigment, often arranged in groups, which appear first in the periphery, and are due to changes in the pigment epithelium. I may mention in this place that very rarely choroidal haemorrhage may occur, giving rise to localised atrophy of this coat and adjacent pigmentary disturbance. Haemorrhages occur mainly into the sheaths of the retinal vessels, so that they are usually longitudinal, running in the course of the vessels. Occasionally they may be more diffuse and occupy a large area, or even burst into the vitreous. Optic papillitis is an interstitial neuritis, with swelling and round cell infiltration of the connective tissue of the nerve, leading in some cases to atrophy of the nerve fibres. In general retinal periarteritis the inflammation of the arteries is associated with numerous haemorrhages. Its pathological anatomy has been studied by Ivanofif, who states that the first appreciable change is a serous transudation into the retina, which is for the most part confined to the neighbourhood of the vessels, the inflammation attacking chiefly the outer coat of the arteries, the middle and inner coats remaining compara- tively healthy. The outer coat becomes infiltrated with nuclei and delicate fibres, which form an opaque white sheath. This causes thickening of the vessels and encroaches on the lumen, so as to obliterate the smaller ones. By the extension of the inflammation from the sheath of the vessels to the disc, this RETINAL CHANGES. 75 becomes swollen. Ivanoff considers the process to be distinct from atheroma on the one hand, or the ordinary arterio-sclerosis of Bright's disease on the other ; Wedl believes it to be atheromatous, and Abadie supported this view by pointing out that it only occurs in elderly people, but Nagel has since published a typical example in a young man of 22. The histological details entirely negative the notion of atheroma, which is essentially a disease of the inner coat, while in this condition it is the outer coat which is almost exclusively attacked. Its relationship to Bright's disease is attested by the fact that in five out of the seven hitherto published cases it was so associated. Among the further changes which occur, apparently by an extension of the same diseased processes, are detachment of the retina, due to effusion taking place behind that membrane, and acute glaucoma from sudden increase of pressure in the posterior ocular chamber. Several cases of this kind have been placed on record by Anderson, Collins, Landesburg, Weeks, and others. Irido-choroiditis has been observed by Leber. Course of the Lesions. — It is undoubtedly the rule that the more important retinal changes persist until the patient's death ; but they may increase or diminish, or even, in some cases, disappear entirely. The last occurs where the renal affection also undergoes considerable improvement or cure, and is most common in the nephritis of pregnancy, which is specially liable to be associated with retinal changes, and yet frequently gets perfectly well, provided that the renewal of the cause is prevented. But, in addition to this qualification of the rule given above, the inflammatory signs, as a rule, diminish and disappear, while the degenerative signs persist. This was shown in the case of a man who was under my care nearly four years ago. He was admitted with loss of sight, headache, and vomiting, but presented all the signs of chronic nephritis, probably due to lead, as he was a house painter by trade. At this time, April loth, he could read no type at all, there was intense papillitis in the left eye, with a moderate degree of the same lesion on the right side, and characteristic radiating patches around both yellow spots. Under appropriate treatment his general condition improved, his headache disappeared, and his vision returned so far that he was able to read a book or newspaper. On May 20th his vision was tested R = I L = 1%, The state of the fundus was 76 BRIGHT' S DISEASE. noted on May 30th, when the inflammation of the discs had subsided, although the peri-macular patches were still present, and had even undergone some increase in number. In 1 88 1 Mr. Eales and I had under observation a young woman, aged 19. She was at that time suffering from dimness of vision,- and the ophthalmoscope showed slight swelling of both discs, with white, soft-edged patches around both disc and macula, but no radiating, bright streaks. The urine was albuminous, and contained casts. She improved under treat- ment and, in spite of a relapse, two years later her fundi were normal, and her V = || in both eyes. We managed to find her again in 1888, and got her to come to see us, when we had the satisfaction of finding that her general health was fairly good, her urine was still albuminous, but contained no casts, and, what is most to our present purpose, her fundi were quite normal, with the exception of a small pigmented spot in each retina, with slight disturbance of the choroidal epithelium. A case ending in recovery in a male has also been published by Adamlick, while Novelli has related one of the not uncommon cases of recovery from puerperal retinitis. It must therefore be admitted that the soft-edged patches may disappear and heal. Haemorrhages undoubtedly become absorbed in course of time. Dr. Miles Miley has mentioned the case of a man, aged 48, under the care of Dr. Stephen Mackenzie, who, on July 2nd, 1885, was stated to have haemorrhage and white patches in both eyes, and on October 17th, 24th, and 30th to have no changes present. Diffuse neuro-retinitis subsides, but always leaves more or less permanent damage behind ; and even the radiating streaks themselves may disappear where the renal disease undergoes marked improvement. The course of multiple periarteritis is probably always progressive. Diagnostic value. — The diagnostic value of these changes is not equal and has marked limitations. For example, haemorrhages occur pretty commonly in blood diseases, such as leucocytha;mia, pernicious anaemia and purpura, while Mr. Eales has described a number of cases in young lads without any constant etiological factors, except their age and constipation. These haemorrhages are as a rule rounded and irregular, but they may be striated and longitudinal like those of Bright's disease. I have seen a case of chlorotic anaemia, who brought with her a note signed by a very competent ophthalmic surgeon to say that the bearer had typical RETINAL CHANGES. 77 albuminuric retinitis, the fundus presenting numerous soft- edged white patches. Moreover, Dr. Edmunds has recorded a case of cerebral tumour where, in addition to intense optic neuritis, there was a group of radiating patches around the macula which appeared absolutely characteristic of albuminuric retinitis. It is also certain that diffuse neuro-retinitis occurs in cerebral tumour and in Bright's disease in a form which is indistinguishable. Brudenell Carter has related a case of diffuse retinitis which was regarded as one due to brain disease by Dr. Hughlings Jackson, Dr. Noyes of New York, and by several members of the Ophthalmological Congress then assembled in London. The boy died of pleurisy supervening upon adv^anced kidney disease, and no trace of brain mischief could be found on most careful examination. Nearly at the same time there was in hospital a young woman whose eyes presented typical examples of the changes often associated with albuminuria, but in whom, after death, a tumour was found in the cerebellum, while the kidneys were perfectly healthy. Lastly, multiple retinal periarteritis, though generally associated with Bright's disease, is met with apart from this condition. We must therefore admit that none of these appearances is absolutely pathognomonic ; and it is certain that a diagnosis based solely upon the appearance of the fundus oculi is fallacious. Ophthalmic surgeons are well aware of this, and always look for some of the more obvious signs of Bright's disease to confirm the ophthalmoscopic appearances. But while we cannot allow them the proud position of being all-sufficient for diagnosis, we must assign them a very high place among those indications of disease which, taken together, lead to an indisputable conclusion. Moreover, their diagnostic value in practice is all the greater because it not uncommonly happens that failure of sight is the first symptom of deranged health observed by the patient, so that the practitioner who is consulted for an apparently trifling impairment of vision must be able to recognise the grave condition of the patient. Among the minor phenomena observed in the fundus oculi of Bright's disease are pallor of the vessels with great sharp- ness of their central light streaks ; often where such vessels cross a vein they may be observed to obstruct its circulation, and such a vein is peculiarly likely to be the source of haemorrhages (MARCUS GUNN). Narrowing of the arteries may be seen associated with 78 BRIGHT' S DISEASE. dilatation of the veins. Gowers believes in a persistent spasm of the arteries, but this narrowing is constantly seen as a consequence of retinal disease apart from Bright's disease. In reference to this question Mr. Eales says, "I cannot confirm the statement of Dr. Gowers, that this (arterial contraction) is common. Only twice, I think, some slight contraction existed, but I did not feel sure that it was abnormal even in these cases. " I have recently had a case of diffuse haemorrhage into the retina ; the haemorrhages have cleared ; the retina looks quite healthy, but vision is imperfect, and the arteries have con- tracted very much since I first saw the case. Here, though no sign of disease is visible, I think we may safely infer that the retina is damaged, and that the contraction is a consequence of degeneration in the retina, as it was not noticeable in the early stage of this case, and contraction of the retinal arteries from this cause is common." Choroidal hcemorrhage may occur leading to circumscribed atrophy and pigmentary disturbance. " Colloid " degeneration of the vessels of the choroid has been described by Poncet. After parenchymatous retinitis there may be some pigmentary degeneration of the choroid in the form of small grey spots arranged in groups (GowERS). Thickening of the adventitia or lymph sheath is very common, but always in association with retinal disease. Evibolism of the retinal arteries has been described, but of late years it has come to be recognised that plugging of these vessels is more usually thrombotic, and it is probable that such statements should be taken to imply that the artery was blocked by a clot, which blocking, in accordance with the prevalent doctrines of that time, was assumed to have come from a distance and not to have been formed in situ, although this last supposition is now recognised to be the more probable explanation. HcEmorrliage into tJie vitreous may occur from the bursting of a large retinal extravasation. It causes permanent damage to vision, and may give rise to glaucoma (GoWERS). Effects on visioji. — In the great majority of cases presenting retinal change, that is, in those in which only a few degenerative specks or haemorrhages are found, vision is unaffected. Acute neuro-retinitis may be present without causing any complaint from the patient, but this is exceptional. As a rule vision is RETJNAL CHANGES. 79 affected in proportion to the extent of the disease, but these patients rarely become quite bhnd, generally retaining percep- tion of light sufficient to enable them to see to get about. Prognostic value. — Valuable as are these signs for the purposes of diagnosis, the information derived from them for prognostic purposes is of a more precise and definite kind, though even here no absolute rule can be established. Putting the matter generally we may say that serious retinal changes indicate advanced disease and the approach of death, the great exception to this rule being puerperal nephritis, which generally recovers if pregnancy does not recur. To be more precise, we may define serious retinal disease as either diffuse neuro-retinitis or well-marked patches of degeneration around the yellow spot. A few white specks are of no definite significance, they may be found in advanced cases, but Mr. Eales observed them in lads with functional albuminuria under my care. By functional albuminuria, I mean albuminuria occurring in persons who show no other sign or symptom of renal disease, and who an experience of many years now enables me to say do not develop any such condition. The soft-edged rounded patches are also to be regarded as not inconsistent with a moderately hopeful view of the case, if other symptoms warrant it. Hsemorrhages are less favourable than either of the last two, but their value for prognosis depends upon the kind of case in which they occur. That is to say, if they occur in chronic Bright's disease they should be regarded as indicating wide-spread arterial changes, which may prove dangerous to hfe in various ways, but apart from these conditions, they do not diminish the prospects of life. I am not in a position to state anything definitely as to the significance of multiple peri- arteritis, but the case recorded by Dr. Mules has since died, and from the nature of the lesion I should be disposed to class it with the gravest forms of retinal disease, and therefore of the worst prognostic meaning. Dr. Miles Miley has, perhaps, made the most important contribution to the statistical side of the general question. He has collected 164 cases of chronic renal disease at the London Hospital, out of which number 5 1 were definitely stated to have had their eyes affected. Of the remaining 113, there died in hospital 28, or 23 per cent. ; while of the 51, there died during the same period 27, or nearly 53 per cent. The mortality of the affected cases was therefore more than double that of the unaffected. But means were taken to trace the So B RIGHT'S DISEASE. remainder of the 51 cases, and 18 more were proved to be dead ; the remainder could not be accounted for. Of those that died, one lived eighteen months, but all the others died within a year. But it must be borne in mind that all these cases were sufficiently advanced to have required treatment as in-patients at the hospital, so that the extremely rapid termination of the greater number must be attributed to the grave nature of the general constitutional condition of the whole group of cases. Had they been selected from an out- patient clinic, I have no doubt the average duration of life would have been longer. Still, I think we are not justified in expecting that a patient who is suffering from chronic non-puerperal nephritis, who has diffuse retinitis, or well-marked degeneration around the yellow spot, will live long, and I should be disposed to place the extreme duration of life under such circumstances at two years, what- ever the state of the general health might be. Dr. Collins thinks detachment of the retina in retinitis is a very bad prognostic sign ; and this is probably worth bearing in mind, as the occurrence of this complication marks an extreme degree of tissue degeneration. He is also of opinion that those with merely fatty degeneration, by which I take him to mean soft-edged patches, or haemorrhages, are the most favourable. Here, again, I am disposed to agree with him, and I have already expressed myself in this sense. Let us now try to sum up the facts and conclusions of this lecture. We have seen that the retinal affections in Bright's disease vary very much in their ophthalmoscopic appearances, their anatomical nature, and in their diagnostic and prognostic value. We have learnt that they are probably all dependent upon a dyscrasia which causes effusion of serum or blood, inflammation of the vascular walls or of the nervous tissues, and secondary degenerative changes. Further, it has been abun- dantly proved that none of these changes, taken singly or together, justifies the diagnosis of Bright's disease, but that they may often be the first indication of the disease, which is easily confirmed by the usual examination of the urine, pulse, etc. ; and we may lay stress upon the imprudence of neglecting to look for these confirmatory signs before committing ourselves to an opinion upon the nature of any case. Finally, we find that, for prognostic purposes, these signs may be roughly divided into two classes: (i,) The grave — which includes diffuse neuro- retinitis, radiating patches around the yellow spot, and multiple RETINAL CHANGES. 8i periarteritis ; (2,) The benign — including" simple oedema, hccmorrhage, and soft-edged round patches ; and we may venture to lay down the rule that, apart from puerperal nephritis, the subjects of the former class will not live long, almost certainly not more than two years ; we should also be distrustful of liJemorrhages, if they occur in persons whose condition is otherwise unfavourable. I do not think we can ever regard any retinal change as favourable. The above classification is only intended to separate those changes which justify, even in the absence of other indica- tions, a very grave judgment of the future from those which do not afford grounds for taking a more gloomy view of the case than may be warranted by its other features. Possibilities of Cure. — Though all authorities admit the possibility of cure and the disappearance of spots, and instances of marked improvement have been already related, such recoveries are rare. This is due, not to any essential incurability in the retinal condition, but to its dependence upon an incurable renal disease in its last stages. Swuinary. i. — The retinal changes of Bright's disease consist of neuritis and neuro-retinitis, periarteritis, haemor- rhages and white patches of degeneration. 2. — These do not possess any specific characters which enable the observer to diagnose Bright's disease with absolute certainty from them alone. 3. — They are dependent chiefly upon the disordered state of the blood, with which, in the case of haemorrhages, the high arterial tension and the diseased vascular walls co-operate. 4. — They may be divided for prognostic purposes into two classes: (i,) The grave — including diffuse neuro-retinitis, radiating patches around the yellow spot, and multiple peri- arteritis ; (2,) The benign — including simple oedema, haemor- rhages and soft-edged rounded patches ; the subjects of the former group, with the exception of cases arising from pregnancy, do not as a rule live more than two years ; of the latter group', it can only be said that their presence does not make the prognosis of the case better or worse ; the apparent exception of the albuminuria of pregnancy is explained by their being due, in that case, to a dyscrasia not dependent solely upon the renal disease. 6 82 BRIGHT' S DISEASE. BIBLIOGRAPHY. Adamuck. Ueber einem Fall von Retinitis hsemorrhagica albuminurica mit Ausfang in Genesung. " Centrlbl. f. Prakt. Augenheilk." Vol. XIII., p. 98. Anderson (J.). A case of subretinal effusion in chronic Nephritis in a Child. "Brit. Med. Jour.," 1888, I., p. 248. Brailey and Edmunds. The relation of the retinal changes to the other pathological conditions of Bright's disease. " Ophth. Soc. Trans.," Vol. I., 1881, p. 44. Collins (W. J.). Central retinal detachment in left eye, with appearances as of albuminuric retinitis in a woman suffering from chronic nephritis, &c. "Trans. Ophth. Soc," Vol. VIII., p. 128. Denissenko (G. S.). The changes in the eye in Bright's disease. " Med. Westnik," 1882, Nos. 49 and 50, and 1883, Nos. 2 and 11. DoBROwoLSKY. Diffusc Netzhautcntziindung bei hochgriidiger Hyperme- tropic. " Klin. Monatsbl. fiir Augenheilkunde," Bd. XIX. Eales (H.). The state of the Retina in one hundred cases of Granular Kidney. " Birm. Med. Review," Vol. IX., 1880, p. 34. Edmunds (W.). The fundus oculi from a case of cerebral tumour: appear- ances like those of albuminuric retinitis. "Trans. Ophth. Soc," Vol. IV., p. 291. Galezowski (X.). Traite iconographique d'Ophthalmoscopie. Paris, 1876. , De la Retinite et de la Retino-choroidite albuminurique : leur traitement. "L'Union Medicale," 1873, p. 924. Gowers (W. R.). a Manual and Atlas of Medical Ophthalmoscopy. Gunn (R. Marcus). Ophthalmoscopic evidence of arterial changes associated with chronic renal disease and of increased arterial tension. "Ophth. Trans.," Vol. XII. Herzog Carl (in Bayern). Ein Beitrag zur pathologischen Anatomie des Auges bei Nierenleiden. Wiesbaden, 1887. HoLSTi. Ueber die Veranderungen der feinen Arterien bei der granularen Nierenatrophie und deren Bedeutung fiir die pathologischer Krankheiten. "Deutsch. Arch. f. klin. Med.," XXXVIII., p. 122. Ivanoff (Conf, Wecker). Traite des maladies des yeux, t. II., p. 316. Jackson (J. Hughlings). Case of double optic Neuritis without cerebral Tumour. " Moorfields Hosp. Repts.," Vol. VIII., part 3. Landesberg (M.). Fulminant glaucoma in both eyes in a case of albumin- uric Retinitis. "Centrlbl. f. Augenheilk." Vol. VIII., p. 292. Leber (T. H.). The occurrence of Iritis, &c. "V. Graefe's Arch,," XXX., I, 4, p. 203. Maguire (R.). Retinal changes in Bright's disease. "Brit. Med. Jour.," 1888, Vol. II., p. 74. Miley (Miles). On the prognosis of Neuro-retinitis in Bright's disease. "Brit. Med. Jour.," 1888, I., p. 248. Mules (P. H.). A case of general retinal periarteritis in chronic renal disease, with remarks. "Trans. Ophth. Soc," Vol. II., p. 47. NovELLi (P.). Un caso di retinite albuminurica in puerperio. "Boll, d'ocul.," XI., p. 97. Poncet. De la Retinite albuminurique. " Gaz. Med. de Paris," No. 32. Saundby (R.). On the Retinal Affections of Bright's disease and Diabetes. "Birm. Med. Rev.," Vol. XXXIII., pp. i and 76,' 1893. Turck. Anatomisches Befund von Amaurose, " Zeitschr. der Wiener Aerzte," No. 4, 1850. Weeks (J. E.). Beitrag zur Pathologic der Retinitis albuminurica. "Arch, f. Augenheilk.," XXL, p. 54. Wells (W. C). Observations on the Dropsy which succeeds Scarlet Fever. "Trans, of a Soc. for the Improvement of Med. and Chir. Knowledge." Vol. IIL, 1812, p. 167. 83 Chapter IX. HISTORY— CLASSIFICATION— ETIOLOGY. Although Van Helmont regarded the kidneys as the seat of the causation of dropsy, and the discovery of Cotunnius that the urine of dropsy was coagulable by heat was pub- Hshed as early as 1770, there can be no doubt that the whole honour of establishing the true relations of dropsy and albu- minuria to disease of the kidneys belongs to the great physician and pathologist of Guy's Hospital, RICHARD Bright. Blackall, of Exeter, would perhaps have forestalled him had he enjoyed equal opportunities for making post mortem examinations ; but, in the fourth edition of his book, pub- lished in 1825, Blackall shows himself to be entirely ignorant of the local causes of dropsy, assigning to it a constitutional origin, and inclining to the opinion that albuminuria was due to the elimination of the dropsical fluid by the urinary passages. Bright's Reports of Medical Cases, published in 1827, present a striking contrast to this vague humoralism by the ■definite solidism of his pathology. He distinctly ascribes albuminuria and dropsy to the altered anatomical condition of the kidneys, and he figures accurately the changes in the kidneys just as they are recognised by us to-day. In his papers in the first volume of Guy's Hospital Reports, published in 1836, Bright added a great deal of clinical and pathological information. He had learnt that dropsy might be slight or altogether absent, and that albuminuria might require looking for. He described the various complications, the inflammations of serous membranes, haemorrhages, apoplexies, convulsions, blindness, and coma ; he drew attention to the frequency of cardiac hypertrophy, and suggested an explanation which still holds its ground. He recognised the importance of alcohol and exposure to cold as etiological factors, while his views on prognosis were truer and more liberal than those which afterwards became current. 84 BRIGHT S DISEASE. But on the actual nature of the pathological process his ideas were cramped by the contemporary state of pathological doctrines. Just as in these days every disease is ascribed to a microbe, in Bright's time everything was regarded as due to a deposit. Laennec called tubercle and cirrhosis of the liver deposits. So Bright thought the various anatomical types of Bright's disease were stages in the evolution of a deposited material, and the hard granular kidney was the ultimate result of the process. Rayer, in 1839, correctly described the inflammatory nature of the lesion, and some years after (185 1) Frerichs explained the different anatomical types by his doctrine of three stages : (i,) Hyperaemia with exudation ; (2,) Fatty degeneration of the exudation ; and (3,) Absorption of the exudate with atrophy of the organ. Johnson, in his " Diseases of the Kidney," published in 1852, made two important additions to the subject: (i,) He showed that the chief seat of acute inflammation was the tubules, and that in the sequel the tubular epithelium under- went necrosis, desquamation, and fatty degeneration ; (2,) He differentiated the small red kidney as a type which occurs independently of acute inflammation. In 1858 Virchow gave an academical form to these dis- coveries by describing three conditions: (i,) Parenchymatous inflammation, originating in the tubular epithelium ; (2), Interstitial inflammation, originating in the connective tissue ; and (3,) Amyloid degeneration, originating in the blood vessels. Amyloid, waxy or lardaceous degeneration had been previously recognised by Rokitansky and Johnson, but only as a complication, not as a distinct type. Rosenstein, in i860, found Virchow's academic classification too rigid, and described: (i,) Hypersemia ; (2,) Catarrhal nephritis ; (3,) Diffuse nephritis ; and (4,) Amyloid degener- ation. Grainger Stewart, in 1868, recognised three forms of Bright's disease: (i,) Inflammatory, having three stages: («,) Of inflammation ; {b^ Of fatty transformation ; ic^ Of atrophy. (2,) Waxy or amyloid, also having three stages: («,) Affecting vessels only ; (^,) Transudation into tubules ; (^,) Atrophy. (3,) Cirrhotic or contracting. In 1872 Gull and Sutton introduced an entirely new doc- trine to explain the pathogenesis of the contracting kidney. HISTOR Y—CLASSIFICA TION—ETIOLOG Y. 85 They re-discovered the thickenhig of the vessels which had been described b}^ Johnson, and announced the existence of a generaHsed affection of the small arteries and capillaries, to which they gave the name of arterio-capillary fibrosis, and of which they maintained the kidney lesion was merely a pro- nounced local expression ; the vascular degeneration having led to atrophy of the surrounding tissues. But the doctrine of interstitial nephritis received a new impetus from the careful work of Kelsch, published in 1874, and in succeeding years it was endorsed by Bartels, Charcot, and Grainger Stewart. It had never been accepted by Johnson, Moxon or Roberts in this country, or by Rosenstein, who declared " That there could not properly be said to be either strictly parenchy- matous or strictly interstitial nephritis," both tissues being affected, and " that large white and small red kidneys were alike the result of diffuse inflammation." Weigert gave great support to this opposition by a paper published in 1879, in which he maintained that the paren- chyma and the stroma are affected in all cases of chronic Bright's disease, and that pure parenchymatous nephritis exists only as an acute disease. These views met with the concurrence of Bamberger, and were supported by the experi- ments of Grawitz and Israel, who found that artificially induced nephritis was followed indifferently by the small red or large white kidney. In 1880 I expressed the results of my own histological observations in the following words : " The small red and large white kidney, and all the intermediate varieties, are the result of inflammation which affects all the tissues, but varies very greatly in intensity. The parenchyma being the most highly organised tissue, suffers most in proportion to the intensity of the inflammation. The large pale kidney is the result of prolonged or repeated severe inflammation ; on the other hand, the small red kidney indicates an inflammatory process of prolonged duration but of minimum intensity ; and the intermediate varieties correspond to all the different degrees of intensity possible between the two extremes. The fact of the existence of an indefinite tiwnber of intermediate or mixed forms between the two typical varieties of the large white and small red kidney is a strong argument in favour of the doctrine of unity." Since that time there has been no conspicuous attempt to 86 BRIGHT S DISEASE. revive the doctrines of Virchow, and the opinion that the lesion is a diffuse nephritis in all forms of chronic Bright's disease has steadily gained ground. CLASSIFICATION. In the preceding sketch of the history of the doctrine of Bright's disease, I have recorded the failure of successive attempts to classify the various clinical forms upon an anatomical basis. I propose to adopt an etiological classification, which I hope will be found to adapt itself to the facts of clinical observation as well as to pathology. The following are the proposed divisions : (i,) Infective Nephritis ; (2,) Toxic Nephritis ; (3,) Obstructive Nephritis. The first division includes all those cases of acute or chronic nephritis occurring as a result of acute or chronic infective diseases. The nephritis is directly dependent upon the infective process, hence its name. Anatomically it includes most cases of acute parenchymatous nephritis, of chronic fatty kidney, and many of typical granular kidney, for numerous observations have proved that acute nephritis following infective disease {e-g-., scarlatina, enteric fever, pneumonia), may develop this form. The second division includes the great group of chronic Bright's disease due to lithaemia, and is specially associated with the small red granular kidney, but owing to the occur- rence of intercurrent acute and subacute attacks of nephritis the kidneys are often enlarged and fatty. It probably depends upon irritation of the kidneys by the excessive elimination of poisons of which uric acid is the type. It includes the acute nephritis of acute gout, of poisoning by animal, vegetable or mineral poisons, and certain cases of primary acute nephritis usually attributed to chill, but in which there is probably an already existing dyscrasia. Such acute cases are met with occasionally in individuals who get drunk on beer and lie out all night. The third division includes all cases dependent upon obstruction to the outflow of urine. They occur commonly in males as a consequence of stricture or enlarged prostate, in females from pressure on the ureters caused by pregnancy or pelvic diseases. HISTOR Y—CLASSIFICA TION—E TIOLOG V. 87 In each of these classes we may meet with the urinary and other symptoms of acute or chronic nephritis, wnile the />osi mortem appearances may be those of acute nephritis, of chronic fatty kidney, or of contracting kidney. Lardaccous or waxy degeneration is not made a special group because it is only when associated with chronic nephri- tis that it deserves to be called Bright's disease. General lardaceous degeneration affecting liver, spleen, kidneys, intes- tinal mucous membrane, lymphatic glands, heart, etc., has no other title to be called Bright's disease than the occurrence of albuminuria, and even that is not always constant (FUR- BRINGER). Whatever may have been the case twenty years ago, it cannot be maintained now, and certainly will not be admitted here, that albuminuria and Bright's disease are synonymous. The lardaceous kidney of most authors is chronic nephritis as it occurs in chronic infective diseases, e.g., long standing suppurations, phthisis, etc., in which lardaceous degeneration may occur just as it may in any other form of chronic Bright's disease. Its relation to suppuration is by no means so constant as has been taught ; for out of sixteen cases of chronic nephritis occurring in these circumstances, collected from the patho- logical registers of the General Hospital, lardaceous degener- ation was present in two only. I admit that lardaceous disease is less common in Birming- ham than in London or Edinburgh ; this is a striking and curious fact ; but the disease is by no means unknown, and its relative rarity makes its true relation to Bright's disease more apparent. This is after all only reverting to the older opinion of Rokitansky and Johnson. GENERAL ETIOLOGY. Predisposing Causes. — There can be no doubt in the minds of pathologists of the remarkable frequency of Bright's disease in this country, although the Registrar-General's returns and even our hospital registers fail to give an adequate account of it. Out of a total number of deaths in England and Wales for the year 1884, amounting to 530,828, only 6,297, o^ I'l pei' cent., are returned as having been registered under the various terms which are included by Bright's disease. In this district, 88 BRIGHT S DISEASE. the West Midland, there were only six hundred and ninety out of a total of 56,938 deaths, or i"2 per cent. In London alone during that year there were 11,000 deaths in persons over fifty years of age, of which only seven hundred and sixty were registered as Bright's disease ; but Mahomed has told us that in the post ino7'tem registers of Guy's Hospital, he found out of a hundred and fifty cases over fifty years of age, sixty-two instances of chronic Bright's disease, a proportion of one in 2 "42, so that instead of seven hundred and sixty, there should have been 4,546 cases of Bright's disease. On examining the pathological registers of the General Hospital for ten years, from 1875 to 1884, out of 1,213 deaths at all ages there were no less than three hundred and eighty- three cases of acute and chronic Bright's disease, giving a percentage of 31 "5 or a proportion of about one in three. But the Registrar-General's returns show that there has been an increase in the number of cases registered as due to this cause, the increase being mainly in the less obvious form of chronic Bright's disease; for while in 1875, out of a popula- tion of twenty-two millions, 3,841 cases were registered under Bright's disease, of which number nine hundred and seventy- eight were described as '■'nephritis" ; in 1893, with a population of twenty-nine millions, 8,098 cases were registered as Bright's disease, of which number only 1,912 were described as "acute nephritis^ The increase of population was thirty-one per cent, of cases of 7iepJuitis sixty-two per cent, and of Bright's disease one hundred and ten per cent! This result is in all probability due to the fact that the profession is beginning to look for latent cases of Bright's disease and has learnt to recognise them better than was formerly the case. I think we may assume the power of recognition to be a uniform factor in the comparison of one registration district with another, for the purpose of ascertaining whether there is any great difference in the frequency of the disease in particu- lar portions of this kingdom. The following are the results of the figures worked out as percentages for the year 1884 : — All England - - - i"i per cent. London - - - r4 „ South Eastern - - - i"4 „ South Midland- - - 1-4 „ Eastern - - - - 0*9 „ HISTOR Y—CLASSIFICA TION—ETIOLOG V. 89 South Western- - - ]'4 per cent. West Midland - - - 1-2 „ North Midland - - I'o ,, North Western • - - ro „ York - - - • ro „ Northern - - - - 07 „ Wales - - - - 1-4 „ This district, the West Midland, is very little above the average. The influence of great towns does not seem to be very decided, looking at the high figure of Wales, and the low figures of all the northern districts. I am not inclined to regard this table as giving information of a too trustworthy character. It is very remarkable that the eastern district, in which stone is so common, stands so low. It is contrary to what we know of the etiology of Bright's disease, and is probably explained by the fact that the form of the disease set up by uric acid is the type most likely to be overlooked. Purdy finds that Bright's disease is very much more com- mon in the Eastern and Northern parts of the United States ; it is most common in New Jersey, New York, Connecticut, Massachusetts and New Hampshire, least prevalent in Georgia, Nebraska, North Carolina and Arkansas. His figures of the mortality in the various regions are very striking : — Eastern States - - I973 per million. Northern States - - I7'38 „ Southern and Western States I'S to 2 ,, The prevalence of Bright's disease is said to be equally great in Holland, Denmark, Scandinavia, and on the shores of the Baltic, which share the common predisposing cause, a COLD MOIST CLIMATE. In such an atmospheric medium the functions of the skin are habitually depressed, and an undue share of the work of elimination is thrown upon the kidneys. A general patho- logical law links together excessive function and proneness to disease. In tropical climates we have a converse illustration in the great prevalence of skin diseases. But, in all probability, it is not simply an excess of work that the kidneys are called upon to do. Garrod states that sup- pression of perspiration is followed by increased acidity of the urine, and from this we may infer diminished alkalinity of the blood, leading to the accumulation of uric acid in the system. Semmola believed the chief effect of chill to be an alteration of the blood albuminoids resulting in renal irrita- 90 BRIGHT' S DISEASE. tion, hypersemia and albuminuria, which is followed by- general nutritive changes and anatomical alterations in the kidneys. In effect he thought that the altered blood albu- minoids act like &%^ albumen when injected into the veins, becoming readily diffusible through the glomerular walls and appearing in the urine. Thus he made albuminuria the first link in the chain of sequences, to be followed by structural alteration in the kidney. Such a theory needs proof, and of this none is offered. On the contrary, the analogy of egg-albuminuria is a weak one, for it leaves no ill effects on the kidneys (Snyers). Moreover, Tizzoni found that albumen from the urine of Bright's disease when injected into the veins of animals did not cause albuminuria, and there are many cases on record or known to me of albuminuria that has persisted for years without giving rise to any other symptom of Bright's disease. Sex. — It is commonly stated that Bright's disease is more common in males than in females. The pathological register of the General Hospital shows its proportion to all deaths in either sex to be in males 43 '4, in females 40"6. Bamberger finds no difference. In women there are special causes, such as pregnancy, uterine and ovarian tumours, and pelvic inflammation, which are important and common factors ; but against these we may place the greater exposure of men, their habits in food and drink, and the frequency of cystitis, stricture, etc. Age. — Acute Bright's disease is much more common in children than adults on account of its relation to acute infective diseases, especially scarlatina. Chronic Bright's disease is more frequent after middle life. The mortality from Bright's disease shows a progressive increase as age advances ; a fact permitting the just inference that chronic Bright's disease is much more fatal than acute. Under 5 5 to 15 15 to 25 25 to 35 35 to 45 45 to 55 55 to 65 65 to 75 Males 168 145 189 290 469 644 724 606 Females 140 123 174 284 412 482 543 488 HISTOR Y— CLASS IFICA IION—ETIOLOG Y. 91 Heredity. — There is an undoubted tendency in Bright's disease to attack members of the same family and to appear in successive generations. In a case of contracting kidney in a lad, seen in consultation with Dr. J. A. Lycett, of Wolverhampton, his father and two paternal uncles had died of Bright's disease. Other striking instances have been published (Meigs, Kidd). This may be attributed to its relation to gout and lithsemia. There is probably an inherited vice of structure or function ; a thin ill-developed skin is undoubtedly a transmissible peculiarity which has come under my observation in this connection. The habit of constipation, upon whatever it depends, is also a feature common to families, as are also the habits of eating and drinking to excess. The following is an example of three cases of Bright's disease in one family. Case 3.*— William E., aged seventeen, waggoner, admitted Dec. nth, 1887, with dropsy of face, legs and abdomen. Four weeks before he had got very wet ; this was followed by shivering, lumbar pain, swelling efface, legs and belly, with diminished urine. In a week the pain went away, the urine increased in amount, and the dropsy diminished. He could remember no previous illness, and his statement was con- firmed by his mother ; he had never had scarlatina. His work exposed him to wet and cold. His father had died of kid?7ey disease^ aged ihirty-iwo ; a}td ait uncle was at present under treatrnetit in hospital for the same co7idition. Patient was a slightly-built lad, with a little oedematous swelling of face and legs. T. 99"2° ; P. 72 ; R. 19 ; tongue clean ; bowels regular; no ascites ; liver and spleen normal. Heart's apex in fifth interspace internal to vertical nipple line ; a systolic murmur at apex. Pulse 72, regular, full. Urine 48 oz. j sp. gr. loio ; acid ; contains albumen and blood. Dec. 14th. Better ; no redema of legs ; urine 60 oz. Dec. 15th. Urine 50 oz. ; sp. gr. 1018 ; acid ; pale straw colour ; mucous cloud ; urea 242 grains pro die ; albumen a cloud ; a trace of blood ; hyaline, epithelial and granular casts, red and white blood cor- puscles and renal epithelium. Dec. i6th. No oedema of face now. Dec. 26th. Urine 52 oz. ; sp. gr. 1014 ; acid; opaque, pale straw coloui- ; mucous deposit; urea 25r68 ; a cloud of albumen; a few granular casts, red and white blood corpuscles and a few renal epithelia. Jan. 4th. Allowed to get up. Jan. 5th. Urine 46 oz. ; sp. gr. 1020 ; acid ; dark straw colour ; mucous deposit; urea 344 grains pro die ; a cloud of albumen ; a very little blood ; no casts or renal epithelium. Jan. loth. Abundant haematuria, causing headache ; sent back to bed. No oedema. * Recorded by Mr. Teichelmann, clinical assistant. 92 BRIGHT S DISEASE Jan. 14th. Urine 52 oz. ; sp. gr. 1015 ; neutral ; pale straw colour ; urea 274 grains pro die ; a laint cloud of albumen ; no blood ; a few hyaline casts. He was discharged on Jan. 25th, without any further relapse Social State. — B right's disease attacks all classes, but there are occupations that are specially liable to it ; these are, the manufacture and sale of alcoholic drinks, brewers, distillers, publicans, and the like ; workers in lead, file casters, glass cutters, workpeople in white lead factories, painters, lapidaries, etc. ; those specially exposed to cold or damp — well sinkers, miners, etc., and to extreme changes of temperature — furnace men, iron workers, stokers, etc. Diet. — Our habits as to food and drink constitute an etio- logical factor of great importance. We are great eaters of butcher's meat, which is not only the great source of urea and uric acid, but also contains a large quantity of acid salts, by which the alkalinity of the blood is reduced with results already detailed. We aggravate this evil by drinking beer, containing a large amount of acid, chiefly in the form of acetic acid. Finally, we consume an enormous quantity of alcohol in other forms, which is almost wholly eliminated by the kidneys, and which certainly leads to structural disease of the liver. Glaser examined the urine of a number of healthy young men before and after taking alcohol, and found that the after urine contained leucocytes, tube casts, and large quantities of crystals of oxalate of lime and uric acid. The effect of a single dose passed off in thirty-six hours but continued excess produced a cumulative effect. Previous Diseases. — Chronic heart, lung, and liver diseases, by leading to impairment of assimilation, and especially to the imperfect fulfilment of the great urea-forming function, are undoubtedly remote causes of Bright's disease. So, too, habitual constipation predisposes by favouring a dyscrasia caused by imperfect intestinal elimination, as well as perhaps by the absorption of animal alkaloids, formed in the putrefactive processes which take place when food remains too long in the alimentary canal. Exciting Causes. — Of the exciting causes of Bright's disease, there are three great groups, whose efficiency is established by an overwhelming mass of evidence. The best known of these clinically is the great group of acute and chronic i^tfective diseases. HIS TOR Y ~ CLA SSIFICA TION—E TIOL OG Y. 93 Acute diseases^ such as scarlatina, pneumonia, ty^^hoid fever, variola, diphtheria, measles, varicella, tonsillitis, vaccinia (Perl), cholera nostras and Asiatica, and acute rheumatism (E. Wagner), give rise to acute nephritis ; while chronic diseases, such as phthisis, chronic septicsernia, and malarial fever cause chronic nephritis. Is there any primary acute infective nephritis which occurs apart from the poisons of these diseases ? Of late years a series of cases supporting this view has been published by Fiessinger, Mannaberg, Letzerich, Black-Milne, and others, which cannot be overlooked. Fiessinger describes an epi- demic of nephritis in the little town of Oyannax in the department of Ain, where there was no evidence of direct transmission, and no concurrent epidemic or fever was present. Mannaberg and Letzerich both isolated organisms which set up nephritis in animals. Gaucher attributes the nephritis to the irritation caused by the increase of extractives (kreatin, kreatinin, leucin, tyrosin, xanthin, and hypoxanthin) in the blood which are eliminated by the kidneys, and which he has proved by experiments on animals can set up nephritis. This suggestion links this with the next great group, that oi poisons. The most interesting and important of these are those substances which are formed in the body, and of which we may take tir'ic acid as the type (MURCHISON). They are normal products of disassimilation, but under certain circumstances are produced in excess. These circumstances have been already alluded to. They are circumstances of climate, of individual conformation, of occupation, and above all, of habits as to food and drink ; also the presence of pre-existing diseases, especially of the heart and liver. Poisoning of this kind is usually a very chronic and insidious process, often giving rise to no symptoms until the destruction of the kidneys has ad- vanced so far that the dyscrasia, which hitherto has been only the cause of the renal disease, now becomes intensified by the failure of the kidneys to eliminate the impurities from the blood, and sets up all the constitutional disturbances known as uraemia. In other cases the disease is discovered earlier, before the kidneys are so far destroyed, when the destructive process may be checked by treatment designed to limit this auto-intoxication. Many other poisons are known to be efficient causes of 94 BRIGHT' S DISEASE. nephritis, but are not of great clinical importance. The following is a list of them : — Animal Poisons : — Cantharides Vegetable Poisons : — Oxalic acid Opium (Nauwerck) Mineral Poisons : — Arsenic Mercury Iron Manganese Cobalt Nickel Zinc Lead Sulphuric Acid Nitric Acid Hydrochloric Acid Carbolic Acid Ammonia Iodoform The third group comprises all obstructive causes from pressure on or diseases in the urinary passages. In males the principal conditions are stricture, enlarged prostate, and tumours and diseases of the bladder, e.g., cystitis, calculus ; in females pregnancy, uterine and ovarian tumours, pelvic inflammations, and bladder diseases. Simple obstruction sets up a chronic inflammatory process tending to contraction of the kidney. Kidneys which are undergoing this process of obstructive atrophy are very liable to attacks of acute interstitial inflammation originating in the medulla and spreading to the cortex. Such attacks may be set up by cystitis, or by even a slight traumatism such as the passage of a catheter for the first time. BIBLIOGRAPHY. Bamberger (H. von). Ueber Morbus Brightii und seine Beziehungen zu .anderer Krankheiten. 1879. Bartels (C). Ziemssen's Cyclopaedia of the Practice of Medicine. Eng. Ed., 1876, Vol. XV. Blackall (J.). Observations on the nature and cure of Dropsies. London, 1824. Black-Milne ( — .). The Etiology of Acute Bright's disease. " Brit. Med. Journ.," 1892, II., p. 1391. Bluhm (Agnes). Zur Etiologie des Morbus Brightii " Deutsches Archiv i. Klin. Med.," XLVIL, 3 and 4, p. 193. 1891. BISTOR Y—CLASSIFICA TION—ETIOLOG V. 95 Bright (R.). Reports of Medical Cases. London, 1827. . Cases and observations illustrative of Renal Disease accom- panied with the secretion of Albuminous Urine. . Tabular view of the Morbid Appearances occurring in one hundred cases in connection with Albuminous Urine. " Guy's Hosp. Reports," Vol. I., 1836, pp. 338 and 3S0. Charcot (J. M.). Le9ons sur les Maladies du Foie et des Reins. Paris, 1S77. CoTUNNius, — ., quoted by Darwin. "Zoonomia," Vol. I., 1794, p. 316. FiEssiNGER ( — .). Le mai de Bright Epidemique. " Revue de Med.," 1893, p. 404. EisENLOHR (C). Zur Entwickelung der Schrumfniere aus akuter Nephri- tis bei Infections-Krankheiten. " Deutsche Med. Wochenschr.," 1892, No. 18. Engel (R. von.). Zwei Fiille von primarer intectioser Nephritis. " Prag. Med. Wochenschr.," XV., 50. i8go. Frerichs (F. T.). Die Bright'sche Nierenkrankheiten und deren Behand- lung. Braunschweig, 1851. FiJRBRiNGER (P.). Zur Diaguose der amyloiden Entartung der Nieren. " Virchow's Archiv," Bd. LXXL, Heft 3. Gaucher (E.). Recherches experimentales sur la pathogenie des Nephrites par Auto-intoxication. " Revue de Med.," 1888, No. 11, p. 885. Glaser (K.). Ueber den Einfluss alkoholische Getranke auf das Harnsedi- ment der normalen Menschen. " Deutsche Med. Wochenschr.," 1891, No. 43. Gull and Sutton. On the pathology of the morbid state commonly called Chronic Bright's disease with Contracted Kidney. " Med. Chir. Trans.," Vol. LV., 1872, p. 273. Johnson (G.). On Diseases of the Kidneys. London, 1852, . Lectures on Bright's disease. London, 1873. Kelsch (A.). Revue critique et recherches anatomo-pathologiques sur la Maladie de Bright. " Arch, de Phys.," Vol. VI., 1874, p. 722. Kidd (J.). The Inheritance of Bright's disease of the Kidney. "Practi- tioner," Vol. XXIX., 1882, p. 104. KoBLER (G.). Beitrag zur Kenntniss der Nierenerscheinungen bei acuten Darmaffectionen nebst Bemerkungen iiber die Bildung der hyalinen Cylindern. "Wiener Klin. Wochenschr.," i8go, No. 88. Letzerich (L.) . Ueber die Aetiologie Pathologie und Therapie der bacillaren interstitieller Nierenentziindung. " Zeitschr. f. Klin. Med.," XVIII. , 5 and 6, p. 528. 1891. Mahomed (F. A.). Some of the clinical aspects of Chronic Bright's disease. " Guy's Hosp. Reports," 3rd S., Vol. XXIV., p. 363. . Chronic Bright's disease and its essential symptoms. " Lancet," 1879, I., p. 46. . Chronic Bright's disease without Albuminuria. A thesis for the degree of Bachelor of Medicine of the University of Cambridge, read June i6th, 1881. Mannaberg (J.). Zur Etiologie des Morbus Brightii acutus nebst Bemer- kungen iiber experimentelle bakteritische Endocarditis. " Zeitschr. f. Klin. Med.," XVIII., 3 and 4, p. 223. i8go. Meigs (A. J.). Clinical observations on Albuminuria, based upon a study of sixty-two cases seen in private practice. " Boston Med. and Surg. Jour.," Vol. CVIL, 1882, p. 409. MuRCHisoN (C). Lectures on Diseases of the Liver. 2nd Ed. London, 1877, p. 573. Nauvverck (C). Akute Nephritis bei Opiumvergiftung, Beitrage zur Kenntniss des Morbus Brightii. Perl ( — .). Akute Nephritis nach Schutzpockenimpfung. " Berl. Klin. Wochenschr.," 1893, No. 28. 96 BRIGHT S DISEASE. PuRDY (C). The distribution of Bright's disease. "New York Med. Jour.," i8go. Ralfe (C. H.). a practical Treatise on Diseases of the Kidneys and Urinary derangements. London, 18S5. Rayer (P.). Traite des Maladies des Reins et des alterations de la Secre- tion Urinaire. Paris, 1839 — 44. RosENSTEiN (S.). Pathologic und Therapie der Nierenkrankheiten. 2nd Ed., Berlin, 1870. 3rd Ed., 1886. Saundby (R.). The Histology of Granular Kidney. " Path. Soc. Trans.," 1880, p. 148. Semmola. Nuove contribuzioni alia patologia ed alia cura del Morbo di Bright. "Med. Contemp. Napoli," 1886, III., pp. 449 to 467. Snyers (P.). Pathologie des Nephrites chroniques. Bruxelles, i885. Stewart (Grainger). Bright's diseases of the Kidneys. Edin. 1868. 2nd Ed., 1871. . On certain morbid states of the Kidney. ' Address in the Section of Medicine, Brit. Med. Assoc, 1878. TizzoNi (G.). Alcuni esperimenti intorno alia patogensi dell' Albuminuria. "Gaz. de'gU Ospit. Milano," Vol. VI., 1885, p. 12. Traube. Ueber den Zusammenhang von Herz- und Nierenkrankheiten. Berlin, 1856. Van Helmont. Oriatrike or Physick refined. London, 1662, p. 507. ViRCHOW (R.). Cellular Pathology. London, 1858. Wagner (E.). Beitrage zur Kenntniss des chronischen Morbus Brightii. " Deutsch. Arch, fiir Klin. Med.," Bd. XXVII., p. 218. Weigert. Die Bright'sche Nierenkrankung vom pathologisch-anatomis- chen Standpunkte. " Volkmann's Sammlung Klin. Vortrage," Serie VI., pp. 162-3. 97 Chapter X. INFECTIVE NEPHRITIS. This division includes all cases of acute nephritis where the inflammation is set up by an acute infective disease. It also includes all those cases of chronic nephritis occurring as the direct result of chronic infective processes as in phthisis, prolonged suppurations, etc., and also those occurring as a sequel to acute nephritis of infective origin. Etiology. — The following infective diseases are known to cause acute nephritis : Scarlatina, diphtheria, pneumonia, enteric fever, exanthematic typhus, remittent fever, malarial fever, variola, measles, varicella, vaccinia, cholera nostras and asiatica, cholera infantum, infantile diarrhoea, suppurative meningitis, acute myelitis, whooping cough, mumps, acute rheumatism, tonsillitis, erythema nodosum, erysipelas, septi- caemia, ulcerative endocarditis, cancrum oris, and anthrax. In the greater number of cases the' disease is not recognised at the time. Phthisis, tubercular diseases of bones and joints, malaria, syphilis, and chronic septicaemia, set up chronic nephritis. The disease is directly due to the infective process, and probably depends upon the irritation of the kidneys during the elimination of toxins. Specific micro-organisms have been found in the kidneys in cases of diphtheria, pneumonia, septicemia, and ulcerative endocarditis, but as they are only exceptionally present, it is reasonable to conclude that they are not essential to the pro- duction of the nephritis ; they are found in the kidney because they exist in the blood, and it is the natural channel for their elimination. That nephritis has been caused experimentally by the injec- tion of micro-organisms (micrococcus pyocyaneus, Charrin and Bouchard) proves that this organism may set up an acute infective process in which the kidney suffers, for as Bluhm puts it, any infection may give rise to Bright's disease, even although it is slight and abortive. 7 98 BRIGHT S DISEASE. The same explanation may be given of some of the cases of so-called mycotic nephritis described by Litten, Bamberger, Aufrecht, and Mircoli, but there is a steady accumulation of evidence pointing in the direction of the occurrence oi primary acute nephritis, as the result of the agency of perhaps several species of micro-organisms which attack the kidneys them- selves, just as the pneumococcus attacks the lung. Non-specific micro-organisms have been frequently found in the nephritis of acute diseases, e.g., variola, scarlatina, and cancrum oris, but they have no pretension to any special etiological significance. ACUTE INFECTIVE NEPHRITIS. Morbid Anatomy. — In the majority of cases during the first week the kidneys undergo no change in size, shape, or colour. After a week, if the disease persists, the kidneys become more or less enlarged, pale in colour, or mottled red and white. On section, the swelling and pallor or mottling are seen to be in the cortex, the outspread pyramids retaining their red colour. Histology. — The following is a brief summary of the changes in acute nephritis (under six weeks) with a magnifying power of 450 diameters : — Blood vessels. — The blood vessels are nearly always full of blood clots, especially below the capsule and in the medulla. They are sometimes greatly dilated. Occasionally thrombi formed of leucocytes are seen in the vessels of the cortex. Glomeruli. — The capillaries are often full of clots ; the endothelial nuclei on the tuft are always distinct and often increased in number. Sometimes the capsular space contains blood clot, at others there is some local accumulation of cells from inflammatory exudation. Tubules. — The epithe- lium of the convoluted tubes and Henle's loops Tia. 18. Convoluted tubule in acute nephritis. The . ,, 1 i.* „ epithelium is cloudy, swollen and ruptured. IS generally VaCUOlatmg {.Pig- 13). that is, undergoing a process of atrophy by shedding its protoplasm, leaving only the basal part with the nuclei. INFECTIVE NEPHRITIS. 99 Fig. 14. Convoluted tubule in a cute nephritis. Epitiielium granular, partially destroyed, only the basal portion remain- ing. The lumen of ihe tubule is filled with protoplasmic droplets and granular matter. The cavity of the tubules becomes filled with spherical droplets and granular matter derived from the epithelium {Fig. 14). In some cases the epithelium appears to be undergoing simple necrosis, breaking down into granular material. The epithelium of the collecting tubes appears to undergo no patho- logical change, but the cavities of many tubes are filled with droplets and granular matter forming casts. Stroma. — In scarla- tinal nephritis the stroma of the cortex and medulla is swollen and often filled with round cells. In other forms there are only a few round cells, and in the majority of cases it is only slightly swollen and hyaline. This description shows the affection to be mainly an acute catarrhal inflammation affecting the epithelium of the convo- luted tubes. In scarlatinal kidneys, interstitial and glomerular affections are often pronounced. Symptoms and Course. — As a rule patients with acute nephritis are pale ; they often complain of headache ; pain re- ferred to the loins is less common than might be supposed. There is usually complaint of weakness ; the tongue is gener- ally clean, and the bowels almost invariably confined. The last circumstance is important in connection with the influence which constipation was proved by Mahomed to have on the development of scarlatinal nephritis. It is probable that there are many cases of acute nephritis which remain latent and get well, and many more would do so but for such an accident as a chill to the surface, or constipation. Dropsy. — More or less oedema is commonly present in acute nephritis, but it is less constant than has been stated. It is notably absent in the majority of cases occurring in the course of acute diseases. The most frequent exception to this rule is scarlatina, in which the presence of dropsy often draws attention to a nephritis which in many other acute diseases would pass unrecognised. The amount of dropsy varies very much, from mere pufifiness loo BRIGHTS DISEASE. of the eyelids to general anasarca with effusion into the serous sacs. The eyelids are the most constant seat next the lower extremities, then the trunk, scrotum, etc. CEdema of the conjunctiva is a common symptom of Bright's disease, giving the eye a peculiar lustre. CEdema of the lungs and glottis are complications which will be described hereafter. Teniperatu7'e. — The onset of acute nephritis does not seem to be attended by any marked inflammatory fever. The temperature in cases seen early in their course is sometimes 1 00°, but after a few days it becomes normal or subnormal, and does not rise except on account of some complication. Heart. — The heart is liable to attacks of acute softening or myocarditis, in which it may become rapidly dilated, and this dilatation may be followed by rapid hypertrophy. As a rule the left ventricle is alone affected. The enlargement of the heart leads to displacement of the apex beat outwards, and a systolic murmur may be audible over it. In other cases the first sound at the apex is reduplicated, and the second sound in the aortic area accentuated. These alterations are the result of the increased pressure in the aortic system, causing delay in the systole of the left ventricle followed by rapid and abrupt closure of the aortic semi-lunar valves. Blood. — According to Lloyd-Jones the density of the blood is very much reduced, being only 1032 instead of the normal 1058-60. Pulse. — The rate of the pulse is at first quick, ninety to a hundred, but falls after the first few days to seventy or eighty, not seldom to sixty. The pulse is usually moderate in volume and not perceptibly hard, but the sphygmograph shows a characteristic curve of high tension {Fig. 15). In explanation of this discrepancy I would repeat my former remark that this curve is not really a measure of blood pressure, but of the duration of the tidal wave, acu?e ieph^ifs*: 'T^Se'curv^e^'^bovrthellne' which depCnds UpOn tWO faCtOrS, thc a b IB the full tidal wave. peripheral obstruction and the force of the ventricle ; whenever the former is too much for the latter the curve of high tension is produced, though in reality the ventricle may be weak and the intra-vascular pressure below normal. INFECTIVE NEPHRITIS. loi OphtJiabnoscopic appeara7tces. — The fundus of the eye pre- sents no change in acute Bright's disease of infective origin ; except perhaps cedematous swelHng in uraemic amaurosis. Urine. — The quantity of urine is always reduced, at any rate for the first few days ; it is generally under 30 oz., often under a pint in twenty-four hours. The density is generally over 1020, often higher ; in fact some of the densest urines are met with in acute scarlatinal nephritis, a sp. gr. of 1065 having been recorded in one instance (W. G. Smith). The reaction is almost invariably acid, unless affected by drugs. The colour and translucency depend mainly upon the amount of blood present ; thus the urine may vary from being merely smoky through various shades of reddish brown to the colour of porter. If blood is present in very small quantity the urine may be yellow and clear. The deposit is always considerable, consisting of mucus, epithelium, casts and blood ; its colour and consistence vary from white and flocculent up to chocolate and dense, the principal factor in the change being the amount of blood present. Uric acid crystals, urates of soda, potash and ammonia, or triple phosphates sometimes occur in the deposit. The urea is generally under two per cent, often little more than one per cent. ; so that as the quantity of urine is small the total eliminated is usually under two hundred grains per diem. Albunieri is often not very abundant. A dense cloud is a fair description of the amount; more accurately from "05 to 'i per cent, but in severe cases it may reach one per cent or more. Willey has shown that acute nephritis is often found post mortem in scarlatinal cases which have presented no albuminuria during life. Blood is most constantly present, generally in large, some- times only in small amount ; it often persists for long and Tig. 16. a. Deposit In acute nephritis show- ing Blender hyaline civbi; l. mucous cylinder; c, hyaline and epithelial cast : d, pear -shaped epithelial cells from pelvis o< kidney ; e, epithe- lium from tubules. I02 BRIGHT S DISEASE. recurs in a troublesome manner. The casts most commonly seen are blood and hyaline, the most significant are epithelial. Epithelial cells are usually abundant. The following may be taken as a typical report of the urine of an ordinary case of acute nephritis : — Urine lo oz. ; sp. gr., 1020 ; acid ; smoky ; brownish deposit ; urea, V2 per cent. ; albumen, '2 per cent. ; under microscope deposit contains epithelial, hyaline, granular and blood casts, red and white blood corpuscles and abundant renal epithelium. Diagnosis.— Even when dropsy is absent, if the urine is scanty, albuminous, and contains blood and epithelial casts, acute nephritis may be safely diagnosed. The difficulty is to distinguish between acute nephritis in previously healthy kidneys and an intercurrent attack in the course of chronic nephritis. This can be only determined with certainty by the history, but the age of the patient is suggestive. Thus in children primary disease is very common, while after forty years of age it is very rare. The presence of albuminuric retinitis or hsemorrhages indicates latent contracting kidneys, as does also, though with less certainty, the discovery of dis- tinct enlargement of the heart early in the case. In intercurrent acute attacks the quantity of urine rapidly rises to normal or more than the normal amount. Complications. — Primary acute attacks are not attended by many complications, but a mild degree of urcemia is often present giving rise to headache and vomiting. Convulsions sometimes occur even in mild cases in children, and these may be followed by coma. Qidema of tJie glottis is a localisa- tion of the dropsy attended by special risk on account of its seat at the opening of the air passages. Duration. — It is not easy to fix the exact duration of an acute attack. The more urgent symptoms usually cease in two or three weeks under suitable treatment, but the kidneys are so far damaged that albuminuria continues as a rule for many months, during which the patient is in imminent danger of a relapse. If the symptoms persist beyond six weeks, the case is usually regarded as becoming sub-acute or chronic. Our language in this respect is defective, and it is plain that no very hard and fast line can be drawn. Prognosis. — The chances of recovery from an acute primary attack are decidedly favourable. Death rarely occurs during the acute stage. It is not easy to speak so confidently as to the ultimate result. A large proportion no doubt gets quite INFECTIVE NEPHRITIS. 103 well ; in a certain number the kidneys remain damaged suffi- ciently to render them very liable to fresh attacks ; while others become chronic. In all cases the utmost care is needed, and an opinion as to the ultimate result must be very guarded until months have elapsed and all trace of albumen has disappeared from the urine. If this account of the prognosis of acute nephritis should appear to some to be too favourable, I would remind them that we recognise the disease much more commonly and in milder phases than was formerly the case. Thus Thomson's statistics show, that out of a hundred and eighty cases of scarlatina, one hundred and twelve, or 63 "2 per cent, were affected with nephritis ; that is to say the urine contained albumen, blood and tube casts, but only twenty-four showed any anasarca. Of the hundred and twelve only eleven died, of whom four are stated to have died from malignant scarlatina. One died from uraemia. Of the eleven fatal cases only five showed any anasarca, though two cases in which this was noted as abundant were fatal. The case that died from uraemia had only slight dropsy. These figures show that the majority of cases, even of post- scarlatinal nephritis, when properly cared for, do well. The guides to an opinion as to the probable termination of the case should be (i,) The evidence of the functional power of the kidneys as shown by the daily amount and character of the urine ; (2,) The degree of dropsy present ILLUSTRATIVE CASES. Case 4.* — Acute Briglifs disease following sore throat {tonsillitis?) ; persistent hematuria. George T., ag-ed twelve, schoolboy, admitted March 4th, 1887, with weakness and haematuria. Eight weeks ago he had a sore throat, and after he had got over that he began to swell. His grandmother, with whom he lived, thought he had got a chill going to school. His family history was imperfect, but negative so far as it could be ascertained ; his parents were not supposed to be dead. His previous health was good, but he had had scarlatina and measles when a baby. He was a fairly healthy looking boy, with rather a puffy face ; skin dry and brown ; slight oedema of the legs. T. 100° ; P. 78 ; R. 18 ; tongue dry, white ; appetite good ; no pain after food, or vomiting ; bowels confined (he said they were regular) ; liver and spleen normal ; no ascites. Heart's apex in fifth interspace inside nipple line ; * Recorded by Mr. Ross Jordan, Clinical Assistant. 104 BRIGHT S DISEASE. a systolic murmur at apex, with accentuation of the second sounds at the base. Pulse irregular ; lungs normal. No lumbar pain ; says he gets up in the night to make water ; urine 14 oz. ; sp. gr. 1014 ; acid ; contains albumen and blood. March 12th. CEdema has disappeared. March 13th. Urine 16 oz. : sp. gr. 1017, acid ; dark smoky red colour; dark reddish brown deposit ; urea "95 per cent. ; albumen quarter column ; epithelial granular and blood casts, red and white blood cor- puscles, squamous epithelium, uric acid, and granular matter in deposit. This condition of urine continued for two months, except that the quantity was, on an average, normal. He was not discharged till June 13th. The last urine report is as follows : Urine 35 oz. ; sp. gr. 1016 ; acid ; straw colour, slightly turbid ; reddish white flocculent deposit ; urea 2 per cent. ; a cloud of albumen ; a trace of blood ; granular and epithelial casts, red and white blood corpuscles, squamous epithelium and uric acid. He was made an out-patient, but did not attend. Case 5.* — Acute Brighfs disease; urcemia; recovery. John B., aged six, schoolboy, admitted April 3rd, 1886, with swelling of legs and face. He had been ill a week. Four years and a half previously he had scarlatina, not followed by dropsy ; two of his brothers had it at the same time. He was a well nourished child with a pale swollen face, and consider- able anasarca of the trunk and lower extremities ; his eyelids were puffy. T. 98° ; P. 102 ; R. 24. Tongue slightly furred ; bowels confined ; no ascites. Liver and spleen normal. Heart's apex in fifth intercostal space just external to the vertical nipple line ; a faint systolic murmur was audible in the mitral area, but the heart sounds elsewhere were loud and accentuated. Pulse small, regular, rather hard. Breath sounds rather feeble posteriorly ; lungs otherwise normal. Ophthalmoscopic appearances normal. Urine, 16 oz. in 24 hours ; acid ; sp.gr. 1018 ; in colour and appearance like beef tea ; \\ in. of brown deposit; urea, \'i per cent.; albumen, 0*17 per cent.; blood in large amount. Epithelial, blood, hyaline, and granular casts, with blood corpuscles and renal epithelium in deposit. He was put on milk diet, and treated by diaphoretics and diuretics. April I2th. The oedema of the legs has disappeared. April 17th. Haematuria still abundant; ordered ext. ergotse Hq. niv, quaj'tis horis. April 23rd. Blood reaction with guaiacum and ozonic ether feeble. April 27th. He had an attack of uraemic convulsions which lasted an hour and a half, but not attended by loss of consciousness. After this attack his pulse fell to 60, and was labouring, irregular and intermittent. April 28th. Ordered solution of nitro-glycerine (i per cent.), mj, secufidis horis. May 13th. He was much better; the pulse still intermits at long intervals ; he was allowed to get up. June 4th. He had been going on very well, when the haematuria recurred. June 12th. By this time the blood was nearly gone. • Recorded by Dr. Stacey Wilson, House Physician. INFECTIVE NEPHRITIS. 105 July 8th. He was discharged free from oedema, and in fair health ; urine 30 oz. ; amber ; acid ; slight flocculent deposit ; urea 17 per cent. ; albumen '05 per cent. ; an occasional hyaline cast and a few blood corpuscles in the deposit. Urine of John B., acute nephritis : — Quantity Quantity Quantity Date. of urine of urea of albumen in oz. in grains. in grains. April 5th . 16 91-52 1 19-6 „ 1 2th . 16 I47'84 70-4 „ 19th . 14 117-04 30-8 „ 23rd . 16 112-64 14-0 „ 28th . 20 123-2 44-0 May 3rd 16 105-6 7-0 „ 1 2th . 24 137-28 IO-5 „ 19th 36 237-6 15-8 „ 25th . 30 145-2 13-2 June 2nd 30 198-0 6-6 „ 7th . 30 A „ 9th 30 118-8 „ i6th . n ■-> 92-4 V Too little to estimate. ,, 23rd . 40 191-2 „ 27th . 26 1 93 '48 J July 8th . 30 7-0 Urea not estimated. Case 6.''= — Ulcerative, endocarditis; sub-acute infective nephritis j urcB7nia. DeatJi. Autopsy. E. S. , female, eighteen, domestic servant, admitted July 2nd, 1886, complaining of pain at the heart and swelling of the legs and face. For the last four months she had been ailing, but her legs began to swell fourteen days before admission. She had had rheumatic fever three times in the last five years. Her previous health was good. Father died of phthisis, aged forty-eight. Mother died of heart disease, aged forty-nine. One brother died of heart disease, aged thirteen. Two died in infancy ; four are living and in good health. Patient has marked cedema of eyelids and face, slight oedema of legs and ankles ; T. 100° ; P. 96 ; R. 30 ; tongue clean ; digestion good ; bowels regular ; liver and spleen not enlarged. Heart's apex beat in fourth left interspace, internal to nipple line, but dulness extends half an inch beyond the nipple in the fifth interspace. A loud systolic murmur in the mitral area ; pulmonary second sound loudly accentuated. Pulse small, but not easily compressed. Lungs normal, except some dulness with deficient breath and voice sounds at left base. She has not menstruated for six weeks. Has no pain or difficulty in making water. * Recorded by Dr. Stacey Wilson, House Physician. io6 BRIGHT S DISEASE. Urine, 26 oz. ; 1014, acid ; straw-colour, blood-tinged ; reddish deposit ; urea, i"4 per cent. ; a cloud of albumen ; numerous hyaline and granular, with a few colloid and epithelial casts, red and white blood corpuscles, squamous and renal epithelium, and uric acid crystals. After admission her temperature assumed a hectic type, rising at night sometimes as high as 103° Fahr. Her urine remained much the same. On August loth she became drowsy, and this was followed by ursemic convulsions. Two days later the convulsions returned, coma supervened, and she died. Autopsy performed by Dr. Crooke. Subject emaciated ; features pale and puffy ; lips livid ; feet and ankles swollen. Abdomen distended. Heart, 1 1\ oz., pericardium universally adherent by old fibrous adhesions ; both ventricles dilated, the left especially. Left ventricle contains dark semi-fluid blood clots ; watery fluid blood, and colourless soft clot in right auricle and ventricle ; valves in right side normal. Aorta, rather narrow, valves normal. Extensive recent endocarditis round mitral valve extending into left auricle on its outer wall, where there is a large patch of vegetations. The mitral curtains are beset with soft greyish friable vegetations. Wall of left ventricle vascular, cloudy, mottled yellow in places, soft and friable. Lungs congested in their lower lobes ; upper lobes cedematous. Liver 56 oz., soft, pale, with hyperysmic patches. Spleen 13^ oz., adherent, contains a large infarct which is breaking down, and another smaller one softening in the centre. Several hemorrhages in spleen substance, which is very vascular. Kidneys 9 oz., capsules strip easily, leaving a characteristic greyish brown and red speckled surface. On section the cortex is increased, pre- senting the same finely mottled, grey brown and red coloration, mixed with a sprinkling of yellow. The cut surface is dotted with whit- ish points, which are the glomeruli altered by inflammatory change. At the inferior end of the left kidney is a small wedge-shaped infarct, yellowish white, dry looking and firm, fringed with a zone of hypersemia. The medullary cones are uniformly hght chocolate brown in colour. Under the microscope the Malpighian bodies are infiltrated with micro-organisms, chiefly streptococci {Fig. 17). Treatment. — The main lines of treatment are rest and warmth, aided by suitable diet, purgatives and diaphoresis. The patient should remain in bed, in a flannel night-dress, wrapped in a blanket, or the sheets may be taken off the bed. The diet should be milk and farinaceous food. No beef tea (according to Masterman, beef tea is analogous in chemical Tig. 17. Sfalpighian Body from case ol sub- acute nephritis in ulcerative endocardilis, showing infiltration of the tuft with micro- organisms (streptococci). INFECTIVE NEPHRITIS. 107 composition to urine except that it contains less urea and uric acid), meat extracts or jellies should be given. The bowels should be kept open by an occasional purgative (bitartrate of potash 5SS, honey or treacle 5j), every second or third day if required. The best diaphoretic is the hot air bath, which should not be prolonged beyond twenty minutes. It will be found that a patient who does not sweat at all in the bath on the first few occasions will do so perfectly well afterwards. The hot air bath may easily be improvised by a spirit lamp set under a stool or cradle in the bed, if one of the cheap tin lamps sold for the purpose is not available. I very much prefer this method to the hot pack, which has been shown by Goodhart to be dangerous by causing pyrexia. I have had the temperature taken many times before and after the hot air bath, and have not noticed any rise. I usually give a pint of Imperial (potassii bitart. §ss., sacch. alb. q.s., aqu3e Oj,) daily as a drink, to keep up the alkalinity of the blood serum and diminish the acidity of the urine, nor have I seen any reason to believe it harmful, in spite of the theoretical importance of potassium salts in the pathogenesis of uraemia. Great responsibility attaches to the medical attendant with respect to the care and conduct of his patient after convalescence is reached. Undoubtedly great, sometimes insuperable diffi- culties are placed in his way, but it is his plain duty to point out as impressively as he can the dangers that lie ahead and the precautions needed to avoid them. The patient must be told of the great liability there is for the disease to relapse from exposure to cold, from injudicious diet, and from the occurrence of any infective disease, however slight. If possible he should spend the winter in a milder climate than our own, or in the mildest parts of this island. He should not be allowed to eat butcher's meat or cheese, or to drink alcohol in any form until all albumen has disappeared from his urine, and even then he should be warned to use these articles of diet very sparingly. His dress should consist of underclothing of wool from head to foot, summer and winter, and he should be prevented from taking part in work or exercise likely to overheat his body or risk the possibility of a chill. io8 B RIGHT'S DISEASE. CHRONIC INFECTIVE NEPHRITIS. Etiology. — As a result of neglect of proper precautions after an acute attack, often in ignorance of its existence, the patient gets a chill, and a fresh attack is lighted up which may pass into chronic nephritis. Moreover such kidneys are specially liable to be irritated by the various poisons which can set up nephritis in healthy kidneys. In chronic infective diseases there is a correspondingly chronic nephritis which often remains latent for a considerable part of its course. Morbid Anatomy. — As a rule the kidneys become larger and paler ; the capsule still strips off readily, leaving a smooth shining surface. On section, the cortex is broad, white, and soft, while the pyramids are pale red and streaked with white lines. The Malpighian bodies often show the reaction of lar- daceous or waxy degeneration with liq. iodi. In its most pronounced type this constitutes one form of the " large white kidney," but this anatomical variety may originate in other ways. In some cases the kidney is no larger than normal or may be even smaller, and instances have occurred in which one kidney is large and the other small, as in the following des- cription of a pair of kidneys copied from the post inortetn register of the General Hospital. Kidneys of H. — The right is enormously swollen, and weighs 14^ oz., while the left is much smaller, weighing only 6 oz., and is much lobulated. Both are pale, soft and flabby in consistence, capsules easily separable, leaving a dull white ground colour mottled with red and yellow (branny kidney). On section, the right or larger kidney presents large white areas in which the fatty changes (yellow branny speckling) are marked : the cortex is much increased in breadth, of a uniform grey white colour, swollen, generally opaque, but in some places semi-translucent in appear- ance, showing also a fine yellow speckling of the surface, and streaked and dotted with lines and points of hyperccmia. The left or smaller kidney presents very similar appearances except that it is rather more vascular ; no difference can be felt in its resistance to the knife, and it is as soft and doughy as the right kidney. At the bottom of the depressions or lobulations the capsule appears slightly thickened and adherent, and a small greyish semi-translucent strand appears to enter the cortex. In other cases, especially in post-scarlatinal kidneys, in which interstitial nephritis was noted as occurring during the primary acute attack, the organs are reduced in size, with thickened and adherent capsules, and pale roughened surfaces. On section, the kidney substance is abnormally tough, while the cortex is narrowed. The atrophic stage may come on INFECTIVE NEPHRITIS. 109 rapidly, marked examples having been met with at the end of two months (ElSENLOHR). This is the type which was formerly described as a third stage, in which the large white kidney had undergone atrophy, but it is now thought more probable that these kidneys have never been much enlarged, and ^<^-'-- Mymst' Fig. IR. Malplghlan body showing marked perl, and endo-capsuUtiB, with increase of the nuclei of the tult. that interstitial inflammation has been a marked feature in the inflammatory process from the beginning. It is not clear under what circumstances, apart from the clinical fact of its frequency in scarlatina, this particular form is developed. As already mentioned, Grawitz and Israel found the two types of kidney occurring in animals in- differently as the result of artifi- cial nephritis induced by tempo- rarily occluding the renal artery. Histology. — The Malpighian bodies present hyaline change of their capillaries. The capsules frequently show marked peri-capsulitis, being swollen and broadened out by concentric bands of nucleated fibres ; while their endothelium is proliferated, sometimes forming a mass of granula- tion tissue (i^z^. 18), " _?Q^ tuft_ jhe 6/ood vessels are dilated and full of clot; they are often thickened by hypertrophy involving all the coats. The convo- luted tubes are di- lated, their epithe- lium is fatty, only the basal portion being left {Fig. 19). The cavities of the tubes contain fat gran- ules and epithelial debris. The straight tubes of the medulla encroaching on the Tig. 19. Oamie acid preparation showing marked atrophy and fatty degeneration of the epithelium of the convoluted tubules. BRJGHT'S DISEASE. preserve their epithelium, but their cavities often contain casts made up of fatty granules and epithelial debris from the convoluted tubes. The stroma is everywhere swollen, nucleated and hyaline. These changes indicate a diffuse inflammation of the glomeruli, coats of the blood vessels, and stroma, with fatty degeneration of the previously inflamed epithelium of the convoluted tubes. The microscopical examination of the pair of kidneys, whose naked eye appearances were described above, showed that the difference between them consisted in the presence in the smaller kidney of large areas of nucleated fibrous tissue, en- closing atrophied tubules. a Fig. 20 is a preparation from such a kidney brushed out so as to remove all but the framework of connective tissue. In the centre of the section there is a wedge- shaped process of nucleated connective tissue enclosing a Malpighian body((a:). This corresponds to the vascular zone, and it is in the neigh- bourhood of the interlobu- lar arteries and around the Malpighian bodies, that the growth of connective tissue is most marked. But the intertubular stroma is everywhere swollen and thickened. The thickening of the walls of the blood vessels in such kidneys is always correspondingly well marked. Symptom.s and Course. — Dropsy. — There is no form of Bright's disease in which dropsy is a more constant accompaniment. It is rarely but occasionally absent. As a rule it is most usually present in the face, feet, and legs, but there may be general anasarca with effusion into the serous sacs. Heart. — The heart is generally hypertrophied, that is to say, the apex beat is displaced outwards. A systolic murmur is often heard at the apex ; when this is absent there is reduplication of the first sound, and the aortic second sound is accentuated. Fiij. 20. Section of kidney from chronic infective nephritis brushed out so as to show the thickened Btrorna. INFECTIVE NEPHRITIS. \\x Blood. — The density of the blood is not so much reduced as in the acute form, owing no doubt to the larger elimination of water from the kidneys. Lloyd-Jones gives it as 1049 against 1058-60, the density of normal blood. Pulse. — The pulse is usually about sixty, and incompressible. The sphygmographic tracing (yFig. 21) shows the character of high tension very well, though this particular instance illustrates the statement already made, that the curve of fxq.ix. Hich tension puisp tracing from . . * . , 111 case of chfoiiic febrile iiepliritiii, high tension represents only the prolonged systole resulting from the effort of the ventricle to overcome the peripheral obstruction, as it was taken from a case where the heart was failing rapidly. Ophthalmoscopic appearances. — According to my experience these are normal in undoubted cases of chronic nephritis belonging to this class. If changes occur they do so very rarely. Urine. — The quantity of urine is generally increased, being from sixty to ninety ounces /^r diem. It is usually acid ; of a density of loio to 1015 ; the urea varies from 7 to i"5 per cent, the daily quantity being from two hundred to three hundred grains ; the albumen is generally considerable in amount, from '4 to i per cent, or more ; blood in traces is commonly present ; numerous epithelial, fatty, granular, and hyaline casts are visible in the deposit, together with red and white blood corpuscles and fatty renal epithelium. Headache and vomiting are of frequent occurrence. Convul- sions and coma and other symptoms oiurcemia are less common than in the acute attack, and much less than in the contracting kidney with which they are specially associated, and where they are described fully. Diagnosis. — When dropsy is present, and the urine is copious, highly albuminous, and deposits numerous casts and renal epithelium, this form of Bright's disease is suggested. The diagnosis may be made quite plain by the history. If this is wanting it may be difficult to decide, as after one or more intercurrent acute attacks the clinical symptoms of lithaemic kidney are so modified as to make the differentiation almost impossible. The presence of retinal changes indicates lithaemic kidney. The age of the patient is of importance, as the latter disease is very common after forty years of age, 112 BRIGHT S DISEASE. while primary acute nephritis and its sequelae are relatively rare. Duration, — The disease always lasts months, and may last years. A gentleman well known to me had an attack of scarlatinal nephritis thirty years ago. According to his medical attendant his urine always has presented the charac- ters which I have observed in it during the last few years. It contains a large amount of albumen with epithelial, fatty, granular, and hyaline casts. It is possible that the disease in this case affects only one kidney or a portion of one, for such cases have been known to occur. At any rate, it shows that persons presenting the urinary signs of chronic nephritis after an acute attack may go on for half a lifetime. This gentleman is now aged forty-six ; he enjoys fair health, and, although he leads a careful life, he takes ordinary diet, with a moderate amount of wine. Prognosis. — Although these cases may last a long time, the prognosis must be very guarded, as they are certainly very precarious lives. As a rule they recover suflficiently to go about, but they are very liable to relapse. The worst prognostic sign is extensive and obstinate dropsy. ILLUSTRATIVE CASES. Case 7.* Phthisis ; chronic infective nephritis; lardaceoiis degener- ation. Death. Autopsy. T. T. , get. thirty-seven, gun finisher, admitted April 6th, 1886, complaining of cough, pain in chest, scantiness of urine, and inability to take solid food. He spits a good deal and the sputa have been once or twice streaked with blood. He has had a cough for eighteen months, and has gradually got weaker, and lost flesh. Six weeks ago diarrhoea set in, and reduced him greatly. He attributes his illness to repeated colds. His work exposes him to dust, but not to cold or damp. His father, aged sixty-three, is at home suffering from his lungs, but his mother and all his, brothers and sisters are alive and healthy. Present condition. — Patient is a sallow, poorly nourished man ; legs and feet cedematous. T. 100*'; P. 96; R. 18; tongue clean, red and dry ; suffers from flatulence, pain between shoulders, and nausea. Bowels confined. Vertical liver dulness six inches in mammillary line. Spleen not enlarged. Heart's apex in fifth intercostal space, where there is a faint systolic murmur ; first sound reduplicated in tricuspid area ; second sound in pulmonary area accentuated and reduplicated. Pulse small, regular, soft and compressible ; voice weak ; phonation not painful ; cough troublesome ; sputa copious, mucous and frothy. * Recorded by Dr. Stacey Wilson, House Physician. INFECTIVE NEPHRITIS. 113 Dulness at both apices, more marked on the right side. Bronchial breathing- heard above right clavicle, and whispering pectoriloquy all over right upper lobe. Everywhere else respiration indeterminate, with scanty crepitations. Urine seventy-six oz. ; sp. gr. 1008; acid; bright amber colour; mucous deposit ; urea 6 per cent. ; a faint cloud of albumen ; hyaline casts and leucocytes in deposit. A sphygraographic tracing showed that the tidal wave was prolonged in spite of the weakness of the heart. The oedema of the legs at first disappeared, but it returned by April 2ist. He got gradually worse. The quantity of urine remained large and the albumen increased in amount. He died on May 14th of a sudden attack of dyspnoea. Autopsy, May 14th. — External Appearafices. — General pallor and emaciation ; oedema of feet and legs. Lungs, adherent ; honeycombed with cavities, but especially the upper lobe of the right lung ; bronchi dilated, containing pus and surrounded by indurated areas. Small patches of grey miliary tubercle scattered through lungs. Both bases congested and cedematous. Heart., 13 oz. ; left ventricle dilated and hypertrophied ; soft reddish vegetations on aortic valve and on aortic segment of mitral valve. Peritonccal cavity full of fluid. Liver, 67 oz. ; smooth, tense, edge rounded, colour dull brown ; on section, translucent, gave waxy reaction with iodine. Spleen, 8 oz., a typical " sago spleen." Kidneys, 9 oz. ; capsules partly adherent ; surface pale yellowish white, with well defined stellate veins on sm-face. On section, cortex of normal width ; mixed greyish white and yellow in colour ; rather ansemic, trans- lucent and shining, giving the iodine reaction distinctly. The mucous membrane of the whole alimentary canal gave the reaction with iodine, but the muscular substance of the heart and tongue was normal. Case 8.* — Chronic infective nephritis ; great iinprovement. Henry M., aged nineteen, warehouseman, admitted March 22nd, 1886, with swelling of the face, feet, and legs. He had been ill since November, 1885, when the swelling began, and he was told at the Dispensary that he had Bright's disease. He had scarlatina when he was four years old, but no other definite illness. His father, mother, and six brothers and sisters were all healthy. On admission he looked very ansemic, with a pale puffy face, and con- siderable oedema of the feel and legs. T. 980 ; P. 72 ; R. 18 ; tongue furred ; bowels confined ; liver and spleen are a little enlarged, the latter can be felt below the ribs. Lungs, resonance deficient, at both apices ; cog-wheel respiration ; no accompaniments or cough. Heart's apex three-quarters of an inch external to verticle nipple line in fifth intercostal space. Sounds in mitral area very loud. A systolic murmur audible in aortic area, faintly conducted into vessels of neck. Aortic second sound accentuated. Pulse full, of high tension, artery feels thickened. * Recorded by Dr. Stacey Wilson, House Physician. 114 BRIGHTS DISEASE. Ophthalmoscopic appearances normal. Urine 60 oz. ; sp. gr. 1015 ; acid ; pale yellow colour, smoky ; mucous deposit ; urea 264 grains p7'o die ; albumen "4 per cent. ; blood in quantity ; fatty epithelial, hyaline and granular casts, with blood corpuscles and fatty epithelium in the deposit. He made fair progress ; he was kept in bed till May 14th, when the oedema had entirely disappeared. On being allowed up it returned slightly in the legs. He was discharged on July 2nd to go to the Sanatorium, and from there he went to take a situation in the South of England, whence he wrote to say that he was going on very well. The following table marks his progress ; — Urine Albu- Urea Date. in Sp.gr. men in oz. in grs. grs. Mar. 24 60 IOI5 los 264 5) 30 56 IOI5 81 369 April 8 72 IOI5 126 285 J) 15 70 IO16 308 277 51 22 72 IOI5 169 221 53 27 70 IOI5 184 215 May 7 76 IOI3 200 299 5) 13 72 IOI2 253 223 3) 19 80 IOI4 150 352 )) 25 7b IOI6 133 334 June n 84 IOI4 221 332 )5 9 74 IOI5 162 205 JJ 16 84 IOI5 147 221 1) 23 76 IOI5 133 367 J) 30 76 IOI4 133 334 Casts. Epithelial, hyaline, fatty & granular Hyaline, fatty, and granular Epithelial and hyaline B^w hyaline and granular Epithelial, fatty and hyaline )) 3) 33 Epithelial and hyaline Epithehal, hyaline, and fatty Hyaline and few granular Hyaline Treatment. — The patient must be kept in bed, clothed in flannel, in a room the temperature of which is carefully regu- lated by day and night to avoid chills, and he should be kept in bed so long as any dropsy remains, though slight swelling of the legs coming on after he is allowed up does not necessarily call for a return to bed. The diet should be at first milk, with bread and farinaceous puddings, white fish and poultry being added as the case progresses satisfactorily. Butcher's meat and cheese should be forbidden so long as the doctor has control of the case. No alcohol should be per- mitted. The treatment should be chiefly directed- to getting rid of the dropsy by diuretics, purgatives, and diaphoresis. The hot-air bath should be used daily. An electuary of bitartrate of potash and honey should be taken freely so as to INFECTIVE NEPHRITIS. 115 act upon the bowels, combined with a diuretic pill such as the following : ^ Pulv. digitalis Pulv. scilke Caffeinte citratis, aa gr. j. Ft. pil. Sig. One to be taken thrice daily. If the dropsy is very great, speedy relief may be obtained by tapping. If there is much ascites this should be done at once. Tapping the legs by the small trocars introduced by Southey is not a very satisfactory proceeding. The fluid drains away so slowly that the dropsy may not be affected by it. This practice is sometimes successful, but it is not one of which I can speak very highly, and I get much better results from massage and bandaging. When convalescence appears to be established iron should be given, preferably the carbonate, citrate or tartrate. The precautions to be taken by the convalescent are the same as those already detailed for the acute attack ; he should especially guard against acquiring the uric acid dyscrasia. BIBLIOGRAPHY. AuFRECHT. " Pathologische Mittheilungen," i Heft, p. 72. Bamberger. Op. cit. Bouchard (C). Des nephrites infectieuses. " Revue de Med.," 1881, I., p. 671. . Legons sur les autointoxications dans les maladies. Paris, 1887. Carpenter (G. A.). Dangers of the continuous hot wet Pack in Acute Renal Disease. " Practitioner," vol. XLI. , 1888, p. 178. Coats (J.) Acute interstitial inflammation of the Kidneys in Scarlet Fever, fatal on the tenth day. " Brit. Med. Jour.," 1874, II., p. 400. Crooke (G. F.). Contribution to the pathological anatomy and histology of Scarlatina. " Birm. Med. Review," vol. XXI., 1887, p. 256; vol. XXII., p. 10. Crooke (G. F.) and Nason (E. N.). Acute hsemorrhagic nephritis in sup- purative meningitis. "The Lancet," 1889, II., p. 1216. Finlayson (J.). The clinical significance of albuminuria ; influence of toxic agencies. " Glasgow Med. Jour.," vol. XXL, p. 262. Greenfield (W. S.). A resume of the present knowledge of Renal Pathology. " New Syd. Soc. Atlas of Pathology," Fasc. II., 1879. Klein (E.). Report on the minute anatomy of Scarlatina. "Reports of Med. Off. Privy Council," N.S., No. VIII., 1876, p 24. . On the minute anatomy of Scarlatina. " Path. Soc. Trans.," vol. XXVIII. , 1877, p 430. LiTTEN (M.). Einige Falle von mycotischer Nierenerkrankung. " Zeitsch. f. Klin. Med.," Bd. IV., p. 191. 116 BRIGHT S DISEASE. Lloyd-Jones (E.). Some blood changes met with in Renal Disease. " The Practitioner," vol. XLIII. Mauriac (C). Syphilose des reins. " Arch. Gen. de Med.," 1886, II. PP- 385. 553. 649- MiRCOLi (S.). Primare mykotische Nierenentziindungen der Kinder. " Cent. f. d. Med. Wiss.," 1887, p. 738. Ralfe (C. H.). Acute hsemorrhagic Nephritis. "The Lancet," 1889,11., P- 1307- ScHELTERNA. Nephritis after Whooping Cough. " Werkbl. van het Nederl. Tijdschr. voor Geneisk.," 1888, p. 166. Smith (W. G.). Op. cit. Stewart (Grainger). The influence of acute infectious diseases upon the Kidneys and their Functions. (Internat. Med. Cong., Copenhagen, 1S84.) " Brit. Med. Jour.," 1884, II., p. 468. WiLLEY (C. H.). A contribution to the pathological anatomy of Scarlatinal Kidney. " Med. Press and Circ," Dec. 26, 1888. n? Chapter XI. LITH.EMIC NEPHRITIS. (SYN. GOUTY KIDNEY.) The most common form includes a number of cases of acute nephritis, e.g., those occurring in gout, and such instances as that of a habitual beer drinker, whose blood is loaded with uric acid, meeting with a severe chill, his kidneys being already more or less irritated or actually altered by the dyscrasia ; as well as the very common intercurrent acute attacks which occur during the course of the chronic process. But the very great majority are chronic cases of the clinical type associated with the small red granular kidney, although it is a mistake to suppose the disease is limited to one anatomical type. Etiology. — As the name implies, it is primarily due to the presence of a poison, e.g.., uric acid, in the blood and to the prolonged effect of its elimination through the kidneys. Age. — It is rare under twenty years of age, less rare up to forty, becomes common after that period is passed, and after fifty is so common that nearly one-third of all persons dying above that age show more or less signs of its action in their kidneys. Sex. — All statistics agree in showing that the contracting type of kidney is less common in females than in males. This is true, but the truth would be more striking if the figures were not vitiated by two circumstances, namely, the frequency of contracting kidney of obstructive origin in women with pelvic diseases, and, secondly, the fact that con- tracting kidney may be of infective origin. Nevertheless, I accept the figures for what they are worth. Dickinson gives the proportion of one female to two males ; Wagner, of fifty-five females to ninety-five males. We are not told whether the numbers were calculated out so as to show the proportion to the total deaths in each sex. This is important, as out of a hundred cases collected without refer- ii8 BRIGHT S DISEASE. ence to etiology from the General Hospital registers, I found thirty females to seventy males, but there were only a hundred and thirty-six female deaths to three hundred and four male deaths, so that the percentages brought the figures very near, namely, twenty-two females to twenty-three males. But on the other hand, the relative infrequency of this form of Bright's disease in females is an incontestable clinical fact. Temperament. — The doctrine has been favoured by author- ity that nervous worry is a cause of contracting kidney, but in my opinion it is the uric acid diathesis which is so often associated with an irritable nervous temperament, the subjects of which are prone to worry. Social condition. — It attacks all classes, but is especially common among workers in lead, miners, brewers, publicans, forgemen, and stokers. Heredity. — There should be no doubt of the existence of a hereditary tendency to this disease. In the case already quoted, as seen with Dr. Lycett, it was this form of Bright's disease from which the patient, his father, and two paternal uncles died. Eichhorst has related the history of a family, in which the grandmother, mother, two sons and a sister suffered from this disease. Mahomed believed in the existence of a diathesis — Bright's diathesis — closely allied to gout, and presenting the following characteristics : " Habitual constipation, some forms of dys- pepsia, often signs of imperfect circulation, such as cold hands and feet, not unfrequently palpitation, sometimes shortness of breath on exertion. Their skins are often thick, of velvet-like softness, and very white." This quotation is given merely to indicate Mahomed's line of thought. So far as my clinical experience goes, I cannot say that it confirms his description of the characteristics of the individuals in whom we commonly meet with this form of Bright's disease, nor am I able to sug- gest a better one, though I incline to the opinion that the spare neurotic type is especially prone to suffer from lithsemic kidney. Dieulafoy also believes in a "diathese brightique," of which the signs are: i, auditory troubles, noises in the ears, Meniere's vertigo ; 2, asphyxia of the extremities, fingers pale, bloodless, and numb ; 3, itching ; 4, pollakiuria or fre- quent micturition ; 5, cryaesthesia or sensitiveness to cold ; 6, LITH/EMIC NEPHRITIS. 119 cramps in the calves of the legs ; 7, epistaxis ; 8, electriform shocks at the moment of falling asleep ; 9, distension and tortuosity of the temporal artery. But he does not suggest that they are all constantly present, or that any one by itself is pathognomonic. Climate. — The mode in which our moist cold climate pre- disposes to Bright's disease has been already explained. Garrod states that chilling the skin increases the formation of uric acid, while it probably gives rise to other alterations in the blood by diminishing elimination. Gotit. — There can be no doubt of the frequent association of these conditions. This was first pointed out by Todd, who gave to the renal disease the apt name of '' gouty kidney." Ebstein says that the kidneys may be perfectly healthy even when the articular affection is very pronounced ; or they may be in a state of chronic atrophy with uratic deposits ; or there may be uratic deposits in the canaliculi or in necrotic foci. He believes the deposit of urate of soda in necrotic foci alone is typical ; he recognises the first stage as an inflamma- tory process set up by uric acid, and this is followed by necrosis, uratic salts being deposited in the cavities thus formed. There is no necessary connection between articular gout and nephritis. The tendenc}^ to accumulate uric acid in the blood may exist apart from articular gout. It is known that the first metatarso-phalangeal joints of the subjects of this form of Bright's disease are generally the seats of uratic deposits, but a history of attacks of gout is exceptional. Both the joint affection and the kidney disease depend upon the accumulation of uric acid in the blood, but for the production of either there is needed the presence of special etiological factors. Lead. — Ollivier originally drew attention to the frequent occurrence of the disease among lead workers. He proved that lead is eliminated by the kidney. We know, too, that lead leads to accumulation of uric acid in the system, either b)' depressing the function of the liver or by forming insoluble urates. There is a general agreement among clinical observers in this country as to its prevalence among patients in whom evidence is to be found of past or present poisoning by lead. Charcot and Gombault succeeded in causing contracting nephritis in rabbits by the prolonged administration of lead. Hard water. — Permanent hardness in drinking water, due to excess of lime salts, is an undoubted cause of the uric acid I20 BRIGHT S DISEASE. dyscrasia in the persons who use it, and thereby it is an indirect cause of Bright's disease. Its modiLs opera7idi has not been clearly explained. Whether it acts by forming insoluble urates or by favouring by its presence the decom- position of soluble urates, are questions worthy of investigation. Throughout this district (Warwickshire, Staffordshire, and Worcestershire) the drinking water is very hard, and its relation to uric acid formations is to my mind beyond all question. Alcohol. — Dickinson's criticisms of the alcoholic etiology of Bright's disease are entitled to great weight, but it is doubtful whether alcohol can be altogether acquitted. The observations of Glaser already quoted (p. 92), prove that its ingestion is immediately followed by signs of renal irritation. Animal food. — The excessive use o'i butcher's meat, such as is common in this country, especially among certain classes of well-paid artizans, is generally and most properly believed to be a very powerful cause of this disorder. It acts by in- creasing the raw material from which uric acid is formed, and also (and this is perhaps as important) by the large amount of salts contained in it (chlorides, sulphates, and phosphates), which diminish the alkalinity of the blood, and prevent the solution of uric acid. Dyspepsia. — Johnson has stated his belief in the frequent occurrence of this disease in persons who suffer from certain forms of dyspepsia, or who eat and drink to excess. Mur- chison was persuaded of its relation to the digestive derange- ment which he called " lith^emia," and associated with a functional deficiency of the liver. Mahomed published certain cases of young adults in whom dyspepsia was associated with albuminuria and high arterial tension, suggesting the belief that some products of faulty digestion were producing a dys- crasia, which affected the vascular system and irritated the kidneys in such a way as to lead in time to the development of contracting kidney with cardiac hypertrophy. This is a view which I have fully accepted. It explains the occurrence of this form of Bright's disease in persons who are in no way given to excess, but whose digestive functions are inadequate, either congenitally or as the result of sedentary habits. Heart Disease. — The relations of heart disease to the con- tracting granular kidney have been insisted upon by Dickin- son, and a study o{ post moi'tem registers proves it to be a fact. LITH^MIC NEPHRITIS. 121 As has been often pointed out, the effect of heart disease is to approximate the mammal to the reptile, to diminish all oxida- tion processes, and to increase the formation of uric acid while diminishing that of urea. Morbid Anatomy. — Acute nephritis is not in itself a disease that often terminates fatally. We know it best in the infective form, where death is due to the primary disease. It is only in very severe cases that we get an opportunity of see- ing the kidneys in acute litha^mic nephritis. They are then swollen, of a red or chocolate colour ; the capsule strips readily off; on section blood drips from the cut surface, upon which the Malpighian bodies stand out as dark red points. The condition is one of intense congestion, with acute catarrhal inflammation of the epithelium of the convoluted tubes. In sub-acute cases the kidneys are still swollen, the cortex increased, pale and mottled ; the capsules separate easily, leaving a pale marbled surface-. The changes are similar to those already described in sub- acute nephritis of infective origin. The epithelium of the con- voluted tubes is swollen, granular, vacuolated and fatty ; in places only a narrow band is left. The glomeruli are swollen, and their nuclei increased. The blood vessels are full of blood. Still later, such kidneys may present the appearance of the large white kidney. They are greatly swollen, very pale, or mottled red, white, and yellow, soft, friable, capsules not adherent ; on section the Malpighian bodies appear very dis- tinct. Under the microscope the epithelium is very fatty ; the Malpighian bodies show well-marked glomerulitis ; the blood vessels are dilated, and their walls thickened by hypertrophy and endarteritis obliterans ; the connective tissue is swollen, hyaline and nucleated. But the typical kidneys of this form of Bright's disease are the small red kidneys. They are small, weighing together less than eight ounces, hard, with opaque thick adherent capsules, which, when stripped off, tear the kidney substance, leaving a dark, red, granulated, often nodular surface, in which are a few small cysts varying" in size from a pin's head to a pea. On section, the organ is tough ; the cortical portion is dark red, dotted with vascular spots and divided from the medullary 122 BRIGHT S DISEASE. cones by a well-marked line of hypera^mia ; the cortex is very narrow, measuring often from \\h to I'nths of an inch in breadth. The medullary portion is purple, and the cones are striated with lines of hypersemia. The mouths of the cut vessels are everywhere patent and stiff Under the microscope the following changes can be seen : — • Connective tissue. — If a thin section is brushed out so as to remove all but the frame-work of connective tissue, it will be seen that wedge-shaped processes of thickened and nucleated connective tissue pass down into the cortex from the capsule, occupying the region of the interlobular arteries and Malpig- hian bodies. The intertubular stroma is generally swollen and nucleated. Malpighiaii bodies. — The most general change is an increase in the nuclei of the capillary tuft and its conversion into a simple cellular mass. In a smaller number a later stage may be followed, in which the cellular mass becomes converted into delicate gela- tinous tissue containing a few stellate Mg. 22.-Maipighian body, Bhow- cclls {Fig. 22). Still later the contents hvlitafd^eueraiiSS^oTthegiomei^^ undcrgo z. complcte colloid change so ular tu£t. . c 1 1 ^ as to lorm a small cyst. Blood vessels. — The capillaries are dilated and full of blood; in places they show concentric hypertrophy (^Fig. 23). The larger vessels are dilated and their walls thickened. This thickening is most generally seen to affect the ^^-:;^ adventitia and the muscularis ; the intima is In the adventitia the change seems to be a \ ^ ^^.-i^ thickened frequently, but not so constantly. purely inflammatory overgrowth which it shares with the neighbouring connective tissue with ^^^^ 23 _capiiiarv which it is directly continuous and forms part. ^IStlf "^'plru-o: The change in the vtusctilaris is generally a true p^yof "swan. muscular hyperplasia, but in some vessels there is dilatation without hypertrophy, as might be expected. In the intima the elastic lamina is always swollen, its layers separated, and interspersed with a few nuclei ; the endothelial layer is often normal, but sometimes there is a considerable overgrowth of tissue on the inner side of the elastic lamina evidently due to lithjEmic nephritis. 123 inflammatory thickening of the endotheh'al layer. Such growths may cause irregular narrowings and even occlusion of vessels {endarteritis obliterans) {Fig. 24). Convoluted tubules. — The tub- ules are in some places dilated, generally they are normal or undergoing diminution in size. They are sometimes filled with amorphous granular matter. In the least affected parts the epithelium is altered ; it has lost its dark striated appearance and has become pale, the in- dividual cells can be seen, the , . . !• • 1 • Pii7.24.— Renal arteriole, showing endarteritis nuclei are quite distinct, but in obliterans, a, SwoUen elastic lamlna, its fibres ^ /- -1 1 separated and cedematoi-is ; 6, Broad growth of some instances fail to take up connective tissue Irom the endothelial layer ; " c. Swollen muscular coat, with large distinct staining fluids {Fig. 25). But ""<=i"- for the most part the tubules are lined by a very flat nucleated epithelium, apparently the atrophied representative of the original cell layer {^Fig. 27) ; the cavities of the tubes contain ¥ig. 25. — Convoluted tubule showing epithe- lium with distinct outlines g mular protoplasm and nuclei ^\ hich take on cai mine staining well. Fiq. 26. — CoiiTOluted tubule, with proliferated epitiieliuni and casts in lumen. rounded protoplasmic masses, nucleated cells, or colloid cast material {Fig. 26). Other tubules are denuded of epithelial lining. In other instances the tubules form cysts. This process is effected in a manner very like that already described in the Malpighian bodies. A cellular mass is formed in the 124 BRlGHrS DISEASE. tube from the proliferation of the epithelium ; this undergoes a retrogressive metamorphosis into gelatinous tissue and thence into simple colloid matter. ^^^^^^ Tig, 27.— Dilated convolutsd tubule, with atrophied epithelium ; a, a, fragments of casts. The basement membrane of the tubule becomes swollen and hyaline, and is lost in the new formation of connective tissue or becomes the wall of a cyst. Straight tubules. — The epithelium is often proliferated ; the lumina of the tubules are filled with colloid material mixed with cells. Other tubules are dilated and lined with atrophied epithelium. In the medulla many of the straight tubes are unaffected, but contain colloid matter (casts) in their cavities ; others are dilated. Acute nephritis is very prone to attack these kidneys at various stages of their evolution, so that their appearance is modified by the superaddition of the appearances of catarrhal nephritis. The kidneys vary in size, are paler, and under the microscope the epithelium is granular, vacuolated or fatty according to the duration of the process. Symptoms and Course. — The beginnings of this disease are usually latent and obscure. Its symptoms are in many cases so little noticeable that patients continue to disregard them until some serious and too often fatal complication necessitates medical advice and leads to the discovery of grave LI THYMIC NEPHRITIS. 125 organic disease, which has advanced to its full development without any means having been taken to arrest it. Even after a warning of this sort, there may be such a return of apparent health that all precautions are neglected, until a fresh attack proves fatal. A case will be quoted in which a single uraemic fit diagnosed correctly at the time was followed by eight years of apparent good health until a sud- den attack of acute osdema of the lung proved fatal. Such patients present themselves under the most varied semeiological conditions ; they may complain of bronchitis or asthma, pain at the praecordia, palpitation or epistaxis, vomiting, diarrhoea, or hasmatemesis, giddiness, headache, affections of sight or hearing, or neuralgia ; they may be attacked by apoplexies, convulsions, or coma ; they may have articular gout, sciatica, lumbago or cramps ; they may suffer from hsematuria or symptoms of gravel or calculus ; or they may chiefly complain of a skin affection — pruritus, eczema, erythema, purpura, etc. Fortunately it is rare before forty years of age, but in patients after that time of life we must be for ever alive to the possibility of this condition underlying the complaint put forward. We can only escape falling into mistakes in prac- tice by care, and the importance of making urinary examina- tions cannot be too strongly insisted upon. Very frequently the patient comes first under observation owing to the supervention of an attack of acute catarrhal nephritis, by which the whole aspect of the case is temporarily altered. TJie iirbie. — The characters of the urinary secretion are naturally the most important, unequivocal and significant of the symptoms of all forms of Bright's disease, nor are they less so in the present form, though the departures from the normal may not attract the patient's attention. It is impossible to state precisely at what period in this insidious malady the urine shows signs of alteration, but it may. be affirmed with certainty that no marked structural alterations can take place without evidence of them being discoverable in this secretion. The quantity of urine, as in other forms of Bright's disease, undergoes alteration ; but in this form it is not diminished in the early stages. On the contrary, when these cases come under observation the quantity is generally above the average, sometimes reaching or exceeding a hundred ounces in twenty- 126 BRIGHT S DISEASE. four hours. But this increase, as indicated by the necessity to rise at night to pass water, is not always an early symptom. William S (Case lo, p. 130), who died six weeks after admission with advanced contracting kidneys, stated that he had only been disturbed at night for a week past. So, too, in the case of Cornelius H (Case 15, p. 138), this symptom had existed only three months, though he had all the other symptoms of an advanced case. On the other hand, Richard J (Case 23, p. 157), had been in the habit of getting up in the night to make water five or six times for the last ten years. But in all these cases its occurrence coincided with the development of the first symptoms which attracted the patient's attention. In a series of cases tabulated some years ago, the necessity to rise at night to pass water was present in seventy out of a hundred cases able to attend as out- patients. It must be remembered that occasional rising at night for this purpose is common as a consequence of too free potations, of dyspepsia, and of excessive tobacco-smoking ; while in local diseases of the bladder and neighbouring organs, it is often a marked symptom. In the later stages the quantity of urine falls ; this is due to failure of the heart, and even before irrecoverable collapse of the heart, the urine is liable to be diminished by its temporary weakness. In the case of George B (Case 21, p. 152) it is recorded that " he used to get up twice at night to make water and filled the vessel three parts full, but since his illness this had passed off." During the occurrence of an intercurrent attack of acute catarrhal nephritis the urine is diminished, and presents the usual character met with in primary acute attacks. The density varies with the quantity, and particular samples passed during the day may be very much higher than the total quantity. In general it is below lOio. The colour is usually pale yellow, and the urine is clear, depositing only a very slight mucous cloud. The reactioit is almost invariably acid, except when the patient is taking alkalies. Bartels and Grainger Stewart state that the tirea may not be diminished. This is true, as, for example, in the case of William S (Case 10), who, after living on milk diet for twenty days, passed 343 grains of urea in twenty-four hours. I have not felt justified in endeavouring to ascertain what maximum amount could be eliminated by these patients on LITH^MIC NEPHRITIS. 127 full diet. As a rule, however, they pass too little urea, that is, the daily output is under 300 grains, The excretion of tiric acid is stated by Frerichs to be lessened, especially towards the termination of the disease. The phosphates are notably diminished ; the cJilorides are diminished, but become normal or in excess (LfiPINE) towards the end ; the quantity of sulphates varies greatly, but is ordinarily low. The deposit, as already stated, is scanty ; it contains a few small h)'aline and granular casts, but although not numerous they are very constantly present, and will be found if looked for in the proper wa}^ In acute attacks the deposit is charac- teristic of acute nephritis. Blood is not commonly present apart from acute attacks, bnt hsematuria may occur, and is sometimes so profuse as to cause death from haemorrhage (WEST) Albumen is generally to be observed, if it is properly looked for. It may be absent in the night, but is present in the urine passed during the day, especially after breakfast. The explanation of the greater frequency with which I met with albumen amongst my out-patients is that I saw them in the morning, whereas in many places, notably in London, out- patients are seen in the afternoon ; also that I always made my patients pass water for me at the time, and did not en- courage them to bring it in bottles, as such urine is generally that passed the first thing on rising and has been secreted during the night. Bartels has recorded a case which was kept under close observation until its termination, without the presence of albu- men having been at any time detected. The best method of testing for albumen is by boiling and acidulating with dilute acetic acid. The quantity of albumen is small, in uncomplicated cases, but rises as the urine diminishes, following the law already established that albuminuria is increased by lowering the blood pressure. It is also increased in intercurrent attacks of acute nephritis. Saliva. — This secretion has been found to contain urea (Fleischer) and albumen (Semmola, Vulpian, and Strauss) in certain cases. The blood.— An^midi is a marked symptom. Leichten- stern found the haemoglobin co-efficient reduced from the normal 1330 to 802 ; Dickinson found the red corpuscles 128 BRIGHT S DISEASE. reduced from the normal 5,000,000 to 3,921,875, and Rosen- stein to 3,000,000. The water of the blood is increased from 784 parts per mille (Christison, Owen Rees, Rayer) to 821-853 parts per mille ; while the albumen is diminished from 73-4 per mille to 68'5-59 per mille (OwEN Rees, and Rayer) ; according to Lloyd-Jones the density of the blood is reduced in cases with gout to 105 1, but in other cases it is normial, 1058. The urea is increased from the healthy standard of 0'0i6 to o'o84. The heart. — The changes in the heart found post mortem in their order of frequency are: (i,) Hypertrophy, which is present in about 60 per cent. ; (2,) Atheroma of the aorta, coronary arteries or endocardium, leading in the latter case to thickening of the valves without definitely impairing their functions ; (3,) Valvular disease affecting in about equal pro- portions the aortic and mitral valves, stenosis of the latter valve being apparently much more common than simple dila- tation ; although this may be because it is so much more definite that the reporter has less difficulty in stating the fact ; (4,) Fatty degeneration (granular atrophy) of the muscular fibre of the wall of the heart ; (5,) Pericardial adhesions ; (6,) Pericarditis. Pericardial effusion as part of general dropsy is not uncommon, but less so than pleural effusion. The most definite sign of cardiac hypertrophy is displace- ment of the apex beat. This is normally in the fifth deft intercostal space, well to the inner side of a line drawn vertically through the nipple. From my own observations, made on numerous out-patients, I am unable to accept the rigid descriptions that limit the normal position more than this. If the apex beat is in the nipple line or to the left of it, the heart is enlarged ; still more manifestly is this the case if the impulse is in the sixth interspace, instead of the fifth. When there is much hypertrophy the impulse of the heart is often strong and diffused over a large area. The first sound of the heart at the apex is commonly re- duplicated, while the second sound in the aortic area is accentuated. Johnson has suggested that the doubling of the first sound is due to the contraction of a dilated and hypertrophied auricle becoming audible, but the more generally accepted explanation is that of Sibson, who ascribed the reduplication to the asynchronous action of the two ventricles, due to the greater difficulty the left ventricle has in discharging its LITH^MIC NEPHRITIS. i-z() contents owing to the increased pressure in the aortic system ; while he explained the unity of the accentuated second sound by suggesting that the increased tension in the aorta allows it to complete the closure of its valves synchronously with the earlier filled but less actively distended pulmonary artery. These changes in the heart sounds are very constant in contracting kidne}', but their diagnostic value must not be over-estimated. Doubling of the first sound may be heard in bronchitis and emphysema when there is obstruction to the discharge of the right ventricle, and in mitral constriction in cases where no murmur may be audible. Accentuation of the aortic second sound is common in }'ouths whose hearts under examination act with more than wonted energy. It may also be present wherever any local cause in the thorax {e.g.., tumour, aneurism) raises the blood pressure in the aorta. But these changes in the heart sounds are so readily ascer- tained that they are of great value, as they often indicate the necessity for further careful investigation, and by attracting attention lead to the recognition of the renal condition which otherwise might pass unobserved. Murmurs are not uncommon in contracting kidney. Systolic mitral murmurs may be due to dilatation or to the accidental association of old rheumatic endocarditis. According to Battels acute endocarditis may occur as a result of renal disease. Aortic murmurs of obstruction or regurgitation, systolic and diastolic, are generally due to chronic endarteritis deformans attacking the aorta and spreading to the valves, but of course they sometimes have a rheumatic origin. The presence of murmurs is an unfavourable element, as the heart has a very hard task to perform to compensate for the renal defect, and if handicapped by a valvular insufficiency it will probably fail early in the struggle. From the point of view of the prognosis of heart disease, the supervention of kidney mischief is very unfavourable. A valvular defect, which was apparently compensated, will acquire fresh importance, and be followed by rapid heart failure and death. Palpitation is a symptom commonly complained of It is probably in many cases toxic in its origin. The pulse. — The pulse rate in contracting kidney is generally- high, from 90 to 100, but it may be normal, 70 to 80, or low, 9 I30 B RIGHTS DISEASE. 60. In character it is usually hard, and incompressible, but varies in size, being sometimes full, more usually small. The hard radial artery, resembling the spermatic cord to the feel, is the typical high tension pulse of contracting kidney. But it is perhaps more commonly absent than present. When the artery is neither hard nor prominent the pulse will still be found to be incompressible, and even when this character is lost, the sphygmographic tracing may still show signs of peripheral ob- struction to the circulation. {Fig. 28 illustrates a typical pulse trac- Fifi.lS. Pulse tracing from case oJ E. J. incrfrom COntracf incr IcidnPV ^ Lithffimic kidney, chronic UTEEmia. ^"fa ilUUi l-UllLl d-LLlli^ KlUllcy.y OpJithahnosco.pic changes. — It is especially (if we exclude the nephritis of pregnancy the statement may be made more absolute) in this form of Bright's disease that we meet with affections of the retina. These have already been fully described (Chap, viii.) ; they consist for the most part of haemorrhages, inflammatory exudations in and around the disc, and degenerative patches chiefly in the neighbourhood of the yellow spot. Sudden loss of vision may be due to haemorrhage into the yellow spot. Case 9. — Frederick J , aged sixty-three, attended as an -out- patient on March 26, 1881, with pain in bowels, dyspnoea, cough and palpitation. He had been ill three months. He was in the habit of getting out of bed four or five times nightly to pass water. Heart irregular and intermittent. Urine albuminous. He returned on April 9th with loss of vision in the left eye and dimness of the sight of the right eye. Ophthalmoscopic examination showed : Right eye., H = i, disc very vascular ; no exudations. Left eye., disc hazy, arteries very small, reduced almost to threads. Several large diffuse hsemorrhages involved the whole region of the yellow spot. The following case is a typical example of albuminuric retinitis, and illustrates not only the various forms of retinal lesion, but the changes which may take place in them. As already explained, there is nothing essentially incurable in the retinal disease ; its gravity depends upon its relation to advanced and incurable organic disease of the kidneys. Case 10*. — Chronic lithcemic nephritis ; albumitiiiric retinitis. Death. A utopsy. William S , aged twenty-three, brass caster, admitted February 24th, 1888, complaining of headache, pain in the loins and dimness of sight. He * Recorded by Mr. T. O. Ci"ump, clinical clerk. LITH^MIC NEPHRITIS. 131 had been subject to headache for ten years, had often been giddy, but had not noticed any affection of his eyesight till a week ago, and lor the last four days he had been vomiting. He had never had a fit, or been dropsical. He was a teetotaller, his work did not involve the use of lead, and he could remember no illness. His father died of dropsy and one sister of phthisis ; his family history was otherwise unimportant. He had lately noticed that his eyelids were swollen in the morning and that his ankles had been cedematous on two occasions ; he had been obliged to rise at night to pass water only for the last week. He was a well made man, with a yellow, waxy complexion, and some oedema of the lower eye- lids. T. 98-4°. P. 90. R. 20. Tongue furred ; bowels confined ; liver and spleen normal. Lungs normal, with the exception of a few catarrhal sounds. Heart's apex in nipple line and fifth interspace ; at apex re- duplication of first sound ; a systolic murmur in aortic area. Pulse incompressible, regular. Urine 30 oz. ; sp. gr. loio ; acid, albuminous ; urea 132 grains ; granular, epithelial and hyaline casts, red and white blood corpuscles and renal epithelium in deposit. Ophthalmoscopic examination of right eye showed papillitis, with numerous radiating liEemorrhages along the course of the blood vessels; left eye, papillitis with several large round soft-edged white patches in the neighbourhood. He went on pretty well for some time. On March 26th the eyes were examined and the right shov/ed still swelling of disc with absorption of haemorrhages ; the left eye showed the outline of the disc well defined, the former rounded patches gone, but a fresh set of oval radiating bright patches on the inner side of the macula liitea. On April 2nd he began to have headache. Temp. 99° F. He was put back on milk diet. 3rd. — Headache continued ; partial unconsciousness ; passed urine in bed; pupils sluggish to light. Temp. 98-4°. 4th. — Conscious. Temp. 98°. 5th. — Temp. 100" F. Face flushed : tongue dry ; headache. 6th.— Temp. M. 100-8". V. 102- r. 7th. — Temp. 101°. Unconsci'~as ; could not be got to take nourish- ment ; breathing labo'':::;u ; pulse very feeble ; heart irregular and inter- mittent ; death at 7. ,5 p.m. Date. Quantity of urine in oz. Quantity of urea in grains. Quantity of albumen in grains. Diet. Feb. 26th ... March 6th ... 1^ 72 274-56 316-8 63 60 Milk „ i6fh ... „ 24th ... 78 66 343'2 261-36 117 60 Chicken or Fish „ 31st ... 1Z 224-84 120 !) )) No lu^Jt e collected aft er this date Autopsy. September 4th, 1888. Features pallid, nutrition visibly impaired ; no oedema of legs, feet or scrotum. Brain 47 oz. ; haemorrhage in patches over lateral aspect of right cere- bral hemisphere ; extensive hsemorrhage with red softening in the white 132 BRIGHT S DISEASE. substance corresponding to the right temporo-sphenoidal and occipital lobes, the softened area surrounded by numerous miliary heemorrhages into the white matter. The hippocampus and the postero-external edges of the optic thalamus on this side were destroyed ; no hsemorrhage into the ventricle, but the haemorrhage had oozed thi-ough the occipital lobe on to its outer aspect and spread over the whole of the cortex on the right side ; serous effusions into the ventricles, the posterior part of the external capsule was involved ; arteries at base of brain appeared normal. Heart 15 oz. ; no valvular lesions ; coronary arteries good ; great hypertrophy of left ventricle ; wall measured y^ in. thick. Muscle some- what pale, but looked fairly normal. Limgs congested and oedematous, especially the inferior lobes. Kidneys barely 7 oz. ; contracted, capsule adherent, surface granulated, but also somewhat hypersemic ; on section, the atrophy was more or less uniform ; cortex of a mixed reddish grey and yellowish grey colour, and offered perceptible resistance to the knife edge. Di'opsy occurs in the acute forms, and has then the ordinary characters of the dropsy of acute nephritis. But in the com- moner chronic form it only supervenes in the later stages as a consequence of heart failure, and then presents the usual char- acter of cardiac dropsy, beginning in the depending parts, and gradually rising as the water gains on the pumping power of the heart. Diagnosis. — The latent nature of this disease has been referred to many times. It comes under so many disguises that it is only by possessing the conviction of its great frequency in persons over forty years of age that the physician will avoid overlooking many cases. The hard pulse is one of the most accessible of signs, and is fairly constant, being present in 62 per cent, of my cases. Accentuation of the aortic second sound was present in 80 per cent. Hypertrophy of the heart, indicated by displacement of the apex beat to the left of the vertical nipple line, was present in 60 per cent ; while a history of rising at night to make water was obtained in 70 per cent. None of these signs taken singly is diagnostic, but they serve as guide posts to point out the way and lead up to the examination of the urine. Albuminuria was present in 91 per cent, of my examinations, and will be very rarely found absent if the precaution be taken of obtaining a sample of the after-breakfast urine. It is worth remembering that a sample of the total mixed urine of the twenty-four hours, so desirable where quantitative analysis is required, is not the best for discovering a faint trace of albu- LITHALMIC NEPHRITIS. 133 men, owing to the greater portion of the urine, namely, that secreted at night, being often non-albuminous. Casts are very constant and of great importance. I have found them in 88 per cent, of all examinations, but I do not think I have ever diagnosed contracting kidney until I had found casts, or ever failed to find them some time or another in every one of the cases of this disease which I have recognised during life. The occurrence of retinal changes is too infrequent to be of great diagnostic value. Retinitis and neuro-retinitis appear to occur in only about 5 per cent., and small specks and haemor- rhages in 25 per cent. Apart from their inconstancy they are not absolutely diagnostic when present. Typical albuminuric retinitis may be met with in anaemia ; and diffuse neuro-retinitis, exactly like that of Bright's disease, has been seen associated with cere- bral tumour. The specks are often extremely small and few in number, and are met with apart from Bright's disease. But combined with the other signs enumerated, these ophthal- moscopic appearances have great weight. In making a diagnosis all the symptoms should be passed in review. Is it possible to differentiate between the two forms of chronic BrigJifs disease ? — It is certain that, except in the case of typical gouty kidneys, it is difficult, if not impossible, to deter- mine the etiology of the kidneys of chronic Bright's disease by their anatomical conditions ; it is therefore not strange that the clinical diagnosis is not easy. The following considerations may guide us : (i,) The age of the patient ; the primary chronic form being very common after forty years of age. (2,) The presence of certain symp- toms, such as polyuria, before the occurrence of an acute attack, although this might be represented as the commence- ment of the illness. (3,) The absence of dropsy or its presence only in depending parts. (4,) The presence of retinal changes. Prognosis. — There can be no doubt that this is an essen- tially incurable disease, and its course is liable to be inter- rupted by so many serious complications that the duration of life is always uncertain. Nevertheless, its normal evolution is slow. Bright was aware that some cases last many years, and that this is possible even under unfavourable external conditions the following brief record shows. 134 BRIGHT S DISEASE. Case ii. — John P , aged forty-eight, cabman, was in Hospital in 1877, with albuminuria and dropsy, under the late Dr. Russell. I examined his urine several times, and found it to contain numerous epi- thelial, hyaline and granular casts. This was probably an intercurrent acute attack. He attended for some time as an out-patient, and was then lost sight of. July 14th, 1881, he brought his son to see me, and I then took the following notes. J. P. gets up once every night to pass water. Urine pale, clear, loio, no albumen or casts. Pulse distinct, but not hard. Aortic second sound accentuated. The disease seemed practically cured, but was only latent. On June 14th, 1884, he came up with diarrhoea, looking very ill. His urine was clear, pale, loio, contained a good trace of albumen, a few granular casts, and blood corpuscles. Heart's apex not displaced ; aortic second sound not accentuated. February 27th, 1887. — Gets up two or three times at night to pass water. Urine pale, clear, looi, a faint haze of albumen. Has athetosis affecting the right hand and forearm. In the month of February, 1888, I instituted an inquiry into the present condition of a few persons presenting symp- toms of contracting kidney, whom I had rejected for Hfe assurance some years back. I. — T. B. D., male, aged thirty-eight ; examined December, t88o; urine contained a trace of albumen with hyaline and epithelial casts. Reported to be quite well. 2. — R. T., male, aged forty-one ; examined February, 1881 ; urine contained a trace of albumen, hyaline and granular casts. Reported to be still alive and well. 3. — J. H., male, aged fifty-eight, examined September, 1881 ; urine contained a faint trace of albumen, and a few hyaline casts. Could not be traced. 4. — C. R. G., male, aged sixty, examined November, 1882 ; urine contained a faint trace of albumen, but no casts. Died rather suddenly in the autumn of 1886. The number is small, but it is noteworthy that there was only one death, and that that was a man at least sixty-five years of age when he died. The most unfavourable symptom is heart faiku^e, indicated by dropsy of the lower extremities, and diminution of the amount of urine. The presence of valvular disease, or any cardiac complication, is also most grave, on account of the dependence of the case upon the power of the heart to compensate for the renal defect. Retinal disease is very unfavourable, because it rarely, if ever, occurs except in advanced cases. Any of the symptoms of urmnia are bad, but life may be prolonged after many of them. LITH^MIC NEPHRITIS. 135 Dyspncea is one of the most fatal of all the uraemic phenomena. Acute cedeina of I he hmg is always fatal. The gravity oi acitte intercitrrent attacks must be estimated by the amount of dropsy, just as in ordinary acute nephritis. The presence of cardiac complications is of course most un- favourable. All acute injlannnatory complications are very serious, especially pneumonia, pericarditis, and cellulitis, which are probably always fatal. Any serious accident such as 2. fracture or condition requir- ing surgical interference usually terminates in death. Surgical statistics, especially of herniotomies in elderly people, are greatly prejudiced by this disease. ILLUSTRATIVE CASES. Case 12. — Sub-acute UtJicemic nephritis in a case of heart disease. Death. A ittopsy. F. I. , male, forty-one, labourer, admitted April 8th, 1886, with shortness of breath. He had been quite well until Christmas, when he left off work owing to shortness of breath and cough. He attributes his illness to catching one cold after another. His urine has always been natural, and there has been no dropsy. He has been doing very heavy work and exposed to all kinds of weather. When he was sixteen or seventeen years of age he had acute rheuma- tism, but can remember no other illness. Father died suddenly of apoplexy. Mother died of bleeding from the nose. One brother died of a growth in the mouth (.'' epithelioma). On admission his legs were swollen, but this disappeared rapidly after he was sent to bed. Tongue pale, moist, slightly lurred ; appetite bad ; bowels regular. Liver dulness commences at sixih rib, and the edge can be felt two and a half inches below the costal border. Spleen normal. Heart's apex in sixth interspace : a loud double mur- mur heard best in aortic area and conducted into the vessels of the neck. Pulse collapsing, 108. Lungs resonant, breath sounds harsh and accompanied by numerous moist sounds. Urine thirty-six oz., 1027 ; acid ; deep yellow, turbid from urates ; urea 2*2 per cent. ; a faint cloud of albumen ; hyaline casts ; leucocytes and oxalates in deposit. Prooress of case. — He improved at first, but towards the end of April his cough became more troublesome. On May 2nd he had a severe attack of dyspncea, his pulse became very weak, and he died at 1.50 a.m. on the following morning. Autopsy, May 4th. — Well-made muscular subject ; oedema of feet and ankles ; slight general oedema of subcutaneous tissue. Lungs very cedematous ; about eight oz. of serum in each pleural cavity. 136 BRIGHT S DISEASE. Hearty twenty-one oz. ; right ventricle dilated and full of clot ; pul- monary and tricuspid valves normal ; left ventricle hypertrophied, walls thickened, cavity dilated, containing a small quantity of dark fluid blood ; anterior cusp of aortic valve thickened and retracted ; base of aorta irregularly dilated and the seat of extensive endarteritis deforntatti, ; mitral valve normal ; muscular wall of heart pale and marbled ; a patch of pericarditis on apex of heart with adherent organised lymph. Liver ^ fifty-six oz. ; a good example of cyanotic induration wilh atrophy ; marked fatty infiltration in portal zones of lobules ; consistence firm, rather leathery. Kidneys, eleven and a half oz., cortex increased, pale, swollen and translucent in places, with brick red and yellowish mottling ; capsules separated easily, leaving a pale marbled surface (red and greyish yellow). On microscopical examination the convoluted tubes were generally dilated, in some the epithelium was swollen, granular, vacuolated and fatty ; in others it was atrophied or reduced to a narrow border of proto- plasm. Except where degenerative changes were present the nuclei stained well. The glomeruli were hypertrophied, the capillary loops appeared cloudy and indistinct and showed an increase of nuclei. They were not congested as a rule. Here and there small stellar patches of interstitial change were met with. In the pyramids the capillaries were considerably engorged. Case 13. — Chronic lithcemic nephritis j chronic endocarditis ; heart failure. Death. Autopsy. Thomas S. , agediorty, gardener, admitted March 28th, 1886, with cough, tightness of the chest, weakness and swelling of the legs. A month ago he noticed his eyelids and hands were puffy, and he made very little water ; then his legs swelled ; and a fortnight ago he took to his bed. He could remember no previous serious illness ; he had never had dropsy or any trouble with his water before ; he had never had gout, or acute rheumatism, but had often had rheumatic pains in his knees and shoulders, and had been confined to the house for a fortnight with them. For the last six months he had been rising at night to pass water. His home and circumstances were comfortable, but his work exposed him to cold and damp, and he was in the habit of drinking four or five pints of " sweet ale " daily. His family history was unimportant ; father died aged seventy-two ; mother died aged seventy-six. Seven brothers and sisters alive and well ; only one had died in infancy. He was a well-built and well-nourished man, with a ruddy complexion ; there was oedema of the conjunctivse, lower extremities and scrotum. T. 97"5"' ; P. 90 ; R. 20 ; tongue furred in centre, red at edges ; bad taste in mouth ; appetite good ; very thirsty ; bowels confined ; abdomen dis- tended ; some ascites ; hepatic and splenic dulness normal. Heart's apex in fifth interspace, inside the vertical nipple line ; no murmur ; no accentuation of aortic second sound. Pulse regular, not hard. Breath sounds harsh, with moist rales posteriorly. Vision good ; ophthalmoscopic appearances normal. LITH.'EMIC NEPHRITIS. 137 Urine 28 oz. ; sp. gr. 1022 ; acid ; urea 217 grains pto die ; albumen 71 grains /"rr' die; epithelial, fatty, hyaline and granular casts, blood cor- puscles and blood casts, with renal epithelium in the deposit. He did not improve under treatment ; he had profuse diarrhoea, and on April 7th he was in a very serious condition. In the evening he complained of feeling very weak ; he became cyanosed, and died at 9.20 a.m. Autopsy, April 9th, i8i8. — Extensive general anasarca; head and face congested ; rigor mortis passing off. Thorax. — About a pint of clear fluid in each pleural cavity. Lungs.- — Congested and cedematous. Heart weighed 17 oz. ; pericardial sac con- tained about 2 oz. of fluid ; right side of heart full of clot ; tricuspid and pulmonary valves healthy ; mitral cusps thickened, shortened and yellow, with small, firmly adherent vegetations on their auricular surfaces ; aortic \alve incompetent ; segments glued together, thickened, stiff and cal- careous in places. Under the microscope the heart fibres showed a little " brown atrophy," but were not fatty. Abdomen. — Liver 79 oz., fatty. Spleen 6 oz., soft, pale. Kidneys together weighed 17 oz., greatly swollen, mottled red, white and yellow (roan). On section, the cortex was of the same colour ; the Malpighian bodies were very distinct, and some showed the waxy reaction with iodine. The consistence of the organs was soft and friable. Under the microscope the following changes were noted : — Malpighian bodies J the capsules were broadened and nucleated {pericapsulitis), and the lining epithelium proliferated {eiidocapsiiliiis) ; the glomerular tufts were covered with nuclei, and one had completely undergone hyaline change. Blood vessels dilated ; there was hypertrophy of the muscular wall, with proliferation of the endothelium of the intima {e7idarteritis obliterans). Connective tissue j this was generally broadened out and full of I'ound brightly stained cells. The great exception was the capsule of the kidney, which did not appear thickened. Epithelium j the tubes were everywhere lined with fatty epithelium ; it was difficult to find one that was not so, even in the medulla. There was no appearance of prolifera- tion of epithelium, though some tubes were filled with debris, in which some small rounded nucleus-like bodies could be seen. Case 14. — Acute attack supervening in the course of chronic lithcemic nephritis. Recovery. Michael H , aged thirty, iron worker, admitted April 4th, 1888. with headache, tightness of chest, and swelling of face and legs. He had scarlatina when a child, but enjoyed good health till eighteen months ago ; since then he had suffered from severe headache and bronchitis. At Christmas he caught cold, and his legs swelled, but this passed off. Three weeks ago he noticed that his water was smoky. He admitted having been a heavy drinker, and his work exposed him to severe changes of temperature. His mother died of asthma. He was a fairly well nourished man, with a flushed face ; when examined the cedema of the legs had passed off from rest in bed. T. 98*5° ; P. 72 ; R. 83 ; tongue clean ; appetite good ; bowels regular ; liver dulness three and a half inches in the vertical nipple line ; some dulness in flanks, which changed with his position. Heart's apex in sixth intercostal space, one and a half inches to the left of the nipple line. At apex, first sound reduplicated ; in aortic area, 138 BRIGHT S DISEASE. second sound accentuated. Pulse was hard and incompressible. Lungs normal. Urine 56 oz. ; sp. gr. 1017 ; acid ; straw colour, smoky ; -white deposit ; urea 344 grains ; albumen y]'] grains ; deposit contained a few epithelial and numerous hyaline and granular casts, with red and white blood corpuscles and renal epithelium. With rest in bed and diaphoresis he improved rapidly. April 14th. — There was no trace of ascites. Urine 60 oz. ; sp. gr. 1022. i8th. — Urine 62 oz. ; sp. gr. loio ; very little blood ; albumen 528 grains ; granular and hyaline casts with blood corpuscles and renal epithelium. There was continued improvement. May 1st. — Urine 60 oz. ; sp. gr. 1006 ; straw colour ; albumen 396 grains. 3rd. — Allowed to get up. Urine 62 oz. ; sp. gr. 1020 ; albumen 327 grains. 8th. — Urine 60 oz. ; sp. gr. 1015 ; straw colour; urea 448 grains ; albumen 316 grains ; a trace of blood with guaiacum and ozonic ether ; a few hyaline and granular casts, blood corpuscles and renal epithelium in the slight white deposit. loth. — He was made an out-patient. After April nth he had milk diet with chicken or fish. Case 15*. — Chronic lith(zinic nephritis ; albuminuric retinitis ; urceniic dyspn<£a. Cornelius H , aged fifty-eight, admitted on June 12th, 1888, with severe frontal headache made worse by lying down, cough, and dyspnoea, trequent micturition, especially at night, partial loss of sight and swelling of the feet towards night. He had been ill six weeks, and worse for seven days. He was sent to me from the Eye Hospital, where he had complained of headache and dimness of sight, and was suffering from nasal catarrh with congestion of the conjunctivas. Albuminuric retinitis was recognised there, so he was transferred to me. His father died of bronchitis, aged fifty-six ; mother died aged seventy, cause unknown. Three sisters died between thirty and forty, cause un- known. He has had three children, of whom two died in infancy ; the third is living, aged twenty-five, and is strong and well. Patient had worked as a match maker all his life, He denied having been intemperate ; his only drink had been half a pint of beer at supper three or four times a week. He had a good home, but his workshop was close. He could remember no illness, except " congestion of the kidney" eight years before. On enquiry about the congestion ot the kidney, he said that he passed blood in his water and was delirious, and that he was ill in bed four weeks. There had been no return of hiematuria. He denied ever having had gout. He was a very old-looking man for his years, with a very puckered, wrinkled face, scanty hair ; skin of face and conjunctivte slightly jaun- diced ; expression of face dull and apathetic. There was slight oedema of the legs and feet. Temp. 98". Lips cyanosed ; teeth very defective ; tongue clean ; mouth very dry ; * Recorded by Mr. F. H. Noott, Clinical Clerk. LITHA^MIC NEPHRITIS. 139 appetite g'ood ; great thirst ; bowels confined ; no ascites ; liver dulness four inches in vertical mammillary line. Heart's apex a little external to the vertical mammillary line in the fifth left interspace ; sounds pure ; aortic second sound accentuated. Pulse full, cord-like, incompressible, 96- . . . Respirations hurried, 48 ; a little cough ; no expectoration ; breath sounds and percussion note normal. There is persistent dyspnoea. Ophihalvioscopic appca7-ances. — Right eye. — One or two small heemor- rhages below the disc, and a number of small round patches of atrophic retinitis on the outer side. Left eye. — No haemorrhages, but a larger group ot the same patches on outer side of disc. Uri7ie. — Slight uneasiness in loins ; water passed six or seven times during the night lor three months past ; 66 oz. ; sp. gr. loio ; pale, acid ; a dense cloud of albumen ; urea "9 per cent. (260 grains) ; under microscope numerous leucocytes and a few hyaline and granular casts. He complained of being unable to sleep in the hospital, and insisted on going out five days after admission. BIBLIOGRAPHY. Charcot and Gombault. Note relative a I'etude anatomique de la Nephrite Saturnine experimentale. "Arch, de Phys.," 1881, p. 124. Dickinson (W. H.). On the Pathology and Treatment of Albuminuria. 2nd edition. London, 1877. Ebstein (W.). La Goutte, sa nature et son traitement. Traduction du Dr. E. Chambard. Paris, 1887. EiCHHORST (H.). Handbuch der speciellen Pathologie undTherapie. 1884, Bd. II., p. 62. Fleischer (R.). Quoted by Rosenstein, op. cit., p. 211. Johnson (G.). Lumleian Lectures on the Muscular Arterioles. London, 1877. Leichtenstern (O.). Untersuchungen uber den Hasmoglobingehalt des Blutes in gesunden und kranken Zustanden. Leipzig, 1878. Lloyd-Jones (E.). Op. cit. Mahomed (F. A.). Some of the clinical aspects of Bright's disease. " Gu3''s Hosp. Reports," 3rd S., Vol. XXIV., 1S78, p. 363. : — Chronic Bright's disease and its essential symptoms. ' ' Lan- cet," 1879, I., p. 46. Ollivier (A.). Essai sur les Albuminuries produites par I'elimination des substances toxiques. Paris, 1863. Todd (R. B.). Clinical Lectures, 2nd edition, London, 1861. West (S.). On the Occurrence of Blood in the Urine in Granular Kidney. " Lancet," 1885, XL, p. 104. I40 Chapter XII. OBSTRUCTIVE NEPHRITIS. (SYN. SURGICAL KIDNEY ; PUERPERAL KIDNEY ; ASCENDING NEPHRITIS.) Inflammation of the kidney which arises in the course of many affections of the pelvic organs has close pathological relationships with what is generally known as Bright's disease. A description of it will make clearer the general doctrine of the broad unity in type of the anatomical changes met with in all cases of nephritis, and it will add an additional argument to the proof of the efficiency of the renal lesion in the pro- duction of the cardio-vascular changes. P^TIOLOGY. — The causes of this form of nephritis are to be sought in some obstruction to the outflow of the renal secretion. It is identical in its simpler form with nephritis produced by ligature of the ureter (Strauss and GermONT), but this primary condition is apt to be complicated by an acute infective process, starting from inflammation or traumatism in the urinary passages, e.g., cystitis, catheterism. The most common causes are enlarged prostate, stricture and cystitis, uterine and ovarian tumours, pregnancy, pelvic inflammation (pyo-salpinx), tubercle and tumours of the bladder, and procidentia uteri ; their degree of frequency being in something like the order given. As in other forms of chronic nephritis, cold may easily set up acute intercurrent attacks. Sex. — My figures give a much larger proportion of males than females, in the ratio of seven to one. The females include the following cases : procidentia uteri, one ; hysterec- tomy for uterine fibroma, one ; removal of appendages for double pyo-salpinx, one ; ovariotomy, one. But as the number of cases of special diseases of women treated at the General Hospital is very small, while the proportion in which this lesion is found is large, there is reason to think that the disease is more common in females than the above figures would suggest. OBSTRUCTIVE NEPHRITIS. 141 Age. — In accordance with the nature of the causes the disease is much more common after middle life. Morbid Anatomy. — The kidneys are usually above nor- mal size, rarely small. The capsule is generally thickened and more or less adherent ; the surface is granular, red in colour or more often pale. On section, the organ is often tough, soft and flabby. The cortex is sometimes swollen, often reduced in width ; the pelvis is always dilated and con- tains purulent urine, while its mucous membrane is congested and oedematous. Patches of opaque greyish infiltration are visible invading the medulla and cortex, and haemorrhagic streaks and spots are often present. When there is tubercular disease of the bladder, tubercles may be found in the kidneys. Both organs do not always present identical appearances. One may look fairly normal and the other be in an advanced state of disease, or one may be enlarged, pale and fatty, while the other is smaller, red and granular ; Crooke has described a case in which one kidney only was diseased, the cause being compression of the corresponding ureter. Collections of pus may be found in the cellular tissue around the kidneys. In recent cases, especially in connection with pregnancy, the kidneys may appear only swollen and hyperaemic. The microscopic appearances are as follow : — Glomeruli. — Some appear normal ; others have their nuclei increased, while others again are in a state of hyaline degener- ation. Blood may be found extravasated in the intra-capsular space. Blood vessels. — In advanced cases the larger vessels show well-marked endarteintis obliterans with hypertrophy of their middle and outer coats. The capillaries of the cortex are dilated and full of blood; others, especially those in the boundary zone, may have their walls thickened. Convoluted tiibules. — These are generally of normal size. The epithelium is in parts normal ; in others it shows the appearances of catarrhal nephritis. Some of the tubules are filled with leucocytes, which infiltrate the basement membrane. Straight tubules. — In the medulla many of these are widely dilated, to a less extent in the cortex, and they often contain colloid material (casts). The epithelial lining is in places being pushed off by invading leucocytes, which may fill up the lumen of the tube. Connective tissue.— ^\i\?> is swollen and hyaline. Here and there areas may be seen so thickly crowded with invading 142 BRIGHTS DISEASE. leucocytes that the normal structure of the kidney is quite hidden, and in places veritable abscesses are visible. This description is based upon cases complicated by more or less acute interstitial nephritis, set up by cystitis ; it is probable that where there is simple obstruction there is no interstitial nucleation (STRAUSS and Germont). Angus Macdonald, in his description of the kidney of eclampsia, found only dilated tubules, with altered epithelium and colloid masses in their cavities. This is no doubt the early stage of the uncomplicated process. If not interfered with and given a persisting cause, e.g., enlarged prostate, it ultimately eventuates in red contracting kidneys, such as are described in the following notes from the pathological register : — Case i6. — Enlarged prostate j cystitis j surgical kidneys. H. C. , admitted August 3rd ; died August 17th. NECROPSY, August 1 8th, 1886. A spare, emaciated subject. Heart 9^ oz. ; large milk spot on right ventricle ; aorta and coronary arteries atheromatous ; right ventricle enlarged ; slight chronic endocar- ditis of mitral valve ; muscle dark, a little fibrous in places. Lungs.— 'Lo'^ ex lobes congested and cedematous ; upper lobes emphy- sematous ; general bronchitis. The base of the left lung was deeply congested and the pleura was slightly inflamed. Liver 52 oz. : capsule a little opaque and thickened ; parenchyma pale, fatty and mottled with congestion. Kidneys Z\ oz. ; capsules adherent ; red granular kidneys j pelves dilated with purulent urine ; on the left side the cellular tissue round the lower end of the kidney was infiltrated with pus ; ureters dilated near their entrance to the bladder. Bladder. —Great hypertrophy of walls ; mucous membrane much in- flamed and discoloured, showing small ulcerated elevations to which phosphatic deposit was adherent ; prostate much enlarged, fibi'ous and indurated : prostatic and membranous urethra showed signs of chronic inflammation. Symptoms and Course. — These cases generally come under medical or surgical observation on account of the local trouble which causes the kidney mischief, for in this, as in the red contracting kidney of dyscrasial origin, the symptoms are latent, while any special urinary symptoms are masked by the local disorder. The disease usually becomes noticeable when acute nephritis has supervened, and this brings with it corres- ponding changes in the clinical phenomena. The urine. — In pronounced chronic cases the urine is in- creased in amount to 80 or 100 oz. ; it is of low density, generally acid unless it has undergone decomposition, usually turbid from some amount of cystitis being present, and con- OBSTRUCTIVE NEPHRITIS. 143 taining a moderate amount of albumen, with a little blood. The deposit is muco-purulent, containing hyaline and granular casts, epithelium, pus cells, blood corpuscles, and often triple phosphates and micro-organisms. When acute nephritis has supervened the urine is diminished, the amount of albumen and blood is increased, the density is higher, and epithelial and blood casts are found in addition to the other elements in the deposit. In the former case the urea may be normal in amount, but in the latter it is greatly reduced. The Jieart is hypertrophied in a considerable proportion ; out of twenty-seven cases it weighed over 10 oz. in twelve, and the left ventricle is described as hypertrophied in one that weighed 10 oz., which may, therefore, be fairly included ; thirteen out of twenty-seven are very nearly 50 per cent. This is confirmed by other observers : in enlarged prostate it was observed in four out of ten cases (Jean) ; in other cases in five out of twelve (Weil) ; while Fere has noticed its frequent occurrence in the bodies of females with procidentia uteri. Dropsy is generally absent or only slight, but when acute nephritis occurs or heart failure sets in, dropsy supervenes just as it does in litha^mic kidney. Urcemia. — In pregnancy ursemic convulsions are common, probably because, as already pointed out, there are other co-operating factors present to produce a dyscrasia. Apart from this condition classical uraemia is not common. The usual form is the typhoid type, with dry tongue and feeble pulse. It is a form in which septicaemia plays an important part. Senator has described the type resembling " diabetic coma " as frequently occurring in cystitis {Vide Chapter VII., p. 62). Diagnosis. — These cases can only be diagnosed when their etiology is thoroughly grasped, and the symptoms looked for carefully in cases where the disease is likely to be present. Evidences of high arterial tension may be found in the character of the pulse, in the accentuation of the aortic second sound and the doubling of the first sound at the heart's apex. Displacement of the latter outwards indicates cardiac hyper- trophy. The urine should be collected for twenty-four hours, its quantity measured, its solids and especiall}^ its urea quantitatively estimated, and casts looked for. Prognosis. — Where the disease is due to pressure only, uncomplicated by cystitis, a good result may be hoped for, 144 BRIGHT S DISEASE. provided the obstruction is removable and is not of too long Juration. This is exactly the condition in most cases due to pregnancy, hence the satisfactory recoveries so often seen after parturition has taken place. In most other cases the cause is of such persistence that the prognosis is very bad. ILLUSTRATIVE CASES. Case 17. — Enlarged prostate j cystitis; asce7iding nef)7iritis. A. B., thirty-five, furnace-man, admitted Oct. 23rd, 1888, complaining of swelling of the legs and face, and pain in the back. His present illness had lasted only a week ; he thought he had caught cold, as his work is very hot, and he was in a draught. The next morning his water was scanty and dark red, and has remained diminished in quantity ever since. Five years ago he was in the hospital with a similar attack, also brought on by cold. He was ill a month. He could recollect no other illness ; he had never had gonorrhoea or gout. He had never had any difficulty or pain in making water or had an instrument passed, or was aware of having any bladder disease. General surroundings at home comfortable ; had plenty of good food ; drank three pints of beer daily, and at one time more than this. Family history good. Present co7idition. — Patient is a well-developed, well-nourished man, wtth a rather sallow complexion. His face looks puffy, but there is no oedema of the eyelids. There is no oedema of the legs or scrotum, but he has been twenty-four hours in bed. T. 97'5° ; R. 24 ; P. 60. Tongue clean at tip, furred posteriorly ; teeth defective ; gums sore ; breath foul ; appetite pretty fair ; no discomfort, bad taste, or flatulence after food ; bowels regular before admission, but not opened since. Vertical liver dulness 4^ inches, reaching just below the costal border. Spleen not enlarged. No ascites. Chest well formed ; respiration ves- icular ; percussion note normal. Heart's apex in fifth interspace inside vertical nipple line ; first sound feeble at apex ; second sound loudly accentuated in the aortic area. Pulse 60, full, not easily compressible. No headache, giddiness, or affection of special sense except shght deafness. Complains of his two forefingers being " dead and white " with the cold in the mornings. No loss of muscular power or common sensibility. Ophthalmoscopic appearances negative. Urine, 24 oz., reddish brown, turbid, faintly alkaline ; sp. gr. 1015 ; urea r6 per cent. ; loaded with albumen ; contains blood and peptone, no sugar ; white heavy deposit, which under the microscope appears to be composed of pus cells, and flask-shaped or spherical colonies of micro- organisms enclosed in the capsule. Some urine was drawn off with a catheter under antiseptic precautions, which was sent to Dr. Crooke, who reported as follows : " Urine acid, straw-coloured, tinged with blood ; muco-purulent deposit ; urea i*i per cent. ; albumen i per cent. ; no sugar ; blood ; pus ; no casts ; zoogloea masses of bacteria and micrococci, of which several varieties are present." Some nutrient gelatine was inoculated with the urine and sent to Prof. Crookshank. OSSTRUCriVE NEPHRITIS. 145 It was noticed that although the bladder was full of water when the catheter was introduced, the patient had had no desire to micturate. The lateral lobes of the prostate were moderately enlarged. Oct. iZth. — Mr. Barling examined the bladder with the cystoscope, and reported as follows : " Direct cystoscope passed without difiiculty ; bladder previously washed out and about six to seven oz. of fluid injected. Medium rather turbid, but not bloody. Mucous membrane on trigone and immediate neighbourhood elevated, oedematous and fluffy on surface. Neither ureteral orifice could be seen. Still further back the changes were the same, but less marked. No ulceration was seen. The ordinary distribution of vessels on the mucous membrane was quite obscured." The urine remained in the same state. On Nov. 1st the bladder was ordered to be washed out with boracic lotion daily. Nov. 6th. — The bladder has been washed out daily since it was ordered. The urine is now pale greenish yellow, turbid, acid, depositing three- quarters of an inch of pus, containing a trace of blood. Under the microscope the flask-shaped and spherical encapsulated masses are much less numerous, but there are plenty of irregular zoogioea masses. Com- plains of epigastric pain ; tongue furred and brown. Has had flatulence. He has been taking saccharin. As washing out the bladder seemed to be followed by an increase in the amount of pus it was stopped on the loth, when the amount of pus at once fell to half, but since then it has varied a good deal. His legs began to get very oedematous, and this remained in spite of his being kept in bed, and of the large amount of water he was passing, which averaged over 80 oz. daily. The following is the urine report for Nov. 25th ; Urine 88 oz., acid, straw-colour, blood-tinged ; sp. gr. 1012 ; deposits muco-pus ; urea '9 per cent. ; albumen "9 per cent. ; blood and pus present ; slight acetone reaction ; one or two flask and hour-glass shaped colonies enclosed with- in a membranous envelope ; also diffuse distribution of bacilli and mycelium-like threads ; some hyaline masses to which large fatty cells adhere as if portions of large hyaline or colloid casts (Dr. Crooke). He left the Hospital in statu quo. Case 18.* Cystitis; bronciiitis ; ascending nephritis ; septicemia. Martha L , aged forty-three, housewife, admitted May 26th, 1886, with swelling of legs, shortness of breath on exertion, and cough. She had had pleurisy ten years ago, but no other illness. There was nothing to be made out of the family history. Her surroundings at home were comfortable ; she had been temperate, taking only one half-pint of beer daily at her supper. A strongly built, well-nourished woman ; her skin had a slightly yellow tinge, but her conjunctivae were white. There was slight cedema of the legs. T. 98'6^ ; P. 66. Tongue furred ; appetite poor ; complained of thirst, of flatulence after food, and of vomiting before admission ; bowels confined ; abdomen distended ; vertical liver dulness one and a half inches in the nipple line ; ascites. Heart's apex just inside vertical nipple line, in the fifth interspace ; there was a diastolic murmur best heard to the left of the apex beat. Pulse full, regular. Urine 10 oz. ; sp. gr. 1017 ; acid ; straw yellow colour, smoky ; * Recorded by Mr. F. H. Noott, Clinical Clerk. 10 146 BRIGHT S DISEASE. deposit leddish brown ; urea Zyd grains ; deposit contained epithelial, hyaline and granular casts, red and white blood corpuscles and renal epithelium. June 1st. — The cardiac murmur had disappeared, and was never heard again. Urine 30 oz. ; Temp. 99*6° ; P. 68. 3rd. — Vomiting ; urine 44 oz. ; Temp. io2*6*. 4th. — Vomiting continued, the patient was pale and sweating pro- fusely ; her tongue was dry ; lungs normal ; urine had to be drawn off with catheter, 28 oz. ; sp. gr. 1026 ; acid ; claret colour ; reddish brown deposit ; urea I47'84 grains ; albumen quarter column ; deposit contained blood corpuscles, pus cells, epithelial, granular and hyaline casts, and renal and vesical epithelium. Evening temp. 104° F. P. 84. 5th. — Still vomiting ; haematuria persisting ; no pain. Temp. ioi"6" ; Urine 42 oz. 6th. — Still vomiting ; sputa blood-stained ; impaired resonance at right apex, with a i&'N rhonchi and rales audible. The patient was becoming distinctly more emaciated and anaemic. Urine 34 oz. Temp. 100°. 8th. — Blood examined with the haemocytometer appeared normal. Urine 44 oz. Temp. 99'4° ; P. 72 ; R. 48. 9th. — Better. Urine 34 oz. Temp. 98''. loth. — Not so well. Urine 36 oz. Temp. 97^. nth. — Better. Urine 40 oz. Temp. 97"2°. 1 2th. — Passed urine without the catheter. There was pain and swelling over the right parotid, causing inability to open the mouth, but fluids were readily swallowed ; there was no redness of the skin ; tongue dry ; bowels confined. Temp. 98'6^. Urme 60 oz. ; alkaline ; sp. gr. 1012 ; slightly blood-tinged ; whitish viscid deposit ; urea 475*2 grains ; a cloud of albumen ; deposit contained no casts, but red and white blood corpuscles, pus cells, mucous corpuscles, vesical epithelium, with crystals of triple phosphate and urate ot ammonia. 13th. — Swelling great, skin over it hot and red. Urine 58 oz. Temp. 104-4°. 14th. — Swelling less, mouth could be opened more freely ; breath foul. Urme 40 oz. Temp. 98"4*^. 15th. — Swelling going down ; vomiting recurred. Urine 38 oz. Temp. 97 •2'^. 1 6th. — Vomiting stopped ; catheter required again ; swelling still less. Urine 40 oz. Temp. 98°. 17th. — Very slight swelling left ; no vomiting ; a few rales at left apex ; no cardiac murmur ; catheter still required. Urine 32 oz. ; sp. gr. 1013 ; alkaline; smoky colour; muco-purulent deposit; urea 239 grains; albumen one-twelfth column ; deposit contained no casts, but pus cells, blood corpuscles, vesical epithelium and triple phosphates. Temp. 97'6°. 1 8th. — Patient looked very ill, and complained of pain in the bowels, nausea and severe diarrhoea. Pulse 160, very feeble ; retention of urine ; pain ceased in the course of the day, Temp. 96*8°. Urine 14 oz. 19th. — She had passed a fair night, but the diarrhoea persisted. Temp. 96*8° ; P. 132, very feeble. She vomited, and the ejected matter contained o"5 per cent, of urea. In the course of the day the diarrhoea stopped, and she complained of no pain. Evening temperature 96'2°. Urine 10 oz. She died the following morning at 6.25 a.m. Necropsy. — Lungs^ right ; oedema and hypostatic congestion of inferior lobe ; diffuse bronchitis and muco-pus in the bronchi. Left ; OBSTRUCTIVE NEPHRITIS. 147 pleuritic adhesions of the base to the thoracic wall ; inferior lobe conges- ted and somewhat collapsed. Heart 9 oz. ; no valve lesions ; lelt ventricular wall hypertrophied. Liver 50 oz., mis-shapen ; right lobe much flattened out, its upper surface grooved by the ribs, and its inferior border reaching nearly to the umlDilicus. Spleen 5 oz., normal. Kidneys 7 oz. ; capsules stripped well ; surface greyish red; stellate veins promi- nent. On section, several abscesses were found in the cortex of the right kidney ; the surrounding substance seemed infiltrated and of an opaque grey reddish mottled appearance, as though it were the seat of an acute interstitial nephritis. Riglit iireter ' half hour to make it ; quantity 54 oz. ; sp. gr. 1012 ; alkaline ; greenish yellow ; deposits white flocculent precipitate ; urea "8 per cent. ; albumen half column; no sugar or blood. Under the microscope groups of leucocytes, hyaline and granular casts, red blood corpuscles, squamous and renal epithelium, triple phosphates, granular debris and masses of micrococci were detected. He complained of dimness of vision, which had come on for twelve or thirteen weeks, being only able to read large capitals. With the ophthalmoscope extensive neuro-retinitis was seen in both eyes, with large white glistening patches of retinal atrophy : both eves were equally bad. Oct. 6th. — Complained of fixed pain in the left side: bowels confined ; tongue foul. 7th. — Vomited about two pints of brownish watery matter, fi-ee from blood ; bowels acted loosely ; tongue very brown. Complained of sick headache all last evening. 9th. — In the afternoon was restless, thirsty and faint. He vomited a good deal, and was given some brandy, after which he improved. loth. — Had a sleepless night, but was quiet ; complained of headache and chilliness ; vomited five times during the night, 15 oz. in all, which contained o" 1 5 percent, of urea. \\\h..—Has been luhistling and singing tnost of the night ; slept only half an hour ; kicked the clothes off continually ; complains stiU of headache. \*omiting again this morning. I2th. — Slept only from 12 to 12.30 a.m. ; restless, noisy, and delirious j he continued delirious all day, and towards evening got out of bed ; he slept with a chloral and bromide draught. To-day, some dulness, friction, deficient breathing, and coarse crepitation were noticed over right side of chest anteriorly. His temperature continued to be normal or subnormal. Pulse 120 ; respirations 36 to 48. He died the following day at 1.15 p.m. without any development of fresh s\-mptoms. AXTTOPSY, October 14th. — Exiernal afypearances. — Features pale; lips bluish ; rigor mortis present ; hypostasis more marked posteriorly. 156 BRIGHT' S DISEASE. Head. — No ti'ace of previous injury to skull ; brain congested ; excess of serous fluid in sub-arachnoid space and ventricles ; no gross lesion in any part of brain substance. Heart. — Pericardial cavity contained 4 oz. serous fluid ; heart 13 oz. ; generally hypertrophied, especially left ventricle ; muscular wall firm and rigid ; valves normal. Ltins^s both adherent by old fibrous adhesions ; old caseous and fibroid phthisis at left apex. In centre of right middle lobe was a small hard nodule, composecl of caseous material, surrounded by a capsule of pig- mented fibrous tissue, while a similar, but rather larger nodule was in the upper lobe of the same lung. The bronchial glands were enlarged, caseous and encapsuled in fibrous tissue ; the left lung contained several smaller caseous nodules of the same kind. liver 51 oz. ; pale, soft and fatty. Spleen 5 oz. Kidneys., right., 5^^ oz., enlarged, surface greyish red mottled with yellow spots ; capsule slightly adherent ; cortex increased, swollen, greyish with yellow mottling and hypersemia intermingled, translucent- looking in places and generally fatty ; medullary cones congested, almost claret-coloured ; left., 4 oz., smaller, more granular, capsule more adherent. Among the minor phenomena of threatening uraemia, Cramps are common. Charcot has seen a kind of tremor resembhng paralysis agitans, and Jaccoud has described tonic spasm of the flexors of the forearm and the posterior muscles of the neck. Headache is a very common prodromal symptom ; it may be frontal or occipital, but the latter is more characteristic. TwitcJmigs are also a common early symptom, and these are closely related to conviilsio7ts ., which may attack single groups of muscles, and to Jacksonian epilepsy, or convulsions without loss of consciousness, which may be unilateral (Ten- NESON and CHANTEMESSE). Convulsions of the epileptic type constitute the common uraemic fit, they are accompanied by total loss of conscious- ness, biting the tongue, and foaming at the mouth, and are generally followed by deep coma. The attack may consist of a single paroxysm or a succession of these, the patient lying unconscious in the intervals, breathing stertorously, or in a sort of deep sleep from which he may be partially roused. Bris- saud and Larring have described a case followed by catalepsy. Coma may be the result of a convulsive attack, or may come on gradually, or suddenly as in apoplexy. Roberts has given several cases of this sudden onset. The temperature during the attack is generally subnormal. Roberts has recorded a case in which the temperature fell as low as 94'4° F., and Hirtz another in which it fell to 93'9°, COMPLICATIONS OF CHRONIC BRIGHT S DISEASE. 157 while Bourneville has pubHshed temperatures as low as 93 '1°, 9ri°, S9-6°, and even 86' 1°. According to Ilutinel these low temperatures are more often met with in those forms of nephritis following diseases of the urinary passages, e.g., surgical kidney, and Netter observed a temperature of 86° in a case of anuria due to purulent nephritis with a twist of the left 'ureter. MacBride gives the following conditions as those under which lowering of the temperature is always present : (i,) In kidney diseases following affections of the urinary passages with complete obstruction ; (2,) In ur?emia in old persons ; (3,) In ursemia occurring in old standing kidney diseases complicated by vomiting, diarrhoea and haemorrhages ; (4,) In uraemia which supervenes in cancerous cachexia and maras- mus. In other cases elevation of temperature has been observed even as high as 105 '8° and I07"4°, but this has always been followed by a rapid fall (RiCHARDIERE, GiLLET). Lepine found that a high temperature could be induced in animals by ligaturing the ureters and connecting them above the ligatures with a reservoir of salt and water under sufficient pressure to drive back the urine into the circulation. This result is singularly at variance with the above noted clinical observa- tions. Carr has recorded a case of recovery after an attack of febrile uraemia. The pulse is generally quick, but may be as low as 60 or even 40. Case 23. — Chronic lit/uemic neph7'itis j tircBmic coma. Recovery. Richard J , aged forty, brewer, was admitted into the General Hospital on March 20th, 1886, complaining of swelling, which began in his legs, not in his face, and at the same time he noticed that his urine was smoky and diminished in quantity. His previous health had been good ; he had never had scarlatina or gout ; he was ridden over about two years ago and got " concussion of the spine." for which he was an in- patient in the surgical wards of this hospital. He was not told that his kidneys were hurt. He had been in the habit of getting out of bed to make water five or six times for the last ten years ; he drank about three pints of beer daily, but no spirits as a rule. He was a stout, well-developed man, with general anasarca, but no fluid in pleurae or peritonaeum. Pulse 84, regular, full ; R. 24 ; T. 98° F. Tongue clean ; fulness after food ; bowels loose from purgatives ; liver normal ; spleen a little enlarged. 158 BRIGHT' S DISEASE. Heart's apex in fifth interspace in nipple line ; systolic murmur at apex, not constant ; aortic second sound accentuated. Lunj^s resonant ; breath and voice sounds normal. Urine 44 oz., acid; sp. gr. 1015 ; smoky, yellow; white deposit ; urea I per cent. ; albumen five-sixths column ; blood present ; peptones present ; fatty, hyaline and epithelial casts ; white and red blood corpus- cles and renal epithelium. He complained of dimness of sight ; there were subconjunctival hcemor- rhages in the right eye. With the ophthalmoscope numerous atrophic patches were seen in both retins, and a recent haemorrhage in the right eye ; the outlines of both discs were gone, the arteries were very small, and the veins large. In spite of purging and diuretics his dropsy increased, and his urea excretion was very little. On ]\Iarch 26th it was 174 grains per diem. He began to complain much of occipital headache and pain behind his eyes. April 4th. — His legs were drained. 5th. — He began to be drowsy, and passed a stool under him. He continued in this apathetic condition, passing urine and f^ces in bed till his tongue grew dr}', sordes appeared on his teeth ; he was delirious and did not seem to recognise people. This continued till April 25th, when he gradually sank into coma. When seen his pupils did not react to light ; he could be partially roused ; he had vomited several times. The coma seemed to deepen, and an ineffectual attempt was made to bleed him. He was ordered a hot-air bath, in which he sweated freely, and next morning was better. After this he slowly improved, and after being for a time at the Jaffray Hospital, was discharged, free from oedema and fairly well, but quite blind. HAEMORRHAGES of all kinds are very common. Profuse haematuria has been already alluded to, but haemorrhage may take place from the bronchial or intestinal mucous surfaces, into the retina, the tympanum and the skin, while probably it constitutes the most common cause of cerebral apoplexy. The cause of the haemorrhage is in all cases the same, — de- generation of the small vessels and increased blood pressure. Case 24. — Chronic lithcEinic Jtephritisj pneumojiia; cerebral hemor- rhage. Death. Autopsy. Edward C , aged thirty-two, foreman at bicycle works ; admitted April 9th, 1886, ^vith headache, shivering and pains in the back, worse on the right side and increased on deep inspiration. He bad been ill one day. Except vague complaints of rheumatism, without joint affection, there was no previous illness. His habits were temperate and his home com- fortable, but his work exposed him to changes of temperature. He was a well-built and well-nourished man, but looked ill ; his face was dusky, and he complained of feeling cold. T. 104°; R. 38 ; P. 120. There was no cough, and no abnormal physical signs could be detected. There was no cedema. Tongue dry in centre. Urine 24 oz. ; sp. gr. 1013 ; acid ; copious brown deposit; albumen "i per cent. ; epithelial, hyaline, and blood casts, with blood corpuscles, and .renal epithelium in the deposit. COMPLICATIONS OF CHRONIC BRIGHT S DISEASE. 159 The next day he began to vomit, and his bowels became loose, but the stools were dark. His evening temperature was 103" F. On the 13th he was delirious, and enteric fever was suspected, but there was no rash, and the stools were not at all characteristic. On the i6th duhiess and coarse crepitation were made out at the right base posteriorly, and on the 17th his temperature came down to normal, and remained down afterwards. He Was some time getting better. The urine continued to be bloody and albuminous, but sufficient in quantity. On May 22nd the urine report is as follows; 56 oz. ; sjd. gr. loio; acid; pale straw colour; urea '95 per cent. ; albumen "5 per cent. ; a trace of blood ; epithelial and hyaline casts, with blood corpuscles, and renal epithelium in the flocculent deposit. On June 8th he was made an out-patient. He was re-admitted on September 29th with effusion in the pleural cavity. On October 6th oedema was for the first time noted in the legs ; this increased, and never left him. His urine contained albumen, and numerous epithelial and hyaline casts, blood and epithelium. He was very noisy and restless for some days, but by October nth he was quieter. On the 17th pericardial friction was heard. He began to vomit and complained of headache on the 2ist. Ascites was noted on the 27th. He remained more than two months in the Hospital, but insisted on going out on December 9th. His legs were still a little osdematous and there was fluid in the peritonEeum ; the urine was tairly abundant, 52 oz. ; slightly albuminous, but in the last examination no casts were seen ; urea ro5 per cent. He was again admitted on January 8th with great swelling of the abdomen, legs and scrotum. Urine 68 oz. ; sp. gr. 1012 ; pale brown colour: slight white deposit ; a quarter column of albumen ; a little blood, and no casts. In the morning of January 18th he vomited again, and at 7.40 p.m. when seen he appeared to be in a fit affecting the left side ; the left eyelid drooped, and the left arm was rigid, with occasional spasmodic jerkings ; he could not speak, but made intelligible signs with his right hand. His teeth were clenched, and now and then ground firmly together. His breathing was noisy and occasionally stertorous. Vomiting came on, and he died at 9.20 the same evening. Autopsy, January 19th, 1887. — Body of a fairly nourished man, rigor tnortis and post mortem staining well marked. Legs and feet osdematous, abdomen greatly distended with a large quantity of clear straw-coloured serum. Pericardium containing" from i to 2 oz. of blood-stained fluid ; there was also a small quantity of lymph on the surface of the heart and serous surface of the pericardium. Heart i lb., hypertrophied, wall of left ventricle f in. thick, muscle substance hard, firm and pale. Cavities not dilated. Musculi papillares and columnse carneee well developed ; aortic and pulmonary valves normal ; mitral orilice admitted three fingers ; tricuspid, only the tips of five fingers ; the posterior cusp of mitral valve shortened but not thickened. Limgs. — Left pleura contained a large quantity of clear straw-coloured fluid ; the parietal pleura was much thickened, and the lung bound down to the spine by firm adhesions, the lower lobe was entirely collapsed and attached to the diaphragm by a short tough fibrinous band about the thickness of the little finger. The upper lobe was crepitant throughout, but much firmer than normal. The whole lung weighed 8^ oz., and had somewhat the appearance of a Florence flask, the lower lobe forming the neck. i6o BRIGHT'S DISEASE. Right lu7ig I lb. 4 oz. ; this was adherent, specially the lower lobe, the surface of the lung being torn in removing it ; the tissue was firm and congested. Liver 3 lbs. 2 oz. Spleen ^\ oz. Kidneys, right, 4 oz. ; left, 3-|- oz., they were small and pale, and on section were found to be hard and fibrous, cutting grittily, the cortex narrowed, of a pale yellowish white colour, hard and fibrous ; the pyramids were pale, also hard and fibrous, the capsule thickened and adherent, on removing it the surface was mammi Hated. JUaddcr -\n2lS einpty and contracted, nothing abnormal was noticed. On removing the brain the convolutions on the (left ?) side were flat- tened, the (left.'') lateral ventricle was much distended with blood and clots, and some blood had found its way into the ventricle on the other side, the corpus sti^iatum and optic thalamus were much lacerated and disorganised by the hcemorrhage. Chronic Pachymeningitis.; — I take the following from the report of \k\.& post inorteiu examination of a man named J. C , in the Pathological Register of the General Ho.spital. Brain. — Dura mater adherent to the calvarium and in part to the sur- face of the brain ; the meninges were generally thickened all over the verte.K, oedematous, and the pia mater was here and there adherent to the vertex, the grey matter of which appeared dull, cloudy and mottled with yellow. There was much serous effusion in the sub-arachnoid space and ventricles. A small "psammoma" was found adherent to the membranes Ijehind the left crus. The under surface of the left temporo-sphenoidal lobe was fcroken down with red and yellow softening ; the corpora striata and optic thalami were cloudy and mottled yellow and pinkish grey. In the softened area the small vessels showed with the microscope fatty degeneration of their walls. Heart 13 oz. ; left ventricle considerably hypertrophied ; no valve lesion. Kidneys 9 oz. ; atrophied, capsules ad- herent ; surfaces granular ; cortices visibly diminished and fibroid. Heart P'AILURE. — This is a very common occurrence in the later stages. It is usually indicated by rapid dilatation of the heart, and there is often pallor, dyspnoea on exertion, or dropsy of the lower extremities. I have met with several examples of infective endocarditis occurring in association v/ith Bright's disease, and in one instance there was extreme hcemorrJiagic myocarditis with recent endocarditis affecting the mitral valve. CEdema of the Glottis. — This is a well-known compli- cation of general dropsy in acute and sub-acute nephritis, but it is not commonly known to occur in chronic Bright's disease. A man was brought into the hospital dead or dying, and on post mortem examination there was well marked oedema of the glottis, without general oedema. He had typical contract- ing kidneys; his heart weighed 13 J oz., its valves were thickened, and the coronary arteries atheromatous ; his lungs COMPLICATIONS OF CHRONIC B RIGHTS DISEASE. i6i were congested and oedematous ; his liver was cirrhotic and his brain oedematous. The larj'nx is not uncommonly the seat of acute or chronic catarrh. Congestion and CEdema of Lungs. — Among the most common post mortem appearances in persons dying with contracting kidney, whatever the cause of death may have been, are congestion and oedema of the lungs. This is the condition which during life probably gives rise to the symp- toms of bronchitis which are so common in these patients. Many elderly patients who complain of " bronchitis," and who have cough and difficulty of breathing, will be found on exam- ination to have no physical signs sufficient to account for their complaint. If the case is gone into and the urine examined sufficient evidence will often be found to enable it to be recog- nised as a latent example of contracting kidney. One of the fatal complications which may arise in the course of latent contracting kidneys is acute oedema of the hmgs. Its explanation is not at all clear, but it is generally attributed in a loose sort of way to the dyscrasia. This is all very well if there is dropsy elsewhere, but is no sort of explanation for the sudden development of dropsy in the lungs when all the rest of the body is free. Acute oedema of the lungs is too rare a condition to have attracted much attention. Standard text books either leave it out altogether or refer to the unimportant forms accompanying pneumonia and bronchitis, or to the pulmonary oedema of mitral disease. In seeking an explanation for it we must apply the princi- ples laid down in the chapter on Dropsy. Gradual heart failure would not give rise to these sudden attacks of oedema. They are not like the creeping dropsy of failing heart, but resemble the outburst of anasarca in acute nephritis. V/e must look therefore to some causes favouring the rapid outpouring of lymph. These may perhaps be found in hypertrophy of the right side of the heart and in increased permeability of the capillaries due to some local poison, possibly such as Wool- dridge found favoured cedema. In the case about to be related oedema of the lungs followed an anginal attack, in which the pulse was not affected. Could the angina have been due to some affection of the right side of the heart ? Could there be spasm of the pulmonary vessels giving rise to heart pain, and followed by paralytic distension and oedema ? These are possibilities. IJ [62 BRIGHTS DISEASE. Case 25. — Chro7iic lithcemic nephritis; icrcEinia; death from oidema of lung. A lady, aged sixty, of gouty antecedents, eight years before had had an epileptiform seizure, recognised at the time to be " ursemic." No other kidney symptoms had developed, except the necessity to rise at night to pass water. For the last few weeks there had been a little dry cough, with some dyspnoea on exertion, and a complaint of pain in the chest. One day, after a short walk, she was seized with a violent attack of pain at mid-sternum, which went through to her back and down the left arm to the thicmb. When seen by me at 2.30 p.m. her face was pale and anxious, extremi- ties cold. The heart's apex was in the sixth left interspace, an inch outside the vertical mammillary line ; the sounds were very feeble. The pulse was full, soft and regular, but she had been inhaling nitrite of amyl. Respiration was easy ; slight cough ; no expectoration ; breath sounds normal. She complained a good deal of the pain, which was not reheved by any remedy. By 4.30, when I left her, her face was less anxious, her hands were warmer, and her pulse was still full and quite soft. She continued better and sat up a little during the afternoon, but about eight o'clock difficulty of breathing commenced. When I returned at 9.30 there was marked oedema of both lungs, moist bubbling rales could be heard all over the chest and she presented cyanosis of the face, cold clammy skin, etc. All remedies were useless ; she gradually became unconscious, and died at 11.30, No urine was passed after the first onset in the middle of the day, when, at the same time the bowels were moved. The pulse remained full till quite near the end. Bronchitis accompanied by emphysema is found post -mortem with some frequency, but, as already hinted, not so frequently as the cough and dyspnoea from which these patients suffer would suggesit. Case 26. — Chronic lithce/nic nephritis ; gout; bro7zchitis ; eczema; urcemic delirium. Death. Autopsy. James W , aged sixty-five, upholsterer, admitted January loth, 1888, with cough, dyspnoea on exertion, and a breaking out on his skin. He had had a cough all the winter, but the eruption came out eight weeks ago. Twenty years before he had a slight attack of acute rheuma- tism, he was ill only a week ; five years ago he had an attack of gout, and for some winters past he had suffered from bronchitis. He had lately been badly off for food, but he had taken one to two pints of beer daily. He was a well-developed, poorly-nourished man ; the skin of his head, face, and forearms was intensely red, and covered with crusts ; he com- plained a great deal of burning and itching. T. 100° ; P. 96 ; R. 24. Tongue furred ; bowels confined. Heart sounds feeble, but no murmur ; pulse weak and compressible. Breath sounds feeble anteriorly ; posterior- ly, harsh and accompanied by moist rales. Urine 50 oz. ; sp. gr. 1026 ; contained a trace of albumen ; uratic deposit. After admission he made no improvement. COMPLICATIONS OF CHRONIC BRIGHT S DISEASE. 163 January 23rd. — T. 100° ; P. q6 ; R. 42. He had been delirious, getting out of bed and asking where he was ; urine 50 oz. ; sp. gr. 1022 ; urea 407 grains ; a thick cloud of albumen ; a trace of blood ; hyaline and granular casts. 27th. — T. io2'8° ; P. 102 ; R. 36. Still delirious and getting out of bed. 28th. — T. 101°; P. 108; R. 50. Quieter; towards evening increased difficulty of breathing. 29th. — Had passed a bad night with his breathing ; his respirations were sighing and laboured ; expiration was greatly prolonged. T. 102° ; P. 90 ; R. 34- 31st. -Pain, redness and swelling over right hip joint. T. ioo"5° ; P. 100 ; R. 48. February ist. — Breathing noisy from rhonchi ; hip very red and swollen. T. 102-5° ; P- 98 ; R- 46- 2nd. — Towards evening breathing very soft. T. 102°; P. 100; R. 52. Urine 28 oz. ; sp. gr. 1020 ; acid, straw colour, smoky ; white flocculent precipitate ; very thick cloud of albumen ; deposit contained cellular hyaline and epithelial casts, blood corpuscles and blood casts, and renal epithelium. 3rd. — Breath very short ; hip much inflamed. Death at 2.50 p.m. Autopsy, February 4th, 1888. — Absiract of notes : — There was a large abscess above the hip joint, connected with dead bone. The lungs showed chronic bronchitis and emphysema, with dilated bronchi. The pericard- ium was adherent, and the heart hypertrophied, weight 15 oz. The kid- neys were typical red granular atrophic kidneys, weight 8 oz. The arteries in the boundary zone were thickened and patent. There were numerous yellow spots in the cortex, which were composed of urate of soda. In the metatarso-phalangeal joints of both great toes there was chronic arthritis, with deposit of urate of soda in the fibrous tissues. Pneumonia. — It is very common to find contracting kid- neys in the bodies of persons dying of acute lobar pneumonia ; eighteen out of a hundred cases of chronic Bright's disease collected for statistical purposes had this association. No doubt the presence of such a condition is a most unfavourable element in the prognosis of acute pneumonia. Lobular pneu- monia may occur in connection with bronchitis, and hypostatic pneumonia may supervene in the later stages of slowly dying cases. Case 27*. Bronchiiis; chronic lithcBinic nephritis j lobular pneumonia. Death. Autopsy. J. J , male, sixty-seven, chaff-cutter, admitted September 20th, 1886, with cough and shortness of breath. Family history unimportant. Had rheumatic fever twenty-four years ago, and has since suffered frequently from rheumatism, colds and cough. Admits that he has not been always temperate, and has frequently been insufficiently fed. Three weeks ago he caught cold, but getting worse, and a sharp pain attacking his left side, he came to the Hospital. * Recorded by Dr. Lewis Hawkes, Acting House Physician. 1 64 BRIGHT S DISEASE. A decrepit old man, lame from rheumatic stiffness of the hip; face pale; conjunctivee jaundiced ; respiration laboured. T. ioo°. Lips blue ; no teeth ; tongue pale, moist, furred at sides ; appetite bad ; constant thirst ; throat dry and parched. Has pain after food ; eructations of wind ; water brash ; bowels confined. Liver projects an inch below ribs. Inguinal hernia on right side. Heart sounds reduplicated in pulmonary and tri- cuspid areas ; apex beat not to be felt, but dulness does not extend outside nipple line. Sputa frothy ; cough troublesome ; respirations 30 ; breath- ing harsh, expiration prolonged, accompanied by musical rhonchi all over chest. Gets up several times at night to make water. Urine 20 oz. ; acid ; sp. gr. 1015 ; deep amber, smoky ; white flocculent precipitate ; faint cloud of albumen ; blood present ; no sugar ; under microscope hyaline casts, a few red blood corpuscles and leucocytes, free renal epithelium, spheroidal and polymorphous epithelium from urinary tract, squamous epithelium, spermatozoa, and uric acid. Progress of Case. — The cyanosis increased ; he was troubled at night with asthma-like attacks of dyspnoea. By the end of September he began to be drowsy. His temperature varied, but never exceeded 101°. His bowels were opened regularly, and were rather loose. The urine was usually scanty, about 20 oz. in twenty-four hours. The drowsiness in- creased, and he died comatose on October 6th. Autopsy, October 7th. — Heart 14 oz. ; right side full of clots ; left ventricle empty, contracted ; valves thickened, but competent ; lelt vent- ricle hypertrophied ; heart's muscle generally pale, soft, and friable. Lungs. — Turbid yellow serum in pleural cavities ; right, 300 ccs., left, 100 ccs. Right lung adherent to diaphragm. Both lungs emphysematous in front, oedematous, congested, and in parts collapsed posteriorly. Scat- tered through the left hmg were patches as large as a bean, some fresh and vascular, others pale greyish and gelatinous-looking, trabeculated and puriform in the centre, which under the microscope showed pulmonary alveoli filled with fibrin, round cells and desquamated epithelium. In both lungs there was generalised bronchitis, with dilatation of the larger bronchi and peribronchial thickening. Liver 42 oz. ; capsule thickened and adherent to diaphragm. On sec- tion, congested, soft and friable. Spleen 3^ oz. ; capsule thickened. Kidneys '&\ oz. ; both kidneys atrophied ; capsules adherent ; surfaces granular. On section, cortex diminished, of a brown red colour, dotted with grey and yellow points ; medullary portions of a darker hue. The Alimentary System, — Catarrh of the stomach is a very common complication. It is generally not very intense, giving rise to flatulence, weight after food, and attended by morning sickness or nausea. There is often some chronic pharyngeal catarrh associated with it. The bowels are gen- erally confiiied, and the action of the liver sluggish. Sometimes constipation alternates with attacks of diarrhcea due to intes- tinal catarrh. Biernocki has found that there is generally diminished gastric secretion, free hydrochloric acid is scanty or absent, pepsine too may be absent, but the motor activity of the stomach is increased. HcEmatemesis and hczmon^liage COMPLICATIONS OF CHRONIC BRIGHT S DISEASE. 165 from the bowel occur occasionally. HccrnorrJioids are not un- common. The liver is generally diseased, most commonly fatty, often more or less cirrhosed or congested, or shows signs of lardaceous degeneration ; in some cases the liver has under- gone simple atrophy. Hanot has described a hypertrophic condition which he calls the uraemic liver and attributes to the nephritic dyscrasia. BIBLIOGRAPHY. Bartels (C). Op. cit., p. 490. BiERNocKi (E.). Ueber das Verhalten der Magenverdauung bei Nieren entziindung. " Berl. klin. Woch.," 1891, No. 25. BoiNET. De I'hemiplegie uremique. " Revue de Med.," 1892, p. 1008. Brieger. "Charite-annalen." Bd. VII. Brissaud and Larring. Attitudes cataleptiques chez un brightique delirant. "Gaz. Hebd.," 1890, Nos. 31 and 32. Brush (L. A.). A case of Cheyne-Stokes breathing persisting for three weeks. "Med. News," 1890, p. 592. Carr (W.). a case of high temperature in ursemic convulsions. "The Lancet," 1890, I. p. 133. Charcot (J. M.). Op. cit., p. 316. Debove. "Bulletin de la Soc. Med. des Hopitaux de Paris." Feb. 27, 1880. DiEULAFOY. "Union Medicale," Aug. 6, 1882; and "France Medicale," 1877, No. 16. Down (N.). A case of urjemia with Cheyne-Stokes respiration lasting six days and terminating in recovery. " Med. News," 1890, p. 589. bowNiE (J. W.). Deafness in Bright's disease. "Glas. Med. Journ.," Vol. XXIV., 1885, p. 410. EiCHHORST. Handbuch der speciellen Pathologic und Therapie. 1884, Bd. II. Gibson (G. A.). A Classical Remedy. " Edin. Med. Jour.," Vol. XXXI.. 1886, p. 912. GiLLET (H.). Uremic febrile. "Rev. de Med.," 1892, p. 163. Haxot (V.). Gros foie dans la maladie de Bright. "Arch. Gen. de Med.," Dec. 1888. Haslund. Quoted by Berger, — Troubles intellectuels dans le cours de la Nephrite chronique. " .A.rch. Gen. de Med.," 1880, II., p. 738. HuTiNEL. Les Temperatures basses centrales. These de Paris, 1880. Jaccoud. "CUnique de la Charite," 1874, p. 499. Knaggs (L.). Two cases of Cheyne-Stokes breathing in Bright's disease. "The Lancet," 1890, I., p. 744. Lancaster (Le C). On eight cases of Uraemic eruption of the Skin. "Clin. Trans.," Vol. XXV., p. 49. Lecorche and Talamon. Etudes medicales, p. 172. Lepine (R.). Ibid., 1889, p. 514. Pye-Smith (P. H.). Affections of the Skin occurring in the course of Bright's disease. "Brit. Journ. of Dermat.," No 83, Vol. VII. Raymond (F.). Relations de I'albuminurie avec les psychoses. "Gaz. Med. de Paris," 1890, Nos. 25 and 26. Richardiere and Therese. L'hyperthermie dans I'uremie. " Revue de Med.," 1891, p. 991. i66 BRIGHTS DISEASE. RosENSTEiN. Op. cit. 3rd. edition, p. 241, et seq. Tenneson and Chantemesse. "Bull, de la Soc. des Hopitaux de Paris," 1869, p. 50. Tuttle. Kidney disease and Insanity. "Amer. Journ. of Insanity," April, 1892. Von Jaeckel. Beitrage zum Symptomencomplex der Uramie. "Inaug. Diss.," Berlin, 1884. West (S.). On the occurrence of Blood in the Urine in granular Kidney. "The Lancet," 1885, II., p. 104. Cheyne-Stokes breathing in granular Kidney lasting three months. Ibid., 1890, I., p. 545. i67 Chapter XIV. THE TREATMENT OF BRIGHT'S DISEASE. Successful treatment depends in the first place upon a cor- rect knowledge of the principles of diagnosis and prognosis which have been laid down. We are all liable to try to do too much in the way of treatment. This arises from our ignorance of the exact nature and probable course of diseases, and our consequent uncertainty as to their result. Our pathological conception of Bright's disease having undergone some modi- fication during the last twenty years, it follows that our treat- ment, so far as that was based on theoretical considerations should be changed also. If we would understand rightly the path by which we have reached our present stand-point, we must remember that at and for many years after Bright's time, albuminuria was held to be synonymous with a grave alteration in the kidneys. It is only within the last twenty years that it has been reduced to its proper position as one of the symptoms of Bright's disease, but which may occur when no such changes exist in the kidney, and that its amount is neither directly nor indirectly a measure of those changes or of the condition of the patient. Moreover, we no longer dread the drain of albumen from the system ; we know that the loss rarely exceeds halt an ounce of dry ^S}owvac.x\ per diem and that there are on record many cases in which albuminuria has lasted twenty years or more without appreciably impairing the patient's health. We have realised that kidneys which have been damaged by inflammation, permit the passage of albumen for a long time after the inflammatory process has ceased to be active, and we no longer look upon albuminuria as an inflammatory exudate, but as evidence of an alteration, transient, persistent, or even permanent in the walls of the renal vessels. We recognise that acute Bright's disease in previously healthy persons, is a highly curable disease and that there are forms of chronic Bright's disease, such as those occurring after repeated pregnancies, in which a cure may be hoped for if a recurrence of the cause can be avoided. We reserve our grave prognosis for two classes of 1 68 BRIGHT S DISEASE. cases, (i,) those in which the amount of disease present is excessive, and (2,) those in which we are unable to remove the persistent and efficient cause. We judge of the amount of renal disease, not by the quantity of albumen in the urine, or even by the tube casts, but by the evidence of cardio-vascular and retinal change, and by the general constitutional state. The most persistent cause is the lithaemic or gouty dyscrasia, which we are, unhappily, too often unable to remove. These cases are grave, and are liable to numerous serious and often fatal accidents, yet they often last a long time under judicious management. « What are the conditions under which the patient should be sent to bed? — Whenever there is dropsy or the urine diminishes, or the albumen is greatly increased, or any inflammatory complication comes on, or there is marked dyspnoea, or any sign of uraemia, it is prudent to send the patient to bed, as it is better to err by being a little over-careful. The treatment of symptoms should not be undertaken too vigorously. Minor ones that are not causing distress are often best let alone, unless they are regarded as danger signals, when a few days' rest in bed on simple diet and treatment will afford oportunity for judging of their value and of what is needed to be done. We should recognise the incurable nature of certain symptoms and avoid treating them. Of two reme- dies or methods of treatment we should choose that which is the less debilitating. If a patient suffering from chronic Bright's disease is in fair general health, and the discovery of the lesion has been made more or less by accident, we should be careful to do nothing that will worsen his condition either by over vigorous treat- ment or too severe regimen, but should be content to relieve the symptoms of which he complains, if it is in our power to do so, while at the same time we endeavour to regulate his habits and mode of life in conformity with principles deduced from our knowledge of the etiology and pathology of his disease, and confirmed by clinical experience. Climate and Hygiene. — It is seldom that our patients have it in their power to choose their residence in strict con- formity with medical advice, but where it is possible they should seek a dry warm climate for the winter. Algiers is uncertain, as the weather is liable to sudden changes from an English summer climate to deluges of rain with cold wind. Egypt is often bitterly cold, but is dry. The uplands of THE TREATMENT OF BRIGHT S DISEASE. 169 South Africa are a long way off, but as our winter is their summer they afford the invalid who is in fair health and can make the change, the opportunity of enjoying two summers, while residence there all the year round fulfils the required climatic conditions. If the patient stay at home, his house should be on a dry soil, and sheltered from the north and north-east winds. Our south coast health resorts, St. Leonards, Ventnor, Bournemouth and Torquay, do not fulfil all the requirements of climate, but offer during the winter, shelter, a comparatively mild climate and a moderate rainfall. During the summer months Europe is less difficult, and a visit to the Black Forest, the Engadine, or to Braemar or Buxton, is greatly calculated to improve the general health, and should be undertaken especially by those unable to get away in the winter. Clothing. — The patient should wear woollen clothing by day and by night, summer and winter, and in all climates. The adoption of the so-called " Jaeger system " is perhaps the very best thing these patients can do. Baths and Bathing. — The use of the hot air or vapour hath in their own rooms once a week is better than taking a Turkish bath away from home. After the bath the patient should be well rubbed down and then go to bed. The duration of the bath should not exceed twenty minutes. The skin may not act well the first few times, but will gradually acquire activity. If the duration of the bath is prolonged it may cause faintness. Cold bathing or sponging should be avoided, but tepid sponging every morning may be allowed. Exercise. — Daily exercise should be encouraged, but violent exercise, such as running or anything approaching fatigue, is to be avoided, having in view the state of the heart and vascular system. Diet. — The proper diet for acute Bright's disease is milk, with the addition of a certain amount of farinaceous matter to supply the alkalies so necessary to the body ; the quantity of milk should not exceed three pints daily. This is the diet which we should always be prepared to fall back upon, in all serious complications, but valuable as it is in its proper place it is not a good or useful regimen when the patient can with satisfaction and safety take a more varied, and therefore more agreeable, less bulky, and more sustaining diet. As the acute stage passes off, vegetables and fruits, eggs and I70 BRIGHT' S DISEASE. light meats, should be gradually introduced, and when the disease is chronic the only general restriction to be laid down is : eat sparingly of butcJiej^'s meat, and avoid spirits, malt liquoj's, and strong wines. The safest drinks are the light Moselle, Rhine, or Bordeaux wines neutralised by the addition of an alkaline mineral water. Ordinary drinking water generally contains a considerable quantity of sulphate of lime, at any rate in this district, and I am convinced is very hurtful. The mineral waters may be the distilled table waters, or Contrexeville, or Vichy water. If the ordinary water supply is very hard, distilled water or filtered rain-water should be used for making tea, coffee, etc. Beef tea and soups of all kinds should be interdicted ; the former has a chemical composition closely resembling that of urine (Masterman), and all soups partake more or less of this character, unless they are made without any stock, as some German soups are made, but these are hardly understood by the British cook. By every means endeavour to keep up the patient's general health and nutrition, and set aside any of the above injunc- tions which interfere with these all-important considerations. Drugs. — In the absence of any specific remedy I generally order : — 9 Ferri Sulph. gr. iij Magn. Sulph. gr. xl Ac. Sulph. dil. niiij Aq. Mentha pip. oj Sig. To be taken three tunes a day. Sig. Albuminuria. — In the last edition of his Urinary and Renal Diseases, Roberts repeats the question : " Are there any medicinal substances capable of exercising control over the quantity of albumen lost by the urine ? " and he answers it as before, by saying : " Exact observations do not give an affirm- ative answer to this question." ?i Tr. Digitahs Pot. lodidi Sp. Amnion. Aromat. Aq. ad ITlX gr. V mxv §j To be taken three times a day, with the use at bed time of the following pill ; occasional i}; Euonymin Ext. Aloes Ext. BelladonnEe gr- J gr. ij gr- i THE TREATMENT OF BRIGHT S DISEASE. 171 Rosenstein deals with this question at length, and mentions a number of drugs tested by his assistant, Dr. Kooi and him- self. He gives his opinion in the following terms : " The physician must be impressed with the idea that we possess no drug which can in any sense act upon the local disorder so as to diminish decidedly the excretion of albumen." The action of drugs on diseased processes in the human organism is always an obscure and difficult problem, on account of the large number and inconstancy of the factors that enter into it. An exact observation demands identity of all conditions except the one to be tested, namely, the drug employed ; but that is impossible, for no two cases are identi- cal, nor is the same patient this week in identically the same circumstances as he was a week ago, or will be a week hence; so we must always allow an element of uncertainty in our most carefully devised experiments with drugs in disease, and our conclusions must be based rather on wide experience than upon the minute observation of particular cases. Nevertheless, I have endeavoured to combine these two methods ; I have made observations upon many cases, and have sought in the practice of my colleagues to learn the results of their treatment, so that by comparison I might eliminate the " personal equation " from my conclusions. It is obviously essential to the proper treatment of this question that we should understand the natural course of the disease or symptom which we seek to influence with drugs. It is to my mind beyond question, and if necessary, I could quote cases to prove it, that in acute Bright's disease and even in subacute Bright's disease, the albumen may diminish and disappear without the use of any drugs whatever. Moreover, cases of chronic Bright's disease are liable to intercurrent acute exacerbations of greater or less intensity, which may clear up just like an acute attack in healthy organs, the subsidence being accompanied by a more or less rapid and considerable reduction in the amount of albumen excreted. Finally, cases of persistent albuminuria present fluctuations in amount which depend upon causes that escape our present powers of observation. Besides distinguishing between these phases of disease and allowing as best we can for these fluctuations, we have to bear in mind that the amount of albumen is influenced by diet, increased by exercise, and diminished by the recumbent position. 172 BRIGHT S DISEASE. Patients with Bright's disease are frequently also the sub- jects of other accidental or secondary organic diseases, such as heart, lung, or liver affections, which probably play some part in the production of albuminuria, and interfere with the action of the drugs we employ, or give rise to fluctuations which depend upon changes originating in altered states of those organs. A more obvious source of fallacy, but one which is certainly apt to be overlooked in private practice is, that the amount of albumen excreted does not always hold the same relation to the quantity of water, so that diuresis, either spontaneous or the effect of drugs, often produces an apparent improvement in the albuminuria, though, in fact, it may remain the same, or be actually increased in amount. Another and less excusable error may arise from comparing samples of urine passed at different periods of the day, as it is well known that the albu- men varies very much, being generally most in the forenoon, other conditions being equal. No comparison should be made for the purposes of exact observation, except between samples of the whole twenty-four hours' urine collected and mixed together. I carefully endeavoured to meet all the difficulties I have enumerated, and to eliminate these sources of fallacy. The quantity of albumen was estimated by Esbach's tubes, generally by myself, always under my supervision ; and I would bear testimony to the constancy of the results obtained by this method, which also gives approximately correct quan- titative results. Before Esbach's tubes were introduced 1 used test-tubes marked with a scratch, and measured by means of a scale, which afforded a rough means of estimating the amount of albumen. Perhaps no cases afford a better opportunity for testing the influence of drugs than those of " functional albuminuria," where the albumen is persistent, and is unaccompanied by any other evidence of disease. Many of my patients, otherwise apparently healthy, have been applicants for Life Insurance, and both they and I have been anxious to remove what appeared to be the only obstacle to their acceptance. Yet I must admit that I have never been able to cure one of these insurance cases. After a few months of non-success, they have passed from under my observation, and I cannot now tell what has become of them. Even those cases of " functional albuminuria " which I have seen ultimately cured THE TREATMENT OF BRIGHTS DISEASE. 173 by time, have not appeared to me to owe this result in any instance to the direct action of drugs. Having made this general statement, I will submit my con- clusions as to the actions of particular drugs a little more in detail. Alkalies. — I have used alkalies in the form of diluents ; for example, a quart of bitartrate of potash imperial (sss to Oj) daily, or a bottle of Vichy water (Celestins or Haute Rive) ; and in a series of chronic cases, with persistent and copious albuminuria, the results were distinctly favourable. In addi- tion to these diluents, I have employed citrate of lithia, bicar- bonate of potash, and benzoate and bicarbonate of soda, and I include them in this favourable opinion. This effect was not due to the formation of alkali albumen, as Esbach's fluid precipitates this. In the following five chronic cases, the average total amount of albumen passed on the first and last two days of the experiment are given. Name. First Two Days. Last Two Days. B 38 grs. 21 grs. R 38 grs. 13 grs. J 123 grs. 64 grs. McD 52 grs. 48 grs. St 16 grs. 21 grs. Tamzate of Soda. — I found the drug supplied under this name so nauseous that I have used in its stead the following formula. I^ Acidi tannici, sodse bicarb., aa gr. x ; glycerini lUxv ; aq. 5J. M. t. d. s. I can report in relatively favourable terms of it. For example : Name. First Two Days. Last Two Days. M 198 grs. 150 grs. J 165 grs. 96 grs. These were both chronic cases. In an acute case I got good results, but the influence of the drug was very doubtful here. Name. First Two Days. Last Two Days. Be 22 grs. II grs. Nitro-glyceri7te. — I have seen cases do remarkably well under the use of this drug ; but I am not able to confirm this by exact observation, except in acute cases. Name. First Two Days. Last Two Days. Be 26 grs. lo grs. In a chronic case I found : Name. First Two Days. Last Two Days. McD 40 grs. 43 grs. 174 BRIGHTS DISEASE. Fuchsin. — Under the most favourable circumstances I have been unable to observe results which bear out the reputation this drug has acquired. Name. First Two Days. Last Two Days, McD 34 grs. 65 grs. St 66 grs. 74 grs. I have used it in a very large number of cases, and I have never seen any good effected by it. Digitalis appears to increase the amount of albumen, and this holds good of other heart-tonics, for example, caffeine., strophanthtis, 3.nd. sulphate of sparteine. Iron, including the acetate, sulphate, and perchloride, has the same effect of in- creasing the albumen. Teipine., in ten-grain doses, three times daily, in one case increased, in another did not diminish the albumen. Apocynmn increased the albumen in two cases, and diminished it in one. I was not able to observe the remarkable diuretic effect of this drug (used as the tincture in drachm doses) which is claimed for it across the Atlantic. I have used turpentine in several cases, without being convinced of any beneficial result, though haematuria has followed the employ- ment of even minute doses (one minim). The bichloride of mercury, recommended by Millard, of New York, and in use by the homoeopaths, has had a fair trial in the suggested doses (gr. loVo), but has entirely failed. Purgatives and diaphoretics, though of great value in its treatment, do not appear directly to influence the amount of albumen excreted in chronic Bright's disease. The following is a list of drugs whose action on albuminuria was tested in these experiments. Bitartrate of potash, bicar- bonate of potash, citrate of lithia, carbonate of lithia, bicarbon- ate of soda, benzoate of soda, tannate of soda, tannic acid, digitalis, scoparium, sulphate of sparteine, strophanthus, pilocarpine. Trousseau's diuretic wine, caffeine, apocynum, cannabinon, ergot, turpentine, terpine, copaiba, oil of sandal- wood, fuchsin, anti-hydropin (pulvis blattae orientalis), cantha- rides, iodide of potassium, chloral, spirits of nitrous ether, perchloride of iron, sulphate of iron, acetate of iron, acetate of lead, tartrate of antimony, sulphate of alum, bichloride of mercury, elaterium, jalap, scammony, guaiacum, and sulphur. Hceviaturia.- — Slight haemorrhage from the kidneys is not of much importance ; in acute congestion it probably does good, at any rate I believe I have noticed that acute cases in which some moderate haematuria has been very persistent have THE TREATMENT OF BRIGHT S DISEASE. 175 eventually done very well, but when treatment is desirable a sinapism may be applied to the loins, or the same region may be dry-cupped. Heemostatic drugs are not very efficient. In urgent cases 2 or 3 grains of crgotin may be injected subcutaneously ; or half- drachm doses of liquid extract of ergot given by the mouth, hourly if necessary, as in those cases of profuse haematuria which sometimes occur. Other remedies are acetate of lead, I to 3 grains every four hours; tincture of hamainelis, 15 to 20 minims every two to four hours; gallic acid, 10 grains every four hours. Dropsy. — The knowledge we possess of the pathology of dropsy enables us at least- to see what are the desirable points towards which to direct our treatment. In the dropsy of acute nephritis and its consequences we should endeavour to keep the quantity of fluid swallowed within moderate limits, and to promote its evacuation by the bowels by the use of purgatives causing watery stools, of which one of the best is bitartrate of potash. This may be given as an electuary composed of one part of the salt to two parts of honey or syrup, a tea-spoonful for a dose, repeated until the desired effect is produced. Although an acid salt, it does not diminish the alkalinity of the blood serum, which would be very un- desirable ; and we may endeavour to maintain this by giving farinaceous food, with Vichy water and lemon juice as a drink. Compound jalap, or compound scammony powder, or the resin of scammony may be used, but very drastic purgatives, such as elaterium, are not desirable. Hot-air baths should be employed daily, or pilocarpine, gr. J, may be injected hypodermically, but in some individuals it causes intense salivation and little or no diaphoresis. There need be no hurry to employ drainage, unless urgent symptoms arise ; if there be much fluid in the serous sacs this can be drawn off by a fine needle with tubing attached, but the cellular tissue is legs easy to drain ; cellulitis is sometimes set up by the attempt, and I have seen the effusion apparently poured out as fast as it was drawn off by the small trochars of Southey, so that although there was a considerable amount of fluid withdrawn the oedema did not lessen. If it has to be done, these small trochars with tubing attached are to be pre- ferred to incisions, however small. In obstinate dropsy of the lower extremities I have observed the very best effects follow elevating the limbs, rubbing them towards the body so as to get 176 BRIGHT' S DISEASE. as much fluid as possible out of them, and then enveloping them in flannel bandages from the toes to the upper part of the thighs. QLdenia of the prepuce and scrotum may be relieved by several punctures with a darning needle ; the parts afterwards being wrapped in absorbent cotton wool. Gidenia of the glottis is treated by ice to swok., puncture, and, in the last resort, tracJieotoniy. It is possible that intubation of the larynx might be effectual in relieving this symptom. The action of the kidneys should be promoted by hot poul- tices to the loins, by diuretics, such as acetate of potash, squill, caffeine, digitalis, triticum repens, broom-tops, Trousseau's diuretic wine, etc., but diuretics are very uncertain remedies. In the dropsy of chronic lithsemic nephritis we have to deal with z. failing heart, and our chief reliance must be upon drugs that increase its energy. Digitalis takes the first rank; if there is aortic regurgitation convallaria, in 1 5 minim doses of the tincture, is a good drug; either may be combined with 5 grains of citrate of caffeine, 10 grains of sodium salicylate, i minim of nitro-glycerine solution (i per cent), and an ounce of infusion of broom-tops. If there is peritoneal effusion this may be removed by tapping. Pleural effusions should not be rashly interfered with, especially if there is reason to believe they are not recent. These cases are eminently unsuited for purging ; it is suffi- cient to keep the bowels open ; for it must be remembered that when dropsy sets in from heart failure, the end is very near, and may be more easily precipitated than averted. Urceniia. — Headache and giddiness are relieved best by citrate of caffeine, i to 5 grains, or nitro-glycerine, i to 2 minims of the i per cent, solution in a little water. To ward off urzemic attacks, sodium benzoate may be given. Thomson reports favourably of benzoic acid. All the minor phenomena of uraemia — blindness, deafness, cramps, formication, numbness and palpitation, should be treated by a svciB-xt purgative and the hot air bath, or the injection of 12-th of a grain oi pilocaj^pine under the skin. Palpitation ma.y be relieved by nitro-glycerine. Convulsions, if soon over, scarcely call for treatment ; they may be stopped by chlorofoi'm inhalation, or by chloral (gr. xx) injected into the rectum, and small doses (gr. v to x) of the same drug may be given every three or four hours to prevent their return ; the skin should be got to act by the Jiot air bath ox pilocarpine, and the bowels freely moved. THE TREATMENT OF BRIGHT S DISEASE. 177 In obstinate convulsions, 12 to 16 ounces of blood may be taken from the arm. Hemiplegia and coma call for bleeding to the like amount, but the hot air bath recovered one patient from coma after the attempt to bleed had failed. It has been suggested to treat uraemia by dilution of the blood, as has been practised in diabetic coma, and a case has been quoted in which temporary improvement followed the adoption of this plan. Vomiting and diarrhoea are natural efforts at elimination which should not be too quickly checked. Urcemic asthma is not at all amenable to treatment. Carter, of Liverpool, recommends drachm doses of ozonic etJier in liq. ammoniae acetatis, but it has not proved of any service in my hands. Inhalations of oxygen have been recommended, but are not very successful. The ordinary treatment for uraemia may be tried. Nit7'0-glycerine or niti'ite of amy I affords some relief Ethyl-nitrite may be tried in half-drachm doses of a 3 per cent, solution (LEECH). Roosevelt has recommended cob alto -nitrite of potassium in half-grain doses every two to four hours. Stephen Mackenzie has advocated the plan origin- ally suggested by Loomis of injecting morphine hypodermic- ally, and W. Carter has added the indication to choose for this treatment those cases in which the pupils are dilated. Epistaxis and other external haemorrhages are best treg-ted by ergotin, two to three grains, injected under the skin, or eigot may be given by the mouth. An ice-bag may be applied locally. Inflammatory Complications. — Pneumonia, pleurisy, pei'icar- ditis and peritonitis, are of most unfavourable prognosis. Very active treatment is hardly judicious. Poultices or hot fomentations should be applied locally, and the case managed on general conservative principles. Gastric Catarrh. — This symptom is often very troublesome. Fats, raw vegetables and uncooked fruits should be eliminated from the diet ; a tea-spoonful of Pulv. Sodii Sulph. Effervesc. {B.P.) dissolved in half a tumbler of warm water should be sipped each morning before breakfast, and the following powder given in a little milk shortly before each meal : — Bismuthi Carb. gr- X Sodii Bicarb. gr. X Pulv. Rhei gi'- ij Pulv. Cinnamoni Co. gr- V Fiai pulvis. 12 178 BRIGHT' S DISEASE. BIBLIOGRAPHY. Bartels (C). Op. cit., p. 490. Carter (W.). Clinical Reports on Renal and Urinary Diseases. London, 1878, pp. 149, 150. Morphine in Uraemia. "Brit. Med. Journ.," 1889, I., p. 943- Leech (D. J.). Nitrite of Ethyl. "Med. Chronicle," Vol. IX., 1888, p. 177. Mackenzie (S.). On the treatment of certain cases of Chronic Uiasmia by Morphine. " Brit. Med. Journ.," 1889, Vol. I., p. 837. Millard (H. B.). A Treatise on Bright's disease of the Kidneys. Second edition. New York, 1886, p. 229. Roberts (W.). Op. cit., Fourth edition, p. 491. Roosevelt. On Cobalto-Nitrite of Potassium. " New York Med. Journ.," Aug. 25th, 1888. Quoted in "The Practitioner," Vol. XLl., p. 457. RosENSTEiN (S.). op. cit. Third edition, p. 345. Stewart (T. Grainger). On the Treatment of Bright's disease. " The Lancet," 1893, Vol. I., p. 99. Thomson (R. Stevenson). Op. cit., p. iS. 179 Section II.— THE URINE. Chapter XV. CLINICAL EXAMINATION OF THE URINE. INSPECTION of the urine is an ancient practice, which, for the most part, was until recent times a meaningless and perfunctory medical ceremony. Healthy urine is a clear, bright yellow fluid, having a not disagreeable but characteristic odour. It is liable to many alterations of quantity, physical properties, and chemical com- position ; so that in judging of a given specimen it is neces- sary to pursue a methodical enquiry. The following table copied from Salkowski and Leube gives a summary of the substances met with in normal urine : — I. Organic. — (i,) Substances belonging to the fatty series : — Urea ; uric acid ; xanthein bodies ; kreatin and kreatinin ; oxalic acid ; oxaluric acid ; volatile fatty acids ; glycerin- phosphoric acid ; sulphocyanic acid ; lactic acid. (2,) Substances belonging to the aromatic series : — Hippuric acid and benzoic acid ; sulpho-carbolic acid ; cresolsulphuric acid ; sulpho-pyrocatechuic acid ; paraoxyphenylacetic acid ; parahydrocumaric acid ; sulphindigotic acid ; skatoxyl-sul- phuric acid; cyanuric acid. (3,) Substances which apparently belong to neither : — Urobilin ; sulphur compounds ; pepsin ; left rotatory sub- stances ; cryptophanic acid ; extractives. II. Inorganic. — Sulphuric acid ; hydrochloric acid ; phos- phoric acid ; sodium ; potassium ; ammonium ; magnesium ; calcium ; iron ; nitric acid ; nitrous acid ; peroxide of hydro- gen ; gases. Physical Properties. Quaiitity. — The quantity of urine in health is usually from 40 to 50 ounces, but it may be occasionally as low as 25 or as high as 70 or 80 without indi- •cating disease. In females it is probably less than in males. i8o THE URINE, Yvon and Berlioz give as the mean of their observations 45 oz. (1360 CCS.) in males, and 36 oz. (iioo ccs.) in females, a proportion of five to four. Under pathological conditions the daily quantity may rise to 40 or 50 pints {polytiria) ; on the other hand it may be reduced to a few ounces {oliguria)^ or completely suppressed {anicrid). In all diseases of the heart or kidneys it is of especial importance to have the urine measured daily ; and in hospital practice it should be the rule to have the urine of all patients measured on admission, and from time to time during their stay. Urine-measures of white earthenware can now be procured which have a vertical scale on the inside. The whole of the urine for twenty-four hours is collected in one of these, and the amount read off from the scale. In this country we usually measure by fluid ounces ; on the continent they measure more accurately by cubic centi- metres, of which about thirty make a fluid ounce. Our method is not very exact, but it is not necessary to be so when the urine is fairly abundant; if it is scanty it can be measured more accurately in a glass graduated to cubic centi- metres. The daily amount of urine should find a place on the tem- perature chart, with the pulse, respirations, and movements of the bowels. Odour. — The odour of normal urine is peculiar ; it has been described as "fragrant" and "aromatic"; and no attempt will be made here to add to these definitions. Certain articles of diet, e.g., garlic and asparagus, communicate to it a very disagreeable smell of sulphides. Turpentine gives it the odour of violets, not only when taken internally, but when the vapour is inhaled, as in polishing furniture or as a medication for bronchitis. Copaiba and cubebs cause the urine to have a peculiar and quite characteristic odour. Fermentative decomposition inside or outside the body is usually alkaline ; by the decomposition of urea, ammonia is set free which has its own well-known smell. In diabetes the urine sometimes has a sweetish smell like hay. Urine con- taining decomposing blood or pus may have a positively putrid odour like decayed fish or flesh. Translucency. — Normal urine is clear and bright when freshly passed, but may become turbid from precipitation of urates, which are insoluble in excess, in the cold. On standing, it may become turbid from decomposition, permitting phos- phatic precipitation, or the growth of micro-organisms. CLINICAL EXAMINATION OF THE URINE. i8l Urine may be turbid when passed from the presence of phosphates ; such urine is alkahne, and if it is persistent the condition calls for treatment. Other causes of turbidity are the admixture of mucus, pus, or blood, decomposition in the bladder, and the presence of fat {cliyhirid). Colour. — The colour of normal urine may vary from the reddish yellow urine of digestion (^urina cibi), to the nearly colourless urine which follows free potations {uruia potus). The normal urinary pigments have not been completely de- termined, only two being known, a — urobilin, and /3— indican. Urobilin is formed indirectly from blood-colouring matter (haematin). The hepatic cells convert the haemoglobin first into haematin and then into bilirubin ; bilirubin is oxidised into urobilin and excreted by the kidney. Febrile urobilin is an imperfectly oxidised form met with in fevers and in cirrhosis of the liver. Variations in the yellow colour of urine are for the most part dependent on the proportion of urobilin present. Indican is the substance formerly called uroxanthin ; it gives the urine a deep yellow colour, but if it becomes oxidised in decomposing urine a film of bluish red crystals of indigo- blue is formed. It is a product of pancreatic digestion. Certain drugs taken internally give rise to alterations of colour ; e.g., rhubarb, deep yellow ; santonin, golden yellow ; cJirysopJianic acid, orange yellow ; senna, brownish ; logwood and fuchsin, reddish ; inetJiylejte-blue, blue ; carbolic acid, tar, and creasote, brown or black. Carbolic acid dressings produce the same effect, if the carbolic acid is in excess. Vogel describes black discolouration of the urine after poisoning by arseniuretted hydrogen. The urine may be coloured red by the admixture of blood, the tint being deep in proportion to the quantity present ; or brownish, r.inging from smoky to porter coloured, from the formation of methaemoglobin, if the urine has had time to act upon the blood. In jaundice, biliary colouring matter (bilirubin) is excreted by the kidneys, giving rise to various tints of saffron yellow, mahogany brown, or dark olive green. When jaundiced urine has been kept some days it may change to a grass green colour (biliverdin), from oxidation of the biliary pigment (Roberts). Pus and fat (chyluria) give the urine a cream colour, while 1 82 THE URINE. affecting its translucency. In diabetes the urine is of a pale greenish colour. In melansemia the urine is often daj-k brown. A blue colour on the surface is due to crystals of indican. Darkening of the urine may also be due to alkapton, pyro- catechin, protocatechuic acid, uroleucic, and uroxanthic acids. Density. — The density or specific gravity of normal urine is usually from i"Oi5 to i'025, but the clear limpid urina potus may be as low as i'005 or less in healthy persons, while urine concentrated owing to free action of the skin in warm weather may be i'028 or even i'030. The normal amount of solids in the urine is about 4 per cent, of which the chief components are urea and common salt ; but the proportion of solids to water varies greatly in health, and still more in disease. In a case of post-scarlatinal nephritis W. G. Smith has recorded a urinary density of i'o65 ; in diabetes mellitus it is generally over i "030, often over i'04o; in chronic Bright's disease it is usually under i'Oi5, while in contracting kidney and diabetes insipidus it is very little over I •000. The density is estimated by means of a urinometer^ an instrument too familiar to need special description. It is floated in the urine, and the density is read off upon a vertical scale. These instruments are not very accurately made ; it should repay some instrument maker to give special attention to their construction. The urine to be examined should be a sample of the whole mixed urine for twenty-four hours, a point very commonly neglected and not always attainable ; but it may be remem- bered that great variations occur in the urine in different periods of the twenty-four hours, so that too much importance must not be made of the result obtained from a stray sample, as in Life Insurance examinations. If there is too little urine to float the urinometer, the ex- amination may be postponed till it is completed on other points, and then one or more equal quantities of distilled water added till the instrument floats ; the last two figures of the result must be multiplied by the number of dilutions to give the true density. The following precautions in the use of the urinometer should be noted : — (i,) The glass must not be too narrow. There should be at least half an inch between the stem of the instrument and CLINICAL EXAMINATION OF THE URINE. 183 the side. The cylindrical glasses supplied with urinometers are frequently too narrow. (2,) The instrument must float freely. (3,) The surface of the urine should be free from froth ; bubbles may be removed by blotting paper. (4,) The instrument should be free from grease. Reaction. — Healthy urine is generally acid. This is due to the presence of acid phosphate of soda. When this salt is submitted to dialysis, a larger amount of phosphoric acid is found on the outside than on the inside of the dialyser, show- ing that the acid diffuses faster than the base ; this experiment may serve to explain how it is we get an acid secretion like urine from alkaline blood. When the urine is alkaline this salt is replaced by alkaline phosphate or by ammonia. The degree of acidity varies, being diminished partly by food, even so as to render it actually alkaline. This maximum effect is reached two or three hours after a meal ; but, as Roberts points out, no alkaline urine may be voided, because it is mixed in the bladder with acid urine secreted before the meal, or remains there until acid urine is again secreted in a quantity sufficient to modify the reaction. This alkalinity is due to the presence of fixed alkalies and alkaline earths ; on the other hand, the urine passed early in the morning, when many hours have elapsed since the last meal, is excessively acid, but prolonged fasting does not intensify this. Vegetable and mineral acids increase the acidity of the urine. In phosphaturia, where amorphous earthy phosphates are passed in alkaline urine, this condition can be speedily remedied by the use of nitro-hydrochloric acid ; but where the alkalinity is due to fermentative decomposition in the bladder, acids administered internally fail to correct it, probably because they can be given in such small quantities only. The urine is highly acid in gout and allied digestive disorders, in diabetes, acute rheumatism, and chronic Bright's disease. Alkaline substances readily make the urine alkaline, but the quantities must be large. Roberts says it requires three to four hundred grains of bicarbonate, acetate or citrate of potash, given in divided doses during twenty-four hours, to keep the urine of an adult steadily alkaline. Lithia is the most powerful base for producing alkalinity of the urine. 1 84 THE URINE. Prolonged immersion of the body in a cold bath is said to render the urine alkaline. The urine is frequently alkaline in debility and debilitating diseases, and in the peculiar form of atonic dyspepsia of nervous origin, in which earthy amorphous phosphates are excreted in large quantities. In all the above cases the urine is alkaline from salts of potash, soda, and the alkaline earths. Ammoniacal urine is due to decomposition of urea under the influence of a special ferment ; this takes place either in the bladder or in the vessel in which the urine is kept after it is voided. Where there is no suspicion of bladder disease the latter possibility should always be excluded by procuring a freshly passed specimen of the urine. The reaction of urine is estimated by litmus paper. This is generally sold in two colours, red and blue, but the latter is alone required, as it soon turns more or less red-violet, and is then most delicate. Acids turn litmus paper red, while alkalies turn it blue ; the red-violet paper indicates both these changes better than quite blue or quite red paper can do. Yellow turmeric paper is turned brown by alkalies, but it has no special advantage. Quantitative estimation of the acidity can be performed by means of a standard solution of caustic soda(i to lo of water) which is placed in a burette and allowed to run into a beaker containing lOO ccm. of urine, the reaction being tested from time to tim.e by litmus paper till the urine is neutralised. Multiply the number of milligrammes of fluid employed by 0*(X)63, the quantity of oxalic acid required to neutralise I ccm. of the standard solution, and the result gives the per- centage acidity (calculated as oxalic acid). For comparative purposes this is quite sufficient. Chemical Composition. Chlorides. — Common salt or sodium chloride (Na CI) forms about one fourth of the total solids of healthy urine, and gives the salt taste to this secre- tion. It is derived from the blood serum, in which it consti- tutes about 4 parts per looo, and ultimately of course from the food. It is increased in ague, in diabetes insipidus and in Bright' s disease. In Bright's disease complicating pneumonia this increase is not observed (Nauwerck). It is diminished in pneumonia, and in all febrile diseases, especially if accom- panied by an exudation ; also in chorea and pemphigus. In pneumonia a vicarious increase of chlorides is said to be found in the sputa (Thudichum). CLINICAL EXAMINATION OF THE URINE. 185 Chlorides are roughly estimated by precipitating the urine with a 10 per cent, solution of filtrate of silver, the resulting chloride of silver occupying in healthy urine nearly the whole column of fluid. In pneumonia there is scarcely any precipi- tate at all. The quantity of chlorides is not of much importance as a clinical sign, and this method is sufficient for ordinary pur- poses. If more accurate estimation is required the operation must be performed with a standard solution of silver. The urine having been previously acidulated with nitric acid is repeatedly precipitated and filtered till no further precipitate forms. In accurate experiments the ash from a given quantity of urine should be employed. The quantity of chlorides excreted daily is about ten to twelve grammes. Phosphates. — From thirty to ninety grains of phosphoric acid are daily eliminated by the kidneys. Acid phosphate of soda (NaHgPO^ + HgO) gives, as already stated, the acid reaction to urine ; a potash salt is also present in small quantity ; they are both soluble salts. Phosphoric acid is also combined with iivie and magnesia, forming salts which are soluble in acid urine, but precipitate out when it undergoes alkaline fermentation. When urine is boiled a milky cloud often forms which is dissolved on cooling, or on the addition of a drop or two of acid. This cloud is due to phosphates, and the change that takes place is explained thus by Walter G. Smith : — 2 (Ca2H2 PPs) + CaH, P.Og = Cag P2O8 + 2 (CaH^ P^g). soluble. soluble. insoluble. soluble. On cooling, this process would be inverted. Salkowski has pointed out that this chemical change may be imitated by a carefully prepared solution of acid calcium phosphate treated with ammonia till a precipitate forms, to which a few drops of acid phosphate are added and the liquid filtered ; this solution gives a cloud on boiling, which redis- solves on cooling or acidulation. This phosphatic cloud is generally met with in the urine of patients whose digestive powers are feeble or overtaxed, but it is not of serious importance. A peculiar greenish phosphatic deposit is described by Ehrlich in the urine of typhus, typhoid and measles, when treated with an acid solution of sulphanilinic acid, alkalinised l86 THE URINE. with ammonia, and allowed to stand for twenty-four hours. He regards it as characteristic of these diseases. When a solution of ferric chlorides is added to urine a brownish precipitate frequently forms, soluble in excess, due \.o phosphate op irojt. This reaction is employed for estimating the phosphoric acid in urine. An increase of the total phosphates has been observed in acute inflammatoiy diseases of nerve structures, and tem- porarily in acute febrile diseases (VOGEL, TEISSIER), occa- sionally in acute mania and brain tumours, also in chorea, acute yellow atrophy of the liver (BOUCHARD), diabetes (LecorchE), phthisis, chronic rheumatism, leucocythsemia and osteomalacia, and as a primary condition in certain cases of so-called phosphatic diabetes (Ralfe, Teissier). A diminution occurs in chronic brain disease, chronic disease of the heart or kidneys, in chlorosis, ague (Gee), rickets, and gout. The excretion of phosphoric acid is increased by lactic acid and carbonate of soda, diminished by morphia, chloral, ether, chloroform, bromide of potassium (SCHULTZE), and alcohol. Phosphates of the alkalies do not form urinary deposits, but earthy phosphates are met with as deposits in three forms : (i,) Ammonium magnesium phosphate, or triple phos- phate ; (2,) Crystalline phosphate of lime ; (3,) amorphous phosphate of lime. Annnonimn-magnesinvLpJiosphate or triple phosphate (MgNH^ PO4 + 6H2O) crystallises out in trian- gular prisms with bevelled ends {^Fig. 29) in urine which has undergone ammo- niacal decomposition, forming a white deposit at the bottom of the glass. It Fig. 29. -Crystals of triple may be met wlth in examining the phosphate. One prism is in- ^ , ._ . ,.,'-^. complete. mucous deposit 01 a urme which gives an acid reaction, decomposition commencing around the mucus. As a rule this deposit signifies only that the urine has decomposed in the vessel after leaving the body, but it may be met with in fresh urine which has undergone fermentation in the bladder, in cystitis, calculus, myelitis, etc. It is the special constituent of secondary calculous formations, on a nucleus of uric or oxalic acid ; or as an incrustation on the walls of a diseased bladder, etc. Crystallijie pJiosp]iate of lime. Acid phosphate of lime (CaH POJ occurs in feebly acid urine. It is met with in CLINICAL EXAMINATION OF THE URINE. 187 phthisis, cancer of the stomach and rheumatism, but it may be present in the urine of healthy persons. Its crystals take the form of rods, stars, rosettes, crosses and feathers {Fig. 30), hence the names of stellar or feathery phosphate. It is a somewhat rare deposit. Neutral phosphate of lime (Ca3(POJo) occurs in neutral or alkaline urine as ^.^ ,« „ ^ „■ ^ ^ ^ . Fig. SO.— Crystallina phosphate ot an iridescent film on the surface. It ^^d j/iihS?° "°^^' '■°°^"^' ""^ has no clinical significance. Amorphous phosphate of lime (3CaO PO-j commonly occurs in urine which is alkaline when passed. It makes the urine turbid and deposits as a copious white sediment, readily soluble in acids. Under the microscope it con- j^- sists of irregular granules and lumps {Fig. 31); '•j;;i-'' on standing, crystals of triple phosphate soon Fig. SL-Amor- form in it. phous phosphate •■ . .,.,,, o£ lime. It IS met With m healthy urme rendered alkaline by food, and in persons who are taking alkalies. As a persistent occurrence it i? specially associated with a form of atonic dyspepsia, first described by Prout, which is greatly benefited by a course of hydrochloric acid or nitro-hydrochloric acid taken regularly after meals. Carbonate of lime (CaCOg) occurs as an amorphous deposit with earthy phosphates ; its crystalline form is very rare. They are spherical bodies ^p ^^ composed of numerous radiating needles @ K^^g- 3^)- Fig. 3*2. — Crystalline Sulphuric acid occurs in very small quan- p^BEMsr'^phefS" titles in the urine combined with alkalies, as ^ra,£^g"odiet?^'^ sulpJiates, and with indol, skatol and pyrocatechin as aromatic ether-sulphuric compounds. Sulphuric acid is chiefly derived from the decomposition of proteids, hence its amount runs parallel with the amount of urea excreted (Landois). The test for it is a solution of barium chloride, which gives a copious precipitate of barium sulphate, insoluble in nitric acid ; Freund has suggested the addition of alizarin-sulphonate of soda to the urine which is then tritrated with baryta water, and the sulphates thrown down as a purple red precipitate ; by this means the amount can be estimated. Sulphur occurs also in cystin, in the sulpho-cyanogen com- pounds, etc. i88 THE URINE. Urea^CH^ N^O). This substance is present in the urine in a larger quantity than any other soHd. Its formation is a function of the Hver, and its principal source is the nitrogenous matter taken as food, but it is also formed from the destruc- tion of red blood corpuscles (in the liver) and other tissues, muscle albumen, etc. The formation of urea is increased by a close atmos- phere, such as a kitchen (Cook), by pepsin, maltin, common salt, phosphorus poisoning, arsenic, sulphuric acid, chlorate of potash, hot baths, by excess of nitrogenous food, by coffee, by drugs which stimulate the functions of the liver, e.g:, euonymin, corrosive sublimate, salicylic acid, benzoic acid, colchicum, by fever, by active congestion of the liver without destruction of its substance, by pernicious anaemia, malaria, etc. It is not increased by muscular exercise. Its elimination is proportional (ccBteris paribus) to the amount of urine excreted, so that copious drinking of water or any fluid, increases the elimination of urea ; it is also increased in diabetes mellitus and insipidus. Willis described and Prout believed in a pathological condition characterized by excess of urea excretion to which the name azoturia was given, but there is no such disease as an independent con- dition. The formjation of urea is diminished by fasting, by drugs which depress the function of the liver, e.g., lead, and by those diseases of the liver which depress its function or destroy its substance. Its elimination is checked by anything which diminishes the amount of urine, by profuse sweating, by diseases of the kidneys and urinary apparatus, by wasting diseases, acute gout, chronic rheumatism, lepra, pemphigus, melancholia, imbecility, catalepsy, hysteria, and cholera. It is supposed by some that the excretion of urea is diminished in a very early stage of contracting Bright's disease, before structural altera- tions have occurred in the kidney ; but this so-called renal inadequacy is quite fanciful. The daily quantity of urea varies at different ages ; according to Ralfe — At 5 years 180 grains. 12 „ 320 „ 21 „ 535 » 40 „ 555 » CLINICAL EXAMINATION OF THE URINE. 1S9 Camerer gives the proportion in children at 0"64 to ri2 grammes per kilogramme of body weight, while in adults the proportion is only 0'5 to 0'6 grammes per kilogramme. Women excrete absolutely less than men, but not relatively in proportion to their weight. The estimates for the inhabitants of different countries show variations, which are probably accounted for by differ- ences in diet : — Englishmen (Ralfe) - - - 555 grains. Bavarians (VoiT, Rubner) - 425 „ Frenchmen (YvoN, Berlioz) - 397 „ North Germans (Flugge) - - 352 „ One day's fasting is enough to reduce the urea excretion to two hundred and eighty-eight grains (Ranke), while after several days it falls to ninety grains (Schultzen). In acute Bright's disease, when the urine is greatly reduced, the elimination of urea is necessarily also diminished ; but the percentage of urea which should be high if there were merely a reduction of the urinary water, is low, generally below 2 per cent. In sub-acute Bright's disease, as the urine increases in quantity the percentage of urea tends to fall lower, averaging about one per cent. In the later stages the percentage of urea remains low while its total amount varies with the quantity of urine ; but as this is sometimes high it may reach a fair figure. On light diet, with chicken and fish, such patients may excrete from three hundred to four hundred grains of urea. In the lithsemic form the urine throughout the early and middle course of the disease is much increased in amount, except during the occurrence of an intercurrent attack of acute nephritis, to which these cases are no doubt very liable. In these early stages and even later, the amount of urea may be normal. W. S., aged twenty-three, was sent to me from the Eye Hospital with bilateral diffuse neuro-retinitis. He was ad- mitted on the 24th February, 1888, and on the 26th his urine was analysed ; it amounted to seventy-eight oz. in twenty-four hours, and contained 0'8 per cent, of urea, equivalent to two hundred and ninety grains in twenty-four hours. On chicken diet he passed three hundred and seventy grains. He died in ursemic coma on April 7th, and his kidneys were found to be in a condition of advanced contraction. This case supports igo THE URINE, the statements of Bartels, Grainger Stewart and others, that so long as there is polyuria, the elimination of urea may not be diminished. Detection of urea. — The presence of urea may best be demonstrated by adding strong nitric acid to a little of the concentrated urine or other fluid in a watch glass, when crystals of nitrate of urea will form, which can be recognised by the microscope {Fig. 33) ; any albumen must be first removed by boiling and filtration. Estimation of urea. — The most convenient method of estimating urea is by decomposing it with hypochlorite or hypobromite of sodium solution, the amount of urea being determined by measuring the volume of nitrogen evolved. This method is sufficiently accurate for clinical purposes. The cheapest and simplest form of apparatus is that invented by Professor Doremus, I-ig. as. — Crystals of nitrate of urea artifi- cially prepared by the addition of nitric acid to urine. Tig. 34. 01 New York, and sold by Messrs. Southall Brothers, Birmingham {Fig. 34). The solution is poured into a tube till it half fills the bulb, then some urine is drawn up into the pipette as high as the CLINICAL EXAMINATION OF THE URINE. 191 scratch, the beak of the pipette is carefully inserted into the curve of the tube, and the urine is made to flow by gentle pressure into the solution, the gas being given off and collected in the tube, where it is read off as a percentage. With a little care and practice there is very little loss, and the apparatus is most manageable and very inexpensive. An excellent ureometer is that known as Gerrard's, made by Messrs. Gibbs, Cuxson & Co., of Wednesbury (yFig. 35). The solution is put into the bottle, and twenty ccm. of urine* are placed in the little tube. The apparatus is filled with water, and the surfaces of the fluid in the graduated tube and in the funnel at the side are brought to the same level by sliding the funnel up or down. Then by partially inverting the bottle the solution in the tube is brought into contact with the urine, the gas is liberated, and the result can be read off as a percentage on the scale. The hypobromite solution is more energetic and rapid in its action than the hypochlorite. Its composition is one hundred parts of caustic soda, two hundred and fifty of water, and twenty-five of bromine. It will not keep well, and is better made fresh, but this is a very disagreeable process, and should be done out of doors, or in a stink-chamber. The hypochlorite solution is simply the liq. sodae chlorinatae of the U.S. Pharmacopoeia made by adding chloride of lime to a saturated solution of washing soda, and filtering or siphon- ing off the resulting solution. In estimating the amount of urea it is essential to take a sample of the whole of the urine for twenty-four hours, as great variations occur in the amount of urea passed under different conditions. Thus the urine after drinking fluids freely is copious and contains a small percentage of urea, while that passed during digestion is concentrated and contains a great quantity both relatively and absolutely. When great accuracy is desired the results should be cor- rected for temperature and pressure (NOEL Paton). Uric acid (CgH^N^Og) is normally present in urine as urate of soda, which is not decomposable by the acid phosphate of soda to which the urine owes its acid reaction. If any free acid is liberated the urates are decomposed, and uric acid crystals are thrown down. ** Albuminous urine must be acidulated, boiled and filtered to remove the albumen before it is used for this test. 192 THE URINE. It is originally formed by the splitting up of albumen, but how and where this process takes place is doubtful, though a good deal of evidence points to the spleen as the seat of the change. The normal daily amount excreted is seven to ten grains ; it is not increased by nitrogenous diet (Garrod). Cook found beef tea, Liebig's extract, pepsin, maltin, euonymin, and con- finement in a close atmosphere increase the amount of uric acid. It may be sometimes increased by excessive use of milk. The urine of newly born children contains much uric acid ; it is increased in febrile diseases, acute rheumatism, pneumonia, ague and malarial fevers, leucocythaemia, cirrhosis of the liver, and diabetes. It accumulates in the blood in gout (Garrod), and is ex- creted in greater quantity after an attack. Its excretion is increased by colchicum, corrosive sublimate and euonymin, diminished by salicylate of soda and benzoate of soda (Noel Paton). It is also diminished in anaemia, chlorosis and gout, and by copious draughts of water, large doses of quinine, caffein, iodide of potassium, common salt, carbonate of soda and lithia, sulphate of soda, oxygen inhalation and slight muscular exertion (LandoiS and Stirling). Crystals of uric acid form a deposit like cayenne pepper on the bottom or sides of the glass ; if larger, they may look like . crystals of brown sugar. They assume ^ U ^ m <^^ various forms, — lozenges, rhomboids, A ^ ^^ A^^ hexagons, stars, spikes, etc. {Fig. 36). /^ /} ^^ The w^^r^.i'/iTz'i? reaction is the ordinary (V\ ^V'-^^^^ chemical test ; a little of the suspected W .£Xl_? ^^"^ -1111 -1 1 r ^. matter is heated slowly with a drop 01 Fig. 36.— Crystalt ot uric acid m . . ■' , i • i i Tarious forms. nitHC acid on a porcelain dish, and allowed to cool ; a drop of dilute ammonia is then added, when a purple red colour due to murexide is developed if uric acid is present. Quantitative estimation may be performed by adding five ccm. of concentrated hydfochloric acid to a hundred ccm. of urine and allowing it to stand for forty-eight hours in the dark, when the uric acid deposits and may be dried and weighed. Haycraft has devised a method by precipitating the uric acid as a silver salt, and Arthaud and Butte employ one which depends upon the formation of an insoluble urate with copper salts. CLINICAL EXAMINATION OF THE URINE. 193 AmorpJious tirate of soda is normally present in urine, form- ing a reddish deposit in concentrated urine after it has cooled; it is also a common deposit in febrile diseases, and in cirrhosis and other affections of the liver. Under the microscope it appears as small irregular -.•v:v- granules {Fig. 37), while on the addition '■■''•^■•' of acetic acid uric acid crystallises out. According to Roberts it consists mainly of quadrurates which are readily decomposed by water, but this change is prevented b}^ the salts of the urine, especially by the sodium chloride and potassium phos- phate. Crystalline urates are rare. Crystalline urate of soda is sometimes deposited in the urine of children during Fuj. 38. -Hedgehog febrile attacks. It forms characteristic yellow cry stills ol urate ol,,, ,._,. . t->i tola. . hedgehog crystals {^r2g. 38). Roberts attri- butes the frequency of vesical calculi in children to this deposit. Urate of aiiniionia is met with in ammoniacal urine ; it has no clinical significance. It forms dark ^ yellow spheres and pale slender dumbells x^ !.© n ^ Hippuric acid (CnHnNOo) occurs to a small ^■'^ . . V 9 _ 9 ^i . ^ Fig. B9.-Urate of am- extent m human urme ; it is lormed when ™"^'^ i" -^^^^ yfHo-^ . ' spheres, palo dumbells, benzoic acid or .some nearly related chemical "°sses and rosettes. body is introduced into the alimentary canal ; and is also formed in the body from proteids (Landois and STIRLING). It crystallises in colourless four-sided prisms {Fig. 40). In the herbivora it appears to replace uric acid to a great extent in their normal urine. ikq. 4ii.-cryBtais of hip- Krcatimn (C.H-NoO) is derived from puvic acid from ihe urine of , . ,^ *.'."* ' the horse. musclc kreatm ; it is a normal constituent of urine. It may be detected by adding to the urine a few drops of a " slightly brownish " solution of nitro-prusside of sodium and weak caustic soda, when a Burgundy red colour is developed which soon fades. On heating with acetic acid the colour changes to green or blue. It is increased in fevers, pneumonia, etc., diminished in anaemia and wasting diseases ; it is not diminished by fasting. XantJiin (CgH4N^02) also occurs in normal urine in very small quantity. When evaporated with nitric acid it gives a 13 194 THE URINE. yellow stain which becomes yellowish red on adding potash, and red violet on heating. It sometimes forms calculi, which are of a deep yellow colour, smooth and spherical. Sarcin or Hypoxanthin (CgH^N^O) has been found only in the urine of leucocythaemia, though a body nearly related to it occurs in normal urine (Salkowski). When evaporated with nitric acid it gives a light yellow stain, which becomes deeper but not reddish on ?A6\n^caustic soda. Succinic acid (C^HgO J occurs chiefly after a diet of flesh and fat, after eating asparagus, and after drinking alcohol. Lactic acid (CgHgO^) is present in normal urine. Colasanti and Moscatelli found it present in large quantities in the urine of soldiers after a march, and they suggest that it is probably a product of muscular activity which passes into the urine. Oxaluric acid (CgH^N^OJ is present in traces in normal urine combined with ammonia. It is a derivative of uric acid, and on being heated splits up into urea and oxalic acid. Oxalic acid (CgH^OJ is a normal constituent of urine, and in combination with soda and potash remains in solution. It is mainly derived from food, e.g., tea, rhubarb, etc., but may be formed by the oxidation of uric acid into oxaluric acid (CgH^NgO^), which splits up into oxalic acid and urea. Oxalate of lime (C2Ca04+2H20). Crystals of oxalate of lime can always be found among amorphous urates, if the urine has stood some time, but they may be deposited alone or with a little mucus in a very characteristic fleecy cloud ; when not very abundant they may be seen glittering on what at first sight looks like a simple mucous cloud. Oxalate of lime is formed by the decomposition of oxalate of soda and potash, and the union of the acid with lime salts. A fleecy deposit of oxalate of lime crystals is associated with a special form of atonic dyspepsia to which the name of oxaluria has been given. The precise conditions under which this deposit occurs can- not be formulated, but debility, anaemia, and various organic diseases of all kinds are predisposing causes. Over-eating under certain conditions may be a direct cause. The crystals can readily be recognised under the microscope with a power of two hundred and fifty diameters by their CLINICAL EXAMINATION OF THE URINE. 195 shape and high refractive powers. They are generally octohedral or pyramidal, more rarely dumbell shaped and not uncommonly spherical or oval {^Fig. 41). These spheres are said by Roberts to be ^ 3 dumbells seen endwise, and Beale speaks of y~) /^ them as discs. I have frequently failed to C) see a single dumbell where these spheroids rw. u.-crystais ot . .11 . . c ,1 . , oxalate of lime, octo- were visible, or to transform them into hedra, pyramids, dum. , 1111 1 • r • 1 1 hi:\\ and spheroid. dumbells by shiiting them about. Cystin (C3NH7SO2) is a left rotatory body which occurs normally in the urine in very small quantities, but very rarely in so large amount as to give rise to a deposit or the forma- tion of calculi. The formation of cystin is associated with the presence in the urine and fasces of certain ptomaines belong- ing to the diamine class, viz. (a,) penta-methylene-diamine (CgHj^N) (cadaverin), and (/3,) tetra - methylene - diamine (C4H^N) (putrescin). These are due to the agency of certain specific intestinal bacteria, and some success has attended the treatment of cystinuria by the administration of salol and sulphate of magnesia to promote intestinal antisepsis. Cystin is recognised by its characteristic crystals in 5^ the form of hexagonal plates (yFig. 42). It is insoluble in water, ether, and alcohol, ^. ,„ „ , but very soluble in ammonia and caustic ¥\r\. 42. — Hexagonal ■' plates of cystin. alkallCS. A very good test for cystin is to boil some of its potash solution, dilute it with water, and add a little nitro-prusside of potash, when a beautiful violet colour is developed. Leiicin (CgH^3N02) and Tyrosin (CgH^^NOg) occur in the urine in acute yellow atrophy of the liver. They are products of the pancreatic digestion, but are normally further oxidised into urea. Leucin, precipitated spontaneously or obtained by evapora- ting an alcoholic extract of the urine, occurs in the form of yellowish brown balls. Tyrosin forms silky, colourless sheaves {Fig- 43) of needles. When slightly heated with a few drops of concentrated sulphuric acid it dissolves with a temporary deep red colour. According to Anderson both are fre- .^%^tk^%f^%^J^^^ _ ,1 i_ • lA • r ^• J" light, sliow a dark cross; 6, quently present in the urme of liver diseases, sheaves of tyrosin. Melmiin is a pigment usually found in the urine of persons the subject of melanotic growths, but exceptionally at times 196 THE URINE. in others (SENATOR). It becomes black on exposure to the air. In a case of mine the urine was a dirty greenish brown colour, which gave the characteristic reaction of becoming perfectly black with solution of ferric chloride. With sodium nitro-prusside and caustic potash it became first violet and then a splendid claret colour ; on adding acetic acid this changed to blue ; other acids produced the same effect. With sodium nitro-prusside and ammonia it first became dull red then dull violet, and on adding acetic acid a splendid dark greenish blue was developed. There were no absbrption bands, and neither indican, pyrocatechin, nor pyrocatechuic acid was present. The test for it is solution of ferric chloride, with which it gives, as already stated, a perfectly black colour. Indican (CgHgNKSOJ is formed in the intestine by the pancreatic digestion, or by putrefactive change. It is derived from indol (CgH^N). By oxidation it forms indigo-blue. It is increased in the urine in intestinal diseases, prolonged constipation, hernia, typhoid fever, cancer of the bowel, in Addison's disease, diabetes, Bright's disease, nervous diseases, peritonitis, cholera, fractures, osteomyelitis, etc. The largest quantity I have ever seen was in the very scanty urine of a hysterical patient. Ord has described a calculus formed from it. The best test is to add to equal quantities of concentrated hydrochloric acid and urine, drop by drop, a solution ot hydrochlorite of lime, and shake until a blue colour is developed ; if the mixture is shaken up with chloroform the blue colouring matter is taken up by it and can be obtained as a deposit when the chloroform evaporates, Hydrochinon (CgHgOa) is the substance which gives the dark colour to urine in cases of carbolic acid poisoning. It is formed by oxidation. CeHgO -f O = CeH.Oo. carbolic acid. oxygen. hydrochinon. Pyrocatechin (CgHgOg) is an isomer of hydrochinon, and also gives a dark colour to urine, especially where putrefaction has occurred. A leap ton ; PyrocatecJmi ; Proiocatechuic, Uroleucic and Uroxanthic Acids. Bodeker discovered a substance in the urine which darkens in the presence of alkalies, named by him alcapton. This is said by Ebstein and Mliller to be pyrocatechin, while Walter G. Smith thinks it protocatechuic acid. CLINICAL EXAMINATION OF THE URINE. 197 Kirk believes it to be a compound body containing at least two components, which he has named uroleucic and uroxanthic acids. In a case observed by Kraske, a man aged sixty-eight had been the subject of alcaptonuria since childhood. His urine contained pyrocatechin and hydrochinon-carbonic acid. Kraske found that the excretion of the latter was increased when tyrosin was mixed with his food. Grape sugar (CgH^^Og) is present in traces (-03 per cent.) in normal urine, but in larger quantities in the urine of diabetes mellitus. Milk sugar is said to be sometimes present in the urine of pregnant or nursing women. Physiological traces of sugar are not recognisable by the ordinary tests. Temporary or intermittent functional glycosuria occurs, but is rare. In various serious organic diseases of the brain and spinal cord glycosuria may be occasionally met with. The mode in which sugar is produced is not yet fully un- derstood. Glycosuria occurs when the centre for the hepatic vaso-motor nerves in the floor of the fourth ventricle is punc- tured, or after section of the vaso-motor channels in the cord, or section of the vaso-motor nerves going to the liver. Glyco- suria so induced may be stopped by section of the splanchnic nerves. Poisons which paralyse the vaso-motor nerves of the liver, e.g.^ chloroform, ether, and chloral, produce the same effect. The prevalent explanation of these facts is that the liver normally converts its glycogen into sugar in such quantities as can be oxidised in the tissues into water and carbonic acid ; but when there is an excessive stimulus to the liver, it converts more glycogen into sugar than can be burnt off, and the excess appears in the urine. Modern observations make it probable that the conversion is a function of the activity of the liver cells on food principles, carbo-hydrates, peptone, and fat The ordinary clinical test for sugar is with Fehling^s solu- tion,* performed in the following manner. * Martindale's formula : — (i,) Copper sulphate, 181 grains ; distilled water, to 6 ounces ; dissolve. (2,) Neutral potassium tartrate, 728 gi-ains ; caustic soda, 360 grains ; distilled water to 6 ounces ; dissolve. On mix- ing these two solutions in equal columns Fehling's solution is formed, of which 10 cc. will be decolorised and reduced by 0*05 grm. of diabetic sugar. 198 THE URINE. Boil about a drachm of the solution in a test tube, add an equal quantity of urine, boil again ; if sugar is present the yellow suboxide of copper is thrown down. Albumen causes a dirty purple precipitate, albumose turns Fehling rose pink, and uric acid, urates, kreatinin, glycuronic acid, aldehyde lactic acid, lactates and lactose, are all stated to reduce copper. The most certain and trustworthy test is fermentation by carefully washed yeast, in a test tube, or special tube inverted over mercury, and kept in a warm place ; if as little as O'l per cent, is present it may be detected by a bubble of COg collecting at the upper end of the tube. TroimneT-'' s test. — The urine is rendered alkaline with liq. potassae and copper sulphate solution, added drop by drop until the cupric oxide formed ceases to be dissolved. The mixture is then boiled, and reduction of the cupric oxide follows if sugar is present. MooTe's test. — The urine is treated with liq. potassae and boiled, when it turns brown in the presence of sugar, but the reaction is neither certain nor delicate. JoJinson's test. — Put about half a drachm of a saturated solu- tion of Picric acid in a test tube, add a few drops of dilute Liq. potasscE (i to lo), boil the mixture, add an equal quantity of urine and boil again ; if as much as one grain of sugar per ounce be present the liquid will become quite opaque, but a certain amount of reddish brown colouration takes place whether sugar be present or not. Rubners test. — To lo cc. of urine add the same amount of concentrated solution of neutral acetate of lead, and filter. To the filtrate add ammonia drop by drop until a thick cheesy precipitate is formed. Heat cautiously to 80° C. (176° F.), when the precipitate will turn a rose red, and on further heat- ing a coffee brown if sugar is present. This test is said to detect the presence of 0*25 per cent, of sugar. P henyl-hydrazin test (von Jaksch). — Two parts of hydro- chlorate of phenyl-hydrazin (twice as much as will lie on the point of a knife) and three parts of acetate of soda are placed in a test tube with 6 to 8 cc. of urine. If the salts do not dissolve when the fluid is warmed a little water is added, and the test tube placed for twenty to thirty minutes in boil- ing water. After this it is taken out and put into a vessel containing cold water. If sugar is present a yellow crystal- line precipitate forms at once, which is seen under the micro- scope to consist of yellow needles detached or arranged in CLINICAL EXAMINATION OF THE URINE. 199 radiating clusters. This test is applicable to any morbid urine, and in the presence of albumen. Other tests, such as indigo-carmine, safranin, and bismuth, exist, but they are not so commonly employed and have no special advantages. The qicantitative estimation of sugar is made with Fehling's solution. The necessary apparatus consists of a burette, a 100 cc. glass measure, a white porcelain dish, and a spirit lamp. Measure off 10 cc. of Fehling's solution with the 100 cc. glass, dilute with distilled water up to 50 cc, pour into dish and set on to boil. Measure 10 cc. of urine in the same way, and dilute up to lOO cc. (that is to ten volumes), and fill the burette with the diluted urine up to the zero mark. If the urine is turbid it should be filtered, and albumen must be removed by boiling. When the diluted Fehling has begun to boil the urine should be run in from the burette drop by drop, the operator stirring meanwhile, and from time to time removing the lamp so as to let the reduced copper settle, and to note the state of the fluid. When the blue colour has entirely disappeared, read off the quantity of diluted urine which has been required to effect this ; this quantity contains exactly 0'05 grm. of sugar. Let us suppose that this was 10 cc. of dilute urine, then in order to find the percentage of sugar present we must say, if 10 cc. of dilute urine contains 0"05 grm. of sugar, how much will lOO cc. contain ? Or as 10 : 100 : : 0'05 : x. 0*05 X 100 5 ■^ = 10 = F8 = °"5. But the urine was diluted to ten volumes, therefore this figure must be multiplied by ten, and the result is 5 per cent. As a rule it is important to determine not the percentage, but the actual quantity passed daily. This is easily done by reduc- ing the number of ounces of urine to grains, multiplying by the amount per cent, and dividing by a hundred. For example, if 43,200 grains of urine have been passed in twenty- four hours, and a portion of this tested as above has been shown to contain 5 per cent, of sugar, then ''^--°°J'-"'^ = 2,160 gi*. of sugar passed in twenty-four hours. A rough quantitative estimate may be made by fermenta- tion ; the urine is divided into two portions, which are placed side by side in a warm place and yeast added to one only. After some hours the specific gravity of both is taken, and, 200 THE URINE. according to Sir William Roberts, the quantity of sugar is represented by each unit of specific gravity lost by fermenta- tion being equal to one grain of sugar per ounce. For ex- ample, the sp. gr. of the urine is 1040; two portions are placed side by side, and yeast added to No. i only. At the end of eight hours No. 2 has a specific gravity of 1042 (due to evaporation), and No. i is only 1006 ; the difference of 36 represents '^^'6 grains of sugar per ounce, or 7'5 per cent. The araosaccharometer is an instrument consisting of a flask with a long neck on which a scale is marked. The flask is filled with urine and ballasted with yeast until it sinks to zero on the scale ; as fermentation takes place the flask rises, and the scale on the neck gives the amount of sugar. The polarinieter affords a ready means of estimating the amount of sugar in urine previously precipitated with lead acetate and filtered. A series of estimations made by Dr. J. W. Russell showed that the results were slightly below those obtained by Fehling's solution or fermentation, but were sufficiently constant to prove that the instrument is trust- worthy in practised hands ; the personal equation forms too large a factor to make it suitable for the use of students. Acetone (CH3COCH3) is met with in the urine of advanced cases of diabetes, of many acute febrile diseases, e.g., measles, scarlatina, pneumonia, after the ingestion of alcohol (BULL), and even in the urine of healthy children (Baginsky). Ralfe's modification of Lieben's iodoform test is performed by boiling a drachm of liq. potassae with twenty grains of iodide of potassium in a test tube, and then upon the surface of this floating an equal quantity of urine. At the junction of the two fluids a ring of phosphates is formed, which in the presence of acetone becomes studded with yellow points of iodoform ; unfortunately alcohol and lactic acid give the same reaction. The best test is that devised by Le Nobel. Pour about an ounce of urine into a urine glass, add a drachm or two of a solution of nitro-prusside of sodium (5 grains to i ounce), and a few drops of strong ammonia. After standing a few minutes a rose violet colour is developed, which, if much acetone is present, will require diluting with water to bring out the brilliancy of its colour. Acetone is probably formed in the urine by the breaking up of aceto-acetic acid into acetone and carbon dioxide. CH3,CO,CH2,COOH = CH3,CO,CH3, 4- CO3. CLINICAL EXAMINATION OF THE URINE. 201 Aceto-acetic acid or diacetic acid (CH3,CO,CHg,COOH) is present in the urine of diabetes, and gives a red coloration with ferric chloride solution, which disappears on heating. This ferric chloride reaction was at one time thought to be a test for acetone. According to Le Nobel the same reaction is given by /3-oxybutyric acid, sulpho-cyanogen, acetic and formic acid compounds, only differing by not disappearing on the application of heat. The large number of substances which give this reaction accounts for its being so commonly met with, as in coma, chronic Bright's disease, perityphlitis, strangulated hernia, after minor surgical operations, and in sulphuric acid poisoning (Windle). Bile pigment or bilirubin (CggHggN^Og) is present in the urine in cases of jaundice, sometimes before any change is to be observed in the skin or conjunctivae. It colours the urine deep yellow, mahogany brown, or olive green. The last colour is due to partial oxidation of the bilirubin to biliverdin (CooHggN^Og). Bile-stained urines may turn grass green from this change, which only takes place when the urine is under- going decomposition. The peculiar colour of bile-stained urine can be usually recognised by the eye, even when only a small quantity of the pigment is present ; but some dark urines look very much as if they contained a large quantity of bile pigment until they are well diluted with water. The best way of testing for bile pigment is to dilute a couple of ounces of the urine to the colour of sherry in a urine glass, add a drachm or two of strong nitric acid containing some nitrous acid (such nitric acid has a yellow colour), or weak liq. iodi (i to 10 of water) ; if bile pigment be present a grass green colour is developed. Sometimes one and some- times the other of these tests gives the best result. The method by dilution in a urine glass is recommended as giving much better results than the plan ordinarily followed of making a play of colours by mixing a drop of urine with a drop of nitric acid on a white porcelain dish. Bile acids, glycocholic (C.^gH^gNOg) and taurocholic (CggH^gNSO^) acids are often present in the urine of jaundice. The various tests for these acids are unsatisfactory. Petten- kofer's well known reaction with sugar and sulphuric acid cannot be obtained when applied to the urine directly, but the acids must be first isolated. 202 THE URINE. The following test is recommended by Hay. Sprinkle a little precipitated sulphur on the surface of the urine. If bile acids are present the grains of sulphur yf^fa:^', instead of sinking as they otherwise do ; but it does not appear to be of any value. Oliver's test consists of powdered peptone 2 grms. ; salicylic acid 0"2 5 grm. ; acetic acid 30 drops; distilled water 240 grms. To 4 cc. of the solution add twenty drops of the urine to be tested ; if bile acids are present an opalescence is pro- duced, varying in intensity with their quantity. Fat or oil globules may be found in the urine after the passage of a catheter, and are of course derived from the oil used on the instrument ; they are met with also in phthisis, pyaemia, long standing suppuration, and phosphorous poison- ing, from fatty degeneration of pus, or of renal or vesical epithelium ; but in all these conditions they are present only in quantities recognisable by the microscope. In chyluria the urine is milky from admixture of fat. This condition occurs sometimes in pregnancy and lactation. Mr. Frost, of Yardley, a year or two ago brought me the urine of a young unmarried girl, who, having become pregnant, had compressed her abdomen so much in order to conceal her condition as to cause oedema of the legs, thighs, vulva, and low^er part of the abdomen. After her confinement the urine became milky and remained so for some days; it contained fatty granules, cholesterin, and albumen, but no sugar. Francotti has described a somewhat similar case in which a woman who had never resided in the tropics passed chylous urine in each pregnancy. With rest it diminished or disap- peared, recurring on going about. In both these cases there was probably some rupture of dilated lymphatics with escape of lymph or chyle into the urine. Rossbach has published a case of a young girl with mitral insufficiency who passed milky urine both by day and by night. The daily quantity of fat excreted varied from r5 to 10 grammes. The urine also contained albumen. The patient had diminished liver dulness, and he suggests that it is possible the condition depended in some way upon disease of the liver. Endemic chyluria occurs commonly in India, China, and the Straits in persons whose blood is infested by the parasitic nematode, 7f/(?rm sanguinis ho7ninis. Chyluria is caused when CLINICAL EXAMINATION OF THE URINE. 203 the lymphatics j^et obstructed through the impaction of abor- tive ova in the ducts (Manson). Fatty acids, e.g., butyric acid, are sometimes present in the urine. Cholesterin (C^^H^^O) is met with in chylous urine, in fatty degeneration of the kidney, in diabetes, jaundice, and in the urine of epilepsy treated with potassium bromide (Pohl), while it enters into the constitution of certain urinary calculi. Its crystals can be recognised under the microscope as large thin rhomboidal colourless plates {Fig. 44). With iodine and sulphuric acid they turn to deep blue or violet colour. A further test may be made by dissolv- ing the cholesterin with chloroform in a test tube, adding concentrated sulphuric . , 1 1 1 • r • j_ ^1 FiiT. 44.— Crystals or plates acid and shakmg lor some mmutes ; the of dhousterm. chloroform in the presence of the slightest trace of cholesterin becomes citron yellow, with a larger quantity, blood red or purple. On the addition of water to the chloroform solution it becomes quickly blue, then green, and finally yellow. With glacial acetic acid the violet solution shows a green fluorescence. Albumen. — By albumen is meant serum albumen, with its acid and alkaline modifications, and serum globulin (para- globulin). It must be borne in mind that the clinical examination of the urine is not a scientific enquiry, but a practical method founded upon empirical as well as upon scientific data. There are albuminoid bodies in the urine which have no known clini- cal significance, and these can only embarrass the practitioner who is looking for a sign to which he attributes a significance based upon a purely empirical foundation. Posner has proved that a minute amount of serum albumen is a constant constituent of normal urine, so that if we could obtain a very delicate test for albumen it would be actually misleading to us. I have defined albuminuria as tJie presence in the urine of a substance wJiicJi is coagulable by heat or precipitated by neutra- lisation. This definition includes serum albumen, with its modifications, and serum globulin, while it excludes a variety of albuminous substances which are sometimes present in urine, but concerning whose pathological relationships we know very little. 204 THE URINE. In order to find minute traces of albumen the following method and precautions should be carefully adhered to. Albu- men is most constantly present in the urine passed in the forenoon, so that it is best to obtain a specimen passed at that time if possible. Putrid urine is unfit for detecting traces of albumen, and turbid urine, unless the turbidity be due to urates which will disappear on heating, should be filtered. Fill a test tube two-thirds full of urine, hold it by the lower end and boil the upper half well over a spirit lamp, then acid- ulate with two or three drops of dilute acetic acid. If there is any difficulty in recognising a cloud, hold the tube against a shaded back-ground with the light falling from above, when the faintest haze will be apparent by contrast with the layer of unboiled clear fluid below. If the room is badly lighted, or the examination is made by artificial light, a very faint haze may escape detection. This haze indicates the presence of serum albumen or serum globulin. There is no single operation by which these can be differentiated. If it is desired to do so a portion of the urine must be saturated with common salt or with mag- nesium sulphate and filtered. By this means the globulin is precipitated, so that if a urine before precipitation gave a cloud on boiling and acidulating, but none afterwards, we should be justified in concluding that the albuminous body was serum globulin. But globulin very rarely occurs by itself, and when it does it has not been proved to have any significance, though Hermann has stated that he found only globulin in a case of eclampsia, while in. the nephritis of pregnancy he found serum albumen. It has been repeatedly suggested that in various forms of " functional " albuminuria, the albuminous body is globulin, but this statement has hitherto in all cases been proved to be erroneous ; there can be no doubt that the presence of globulin unaccompanied by albumen is very exceptional and has at present no defi- nite meaning. Noel Baton has devised a simple and fairly accurate pro- cedure for the quantitative determination of serum-albumen and serum-globulin based on Esbach's method. It may be contended that it would be better to have a test which does not throw down globulin, and this may be readily granted, but there is no test which is perfect. This trifling imperfection will never lead any one astray who bears in mind CLINICAL EXAMINATION OF THE URINE. 205 that the discovery of albuminuria is not a fact ''per se" of defi- nite pathog}ionwnic significance. It has been objected that urine which contains oxalate of Hme gives a reaction resembhng albumen with this test. This is true if urine is saturated with oxalic acid, filtered and then tested, but the haze is a very faint one, and it is not true in my experience of oxaluria as observed clinically. One observer has stated that mucin gives a cloud resem- bling albumen, but this is not the case. On adding acetic acid mucin coagulates in tiny filaments easily distinguished from albumen. Heller's test, with cold nitric acid, is a very good plan. It is performed by pouring a few drops of nitric acid into a test tube and then floating half a drachm of urine by means of a pipette on its surface. Where the liquids come in contact a cloud forms when albumen is present. The objections to this method are: (i,") That it is not so delicate as the heat and acetic acid plan, though, like that, it throws down globulin ; (2,) That the reaction is simulated in the urine of patients taking copaiba, cubebs or salicylic acid ; (3,) That nitric acid is hurtful to one's fingers, clothes and carpets, when it gets spilt, as in the course of daily use it is certain to be sometimes ; (4,) That it gives a cloud with uric acid, and that urea may crystallise out. The use oi picric acid has been strongly advocated of late years. It is recommended to employ a double saturated solution of common salt and picric acid, which is heavier than most urines, and it is then used like cold nitric acid as just described, a cloud forming where the two liquids come in contact. The objections are: (i,) That this reaction occurs with albumose, an albuminous body of no known pathological sig- nificance, which is frequently present in urine ; with alkaloids, such as quinine, and with mucin. The cloud given by albumose and alkaloids disappears on heating ; but if the spirit lamp is to be employed in every case the test loses its principal advantage of simplicity. Unfortu- nately the fallacy from mucin cannot be got rid of except by testing separately for mucin. (2,) Picric acid is not so delicate as either of the above described methods. There is some con- flict of testimony on this head, but this is my experience, and it is supported by Roberts, Lauder Brunton, Harris, and Stirling. 2o6 THE URINE. Ferrocyanide of potassium and acetic acid give unsatisfactory results in the examination of urine, as they throw down albumose, as well as albumen proper. Tanret's test, potassio-mercuric iodide, also throws down albumose as well as albumen, the cloud produced by the former substance not disappearing on heating. Tungstate of soda possesses the same fallacious power, and also gives a cloud with mucin. It is unnecessary to go further through the various tests which have been recommended. It is possible that individuals may find themselves able to get better results with one test than another ; but the three methods described fully, namely, boiling and acetic acid, cold nitric acid and picric acid, are those which have received the support of the best authorities ; all others are for various reasons useless or fallacious. When a quantitative analysis is required the most accurate way is to boil a known quantity of urine, acidulate it, and collect it on a weighed filter paper, dry it over sulphuric acid in a bell jar, and weigh it carefully, deducting the weight of the paper. But this is a method unsuited to the needs of practitioners. A very easy and fairly accurate method has been invented by Esbach. The only apparatus required is a specially graduated tube {^Fig. 45). The urine, dil- uted with one or more volumes of water, is poured into this tube up to the line marked U, and the albu- men is precipitated by a solution of picric and citric acids (ten grammes of picric acid, and twenty grammes I illi of citric acid, dissolved in eight hundred or nine hun- is dred ccm. of boiling water, and enough water added to p make up one litre), the tube being then allowed to i| stand a few hours when the result is read off as a i Jill percentage, and corrected according to the number of volumes of water added. When we wish to estimate the amount of albumen *^' ■ by either method, it is necessary to make use of a sample of the whole twenty-four hours' urine in order to give the observation any value, as the proportion of albu- men varies very much at different times of the day and night. Albumose has no known pathological significance, but is met with in many acute diseases ; it was formerly called peptone, but all modern observers are agreed that it is more CLINICAL EXAMINATION OF THE URINE. 207 properly described as albumose, being thrown down by- ammonium sulphate (VON NOORDEN). The test for it is that it gives a pink colour with Fehling's solution in the cold ; it is better to dilute the reagent with an equal quantity of distilled water. Mucin is commonly present in the urine of even healthy persons, causing a light flocculent cloud which gradually settles to the bottom of the vessel. In catarrh of the urinary pass- ages it is much increased and mixed with pus. It is precipitated by acetic acid in the form of fine filaments, and by alcohol, citric acid, picric acid, tungstate of soda, etc. After boiling with hydrochloric acid, mucin reduces cupric oxide like sugar. Blood. — The presence of blood in the urine is a symptom common to a number of pathological conditions, differing essentially in their seat, nature, and relationships. It may appear in a corpuscular or non-corpuscular form ; the latter is called hsemoglobinuria. In paroxysmal haemoglobinuria the primary cause is cold, acting on the blood in the vessels of peripheral parts, e.g., hands, feet, ears and nose, where the circulation is sluggish. There is a nervous factor co-operating which probably acts by slowing the circulation in certain parts, and it is particularly liable to come on in predisposed persons after muscular exer- tion. Blood can generally be recognised in the urine by the eye, even when present in small quantities. It is characteristic of blood that its solutions are dichroic, appearing red by reflected and green by transmitted light. But acid urine soon changes the bright red colour into a dirty brown (methaemoglobin), so that urine which has remained in the bladder mixed with blood is smoky brown or porter-coloured, according to the amount of blood present. The inicj'oscope is undoubtedly the best means of detecting corpuscular blood in the urine. A drop of urine should be taken up by a pipette and placed on a glass slide, covered with a thin cover-glass, and examined with a lens of at least two hundred and fifty diameters magnifying power. If traces of blood only are present the lowest stratum of urine should be examined after standing some time. The cor- puscles undergo many changes, swelling up so as to lose their bi-concave form, or shedding their haemoglobin, by which they alter in shape, appear vacuolated, and ultimately colourless. 2o8 THE URINE. {Fig. 4,6.) Such colourless discs may possibly be confounded with discoid oxalates and torula;, but both these are smaller, while the latter contain bright nuclei and (^"^ are generally oval. @ C) Q ^ ■, Ihe Guaiacum test. — This depends upon g) © O Q the ozone-carrying power of haemoglobin. I&p It is best performed by dissolving one or ^. ,, ^, , ,. . ,,;,,= two drops of fresh tincture of ouaiacinn />(7. 4(i. Blood discs: a, Discs i o shfp1f"b^DisclswoiieS°b°yim- in about half a drachm of ozonic ether, k!&»™"oiC'knl''bec''om^ whlch Is a solution of peroxide of hydro ing colourless. ^^^^ j^ sulpJiiiric etlier^ and then adding about a drachm of urine and shaking the mixture. If haemoglobin be present a blue colour appears. Another method is to dip strips of blotting-paper in the tincture and dry them. These are used by touching them with a drop of urine and a drop of ozonic ether successively. Turpentine which has been exposed to the air always con- tains ozone, and may be substituted for ozonic ether but cannot be depended upon so well. Unfortunately this test is not quite perfect. The urine of patients containing iodide of potassium gives a blue colour although no blood be present, while I have often observed that corpuscles are to be seen with the microscope when the chemical report says " no blood re- action." With respect to this want of delicacy two cautions may be given. The guaiacum tincture should not be kept longer than two months : and, secondly, the urine to be tested should be drawn up with a pipette from the lower stratum, just as it would be for microscopical observation, as the corpuscles naturally sink to the bottom of the glass. It is stated that fibrin possesses the power of decomposing peroxide of hydrogen, giving a blue colour with the guaiacum test. I have not been able to obtain this result with well- washed fibrin, but in any case fibrin is not likely to be met with in urine apart from haematuria. The spectroscopic examination of blood in solution is easy, and may be made by holding the vessel containing the urine between the source of light and an ordinary pocket spectro- scope applied to the eye, when two dark bands will be visible between Fraunhofer's lines D and E in the yellow and green of the spectrum ; if the colouring matter is converted into methaemogiobin, a band in red will appear in addition to the other two. When the blood is present in an insoluble state the urine must be filtered, and the filter paper with the deposit CLINICAL EXAMINATION OF THE URINE. 209 upon it digested in alcoJiol and aunnonia. This fluid should be examined as in the other case, but if httle blood be present the faintest possible shadow in the orange of the spectrum may alone be visible ; on adding aimnoniuni sidpJiide to the fluid the two bands will show themselves, but disappear when the fluid is shaken with air, to reappear on standing. HaiiiatoporpJiyrin is a beautiful red pigment derived from the blood, said to be present in traces in normal urine, but found in excess in many acute and chronic diseases, but especi- ally after taking large doses of sulphonal. It may be thrown down by treating the urine with excess of caustic potash or caustic soda; the precipitate should be washed with distilled water, and treated with acidulated alcohol when an almost pure solution of hsematoporphyrin may be obtained (Salkowski, Copeaian, Garrod). Pus may be found in the urine whenever inflammation affects any part of the urinary tract, but it is most commonly met with in catarrh of the urethra (^gonorrJiced), of the bladder (cystitis), or catarrh of the pelvis of the kidney (^pyelitis). In the second condition the urine is generally alkaline, and triple phosphates are found with the pus ; in the latter the urine is generally acid and the deposit commonly contains oxalates. Pus is best detected by the microscope {^Fig. 47), the round leucocyte-like cells are easily recognised ; by © ^ adding acetic acid they become clear and show © @@ two or more nuclei; sometimes they are opaque ^ ^ from infiltration with micro-organisms, when acetic acid will fail to clear them. \Z) (3) When pus is present in quantity it effervesces (5) 7 with ozonic etJier^ but this is not a delicate reaction. On the addition of liq. potassce the v^lli^^- b.'^YInx^d I . . -, 1 1 1 by acetic acid, show- hquor puns becomes ropy, even when a small inR two, tiuee, and ^ , ^ . i. J ' four nuclei. quantity is present. Pus when present in quantity in the urine forms a cream- coloured deposit, which is not readily diffused into the super- natant fluid. Casts are moulds of the tubules of the kidney and are of three kinds : (i,) Blood casts, formed of red corpuscles stuck together by fibrin ; (2,) Hyaline casts, originating in various ways : (<^,) From fibrin ; [b^ From a protoplasmic exudation from the renal epithelium in the early irritative stages of acute nephritis or in chronic inflammation ; (c,) From the colloid degeneration of desquamated epithelial cells. The second is 14 THE URINE. probably the most common type ; such casts are slender, while the third kind are broad and have the same meaning as epithe- lial casts ; (3,) Epithelial casts, formed either by the packing together of desquamated and fatty epithelium, or by masses of round cells derived by proliferation from the epithelium of the Fig. ^. a. Blood cast: h. Epithelial cast composed of small round cells: r, E'"ithelial cast formed of desquamated and fatty epithelium ; d, Granular hyaline cast; e, Hyalo-epitheliiil cast. tubules, indicate a high degree of active inflammation of the renal parenchyma {Figs. 48 and 49). To find casts use a half-inch objective, with a good light. Take up a drop of the deposit or lowest stratum of the urine with a fine pipette, and place six drops on as many slides. (Very suitable pipettes are sold as " biological pipettes," made of thick glass with a bore of about one-sixteenth of an inch.) Cover each drop with a thin cover-glass, and examine the slides in succession ; if no casts are found on any of them the result may be regarded as fairly indicating their absence from that specimen of urine. In acute Bright's disease casts are very abundant. Out of sixty-seven observations only nine were negative, and these were all at the termination of the cases when they were nearly cured, though it is noteworthy that albuminuria still persisted. CLINICAL EXAMINATION OF THE URINE. In chronic Bright's disease associated with dropsy, where there was a recent history of acute nephritis, they were absent in only four out of ninety-five observations. In chronic Bright's disease with Httle or no dropsy they were also very constant, being present in sixty-eight out of seventy-seven observations ; but they were not abundant. In cases of contracting kidney seen in the out-patient room, and diagnosed as such from other signs and symptoms, casts were present in sixteen out of twenty-five observations. Epithelium of various kinds occurs in the urine. Large squamous cells from the vagina and urethra of women, and the bladder of both sexes, are com- mon. The epithelium from the male urethra is columnar. Pear-shaped or tailed cells may come from Cowper's glands, Littre's glands, the prostate, the ureter, and pelvis of the kidney. Small round cells, derived by proliferation from the renal epithelium, may be seen in acute Bright's disease. {Figs. 49 and 50.) It is not always possible to say whence given cells are de- cylinder rived; they often have under gone fatty degeneration or infiltration by microbes, or are broken up into fragments. Epithelial cells must be looked for with a good quarter-inch glass. Micro-organisms are not present in normal urine, as it may be kept for months in a warm place without under- going any change ; but Kannenberg states that he has found spheroid and rod-shaped forms in the urine of healthy persons, though much more abundantly in all acute diseases. Lustgarten and Mannaberg also found organisms in the urine of healthy persons, for the urethral mucus of eight healthy persons contained ten different kinds of microbes (in four cases bacilli and in six micrococci). Of these ten Fig. 49. a, Slender hyaline cast ; 6, Mucous ylinder; c, Hyaline and epithelial cast ; d, Pear- shaped epithelial cells from pelvis ol kidney; e, Epitheliuni from tubules. Fig. SO. rt, Large Bquamousepi the lium from vagina; b, Epitheliun; trom bladder. 212 THE URINE. varieties, two were especially notable, one being a bacillus giving the staining reactions of the bacillus tuberculosis, the other a micrococcus indistinguishable from the go7tococcus or microbe of gonorrhoea. They found that it was necessary to take the precaution of drawing off the urine by a catheter in order to obtain a secretion which on cultivation was free from organisms. They found numerous streptococci (organisms arranged in chains) in the carefully drawn off urine of three cases of acute Bright's disease, which disappeared on the decline of the disease. They did not succeed in obtaining a pure culture of these organisms. Undoubtedly many organisms find their way into the urine after it has left the body ; tortUcE are not uncommon, especially in urine containing sugar. These torulcB are the sporules of the common moulds {J)enicilliuin glaucuni and aspergillus uiger), and of the yeast plant {saccharomyces cej^evisics). Putrid urine swarms with bacteria, of which the best known is bacter- ium terino. The am.moniacal decomposition of urine is said to be due to the action of a minute spherical bacterium called by Cohn micrococcus ttrecE. In morbid conditions of the urinary tract, as well as in many specific diseases, organisms are found in the freshly passed urine which do not give rise to any chemical changes in it ; one of the earliest known was sarcina ventriculi, which appears in the urine in certain cases of vesical catarrh, but seems to be invariably introduced by surgical interference (catheters) ; it may persist for years and does no harm (FiNLAYSON). Roberts has described three cases of bacteruria associated with bladder troubles. Tubercle bacilli have been found in the urine in tubercular diseases of the urinary organs, and of the epididymis (Rosenstein). Bouchard found micro-organisms in the urine of typhoid fever, puerperal fever, measles, erysipelas, dysentery, osteomyelitis, diphtheria and phthisis. Berlioz found the typhoid bacillus in the urine of two out of fourteen cases, in one instance on the twentieth day of the dis- ease. In two cases of pneumonia and five of erysipelas his results were negative. In animals inoculated with charbon he observed the passage of bacteria into the urine in two cases accompanied by haemo- globin. The passage was found to be facilitated by canthari- din poisoning, by which the kidneys were irritated. He also CLINICAL EXAMINATION OF THE URINE. 213 observed the passage into the urine of the micrococcus tetragomis, the bacillus pyocyaneus, and t\iQ pneuinococctis of Fraenkel. He believes that these appearances always denote a morbid local- isation in the urinary apparatus. Schweiger found that organisms injected into the renal vein or artery soon appeared in the urine, and conversely when injected into the pelvis of the kidney could be found by cultivation in the blood. He attempted to determine where the passage takes place, but was unable to detect them in transitu. In many conditions micro-organisms have been observed in the kidneys post inorteni when they have not been found in the urine, e.g., micrococcus dipJitherice^ the micrococcus of ulcerative endocarditis^ microsporon septicttm, Friedlander's pneumococcus, etc. The method of examining urine for micro-organisms is the following : Place a drop of the deposit, or of the urine on a cover-glass which has been cleansed with nitric acid and dis- tilled water. Place another cover-glass upon the drop and press the two together, then separate them, by sliding one over the other. Allow the films of fluid to dry, then holding the covers with a pair of forceps pass each two or three times quickly through the flame of a spirit lamp or Bunsen's burner. Stain them with methyl violet solution. Saturated alcoholic solution of methyl voilet 11 parts. Aniline water ... ... ... ... no „ Absolute alcohol ... ... ... 10 „ They may be left in this solution several hours. Wash with alcohol for three minutes, then in a solution often parts iodine, twenty parts iodide of potassium, and three thousand parts of distilled water, until the dark blue violet is replaced by a dark purple red. Wash in alcohol till most of the colour is removed. The covers may be mounted at once on glass slides with a little Canada balsam. This is Gram's method as given by Woodhead and Hare, to whose book readers are referred who want information about special stains and methods of cultivation. The accompanying woodcut shows various forms of micro- organisms {Fig. 51). Fenne^its are stated to be present in normal urine. Trypsin, the proteolytic ferment of the pancreas which occurs in normal urine, is said by Mya and Belfanti to be replaced by pepsin in Bright's disease. 214 THE URINE. Holvotschiner and Breusing have found that there is an amylolytic ferment present which is capable of converting starch into erythro- and achroo-dextrines, but not farther accordinsf to the second of these two observers. -^> f i\ -S^-^ / ' '// Fig. 51. o, Micrococci ; 6, Diplococoi ; c, Cocci in fours ; d, Streptococci, or cocci in chains ; e. Bac- terium termo ; /, Bacillus subtilis ; g. Bacillus tuberculosis; ft, Sarcinte ventriouli; i, Torulse; ft, Mycelium ; I, Zoogloea. Bechamp's " nephrozymose," an albuminous body in urine with the power of converting starch into sugar, is said by Leube to be a compound of albumen with some amylolytic ferment. There is no reason to think that the amylolytic ferment, even if capable of converting starch into sugar, is ever responsible for the occurrence of paradoxical glycosuria, as there is no carbo-hydrate in the urine upon which it could exercise its powers. Ptomaines of both the alpha and beta series have been found in the urine, not only as already mentioned in association with cystin, but in exophthalmic goitre, and other diseases (BOINET, SiLBERT, ROOS), and it is probable that the toxic character of so many morbid urines is due to the presence of these sub- stances (BOUCHARD, LfiPINE); for the methods of detecting these poisons the chemical text books must be consulted, as they are too complicated for description in a work of this kind. BIBLIOGRAPHY. Anderson (E. C). Leucin and Tyrosin in fresh urine. " Brit. Med. Jour.," 1887, II., p. 673. AuFRECHT. Die diffuse Nephritis und die Entziindung in allgemeine. •' Cent. f. d. Med. Wiss.," 1878, p. 337. Baginsky (A.). Ueber Acetonurie bei Kindern. " Arch. f. Kind. ," Bd. IX, 1887-8, p. I. Berlioz. Clinical and Experimental Researches on the passage of Bacteria into the Urine. Paris: O. Doin, 1887. BoiNET AND SiLBERT. Dcs ptomaincs urinaires dans le goitre exophthal- mique, " Revue de Medecine," 1892, p. 38. CLINICAL EXAMINATION OF THE URINE. 215 Bouchard (C). Le9ons sur les auto-intoxications dans les maladies, Paris, 1887. Breusing (R.). Ueber das " Starke Umwandelnde" Ferment im mensch- lichen Harn. " Virchow's Archiv," Bd. CVIL, p. iS5. Brouardel (P.). L'Uree at le Foie. Paris, 1877. Bull (G. C). A Preliminary Report on the Presence of Acetone in the Urine. " Birm. Med. Review," XVII., 1885, p. 211. Camerer. Quoted by Salkowski and Leube, op. cit., p. 80. Cook (E. A.). Production and Excretion of Uric Acid. " Brit. Med. Jour.," 1883, I., p. 245. Influence of Drugs on Urea and Uric Acid. Ibid., pp. 857, 1060. CoPEMAN (S. M.). Hsematoporphyrin in Urine. " Brit. Med. Jour.," 1891, I., p. 175. FiNLAYSON (J.). Clinical remarks on Sarcinse in the Urine for fifteen years without accidents. " Brit. Med. Jour.," 1891, I., p. 1371. Flugge. Beitriige zur Hygiene. Leipzig, 1879, p. 117. Francotti. Non-parasitic Chyluria. "Ann. de la Soc. Med.-Chir. de Liege," Sept., 1886. Freund (E.), Eine Tritrirmethode zur Bestimmung der Schwefelsaure im Harn. "Wiener klin. Wochenschr.," 1891, No. 51. Garrod (a. B.). Lumleian Lectures on Uric Acid. " Brit. Med. Jour.," 1883, I., p. 495. Garrod (A. E.). On Hsematoporphyrin as a Urinary pigment in Disease, "Jour, of Path, and Bacteriology," Vol. I., p. 187. Haig (A.). The Relation of a certain Form of Headache to the Excretion of Uric Acid. " Med. Chir. Trans.." LXX., p. 355. Harris (T.). The Relative Value of the more commonly employed Tests for Albumen in the Urine. " Med. Chron.," II., 1885, p. 459. Haycraft (J. B.). A New Method for the Quantitative Estimation of Uric Acid. " Brit. Med. Jour.," 1885, II,, p. iioo. Herman (G. E.). A Case of Eclampsia of Pregnancy, with Observations on the State of the Renal Function. " Brit. Med. Jour.," 1887, II., p. 1334. Bright's Disease during Pregnancy. Ibid. Hunter (W.). An Investigation into the Pathology of Pernicious Anaemia. " Lancet," 1888, II., pp. 555, 608. Jaffe. Zur Lehre von den Eigenschaften und der Abstammung der Harn- pigmente. " Virchow's Archiv," Bd. XLVII., p. 405. Johnson (G.). On Picric Acid as a Test for Albumen and Sugar in the Urine. "Brit. Med. Jour.," 1883, I., pp. 504, 515. KiENER and Kelsch. Les alterations paludeennes du rein. " Arch, de Phys.," 1882, L, p. 278. Kirk (R.). Report on a New Acid found in human Urine which darkens with Alkalies (Alcaptonuria), " Brit. Med. Jour," 1888, II., p. 232. Kraske (P.) and Baumann (F.). Zur Kenntniss der Alkaptonurie. " Miinch. med. Wochenschr.," 1891, No. i, Landois (L.). a Text-book of Human Physiology. Stirling's Translation. 1885. Langhans (T.). Ueber die Veranderungen der Glomeruli bei der Nephritis nebst einigen I3emerkungen iiber die Entstehung der Fibrincylinder. " Vir- chow's Archiv," Bd. LXXVI., p. 85. Lecorche. Traite du Diabete. Paris, 1877. Legg (J. Wickham), On Paroxysmal Haematuria. " St. Barth. Hosp. Rep.," X., 1874, p. 71. Le Nobel (C.) Ueber einige neue chemische Eigenschaften des Acetous und verwandter Substanzen und deren Benutzung zur Losung der Acetonurie- frage. " Arch. f. exp. Path.," Bd. XVIII., p. 6. 2i5 THE URINE. Lepine and Aubert. Contribution a I'etude de la Secretion urinaire. " Compt. Rend, de la Soc. de Biol.," Jan. 9, 1888. Lepine (A.) and Guerin. Revue de Medecine, 1885. LusTGARTEN and Mannaberg. Ueber die Mikroorganismen der normalen, mannlichen Urethra und des normalen Harnes, mit Bemerkungen liber Mik- roorganismen im Harn bei Morbus Brightii acutus. " Viertel. f. Derm, und Syph.," 1887, p. 905. MacMunn (C. a.). Researches into the Colouring Matter of Human Urine, with an Accountof the Separation of Urobilin. " Proc. Roy. Soc," No. 206, 1880. Maguire (R.). The Darkening in Colour of certain Urines on exposure to the Air. " Brit, Med. Jour.," 1884, II., p. 808. MiDDLETON (G. S.). A Case of Sarcinse in the Urine. " Brit. Med. Jour.," 1891, II., p. II. MoNVENOUx. Les Mati^res grasses dans I'urine. Paris. Nauwerck (C). Beitrage zur Kenntniss des Morbus Brightii. Ueber Morbus Brightii bei crouposer Pneumonic. Neubauer and Vogel. A guide to the qualitative and quantitative Analysis of the Urine. 4th edition, London, 1863. Noel-Paton (D.). The commoner methods for the estimation of Urea in Urine. "The Practitioner," XXXVI., 1886, p. 168. Report on the relationship of the formation of Urea and Uric Acid to the Secretion of Bile. "Brit. Med. Jour.," 1886, 1., pp. 377 and 433. The systematic examination of the Urine for Proteids, vkfith a simple method for the quantitative determination of serum albumen and serum globulin. " Edin. Med. Jour.," 1888, p. 522. NooRDEN (C. von). Ueber neuere Arbeiten zur Peptonurie. " Berl. klin. Wochenschr.," 1893, p. 72. Ord (W. M.). Urinary Crystals and Calculi. " Med. Chir. Trans.," LVIIL, 1875, p. 165. Posner (C). Studien liber pathologischen Exudatsbildungen. "Virchow's Archiv," Bd. LXXIX., p. 311. Prout (W.). On the nature and treatment of Stomach and Renal Diseases. 5th edition. London, 1848. Ralfe (C. H.), a practical treatise on Diseases of the Kidneys and Urin- ary Derangements. London, 1885. Phosphatic Diabetes. " Lancet," I., 1887, pp. 411, 462. Ranke. "Virchow's Archiv," 1862; quoted by Salkowski and Leube, op. cii., p. 80. Ribbert (H.). Ueber die Eiweissausscheidung durch die Nieren. " Cent, f. d. Med. Wiss.," 1879, p. 47, and 1881, p. 17. Roberts (W.), A practical treatise on Urinary and Renal Diseases. 4th edition. London, 1885. On the chemical constitution and physiological relations of the amorphous Urate Deposit. " Med. Chron.," March, 1888, p. 441. Roos (E.). Ueber der Vorkommen von Diaminin bei Krankheiten. " Zeitschr. f. Physiol. Chemie," XVI., p. 192, 1892. RossBACH. Ueber Chylurie. " Verhandl. d. VI. Congr. f. innere Med.," Wiesbaden, 1887, p. 212. Rubner. Quoted by Salkowski and Leube, op. cit., p. 80. Salkowski and Leube. Die Lehre vom Harn. Berlin. 1882. Salkowski (E.). Ueber das Vorkommen von Hsematoporphyrin im Ham. " Centralbh. f. d. Med. Wissenschft.," 1891, No. 8. Saundby (R.). Case of Melanotic Sarcoma with Melanuria. "Birm. Med. Review," Vol. XXIX., p. 147, i8gi. ScHULTZEN. " Virchow's Archiv," 1863; quoted by Salkowski and Leube, op. cit., p. 80. CLINICAL EXAMINATION OF THE URINE. 217 ScHWEiGER (F.). Ueber das Durchgehen von Bacillen durch die Nieren. " Virchow's Archiv," Bd. CX., p, 255. Seegen (J.). Ueber Diabetes mellitus mit Riicksicht auf die neugewonnenen Tatsachen iiber Zuckerbildung im Tierkcirper. Senator (H.). Ueber schwarzer Urin und schwarzer Ascites. " Charit6- Annalen," XV. Ueber renale Haemophilie. " Berl. klin. Wochenschr.," 1891, No. I. Smith (W. G.). Note on a case of peculiar Albuminous Urine. " Brit. Med. Jour.," 1880, II., p. 847. On the occurrence of Protocatechuic Acid in Urine. " Dub. Jour. Med. Sci.," June, 1882. On the nature of the Phosphatic Precipitate obtained upon heating Urine. Ihid,., July, 1883. On the conditions affecting precipitation of Phosphate of Lime from Urine by heat. " Brit. Med. Jour.," 1883, II., p. 68. Strauss and Germont. Des lesions histologiques du Rein chez le Cobaye a la suite de la Ligature de I'Uret^re. " Arch, de Phys. ," Vol. IX., 1882, p. 386. Thomson (R. Stevenson). Scarlatinal Albuminuria, and the pre-albumin- uric stage. " Med.-Chir. Trans,," Vol. LXIX., p. 97. Voit. Quoted by Salkowski and Leube, op. cit., p. 80. Voorhoeve (N. a. J.). Ueber das Entstehen der sogenannten Fibrincylin- der. " Virchow's Archiv," Bd. LXXX., p. 247. Weissgerber and Perls. Beitr. zur Kenntniss der Entstehung der sog. Fibrincylinder nebst Bemerk. iiber Mikrokokkenanhaufungen in der Niere bei Blutstauung. "Arch. f. exp. Path.," Bd. VI., p. 113. Windle (B. C. a.). On the Ferric Chloride Reaction in Urine. "Liver- pool Med. Chir. Jour.," July, 1884. WooDHEAD and Hare. Pathological Mycology. Edinburgh, 1885. - YvoN and Berlioz. L'Urine normale. " Revue de Med.," Sept. 1888. ZiEGLER and Nauwerck. Beitrage zur pathologischen Anatoniie und Physiologic. Jena, 1887. 2l8 Section III.— DIABETES. Chapter XVI. DIABETES MELLITUS. DIABETES Mellitus is essentially one of those rarer diseases which can only be effectively studied, at least in this country, by those who reside in great centres of popu- lation and have the extensive practice of a large hospital from which to draw their cases, as well as the opportunities of treating numerous individuals suffering from this malady under those conditions of control which can rarely be obtained except in the wards of such an institution. In the following lectures it is my purpose to describe this disease in the light of the clinical and pathological experience acquired in many years of hospital study, and I shall try to infuse into them as much as is possible of the results of my bedside observations and post niortein examinations, testing all theories by these standards. There is probably no disease which is so overweighted by theoretical considerations derived from an overwhelming amount of physiological experiment. But it is absolutely necessary to keep such physiological considerations in their proper place, using them only for the purpose of elucidating the facts of disease, not substituting one for the other, as if a frog with its spinal cord divided, or a rabbit with its medulla injured were really and truly a case of diabetes. HISTORY. Hirsch can hardly be held to be free from a tendency to exaggeration when he says that the history of diabetes goes back to the most remote antiquity. He is doubtless right in quoting the passages from the Ayur Veda in proof that the disease was known long ago to the Hindoos, but this Veda was certainly not written till the sixth century of our era, and is supposed to have been in great part a copy of Greek medi- cine transmitted through Arab sources. It is, however, very DIABETES MELLirUS. 219 noteworthy that in these quotations the urine is said to be sweet, and in a Cingalese treatise of the fifteenth century the disease is described as " Madu mehe " or " honey urine," though no reference to this very singular peculiarity can be traced among European writers until two centuries later. No mention of diabetes can be discovered in the writings of Hippo- crates ; and though Celsus described a disease attended by polyuria, wasting and bodily illness, the term diabetes was first used by Areta^us (A.D. circa 1 50). Galen wrote on the disease at some length. But neither of these authors referred to the sweetness of the urine, and this important fact remained un- described until it was noted by Willis (1679). Sydenham, contemporary with Willis, wrote a good account of diabetes in which he drew attention to the importance of abstinence from vegetable food. " Let the patient," he wrote, " eat food of easy digestion, such as veal, mutton, and the like, and abstain from all sorts of fruit and garden stuff." A century later Dobson (1776) evaporated two quarts of diabetic urine and obtained a cake which weighed 4 oz. 2 dr. 2 scr. This cake " smelt sweet, like brown sugar, and could not be distinguished from sugar, exeept that the sweetness left a slight sense of coolness on the palate," probably due to the presence of a certain proportion of sodium chloride. Cullen, in the first edition of his " Practice of Physic " (1784), wrote that the urine in diabetes contained a considerable quantity of a saccharine matter which seemed to be exactly of the nature of sugar. So impressed was he with this discovery that he would hardly admit the existence of a non-saccharine variety (diabetes insipidus), though he thought he had seen a case. The publication of Rollo's excellent cases (1797) marks an era in the history of this disease, because of his powerful advocacy of meat diet, and the success which attended the method of treatment he employed, so that he may be said to have established the foundation of our modern practice. Latham (18 10) went a step farther in recognising two types of diabetes, one saccharine, and the other serous, and combined Rollo's animal diet with such excellent remedies as opium, iron, and alkalies. Gregory, in the appendix to his edition of Cullen's " Practice of Physic" (1829), described two forms, D. insipidus and D. mellitus. He wrote slightingly of Rollo's treatment, which seems to have suffered a check in its popularity, when it 220 DIABETES. became known that in very many cases it failed to cure the disease. Nevertheless this method held its ground until modified by Bouchardat (1841), who introduced gluten bread. In 1848 Claude Bernard discovered sugar in the liver after death, and in 1859 he proved that this sugar existed in the liver during life in the form of glycogen. He believed that glycogen was converted into sugar by the action of a diastatic ferment contained in the blood. In 1858 Pavy proved that the formation of sugar in the liver in such large quantities was a post mortem phenomenon, and he disputed the conversion of glycogen into sugar at all as a physiological process, suggest- ing that it really left the liver in some other lorm, such as fat. The great discovery of Bernard that puncture of the floor of the fourth ventricle was followed by glycosuria, gave, however, a possible explanation of the pathology of diabetes, though this has been greatly diminished in value by the subsequent experiments which have shown that lesions of many parts of the nervous system are followed by the same phenomenon. The present position of the problem cannot be described adequately by continuing the historical method. In order to render it as clear as possible the physiology of glycosuria will be explained at length in the next section, while the etiology, morbid anatomy, and pathology of diabetes will be dealt with separately in subsequent pages, THE PHYSIOLOGY OF GLYCOSURIA. By glycosuria is understood the presence in the urine of glucose (CgHjgOe). That this substance is present in small quantities in normal urine has been long known, but in such small amount (about O'S per looo) that it can only be demonstrated by the usual tests after concentrating a large bulk of urine. Wedenski has utilised Baumann's discovery, that benzoyl chloride forms insoluble compounds with carbo- hydrates, in order to demonstrate the existence of this physio- logical glycosuria. G. S. Johnson has disputed its occurrence, relying upon the negative result of the phenyl-hydrazin test, but he uses this test in a way which is not recommended by its originator, and is, in my experience, quite untrustworthy. The glucose found in the urine, whether normally or under pathological conditions, is as a rule grape sugar (dextrose). Lccvulose or intestine sugar is stated to occur rarely, but is not distinguished from it by the ordinary tests. Inosite or muscle sugar is an isomer of glucose, but occurs very rarely in DIABETES MELLITUS. 221 the urine, and is of little practical importance ; it does not reduce cupric salts. Lactose (C^gHo^O^J or milk sugar, is a sucrose, but it is sometimes present in the urine during pregnancy or lactation, and reduces copper salts, though less actively than glucose, so that its presence is liable to be mistaken for that of the latter. The reduction of copper in Fehling's or Trommer's test is so very generally regarded clinically as proof of glycosuria that great interest attaches to the discovery of the not un- common occurrence of a non-saccharine body in the urine which possesses this power in a high degree. Schmiedeberg and Meyer have shown that this substance is glycuronic acid. It is found in the urine after the administration of various drugs, chloral hydrate, croton chloral, camphor, phenacetin, morphia, chloroform, and curare. Ashdown met with it in the urine of a young man, aged twenty-four, who enjoyed perfect health, or at least a complete sense of well-being. Glycuronic acid (CgH^gOy) occurs in the urine in combination with urea, but the nature of the compound has not been definitely determined. Ashdown recommended that in all doubtful cases the urine should be fermented. Glucose is regarded by modern chemists as an aldehyde or ketone of a hexatomic alcohol (CgHg(OPI)f.), which by oxida- tion yields (CgH^^gOe) '^'^ glucose. This unit is called a mono- saccharid ; if two such units are linked together we get a di-saccharid, and this is the composition of the sucroses, e.g.^ cane sugar, milk sugar, maltose, etc. The products of the actions of salivary and pancreatic diastase on starch are probably maltose, but by the time this reaches the portal vein it has become glucose. When more than two such units are linked together the result is a polysaccharid, e.g., dextrine, starch, and glycogen. We know that the action of certain fer- ments can break up the polysaccharid into its components, and the liver, muscles, etc., possess a double power, being able to build up glycogen out of glucose, or to break up glycogen to form glucose. Glycogen {6{Q^^^f)^ -f- H2O) is formed in the liver cells in the form of amorphous granules collected around their nuclei, and is irregularly distributed through the liver. It is soluble in water, but not readily diffusible, and gives a deep red colour with iodine solution. With diastatic ferments, or when boiled with a mineral acid, it forms grape sugar. The following directions for its preparation are taken from Lan- 222 DIABETES. dols and Stirling : " Let a rabbit have a hearty meal and kill it three or four hours thereafter. The liver is removed imme- diately after death ; it is cut into fine pieces, plunged into boiling water and boiled for some time in order to obtain a watery extract of the liver cells. To the cold filtrate (of this extract) are added alternately dilute hydrochloric acid and potassio-mercuric iodide as long as a precipitate occurs. The albuminates or proteids are precipitated by the iodine com- pound in the presence of free HCl. It is then filtered, when, a clear opalescent fluid, containing the glycogen in solution, is obtained. The glycogen is precipitated from the filtrate, as a white amorphous powder, on adding an excess of 70 to 80 per cent, alcohol. The precipitate is washed with 60 per cent, and afterwards with 95 per cent, alcohol, then with ether, and lastly with absolute alcohol ; it is dried over sulphuric acid and weighed" (Brucke). The quantity in the liver is increased by adding starch, milk, fruit, or cane sugar, alkalies (DUFOUR), glycerine, or inosite to the food, while it is diminished by a purely albuminous or purely fatty diet, and disappears during hunger. It is also diminished by cold and violent muscular exercise (KiJLz), and by ligature of the bile duct (WiCKHAM Legg,VON Wittich). When rabbits are kept without food for six days, it is at least four hours after feeding before glycogen is found in their livers (KiJLZ). It is noteworthy that in dia.betes an increase of sugar can be noted in from i to 1 1 hours after the use of starchy food. Glycogen is not a product peculiar to the liver ; in foetal life it is found in all the tissues of the body, and in the adult occurs in muscle, cartilage, the colourless blood corpuscles, the testicles, etc. It can be formed directly from sugar in muscle, and by injecting syrup into the circulation a direct conversion of sugar into glycogen can be proved to take place. As has been already stated, under physiological conditions glycogen is formed in the liver cells from the products of digestion of starchy and saccharine food. It is probable that in health the glycogen is very gradually converted into sugar, in very small quantities (Landois), as it is found to diminish during hunger (Pavy), exercise and ex- posure to cold. The sugar so produced passes into the circu- lation where it is rapidly used up as it passes through the systemic capillaries. DIABETES MELLITUS. 223 But whenever there is derangement of the hepatic circula- tion, permitting a greater afflux of arterial blood to the liver, the formation of sugar from glycogen is increased, and sugar in larger quantities passes into the general circulation. This sugar production is now thought to be a product of the vital activity of the liver cells (Paton) under the stimulus of the excito-secretory nerve, or according to Pavy, it results from the contact of arterial blood. The vascular derangement which permits this great afflux of arterial blood to the liver is assumed by Pavy to be a vaso- motor paralysis of the splanchnic area, in consequence of which the blood reaches the portal vein without becoming deoxygenised. Kuhne and Heynsius have suggested that glycocholic acid may split up into urea and glucose, and they found that the introduction of glycocin (CgHgNOg, or sugar of gelatine, a constituent of bile) into the blood is followed by an increase in the amount of urea in the liver and urine, and of glycogen in the liver. According to Seegen, the liver contains at the instant when life ceases 0'4 to 0"6 per cent, of sugar (Bernard, 0"2 to 0"3 per cent; Dalton, 0"2 to 0*4 per cent; Pavy, 0'02 to 0"05 per cent) Also while carotid blood and mixed venous blood from the right side of the heart contain about the same amount of sugar (0"I09 to 0"i53 per cent, a little in excess of the portal blood,) the blood of the hepatic vein contains twice as viuch sugar as the portal vein (Seegen). Bernard thought that the glycogen of the liver, formed from the starchy matter of food, is stored up and converted gradually into sugar by a ferment in the liver. This ferment Bernard believed he had isolated, but it has since been shown that any soluble albuminous body may be made to yield a solution capable of converting starch into sugar (L£PINE), such sugar being always a glucose, while the sugar produced by true ferments {e.g., ptyalin, diastase) has a slighter reducing action with a greater rotatory power and is probably identical with maltose. According to Dastre, the liver contains no diastatic ferment, but the liver cells possess the power of converting sucrose into glucose. Again, according to Bernard, as the sugar is formed the glycogen should diminish; there should be a definite relation between them ; this, Bernard thought he had proved. 224 DIABETES. Seegen thought he had disproved this in the following manner : Having first ascertained that glycogen is always evenly distributed throughout the liver, and is not accumulated in certain parts of it, he took a piece of the liver of a recently- killed or of a still-living animal, weighed it, scalded it, and determined the glycogen and sugar it contained. This opera- tion was repeated at intervals with other portions of the liver. In this manner he discovered that the amount of sugar in- creases steadily from the moment of death, a process which appears to correspond with the death of the liver tissue and the cessation of its metabolic activity. On the other hand the glycogen does not undergo any corresponding diminution, except in rabbits in which it begins to dwindle at once and diminishes rapidly as the production of sugar increases. Seegen denied that glycogen is the source of sugar, and suggests that the liver converts peptone into sugar. He found that when peptone solutions were introduced into the stomachs of dogs the liver sugar was increased by from 50 to 200 per cent. Fie also observed that when peptone solution was injected into the portal, vein in 30 — 40 minutes the liver sugar increased from 100 to 300 per cent. He also estimated the amount of sugar which passes into the hepatic vein of a dog, and has found that the amount of carbon in the food of a dog on meat diet, neither losing nor gaining weight, is sufficient to account for the carbon of the sugar. He therefore held that sugar formation is a normal function of the liver, the quantity being considerable, looo grammes in twenty-four hours for a man weighing 80 kilos, the sugar being decomposed in the body. He believed that this is a true liver sugar distinct from that derived from glycogen, that it is formed in the liver post mortem, but not at the expense of the glycogen present, that it does not disappear if the animal is starved or fed entirely on fatty food, and that it is formed from peptone, for after feeding with peptone its quantity becomes increased three-fold. It seems to be admitted on all hands that carbo-hydrates may be formed in the body from proteids, either by splitting off (Pavy), or by complete decomposition and building up again (Pfluger), and it is even contended by some that every lOO grammes of albumen converted into urea yields 45 grammes of sugar, or for every gramme of nitrogen eliminated DIABETES MELLITUS. 225 by the urine 2'8 grammes of sugar are formed. It is believed that this formation of sugar takes place in the liver. Obviously when we reflect on its various sources the amount of sugar produced in the liver must be enormous, yet what becomes of it? Pavy maintains that there is less sugar in the hepatic vein than in the portal vein, and although he is in this respect stoutly opposed by Seegen, who in sixty-four observations found the sugar increased from 80 to 100 per cent, in the hepatic vein, he has found many observers to support his assertion that arterial blood contains no more sugar than venous blood (Abeles, Beck and Hoffmann). Chauveau and Kaufmann find that arterial always contains more sugar than venous blood, so that it may be wise for the present not to abandon the notion that sugar is poured into the circulation by the liver in such quantities as can be dealt with by the tissues, in which it is ultimately utilised and decomposed. But it has been asked. What becomes of the enormously larger amount of glycogen formed by vegetable feeding animals ? The slow and sedentary ox does not seem likely to use up as much glucose as the restless tiger, and Pavy thinks this difficulty so great as to be fatal to the above ex- planation. But modern physiologists admit that carbo- hydrates may be stored in the body, not only as glycogen but as fat, and that it is in the latter form that the excess of sugar accumulates in the bodies of vegetable feeding animals. EXPERIMENTAL GLYCOSURIA. Glycosuria may be produced experimentally on animals by various lesions. Since Claude Bernard discovered that sugar appeared in the urine of an animal after puncture of the floor of the fourth ventricle, an immense mass of facts of a similar order has been accumulated, so that now it would seem as if almost any lesion of the nervous system, central or peripheral, may cause gly- cosuria, while a whole host of toxic substances have been shown to possess, with more or less certainty, the same power. In addition to the "Diabetic Puncture," the following lesions of the nervous system are stated to be followed by glycosuria : — I. — Injury to the verniifonn process of the cerebelhnn (ECKHARD). 2. — Section of the Spinal Cord at various levels (SCHIFF). 15 226 DIABETES. 3. — Section of the antei'ior cervical nerve roots causes per- manent glycosuria ; section of corresponding posterior roots causes only temporary glycosuria (SCHIFF) ; artificial neuritis of the first pair of dorsal nerves (Arthaud and Butte). 4. — Destruction of various sympathetic ganglia, e.g., the superior and inferior cervical (Pavy) ; the first thoracic (Eckhard) ; the abdominal (Klebs). 5. — Section of the splanchnic nerves (Hensen), or ligatur- ing them (Arthaud and Butte). Glycosuria caused by puncture of the floor of the fourth ventricle may be set aside by section of the splanchnic nerves. Other experimenters too have found that section of the splanchnics is not followed by glycosuria, and Cyon explains this by supposing the operation to give rise to such general dilatation of the intestinal blood-vessels that there is not enough blood to increase the circulation through the liver. He says, if the hepatic vessels be first dilated and the spinal cord and splanchnics then cut, the formation of sugar is not arrested. 6. — Glycosuria in certain cases follows irritation of the right vagus nerve (Arthaud and Butte). 7. — Similar results may follow section and stimulation of the central end of an ordinary sensori-motor nerve, such as the sciatic (Schiff). 8. — According to von Mering and Minkowski the complete removal of the pancreas in dogs is always followed by glyco- suria, but this is prevented by leaving a small part of the gland even though the duct be removed. The result therefore cannot be due to the absence of pancreatic juice in the intestine. Lepine suggests that the pancreas forms a sugar-destroying ferment which is absorbed by the veins and carried to the liver by the portal vein. He performed .the following experi- ment : Two dogs were chosen of equal size and kept fasting for ^^6 hours, the pancreas was then completely removed from one, and both were left unfed for 60 hours, when they were bled to death. In the blood from the one without the pan- creas there was nearly three times as large a percentage of sugar as in the blood of the other, while in fifteen hours the blood of the latter had lost 33 per cent, of its sugar, while that of the former dog had lost only 6 per cent. Minkowski has given the results of further experiments on this point. It is noteworthy that dogs deprived of the pancreas, present not only glycosuria, but all the charac- DIABETES MELLirUS. 227 tcristic symptoms of diabetes, polyuria, thirst, hunger, and emaciation ; the glycogen rapidly disappears from the liver, and there is diminished absorption of albumens and fats. After partial extirpation of the pancreas as a rule diabetes mellitus does not appear, even when the remaining portion is no longer connected with the intestine. Still, these remaining portions must not be too small. In two cases in which the remaining pieces of the pancreas had only xVth or tVth the size of the normal organ glycosuria in its severest form was observed similar to that after total extirpation. It is doubt- ful in these cases whether the remaining portions retain their functions. In two other cases after partial extirpation a transitory glycosuria occurred, which only continued a few hours, and later even after abundant carbo-hydrate food it did not return ; this transitory glycosuria may perhaps be regarded as a result of the injury which the rest of the pancreas had suffered by the operation. In one case, by partial extirpation of the pancreas, diabetes was produced corresponding to the slight form of this disease in man. In a dog weighing 12 kilos, a portion of the pancreas, 31 grammes in weight, was removed; only the outermost point of the tail end remaining. No sugar appeared in the urine for the next five days, even when the dog was fed with meat and milk. But after carbo-hydrates sugar appeared in the urine. After 20 grammes of grape sugar, 78 appeared in the urine. By flesh diet the sugar disappeared from the urine, to return again in great amount after a diet of cane sugar. There was therefore, in this case, after the partial extir- pation of the pancreas, an injury of that specific function of this gland, the complete deficiency of which, after total extir- pation, causes the severe form of glycosuria. In a still more remarkable case, the pancreas was partially extirpated and the stump retaining its vascular attachments grafted below the skin of the abdomen. Even thus displaced the gland appeared capable of exercising its function, for the urine remained free from sugar ; the graft was ultimately excised, and the dog became diabetic (MINKOWSKI and H£don). Puncture of the floor of the fourth ventricle after extirpation of the pancreas, increases the glycosuria by 30 or 40 per cent. (H£don) ; while if the medulla be so divided that the liver is cut off from the sympathetic, no glycosuria follows cxtirpa- 228 DIABETES. tion of the pancreas (Chauveau and Kaufmann) ; on the other hand glycosuria follows puncture, but does not occur after removal of the pancreas in fasting animals (Thiroloix). Lepine also removed the pancreas from a starving dog, the operation being followed by glycosuria, which was temporarily controlled by injecting into the jugular vein chyle taken from the thoracic duct of another dog during digestion. He also found that chyle added to a solution of glucose, maintained at a temperature of 38° C, caused a sensible diminution of the amount of sugar in some hours. He also found that malt diastase diminished the glycosuria of an animal rendered dia- betic by the removal of the pancreas. Chyle from an animal deprived of its pancreas had no effect upon sugar. Lannois, at the instigation of Lepine, made subcutaneous injections of pilocarpine on a diabetic woman with the result that there was a very notable diminution of the glycosuria, in conse- quence, it is suggested, of the stimulation of the pancreas by this drug. Arthaud and Butte dispute the theory of Lepine on the ground of experiments in which they ligatured all the pan- creatic veins of a dog, without increasing the amount of sugar. On the other hand by ligaturing all the branches of the coeliac axis, except the hepatic artery, so as to cause an exces- sive flow of arterial blood to the liver, they caused glycosuria, and the animal died after three months. The pancreas showed no alteration, as its circulation had been re-established by the mesenteric artery which had not been tied. Lepine now maintains that blood and chyle contain a powerful glycolytic ferment, which is absent or greatly diminished in animals deprived of the pancreas. He believes that this is a product of the internal secretion of the pancreas, and that normally it destroys a large part of the sugar before it reaches the liver. His statements lack confirmation, and the theory is a very unreasonable one, as it would imply a great waste of nutritive material. Kaufmann has suggested that the pancreas secretes a substance which exercises a con- trolling influence over the liver, and that in its absence this organ permits an excessive amount of sugar to pass into the circulation. Arthus denies the existence of Lepine's glycoly- tic ferment in living blood, and contends that it is a cadaveric phenomenon ; and Hedon could find no glycolytic substance in the pancreas, nor any diabetogenic substance in diabetic blood. DIABETES MELLITUS 229 9. — De Renzi and Reale say that glycosuria is caused by resection of the duodenum and extirpation of the saHvary glands. 10. — Gley states that dogs deprived of their thyroids become temporarily glycosuric ; but Minkowski denies this. II. — Hay found that the injection of neutral salt solution into a ligatured loop of intestine was sometimes followed by glycosuria. 12. — Kolisch produced glycosuria by tying the superior mesenteric artery. 13. — Glycosuria may in addition be determined by pro- cedures directly occasioning increased flow of blood to the liver, as in the following examples : — a. — Tying the accessory branch of the portal vein in frogs, so as to make the whole of the abdominal blood pass through the liver (Schiff). b. — Irritation of the liver with needles (Schiff) or by elec- tricity (Pavy). c. — Compression of the aorta or portal vein. d. — Injecting defibrinated arterialised blood into the portal vein. The same phenomena may also be caused by a great many toxic substances : — a. — By the inhalation of chloroform, of carbonic acid, car- bonic oxide, sulphuretted hydrogen and carbon disulphide. b. — By strychnine (M. FOSTER), salicylic acid (BURTON), phosphoric acid (Pavy), turpentine (Alm^n), corrosive sub- limate (Rosenbach), uranium nitrate (Leconte), benzol, acetone, aldehyde, ether, chloral, amyl nitrite, amyl alcohol, morphia, opium, and curare.* c. — Dimethyl aethal carbinol (Thierfelder). d — Phloridzin. Phloridzin is a glucoside discovered in 1885, by von Kormick, in the bark of apple, pear, cherry and plum trees. It forms silky, shining, needle-like crystals, soluble in cold water. Its formula is — .CqiHo^O^o 4- H2O which may break up into — CisHi^Oj; and CgH^oOg Phloretin. Phlorosin. * Ashdown believed that in many cases it is glycuronic acid and not glucose which appears in the urine in these circumstances {op. cit.). 230 DIABETES. The latter substance has the formula of sugar, and like it reduces copper salts and undergoes fermentation. When phloridzin is administered to animals it causes glycosuria, even when the liver has been rendered free from glycogen, or extirpated. The action of this substance has been studied by von Mering, who considers that he has proved that the sub- stance excreted is really grape sugar, and not phlorosin. Phloridzin caused glycosuria when given by the mouth or injected subcutaneously, or introduced into the veins. The sugar in the blood was not increased, while the hepatic glycogen diminished. The glycosuria continued even when the animal was starved for a long period. Occasionally in long-standing cases acetone and /3-oxybutyric acid were pre- sent in the urine, and symptoms like diabetic coma occurred. The sugar was shown to be derived from the albumens of the body. Phloretin is the only decomposition product of phloridzin which produced glycosuria; phlorose, phloritinic acid and phloroglucin being inert. After the administration of phloridzin and chloral-hydrate, sugar and uro-chloral acid appeared in the urine. Phloridzin was given to three persons, and sugar in con- siderable quantity formed in their urines. One gramme of phloridzin caused a daily excretion of 97 grammes of sugar ; on the day after the phloridzin was stopped the sugar dis- appeared. No ill effects were produced through the use of the drug, which was continued for a month. Zuntz proved that when injected into one renal artery, it caused glycosuria from the corresponding kidney only, for at least half-an-hour, and Minkowski found that after extirpation of the kidneys the administration of phloridzin was not fol- lowed by any increase of sugar in the blood ; in man also the ingestion of phloridzin causes glycosuria without hyperglycse- mia. Where the renal epithelium is already gravely compro- mised, phloridzin may fail to cause glycosuria, as was the case in seven out of ten cases of granular kidney to whom Klemperer administered it. As phloridzin causes no increase of sugar in the blood, von Noorden believes it causes glycosuria by paralysing the renal epithelium so as to permit the passage of sugar into the urine. With reference to some of these effects it is of interest to note that Masoni states that curare diabetes may be prevented by the previous administration of arsenic, while Kirk thinks DIABETES MELLITUS. 231 that the substances found in the urine of persons taking saHcylates are chiefly other reducing bodies but that a trace of sugar may perhaps be produced by the action of the salt on the blood corpuscles. It has been already mentioned that ligature of the bile ducts causes glycogen to disappear from the liver, and under these circumstances puncture of the floor of the fourth ventricle fails to cause glycosuria (WiCKHAM Legg,VON Wittich, E. KtJLZ, Frerichs). Wyatt has recently related the case of an old diabetic lady in whom the sugar disappeared from the urine during an attack of jaundice, but this, though usual, does not always follow, as the following case shows : — Case 28. — Diabetes Mellitiis — early diarrlicea — inte7xurrent jmmdice — fersisience of glycosut ia. William J., aged forty-five, blacksmith, attended as an out-patient on June I2th, 1887, complaining of pain in the loins and hypochondrium. His illness began twelve months before with diarrhoea, and three months later this was followed with jaundice, which had persisted. His urine was dark amber, acid, 1026, loaded with sugar, containing a faint haze of albumen and a little bile pigment. PATHOGENY OF DIABETES. The true bearing of all these facts upon the pathogenesis of diabetes must remain for the present unsettled. Let us take note for a moment of the gaps in our knowledge. I. — It is not known definitely in what form the products of saccharine and starchy food leave the liver, whether as sugar in small quantities to be rapidly destroyed, or partly as sugar and partly as fat, as Pavy thinks. 2. — It is not known by what paths the influence of the various nerve lesions, which produce glycosuria, reaches the liver, though this is probably through the pneumogastrics (Arthaud and Butte). 3. — We are still uncertain of the nature of the influence of the pancreas on the production of sugar. Until these questions have been settled we have not a proper basis for a rational pathology of diabetes. There are two main theories which receive a large amount of support : i, that of overproduction by the liver : 2, that of diminished destruction by the tissues ; and to these we may add, 3, paralysis of the renal epithelium, which is a return to the old view of the renal origin of diabetes. The first of these is generally accepted, and modern opinion 232 DIABETES. inclines to the view that the overproduction is the consequence of either direct nerve stimulus to the hepatic cells, or removal of some influence which normally controls them, e.g., the pancreatic secretion. Pavy, as is well known, regards the excessive activity, or as he thinks it, morbid function of the liver, to be due to vaso-motor paralysis ; but Michael Foster points out that strychnine poisoning, in which the vessels are strongly contracted, causes glycosuria. It is possible that strychnine causes a rapid discharge of sugar before the vaso- motor spasm has taken place ; but the curious effects of phloridzin indicate that in the action of drugs we may have to do with a quite different mechanism. Hamilton, accepting the vaso-motor theory, says there are two possible modes in which it may act : (i) By diminishing glycogenesis, so that the sugar brought to the liver leaves it unchanged ; and in support of this he quotes Ehrlich's observation that very little or no glycogen can be found in fragments of liver withdrawn by a trochar from diabetics during life ; (2) By excessive conversion of glycogen into sugar. Kaufmann, in support of the theory that diabetes is the result of overproduction of sugar by the liver cells, has shown that suppression of the function of the liver diminishes the amount of sugar in the blood of dogs rendered artificially diabetic as well as in that of healthy animals. He points to the observations of Voit and Leo which show that diabetics use up as much oxygen and excrete as much COg as healthy persons, and his analyses of venous and arterial blood indi- cate that the tissues consume the same amount of sugar in diabetic and healthy animals. The view that glycosuria depends upon non-destruction or diminished consumption of sugar in the tissues has been main- tained by Seegen and Ebstein, and has recently found a brilliant defender in von Noorden. Von Noorden explains that in health the carbo-hydrates are stored up in the body as glycogen and fat, while a certain proportion is constantly consumed by the tissues. If a greater quantity reaches the tissues than these can consume, the sur- plus appears in the urine. Glycosuria following Bernard's puncture, results from this injury causing the liver to suddenly discharge its store of glycogen, giving rise to hyperglycsemia and temporary glycosuria. An analogous result is seen in the glycosuria which follows concussion and apoplexy, while the DIABETES MELLITUS. 233 glycosuria which sometimes follows attacks of biliary colic is comparable to the discharge of glycogen which follows ligature of the bile duct, but these can only cause tem- porary glycosuria. In diabetes there is no proof of over- production of sugar, the occurrence of which could only be admitted when the excretion of sugar exceeds the sugar derived from the food, including that formed from albumens as well as that due to carbo-hydrates. He confesses that the observations of Kaufmann, already quoted, as well as those of Leo and Voit, are opposed to his views, but he doubts the accuracy of the methods in use for the estimation of sugar in the blood. Yet he has to make the important admission that the natural glycogen reservoirs (liver, muscle, etc.) must have become insufficient, and that the body must also have lost its capacity to compress sugar molecules into fat. That the influence of the nervous system upon the liver is limited to causing a discharge of glycogen is disproved by the fact that puncture will cause glycosuria in an animal which has been starved for a week and which therefore no longer has glycogen stored up in its liver (THIROLOIX). But it seems to me that the admission, that the liver has lost its power to retain glycogen, and passes into the circulation in the form of sugar all the carbo-hydrates it receives, concedes nearly all the other side claims. The only point is whether the produc- tion of sugar is an active vital function of the liver cells or the result of some defective power ; in either case, an excessive output of sugar is the consequence. I think the balance of evidence in favour of those who believe in the theory of over-production by the liver as the cause of diabetes, and I incline to the opinion that this is an excess of a normal vital function of the liver cells. The third theory need not detain us ; it merely amounts to a suggestion that glycosuria may under certain circumstances be of a renal origin. Klemperer believes that this condition exists, but is extremely rare. We not very uncommonly meet with cases in which slight glycosuria accompanies well- marked albuminuria and other signs of chronic Bright's disease in elderly persons, and these may be examples of this renal glycosuria. Jacoby, of Strasburg, has observed glyco- suria in rabbits fed on carrots, when diuresis was produced by caffeine, and glycosuria has been observed to accompany the diuresis caused by digitalis. Klemperer has observed a case of interstitial nephritis with slight glycosuria, which was not 234 DIABETES. increased by a diet composed largely of carbo-hydrates, or diminished by exclusive meat diet. I shall onl}^ mention the theory of Cantani and B. W. Foster, that the liver in diabetes forms an inoxidisable form of sugar, the so-called para-glucose, as this is not supported by any recent observations. Apart altogether from this hepatic pathology are the theories of Ziemssen and Latham, who place the production of sugar in the muscles. According to Latham a degeneration takes place in the muscle albumen due to vaso-motor paralysis and vascular dilatation, leading to imperfect oxidation and the production of sugar in the following manner: the lowest cyan- alcohol CHaj-^TT instead of being oxidised to CO2 and roFT H2O, is stopped at CH2 ] roOH S^y^°^^^^ ^^^^ ' ^^^^ ^^ further oxidation forms methyl aldehyde, thus :- — CH^^OOH + O = CO. + {^0H+ "^O Then six molecules of methyl aldehyde may condense, as has been shown to occur in plants, to form glucose thus : — 6HCOH = CgHjA But if this were true the venous blood in diabetes should show an excess of sugar, which is certainly not the case. BIBLIOGRAPHY. Arthaud and Butte. Recherches sur la pathogenie du diabete, du syn- drome clinique et des lesions anatomo-pathologiques determinees chez les animaux a la suite de la nevrite des nerfs vagues. " Arch, de Physiol.," 1888, p. 344. Arthus. Glycolyse du sang et le ferment glycolytique. " Arch, de Physiol. ," 1891, No. 3. AsHDOWN. Laboratory Reports of the Royal College of Physicians. Vol. II., Edinburgh, 1889. Berenger-Feraud. Diabetes in an Ape. " Comptes Rendus," I. , 1864. Bernard (Cl.). Sur le diabete. Lefons de pathologic, experimentale. Tome I. Paris, 1855. Bourchardat. Nouveau recherche sur le diabete. "Compt. Rendus," 1841. Brucke (E.). Vorlesungen iiber Physiologic. I. Bd. 2nd edition. 1875. Cantani (A.). Researches on Diabetes Mellitus. " Brit. Med. Jour." 1871, I., p. 208. Chauveau and Kaufmann. Sur la pathogenie du diabete. " Le Progres Med.," 1893, I., p. 120. Dalton (J. C). A Treatise on Human Physiology. 7th edition. London, 1882, p. 206. Dastre (A.). Recherches sur les ferments hepatiques. " Arch, de Phys.," 1888, Vol. I., p. 69. DIABETES MELLITUS. 235 De Renzi and Reale. Ueber die Aetiologie und Behandlung des Dia- betes Mellitus. " Wiener med. Woch." 1891. No. 33. DoBSON (M.). Experiments and Observations on the Urine in Diabetes. " Med Ob. and Enq.," Vol. V. London, 1776. DoMiNicis (N. de). Studii sperimentali intorno agli effetti delle estirpazioni del pancreas negli animali. Diabete mellito sperimentale. " Giorn. inter, delle Sci. Med." 18S9, p. 801. Weitere Mittheilungen iiber Diabetes pancreaticus. " Miinchener med. Woch.," 1891. Ebstein (W.). Die Zuckerharnruhr, ihre Theorie und Praxis. Wiesbaden, 1S87. EcKHARD (C). Die Stellungen der Nerven beim kiinstlichen Diabetes. "Beit, zur Anat. und Phys.," Bd. IV., 1867. FiNKLER. Fifth Congress for Internal Medicine, Wiesbaden, April, 1886. Fort (A.). Diabete consecutif a la chloroformisation pour une operation de retrecissement de I'uretre. " Gaz. des Hop.,"' 1883. No. 148. Foster (B. W.). Clinical Medicine: Lectures and Essays. London, 1874. Foster (M.). A Text-book of Physiology, Part II., Book 2. London, 18S9. Frerichs (F.T.). Ueber den Diabetes. Berlin, 1884. Ueber den plotzlichen Tod und iiber das Coma bei Dia- betes. " Zeit. fiir klin. Med.," Bd. VI , Heft i, 1883. Gley (E.) De la glycosurie chez les chiens thyroidectomises. " Arch, de Physiol." 1893, No. 2. Gregory (W.). First Lines of the Practice of Physic, by William Cullen, continued and completed. Edinburgh, 1829. Griesinger. Studien iiber Diabetes. "Arch. d. Phys. Heilk. ," 1859. Hamilton (D. J.). A Text-book of Pathology, Vol. I. London, i88g. He DON (E.) Influence de la piqure du plancher du quatr. ventr. chez les animaux rendus diabetiques par I'extirp. du pancreas. "Arch, de Physiol.," 5th s. Vol. VI., p. 269. Sur la production de la glycosurie et de I'azoturie apres I'ex- tirpation totale du pancreas. " Comptes Rendus." 112, No. 18. Greffe sous-cutanee du pancreas. "Arch, de Physiol." 1892. 5th series., vol. IV., p. 617. Sur le pathogenic du diabete. Ibid., p. 247. Hirsch (A.). Handbook of Geographical and Historical Pathology. Lon- don : New Syd. Soc, 1883—86. Johnson (G. S.) On the absence of Sugar from Normal Urine. " Med. Chir. Trans." Vol. LXXVI., p. 151. Kaufmann (M.). Mecanisme du diabete pancreatique. " Le Progres Med." 1894, I., pp. igi, 223, 285. On the Pathogeny of Diabetes Mellitus. " The Medical Week," 1895, p. 73. Recherches exper. sur le diabete pancreatique et le mecanisme de la regulation de la glycemie normale. " Archives de Physio- logie," 1895, 5th series. Tome 7, p. 209. Nouvelles recherches sur le mode d'action du systeme nerveux dans la production de I'hypo-glycemie. Ibid. p. 287. Aper9U general sur le mecanisme de la glycemie normale et du diabete sucre. Ibid., p. 385. Kirk (R.). On Artificial Glycosuria. "The Lancet," 1888, IL, p. 87. Klebs (E.). Handbuch der path. Anatomic. 1870. Klemperer. Regulatory Glycosuria and Renal Diabetes. " The Medical Week," 1896, Vol. IV., p. 259. KoLiscH (R.). Exp. Beitrage zur Lehre von der alimentaren Glycosurie. " Centrlbl. f. k. Med.," 1892, No, 35. 236 DIABETES. KiJLZ (E.) Beitrage zur Lehre von der Glycogenbildung in der Leber. "Arch. f. Physiol." XX. Landois (L.). a Text-book of Human Physiology, edited by Stirling. 3rd edition. London, 1888. Latham (J.) Facts and Opinions concerning Diabetes. London, 181 1. Legg (J. Wickham). On the Bile, Jaundice, and Bilious Diseases. London, 1880. Leo (H.). Ueber die Ebstein'sche Theorie des Diabetes mellitus. "Centrlbl. f. k. Med.," 1892, No. 25. Lepine and Barral. Sur le pouvoir glycolytique du sang et du chyle. "Comptes Rendus," 90, 1890. Lepine (R.). Le ferment glycolytique. Paris, idgi. Masoni (E.). Diabete artificiel, moyens de le produire, et moyens qui pourraient empecher sa production. "Revue Med. de Louvain," 1884. Mead (R.). A mechanical account of Poisons. London, 1747. Minkowski (O.) Diabetes Mellitus nach Extirpation des Pancreas. "Arch. f. Exp. Path.," vol. XXXI. p. 85. The Physiology of the Carbo-hydrates ; their applicatior as food and relation to Diabetes. London, 1894. MoRAT and DuFOUR. Les nerfs glycosecreteurs. "Arch, de Physiol.," 5th 5., vol. VL, p. 371. NooRDEN (C. von). Art. Diabetes, xxth Century Practice of Medicine. London, 1895. Paton (D. Noel). On Hepatic Glycogenesis. "Phil. Trans.," vol. CLXXXV., B. pp. 233—77. Pavy (F. W.). Researches on the Nature and Treatment of Diabetes. 2nd edition. London, 1869. The Physiology of the Carbo-hydrates. London, 1894. RoLLO (J.). Cases of the Diabetes Mellitus. 2nd edition. London, 1798. ScHiFF (J.M.). Untersuchungen iiber die Zuckerbildung. Wiirzburg, 1859. Schmiedeberg and Meyer. Ueber Stoffwechselprodukte nach Campher- fiitterung. " Zeitschr. f. Physiol. Chemie," Bd. III., p. 422. Seegen. Der physiologische Auflage der Diabetes Mellitus. " Zeitschr. f. Klin. Med.," Bd. VIII., p. 328—363, and Bd. XIIL. p. 267 ; also " Pfliiger's Archiv," Bd. XL., p. 48. Der Diabetes mellitus. Berlin, 1893. Senator (H.). Ziemssen's Cyclopsedia of the Practice of Medicine. Vol. XIL London, 1887. Thierfelder (H.). Ueber die Bildung der Glycuronsaure beim Hungertier. " Zeitschr. f. Phys. Chem.," Bd. X., p. 134. Thiroloix. Influence du regime alimentaire sur la production du diabete experimental. " Le Progres Med.," 1894, I., p. 286. Von Mering Q.). Ueber Diabetes Mellitus. "Zeitschr. f. klin. Med.," Bd. XIV., p. 405. and Minkowski (O.) Diabetes Mellitus nach der Extir- pation des Pancreas. "Arch. f. exp. Path.," Bd. XXVI., Heft 5 and 6; and " Centralb. fiir klin. Med." June 7th, 1890. Wedexski. Zur Kenntniss der Kohlehydrate im normalen Harn. "Zeitschr. fcir physiol. Chemie.," Bd. XIIL, p. 122. Weintrand and Laves. Ueber den respiratorischen Stoffwechsel im Dia- betes Mellitus. " Zeitschr. f. physiol. Chemie," Bd. XIX., p. 574, 1894. Willis (T. ). Pharmaceutice rationalis sive diatriba de medicamentorum operationibus in Humano Corpore. Oxonio, e theatro Sheldoniano, prostant apud Ric. Davis, 1679. Part I., Sect. IV., Cap. III., p. 85. Wittich. Ueber das Leberferment. " Pfliiger's Archiv," Bd. VII. Wyatt (W.T.). The connection between Glycosuria and Biliary Obstruc- tion. "The Lancet," 1886, Vol. I., p. 918. ■^1>1 Chapter XVII. ETIOLOGY OF DIABETES PREDISPOSING CAUSES. Geographical Distribution. — Very little has been hitherto published respecting the geographical distribution of diabetes. This is in part due to the absence of trustworthy statistical data and also because the incidence of a disease, the mortality of which is on an average less than i per 50,000 of population, is a subject upon which the experience of individual practition- ers must be a fallacious guide. By the kindness of numerous friends I have been able to obtain statistics from which the following figures are calculated (1891). TABLE L Showing the mortality from Diabetes Mellitus in some of the principal cities of Europe. Name. Rate per ioo,oco of population. Name. Rate per loo.coo of population. Paris * Copenhagen! Leipzig London Berlin 9-6 7-2 6-4 5-88 5-04 Dresden Vienna Christiania Naples Rome 4-6 4 "2 3-9 3'2 '•67 . * Paris has since risen to 14, as shown in Table IL f This includes 72 provincial towns also. These figures are calculated from the averages of five years at least, and are probably fairly trustworthy, as the registration in these cities is carefully carried out. Trousseau regarded the disease as rare in Paris, and there can be no doubt that it has greatly increased of late years, as shown in the following table compiled by Dr. Jacques Bertillon, Chef des travaux statistiques de la ville de Paris. :38 DIABETES. TABLE II. Mortality from Diabetes Mellitus in Paris for each 100,000 of population. ON ^ ui u-i VO t^ t-^ 00 00 ■0 I~^ 00 l_l M CO 6 ^ CO CO CO CO ON ON ON VO (^ 00 CO CO 00 CO CO CO 00 CO CO 00 00 CO CO *"* *~^ •"• •^ '"' 1— » •^ ^^ '^ *"• •"■ •^ 1— ( 4 3 3 5 8 II 12 13 14. i3 13 12 14 English statistics show no such rapid rise of late years either in London or the country : in both the rate per 100,000 of population was, in 1893, only a little over 7. TABLE IIL Showing the mortality from Diabetes Mellitus in certain European countries and British colonies (1891). Rate per 100,000 Name. Rate per 100,000 ot population. England 5-8 Western Australia 1-9 Ireland 32 New Zealand 2-6 Scotland 2-1 Jamaica 17 Prussia I "3 British Guiana 0*24 Norway 1-9 Montserrat 6-0 Italy 1-6 Bahamas 0'2 Gibraltar 6-8 St. Kitts 0*2 Malta 13-1 Bermuda 07 Cyprus no deaths Natal 07 Heli2:oland St. Helena 0-5 New South Wales 27 Sierra Leone o*i6 Victoria 1-6 Ceylon* 2-4 Queensland o-S Hongkong ... .'. O'l Tasmania 3-2 Mauritius I "4 South Australia ... 1-6 '''■ Said to be untrustworthy. The figures for the Colonies are based on official statistics supplied me through the Colonial Office by the courtesy of the Rt. Hon. Lord Knutsford, at that time Secretary of State for the Colonies, and are calculated on the average of ten years. In addition to those placed in the table the following were returned as having had no deaths from diabetes regis- tered within the period taken (the last ten years) ; viz., Fiji, Trinidad, St. Lucia, St. Vincent, Nevis, Antigua, Dominica, Virgin Islands, Falkland Islands, Lagos and Labuan. There was no general return from Barbadoes, but the mortality is ETIOLOGY. 239 estimated at i per 100,000 of population; Cape Town has an estimated mortality of only 0"4 per 100,000 ; and there is no return from the Gold Coast, but the principal medical officer reports the disease to be very rare. With respect to Ceylon, the principal colonial medical officer, Dr. W. R. Kinsey, writes in his official despatch to the Secretary of State: "The Registrar-General's figures, if forwarded without explanation, will convey a very erroneous idea of the prevalence of diabetes in Ceylon, because the registration of causes of death is wholly unreliable, as no medical certificate is required .... and the natives of Ceylon are peculiarly sensitive on the subject of diabetes; they consider it disgraceful to have it, they never speak of it, and conceal its existence as long as they can, for it is looked upon as a punishment for illgotten wealth, and that it is necessarily fatal and unamenable to treatment." He goes on to say that "it is most prevalent amongst the well-to-do natives." One doctor in private practice informed him that he sees in his practice an average of two fresh cases of diabetes a week, and that temporary glycosuria is very frequent. He has no hesitation in saying that it is a common disease among all races, alike among Hindus (Tamils), Mahommedans, and Cingalese. It is certainly hereditary and most common among the well-to-do class. He is thoroughly of opinion that over-indulgence in starchy foods and sugar, combined with sedentary habits and resulting corpulence, and sexual excesses, indeed, excesses of any kind, are important factors in its causation ; he thinks that congestions of the liver which are apt to occur .in hot climates in those persons who indulge freely in the pleasures of the table, favour its production. He believes it to be much more common in males than in females, and between the ages of thirty-five and fifty, while it is very rare in children. It has not been possible to obtain any official statistics respecting the mortality or incidence of diabetes in India, but there is strong testimony to its occurrence very commonly in all parts of that country. In answer to my enquiries, Surgeon- General Cornish (late of the Madras presidency) wrote to me as follows: — "The frcquenc}^ of diabetes amongst the better classes, i.e., those who do not engage in manual labour, is a matter of common notoriety amongst Indian practitioners. The causes of the disease I am not so clear about. Diet, chiefly farin- 240 DIABETES. aceous, oily, and saccharine, may have something to do with It. But personal habits in regard to venery and other things may also have to be considered. It should be noted also that young India is subject to much brain stimulation. " The craving for higher education and for learning western ideas through a foreign language may unduly stimulate the mental and reasoning faculties in bodies perhaps insufficiently nourished and undeveloped. Whatever the causes are, we practically find some of the best intellects in India prematurely extinguished by diabetes. "Over and over again it has been within my experience to find that the most promising men amongst the lawyers and university graduates have been cut off in the prime of life by this disease. " Since I left India, I think the subject has attracted attention in Calcutta, and I daresay the Indian Medical Gazette, of the last five years, may give you some facts in regard to the matter. My own observations seemed to show that the educated and learned classes (chiefly non-flesh eaters) suffered in the greatest proportion, and that it was rare to find men of these classes lasting to a robust old age. The subject is a very interesting one, and well merits searching inquiry." Norman Chevers wrote to the same effect, referring to its frequency among rich elderly natives in Calcutta, many of whom are fat and indolent, and immoderately fond of sweet- meats. The editor of the Indian Medical Gazette, writing in 1 87 1, stated that among the upper and middle classes of natives in Calcutta almost every family had lost one or more of its members from this disease. No statistical information could be obtained from the Straits Settlements (Singapore), but the disease is said to be not uncommon. A statement was forwarded from a Chinese doctor, in which he observed that while the disease is very rare in China, in Singapore he had met with seven or eight cases, in fifteen years' practice. Dr. Graham, of Sumatra, wrote that in seven years' practice among 15,000 Chinese labourers, he had met with only one case. The statement of the Chinese doctor above quoted, con- cerning the rarity of diabetes in China, has been fully borne out by all the information I have been able to obtain. Dr. Burge, of Shanghai, was exceedingly kind in making enquiries amongst his colleagues, and their unanimous testimony is that ETIOLOGY. 241 the disease is very rare in China. It is also equally rare in Japan, so far as my information extends. The statistics from Mauritius were followed by a report ol a discussion on Diabetes, which was instituted in the local medical society as a result of Lord Knutsford's circular, and this fully bore out the testimony of the figures that the disease is rare in the island. The fact, taken together with the rarity of the disease in British Guiana, is interesting, because both countries employ a large number of natives of India as coolies on sugar plantations. It seems to afford a strong confirmation of the views expressed by Indian practitioners in favour of the exemption of those classes engaged in manual labour. From Madagascar no statistics were obtainable, but Mr. S. Blackwell Fenn stated that it is very rare. No statistics were to be obtained from Persia, but Dr. Tholozan kindly wrote me a letter giving me the result of his long experience in that country. He believes it is less frequent than in Europe, and more common in individuals of Turkish race than among native Persians. He attributes the disease to the immoderate use of rice, sweet sherbets and sweetmeats. Dr. Hessenauer wrote that in five years' practice he had not met with a single case of the disease in Palestine. The official statistics of the town of Smyrna were applied for but did not come to hand, though they were promised. My application to official sources for statistics for Eg}'pt was refused on the ground of insufficient clerical assistance to compile the information, but Dr. Grant Bey kindly wrote me that the disease is not uncommon and that according to his experience it prevails chiefly among Europeans, Syrians and Turks, the Copts and Arabs being less subject to the disease, though not exempt. In Cyprus there had been no death from diabetes for ten years, and the chief medical officer in ten }'ears' practice had seen only two cases, one in a Cypriot. Respecting America, it was found very difficult to get any information of value. Tyson estimates the mortality from diabetes in Philadelphia at ii per 10,000 deaths, and in New York 7, whereas in London the proportion is 26, and in all England 25. According to the editor of the New York Medical Record the mortality from diabetes in the United States was 837 or 2'i per 100,000 living in 1 870, and 1443 or 2'8 per 100,000 t6 242 DTABETES. living in i88o. The article goes on to say that glycosuria is very prevalent in the north-west where the air is very dry, business competition exceedingly keen and nervous wear and tear consequently very great. It is to be feared that at present no statistics can be obtained in the United States which can be fairly compared with the figures obtained from European sources. The disease seems to be rare in California, the statistics of San Francisco returning the mortality at only 0"6 per 100,000 living. Dr. Gresham, of Los Angeles, wrote that in seven years' practice he had not met with a single case. From South America it is even more difficult to get any information. Dr. Louis Colbourne, of Buenos Ayres, wrote that there are no statistics, but that in his opinion it is very rare, and Dr. Flarvey reported the same of Chili. Its rarity in British Guiana is shown by the figure in Table III., and this is confirmed by a private letter from Mr. C. Mac- namara, lately Colonial Surgeon at Essequibo. This information, by no means complete, has been obtained with a vast amount of labour, and probably represents all or nearly all that can be learnt upon the subject at present. These figures show that the African and Mongolian races enjoy considerable immunity from the disease in their own countries. Dr. Tyson, of Philadelphia, (U.S.A.) has stated that he has never seen a case in a negro in the United States, but he has informed me since making this statement that he has been assured of the existence of such cases. The high rate of mortality in Malta is very remarkable, and it is curious that the report was not accompanied by any comment by the officer who sent in the figures. There might at first sight appear to be a decided advantage in the country over the towns, as the great cities have a far higher average than the countries in which they are situated ; but it must be remembered that the country statistics are always less reliable than the towns, and if we look to English figures we find reason to think that there is no such immunity in country districts. Taking the average of England and Wales as 25 per 10,000 deaths, we find the following counties above the average : — Berkshire ... ... 100 Cambridgeshire ... 93 Oxiordshire ... ... 80 * Rutland ... ... ... 80 Lincolnshire ... ... ^o Buckinghamshire . . 64 S^fiolk j^^ Sussex ... ... ... \ *The figures are too small to be of value. ETIOLOGY. 243 These are not counties in which many large towns exist. On the other hand the following counties, teeming with urban populations, give the following figures: — Yorkshire... ... ... 31 I Lancashire ... ... 22 Staffordshire ... ... 30 | Warwickshire ... ... 17 In Scotland and Ireland the same facts are apparent, though in these countries the figures to be dealt with are so small that there is too much risk of fallacy for us to lay much stress upon them. It is stated that in France diabetes is very common in the province of Normandy. Dr. Coldstream, of Florence, who kindly obtained for me a good deal of information respecting what is known of the incidence of the disease in Italy, points out that it is more prevalent in Tuscany than in the rest of that kingdom. Race. — Diabetes mellitus is not confined to the human race. . It is said to occur spontaneously among dogs (Ferraro), and to be more common among those kept for sporting purposes (Robertson). Its frequency among Jews is well known ; Frerichs has stated that out of his 400 cases, 102 belonged to this race of people. It does not appear, however, that other Semitic nations suffer in the same way, unless we accept Dr. Tholozan's opinion concerning the special liability of the Turks as indicating this. Scudamore thought the Scottish people were specially liable to diabetes, and Fagge made use of this supposed liability as an argument against the relation of diabetes to gout, but there is no statistical evidence in its favour. Prout believed that red hair was particularly common among diabetic subjects, and Fagge endorsed this opinion, but the fact itself is doubtful, and its relation to race still more so. The apparent immunity of the Mongolian and African races has been referred to in the preceding section. Prevalence of Diabetes. — In the ten years from 1884 to 1893, I7>794 persons were registered as dying of diabetes mellitus in England and Wales. This is a very great rise over the number given by Roberts as dying in the decade 1851-60, which was only 4,546, and there can be no doubt that the disease is increasing in this country (see Table IV., next page), the proportion to the total mortality having risen in these fifteen years (i 878-1 893) nearly 90 per cent, and to the population more than 70 per cent. 244 DIABETES. TABLE IV. Year. Deaths from Diabetes. Total Deaths. Proportion per 10,000 Deaths. Proportion per 100,000 Living. 1878 1057 539,872 19 4-2 1879 1048 526,255 20 4'i 1880 1059 528,524 20 4-1 I881 1237 491,935 25 47 18S2 1253 516,654 24-4 47 1883 1369 522,997 26 5'i 1884 1475 530,828 27"6 5-4 1885 1522 522,750 29 5-5 1886 1634 537,276 30 5-9 1887 1750 530,758 32 6-i8 1888 1773 511,071 34 8-19 1889 1754 518,353 33 6-00 1890 1863 562,248 33 6 '40 189I 1930 587,925 32 6 -60 1892 201 I 569,684 35 T?>o 1893 2082 569,958 36 7-20 1 Age. — Diabetes occurs at all ages, but is less common at the two extremes of life. The youngest instance known to me is a case recorded by Deane in an infant aged three weeks. Schmitz gives the following table of the ages of tiis 60c patients. TABLE V. I to 10. 10 to 20. 20 to 33. 30 to 40. 40 to 50. 50 to 60. 60 to 70. 70 to 80. 5 25 56 104 134 196 60 20 Pavy has tabulated his 1500 cases under the age at which the disease sets in. TABLE VL Age. Actual Numb er. Percentage Ratio. Males. Females. Total. Males. Females. Total. Under 10 3 5 8 0'22 0-36 0-58 I -• to 20 35 22 57 2-57 I-61 4-19 20 „ 30 69 28 97 5-07 2-05 7-13 30 „ 40 154 70 224 11-32 5-14 16-4 40 „ 50 260 79 339 I9-II 5-80 24-92 50 „ 60 281 137 418 20-66 10-07 3073 60 „ 70 138 44 182 10-14 3-23 13-37 70 „ 80 25 9 34 iv^3 0-66 2-49 Over 80 I — I 0-07 — 0-07 ETIOLOGY. 245 The following table is taken from the Report of the Registrar-General for England for the year 1886. TABLE VII. ^ P All Ages. I I 2 5 3 I 4 5 8 TO 22 15 40 20 25 35 45 55 65 75 85 Males 978 2 2 43 no 118 143 246 189 49 — Females 1 656)' — 2 2 7 — I 9 17 26 48 41 81 38 81 62 91 i lOI 136 lOI 44 4 Total 1634 I I 172 ! 209 244 382 290 93 4 These tables all agree very closely, though the maximum mortality, as might be expected, occurs a few years later than the maximum of living cases. Thus Schmitz and Pavy agree in finding the largest number of cases between the ages of forty and sixty, while the maximum mortality is from fifty- five to seventy-five. This would appear to indicate that such elderly diabetics live a considerable time, which is strictly in accordance with our clinical knowledge. Sex. — Diabetes is more common among men than women, in the proportion of rather more than 3 to 2. But this dis- parity does not seem to hold good amongst children. In Table VII. the numbers under twenty give 80 males to 79 females, the proportion under fifteen being 40 males to 38 females. In Table VI. (Pavy's) there were 3 males to 5 females under ten years of age, though under twenty there were 38 males to 27 females; in Stern's 117 cases the girls were more numerous than the boys in the proportion of 5 to 3 ; as age advances the proportion becomes nearly 2 males to i female, until in old age it comes back to the equality of childhood. Social Condition. — The reports from India and Ceylon emphasize the fact that the disease is most common among the well-to-do classes. This is also illustrated in a table compiled by Dr. Bertillon, showing the deaths from diabetes 246 DIABETES. in the various districts of Paris, distinguished according to the means of their inhabitants. Deaths per ioo.ooo Arrondissements. of Population. Opera. R.* ... 20 Passy. R. - - - 18 Elysee. V.R. - - - 16 Temple. E. - - - 16 Luxemburg. R. - - - 15 Palais Bourbon. R. - - 14 Vaugirard. P. - - - 14 Batignolles. E. - - - 14 H6tel-de-Ville. E. - - 13 St. Laurent. V.E. - - 12 Louvre. V.E. - - - 11 Popincourt. P. - - - 11 Neuilly. P. - - - 11 Bourse. V.E. ... 10 Pantheon. E. - - - 10 Gobelins. V.P. • • - 9 Observatoire. P. - - 9 Montmartre. V.P. - - 9 Menilmontant. V.P. - - 8 Buttes Chaumont. V.P. - - 7 *R. = Rich; V.R. = Very Rich; E.-Easy; V.E. = Very Easy ; P. = Poor; V.P. = Very Poor. Heredity. There can be no doubt that diabetes melHtus is hereditary. Chevers quotes the following statement from the Indian Medical Gazette for 1871: "In one of the most influential native families in Calcutta, No. i died of acute diabetes at the age of sixty-five; No. 2, his eldest son, died of chronic diabetes ; No. 3, his third son, had chronic diabetes ; No. 4, his fourth son, died of acute diabetes; No. 5, his daughter, aged sixty-five, had diabetes; No. 6, eldest son of No, 2, died of chronic diabetes; No. 7, second son of No. 2, had diabetes ; No. 8, eldest son of No. 4, had diabetes." Thus the disease affected eight members of the same family, extending over three generations. Auerbach has related the history of a family, in which the father died insane and the mother diabetic. Of eleven children, one died insane, one of diabetic coma, four others were insane, and one was diabetic. Frew has recorded a more remarkable case in a little girl aged nine, suffering from diabetes, whose paternal grandfather, uncle and aunt, had all died of the same disease. Nevertheless in the majority of cases there is no evidence ETIOLOGY. 247 that the disease has been inherited, and it is more common to obtain a history of a diabetic brother or sister than of a diabetic parent. This is perhaps due to obvious causes, as it is ahva}'s exceechngly cHfficult to get mformation which goes back any number of years. Trousseau thought that phthisical parents often had diabetic children, and there can be no doubt that a history of tubercular disease can often be traced in diabetics. Excessive Jise of Sugar and Starchy Food. — There is a very widespread belief that the excessive use of sugar tends to diabetes. Eichhorst has met with the disease among the workpeople in sugar factories. Christie, who first described the prevalence of the disease in Ceylon, referred it to the excessive use of sugar and starchy food. Tholozan regards the disease among the Persians as caused by sweetmeats and sweet sherbets. Indian practitioners recognise the effects of the same causes; yet, as has already been mentioned, in Mauritius and British Guiana, where the people are chiefly employed in sugar factories, the disease is very rare. Charcot states that glycosuria is frequently produced among the novices in the Monastery of La Trappe. Collins has recorded two examples, one of which was persistent but disappeared under diet and opium. Bee}-. — Kratschmer thinks that the urine of great beer drinkers always contains more or less sugar, but there is certainly no evidence that beer drinking per se is a common cause of diabetes. Were it so, it is scarcely conceivable that the kingdom of Prussia would occupy such a relatively favour- able position in the table. Cider has been said to have some relation to diabetes, and the prevalence of the disease in Normandy is ascribed to this cause, but the cider counties in England show a mortality much below the average. Obesity. — Many diabetics are, or have been, very stout. It is general!}' in elderly persons that this connection is observed. Kisch has observed temporary glycosuria as a frequent occurrence in general obesity. Seegen said that 30 per cent, of the cases he had analysed were excessively fat at the beginning of^ their illness. Kisch says that in all cases where hereditary obesity comes on in youth and progresses rapidly, and in non-hereditary cases where treatment is not beneficial, diabetes must be looked for as a possible occurrence. He believes one-half of the former and i^ per cent, of the latter 248 DIABETES. become diabetic. In many families it can be shown that some members are fat from childhood and others are diabetic, or the fat individuals become diabetic about the fourth decade. It is probable that one of the first results of excess of sugar poured into the circulation is an increase of fat, and so long as the surplus sugar can be stored up in this way glycosuria is postponed. But a time comes when either the activity of the liver is greater and the sugar is more than can be so stored up, or the limits of the fat-forming capacity of the body are reached, and then sugar appears in the urine. EXCITING CAUSES. Frerichs gives the following classification of the causes of glycosuria. r. Toxic Glycosuria. Curare. Carbonic oxide. Amyl nitrite. Ortho-nitro-phenyl-proprionic acid. M ethy 1-delphinin. Morphia. Chloral. Hydrocyanic acid. Sulphuric acid. Mercury. Alcohol. Also from morbid poisons. Cholera. Anthrax. Diphtheria. Enteric fever. Scarlatina. Malaria. 2. Glycosuria from Digestive disturbance. Gastric catarrh. Gout. 3. Glycosuria from Nervous disturbance. Psychoses. Neuralgias. Injuries to brain and cord. Brain diseases. Apoplexies, aneurisms of cerebral arteries, meningitis cere- bro-spinalis, etc. ETIOLOGY. 249 But in many of these instances it is not certain that glycosuria occurs, and in most it is only transitory. CJilorofovjii. — This may not only give rise to temporary glycosuria, but occasionally causes acute and fatal diabetes (Fort). Bromide of Potassium. — Weber has described a case of acute and fatal diabetes in a little girl of seven, the effect of swallowing an ounce of this drug, which she took by mistake. Infective processes. — On the other hand, the morbid poisons or infective processes, as it is better to speak of them, are un- doubtedly true causes of diabetes. Whether this effect is pro- duced by the influence of their toxins on the nervous system, or whether they lower the vitality of the pancreas, and so permit it to be invaded by intestinal microbes which set up pancreatitis, may be uncertain. In this connection I may refer to the fact that Debove has collected fifty cases of diabetes, in five of which the husband and wife were attacked simul- taneously. Lecorche, who had observed the same facts, attributed them to community of anxieties and nutriment ; but Debove thinks that the lives of men and women are very different, and he remarks that husband and wife are rarely both gouty ; though in England this is not uncommon, and possibly husbands and wives live a life more in common in England than in France. However, these observations on the frequent occurrence of diabetes in husband and wife are sup- ported by Dreyfous, Gaucher, Labbe, Lettulle, Schmitz, and Rendu, and the inference is that under certain circumstances, or in some obscure way, diabetes may be contagious. Such a view is not altogether impossible, taking into account the number of infectious processes which exist, some of them little known to us, and many capable of running their course with- out marked derangement of health. Acute Tonsillitis. — Rogers has published a case of acute tonsillitis in a gentleman aged forty-four, which was followed by diabetes, terminating fatally from coma twenty hours after being first recognised. Diphtheria. — Glycosuria may follow diphtheria, as in a case reported by Zinn, which, however, ended in complete recovery after lasting ten weeks. Erysipelas. — Glycosuria often occurs in connection with surgical sepsis, phlegmonous and gangrenous inflammations, anthrax, lymphangeitis and erysipelas, and true diabetes may follow. 2 so DIABETES. Case zi^.— Diabetes Mellitus — followhig erysipelas — loss of sexual desire — slight polyuria — slight thirst — no kneejerks — no wasting. Mr. Paul R., aged forty-eight, consulted me in March, iS88, complain- ing of diabetes, of which he had been aware for three or four months after an attack of erysipelas supervening in his foot from a cut got by treading on broken glass. The polyuria and thirst were slight, and there was no wasting ; his chief complaint was his loss of sexual desire, which seemed to depress him mentally, although he was unmarried, His knee jerks were absent. The urine measured from four to five pints daily, sp. gr. 1029, loaded with sugar. Influenza. — I have already published the notes of two cases of diabetes following attacks of influenza in the epidemic of 1889-90. They are of sufficient interest to be reproduced here : — Case 30. — The earlier in point of date was that of a girl named O.B.. aged twenty-two; she had never been very strong, and at Christmas, 1889, she had an attack of influenza. Shortly after this she began to suffer from thirst and frequency of micturition, when she was passing about 100 oz. of urine daily containing 10 per cent, of sugar. The case improved under treatment but did not recover. Case 31. — C. A., a glassblower, aged thirty, was in bed for a week at the end of January, 1890, with a severe attack of Influenza. Immediately after this he began to suffer from thirst and loss of weight. He had been in the habit of weighing himself at intervals and was sure that up to the time of the attack of influenza he had not been getting thinner, but since then, though a spare man, he had lost 17 lbs. He was passing 200 to 300 ozs. of urine daily, containing 7 to 8 per cent, of sugar. Malaria. — The importance of malaria as a cause of diabetes is doubtful. Burdel believes that glycosuria occurs very com- monly in connection with this infection, and gives the following table of cases : — Cases. Febris quotid. ... 134 „ tert. ... 122 ,, quart. ... 76 „ perniciosa ... 11 Severe cachexia ... 40 Calmette supports this view, stating that while acute malarial affections are sometimes attended by transitory glycosuria, severe malarial cachexia is a distinct cause of diabetes. On the other hand, in the course of a recent discussion at the Society Medicale, of Mauritius, the great majority of the speakers were opposed to the belief in any relation between these diseases, and this seems to be the general view of British practitioners residing in malarious countries. It is strange if this relationship were true that the disease should be so rare on Sugar. Percentage. 29 22 17 14 II 14 3 27 32 80 ETIOLOGY. 2Si the West Coast of Africa and in British Guiana, while we should expect it to be more common in Italy than statistics show it to be. It is a point upon which additional information is wanted, and it is worth noting that the malarial counties of England are those which stand among the highest in the mortality from diabetes. E)iteric Fever. — The following case of diabetes followed enteric fever. Case 32. — Diabetes Mellittis — followiitg enteric fever — cedema of legs. Annie S. — , aged thirty-nine, housewife, was admitted to hospital on September 23rd, 1890, complaining of great thirst, increasing weakness, pain in eyes, and dimness of vision and polyuria. Duration thirteen months. Family History. — Father and mother both dead, the former from apo- plexy, aged forty-seven ; the later from cancer of liver, aged lorty-nine. Previous Health — Patient had measles when seven years old, scarlet fever when a baby, small-pox since marriage (at twenty-one), from which she quite recovered, and was in good health until thirteen months ago. In August, 1889, she had enteric fever for four months, and ever since she had suffered from thirst and polyuria. Present Condition. — She was a fairly well developed woman, but ill nourished and thin ; there was no cyanosis or jaundice, but some slight oedema of legs ; skin moist. Temp. 98'4°. Resp. 16. Pulse 84. Teeth good, gums red, tongue thick, marked at edges by the teeth and covered with a thick whitish fur; appetite very good. Thirst very great; had pains in the stomach when fasting; bowels confined ; abdomen full, with some tenderness over the epigastrium ; there was no dulness on percussion. Liver dulness in V.M.L., 4 inches. Splenic dulness in M.A.L., 2 inches. Respiration, 16. Movements of thorax, regular and equal. Percussion note resonant, V.R. and V.F. equal on both sides. Breath sounds normal ; no adventitious sounds were heard, but she had slight cough. Heart sounds clear, no murmurs were heard ; cardiac dulness, upper limit, 3 C.C. Left limit internal to V.M.L. Right limit X inch to right of sternum. Apex beat in 5th space internal to V.M.L. Pulse 84, regular, full ; the tracing {Fig. 52) shows a very fair amount of tension. She had som.e dyspncea on exer- tion, but not to any marked extent. Urine quantity 76 oz. ; sp. gr. 1037 ; acid ; no albumen ; Tig.:.".. loaded with sugar ; complained of a burning sensation on passing water. Had always been regular until now, last time it was very scanty, and she had missed this time. She was sensitive to pain, heat and cold ; no numbness or tingling, pupils equal, slightly dilated, responded readily to light. Patient could not see to read even with her glasses, but could see and distinguish in- 252 DIABETES. dividuals in a good light and could see much better with glasses; her sight was much worse the last six weeks. Hearing very good. Taste and smell unimpaired. Patellar reflexes were absent on both sides, both plantar reflexes present. Did not sleep well. Syphilis. — From what has been said in connection with diseases of the nervous sj^stem, it will be readily understood that gummata in the brain may give rise to glycosuria or to all the symptoms of diabetes, but Ord believes he has met with several cases of ghxosuria without any evidence that the medulla was implicated. Decker has reported a case of diabetes occurring in the course of a syphilitic affection of the eye, which was cured by mercurial inunction without any dietetic restrictions. Soon after Christmas, 1889, I saw a man who had diabetes and a syphilitic sore mouth, but there were complicating factors in the etiology, as he had had influenza, and had received a severe blow on the loins from a heavy iron bar. Moreover anti-syphilitic treatment, which cured his mouth, did not cure the diabetes. Decker attributed his case to syphilitic disease of the cerebral arteries. Injuries. — Durham and Bellingham Smith state that gly- cosuria is an almost constant, although usually transitory, effect of injuries to the head and spine, but it generally passes off in four or five months, yet lasts sometimes as long as two years. They say that the later the onset the more grave the prognosis, and it is unquestionable that diabetes may be so engendered. In a case of Dale's, a child fell on the back of its head, and months later acute and fatal diabetes set in ; and in the case of an officer related by Aloosdorf, he became diabetic after a bullet wound in the neck. Scheuplein has published the case of a young dragoon who fell from a window forty feet high, and dislocated the t^^'elfth dorsal vertebra. He was treated by extension, but eleven days after the injury acute diabetes set in, which lasted about a m.onth, and then gradually disappeared, the patient making a good recovery from his accident, and being quite well two years afterwards. Pavy has recorded a case following a kick from a horse. In a case of Ebstein's, a boy aged fourteen was struck by a. stone in the region of the stomach. This was followed by pain and increase of the liver dulness, which gradually disappeared ; but three months later diabetic symptoms set in. A patient of Lindsay's fell and struck his right loin. This was followed by pain and ETIOLOGY. 253 local swelling, which disappeared in time, to be in turn followed by thirst, j^olyuria, and emaciation. Case 33. — Diabetes Mcllitus — dice to a blow — thirst — polyuria — zuasting. John B., fifty-four, wire drawer, admitted as an out-patient on March I2th, 1889, complaining of thirst and polyuria. He had been ill six months, and had been treated with brown bread czc/ //^//////^ and codein (^r. j) three times a day. Just before this illness began he bruised his hip at his work. There was no family history of diabetes, but one of his grandfathers had gout. The c|uantity of water varied from 4/2 to 6 pints, sp. gr. 1032-35, loaded with sugar. He weighed jst. On probably the same diet, though he was told to eat bread very sparingly, Jambul perles (Christy) given in as large a dose as four, three times a day, produced no eftect : and as much could be said of antipyrin. The quantity of water gradually diminished to three or four pints, and his weight was 6 st. 13 lbs., on April 30th, 1889. Redard has recorded a case in which a small abscess by the side of the rectum was accompanied by polyuria (2^ litres) and glycosuria, which symptoms disappeared when the abscess had completely healed. But in certain instances true diabetes may follow, as in a case recorded by Frerichs, where the ex- citing cause was an abscess connected with a tooth. Spencer says passing glycosuria is very frequent in association with carbuncles and severe boils, in patients whose urine was pre- viously free from sugar. M'Nish has recorded the case of a blacksmith, aged fifty-six, who was severely burnt by a bottle of paraffin oil taking fire. Twelve days after the accident his urine became saccharine, and this continued for twenty-five days, until the burn was healed. Albert and de Renzi have observed glycosuria occurring in gangrene. Malignant Disease. — Spencer has observed glycosuria in cases of malignant disease not affecting internal organs, but it does not amount to diabetes. In cancer of the pancreas true diabetes may develop ; a very well-marked case of the kind was under the care of my colleague. Dr. Simon ; and Dresch- feld has recorded one quite recently. The following case is an example of glycosuria in connection with malignant disease of the pancreas. Case 34. — Diabetes mellitus — jaundice — cancer of -pancreas. G. S., forty-four, labourer, was admitted with epigastric pain and jaundice. on June 22nd, 1895. He had been ill three months, and attributed drinking a great deal of beer and getting chilled when heated ; the jaundice came on about a week later, and his motions were at first quite white. He had no pain for the first month, but since then it has been continuous, and aching in character, a', orse at night ; it is localised and does not shoot in any direction, nor is it made worse by eating. Up to the time of this illness he 254 DIABETES. had always been a healthy man, and he comes of a family which has always been long-lived, though a brother, who was a hard drinker, died of an en- larged liver. On admission his conjunctiva and skin were stained deep yellow, and he complained of great irritation of the skin, for which he was always scratching himself. He was well developed and fairl)'- well nourished, but had been losing weight; when weighed in the hospital, on July 7th, he was only 8 stone, and a fortnight later he had lost six pounds more. The right lobe of his thyroid was enlarged, but he attributed it to an injury received in an attempt to throttle him twenty years ago. Temp. 97"6'^. Pulse 72. Resp. 22. He sufifered from flatulence and pain after food, and his tongue was coated with a white fur, but there Avas no eructation or vomiting; his bowels were moved spontaneously. The abdomen was flat and retracted, somewhat tender every where, but allowing the' enlarged liver to be felt projecting nearly a hand's breadth below the costal margin ; it was quite smooth, and the gall bladder was distended. There was no ascites. The heart and lungs were normal. His urine was not increased in amount, but was a deep olive green colour; it gave all the tests ior bile pigment, contained a trace of albumen, 364 grs. urea, 1240 grs. sugar, no casts. While in hospital on a diet from which sugar (but not carbo- hydrates) was excluded, he passed only two to three hundred grains of sugar, but, as already stated, he lost weight. I was away at the time, but he probably ate little, and we know that under such circumstances, digestion and absorption are both greatly diminished. He died some little time after this, and cancer of the head of the pancreas was found. Cold. — Prout believed that cold acted as an exciting cause, and he quotes a case of Marsh's, where the patient had been exposed greatly to cold at sea for four days. Rollo quotes a case of Marshall's, Avhich was apparently caused by drinking cold small beer when in a state of profuse perspiration ; and Peiper relates the case of a girl, aged seventeen, who was attacked with symptoms of acute diabetes after drinking a glass of iced water when heated from dancing. She recovered after eight weeks' treatment. Poniklo has recorded a case in which at least temporary glycosuria followed eating iced cream. Cold Climates certainly do not show any high mortality from diabetes, Scotland having a lower average mortality than Ire- land, while Norway is still lower; Prussia has a lower mortality than Italy, and as we have seen the disease is very prevalent in India and Ceylon. Lightning Stroke. — A case of diabetes following lightning stroke has been reported by Hermanides. Nervous Diseases. — Maudsley and Savage consider diabetes in the parent is often followed by insanity in the child; on the other hand Schmitz states that 248 out of his 600 cases of diabetes had a family history of insanity. ETIOLOGY. 255 Although glycosuria may occur in the course of many diseases of the central nervous system, especially in general paralysis of the insane (HAMILTON), and epilepsy (EnSTEIN), it is not very common. Bond met with it in 12 only out of 175 cases, and most of these showed an absence of many of the chief signs of diabetes. In two melancholies who recovered, on coincided with the The cases were: — the improvement in their mental conditi gradual disappearance of the glycosuria. General paralysis Melancholia Organic Dementia Senile Insanity True diabetes is more often connected with some localised lesioH, such as a tumour in the floor of the fourth ventricle or on the vagus nerve. It has been met with in association with locomotor ataxy of syphilitic origin (Reumont), in in- sular sclerosis (EDWARDS, RiCHARDlfeRE), and frequently after injuries to the head or spine. The association of diabetes with locomotor ataxy has been observed in the same family. In one case the mother was diabetic, in another the son, in a third the father, in a fourth the father and brother, and in a fifth the brother and nephew (GUNION and SOUQUES). My colleague. Dr. Stacey Wilson, has recorded a case of diabetes occurring in association with Friedreich's ataxy ; death occur- red from coma, and the brain, medulla and pancreas were stated to be normal. Shingleton Smith has recorded a case of gly- cosuria occurring in the later stages of a case of tumour of the cervical portion of the cord. I have had under my care a curious case of acromegaly associated with enlarged thyroid and diabetes ; she improved under treatment, but her mental condition was peculiar, and I lost sight of her after a time. There is a considerable amount of evidence that mental emotion may often be the starting point of an attack of diabetes. Losses in business, family affliction, danger to life, etc., have been recorded as immediately preceding the onset of the disease. The association between hysteria and diabetes has been insisted upon by Grenier, but without sufficient evidence that this amounts to anything more than a casual coincidence. It may be, however, that the diabetic dyscrasia, like plumbism, favours the development of hysteria. Manby has recorded three interesting cases, illustrating the 2S6 DIABETES, connection between exophthalmic goitre and diabetes. In the first a diabetic father had two children, of whom one was dia- betic and the other the subject of goitre, exophthalmos, and irregular action of the heart ; in the second, one brother was diabetic, the, other brother lost two children with acute diabetes, and the sister had Graves' disease ; in the third, two sisters were diabetic, and a third the subject of Graves' disease. In connection with these observations it is interesting to note that transient glycosuria has been frequently observed during the administration of thyroid gland extract. Acute Rheumatism. — Diabetes may follow acute rheuma- tism (Hughes Bennett), and Dyce Duckworth states that glycosuria is common in " chronic rheumatoid arthritis," which is, however, a somewhat ill-defined condition. * Gout. — Diabetes is a common phenomenon in gout ; it is not uncommonly attended by polyuria and thirst, but there is very slight loss of weight. I Case '^'^.— Diabetes Mellitus-—;polyu}-ia — thirst — atbiinimzii-ia — gout — disappearafice of siigar. Mr. Frederick W. W., aged fifty-six, consulted me first on March 31st 1883, being sent to me by my friend Mr. Eales, who had discovered sugar in his urine. He had been passing too much water for five months, and suffering from thirst. He had had gout several times. Weighed 13 st. 2 lbs.; had not lost flesh. Tongue clean ; appetite good; bowels regular. Fundus of eyes normal. Urine, 1028, contained sugar and a trace of albumen. On anti-diabetic diet, using toast moderately, and extract of opium (gr. J) three times a day, his urine was diminished by two-thirds, its specific gravity came down to 1020, but there was some loss of flesh — by May 5th, he had lost 5lbs. By June i6th the sugar had disappeared, and did not return at nil after June 30th. On his last visit, Aug. i8th, 1884, he weighed 13 st. 3 lbs., his urine amounted to two quarts daily ; it was free from sugar and he felt very well. Liver Diseases. — Roger asserts that he has met with glyco- suria in various affections of the liver, including cirrhosis and persistent jaundice. Hull has recorded a case of severe and fatal diabetes which set in ten months after the bursting of an abscess of the gall bladder. Some years ago I attended with my friend. Dr. R. Norris, of Birchfields, a gentleman who had been suffering from diabetes, v\^hen he was suddenly attacked by jaundice, with complete obstruction of the common duct. The sugar disappeared from his urine and did not return after the bile regained its passage into the intestine. Pregnancy. — Bennewitz, in 1828, recorded the case of a stout young woman, in whom diabetes with severe thirst ETIOLOGY. 257 and polyuria came on during the fourth pregnancy, left her as soon as she was delivered, and recurred during the fifth and sixth pregnancies — leaving her during the intervals. Poulet has published the case of a girl of sixteen, who became pregnant at fifteen, and aborted at the eighth month. Soon after she began to suffer from thirst, polyuria and emaciation. Matthews Duncan, after reviewing the whole subject, formulated the following conclusions : — 1. Diabetes may come on during pregnancy. 2. Diabetes may occur only during pregnancy, being absent at other times. 3. It may cease with the termination of the pregnancy, returning sometime afterwards. 4. Diabetes may come on soon after parturition. 5. Diabetes may not return in a pregnancy occurring after its cure. 6. Pregnancy may occur in diabetes. 7. Pregnancy and parturition may apparently be unaffected in their healthy progress by diabetes. 8. Pregnancy is very liable to be interrupted in its course in diabetes, and probably always by the death of the foetus. There is no doubt that pregnancy may give rise to true diabetes, and that Griswold is wrong in asserting that it is always temporary glycosuria unworthy to be called diabetes, being attended by neither polyuria nor thirst nor any other symptom of diabetes. Sinclair says that the glycosuria of lactation is always present in nursing women when the breasts become engorged with milk from weaning, death of the infant, or other cause, and he quotes numerous cases in support of his statement, but Davenport says that it is only when lactation has existed for five or six months that its sudden suspension gives rise to the presence in the urine of lactose in large quantities. CltJiiactei'ic Diabetes. — It was supposed by Lecorche that the climacteric period favoured the occurrence of diabetes in women. Unquestionably elderly women get diabetes, but in some instances, as in the following, there is an apparent con- nection between the two events. Case 36. — Diabetes Mellitus — glycosuria — polyima — wasting — sudden onset at the vie7topause — cystic goitre. Elizabeth K., fifty, attended as an out-patient on May 7th, 1889, com- plaining of thirst, hunger, and her "flesh all leaving her." She had been ill a year and nine months. She had never had gout, rheumatism, or any 17 258 DIABETES. serious illness or accident. She was married, and had had eight children. She knew of no member of her family who had suffered from diabetes or gout. Menstruation ceased quite suddenly at the time that these symptoms came on. Patient was a fairly developed woman, with a flushed face and dry skin; much emaciated, weighing only 7 stone. There were no symptoms of dyspepsia ; her bowels were regular. She had a large cystic goitre, which she had had since puberty. Her pulse was quick, 144 ; physical signs normal. Urine, 1035, loaded with sugar. She had to rise three or four times each night to pass water. Mr. Lawson Tait believes that it is of essentially good prognosis, and can be treated by opium alone without dietetic restrictions. Imlach has recorded a remarkable case of a diabetic woman, aged thirty-one, on whom he operated for pyosalpinx by re- moval of the appendages, and in whom the operation was not only perfectly successful in curing the local trouble, but was followed by the complete disappearance of the diabetes. Excessive sexual indulgence is apparently, at times, an ex- citing cause of diabetes. Dickinson mentions the case of a young man who died at the early age of twenty-five, in whom he could find no other cause but excessive promiscuous sexual indulgence, to which he had been addicted since the age of seventeen. Masturbation is another alleged cause, but Yarrow has recorded a case of temporary glycosuria attributed to en- forced sexual continence. Under treatment with bromide of ammonium, fluid extract of jaborandi, and external local ap- plications to the neck and loins, he recovered in eight days, and on the disappearance of the sugar a spontaneous pollution occurred ! BIBLIOGRAPHY. Albert (E.). Diabetes Mellitus and Senile Gangrene. " Allgem. Wiener mad. Zeit.," 1885, Nos. i, 2, 4, 5, 8, and g. AuERBACH (L.). Ueber das Verhaltniss des Diabetes mellitus zu Affectionen des Nervensystems. " Arch. f. klin. Med.," Bd. XLI. , 1887. Bennett (J. Hughes). Clinical Lectures on the Principles and Practice of Medicine. 3rd edition, p. 898. Bennewitz. 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The significence of Glycosuria in connection with Disease of the Brain and Cervical Cord, and with Dementia Paralytica "New York Med. Jour.," 1884, II., p. i. Hermanides (S. R.). Eene ziekte-geschiedenis waaruit het verband blijkt tusschen corticale hersen-laesie eenerzijsts en diabetes, hemianopsie en vaso- motorische stoornis anderzijds. " Deut. med. Woch.," Oct. 4th, 1888. Hull iG. S.). Diabetes Mellitus following Abscess of the Gall Bladder. "Med. News," XIIL, 1882. 26o DIABETES. Imlach (F.). a case of Diabetes Mellitus cured by the removal of the Uterine Appendages. " Brit. Med. Jour.," 1885, II., p. 61. Kratschmer. Zur Frage der Glykosurie. Centralbl. f. d. med. Wissen.," 1886, No. 15. p. 257. Leo (H.). Ueber den respir. Stoffwechsel bei Diabetes melHtus. "Zeitschr. f. khn. Med.," XIX., suppl., p. loi, 1891. Lindsay (J. A.). Diabetic Coma, with some remarks on the pathology and treatment of Diabetes. "Dub. Med. Jour.," 1883. McNiSH. Glycosuria complicating a severe burn. " Australasian Med. Gaz.," 1889. Manby (A. E.). The connection between Diabetes and Graves' Disease. " Brit. Med. Jour.," 1889, I., p. 1025. Marshall. Quoted by Rollo, op. cit. Maudsley (H.). The Pathology of the Mind. 3rd edition. London, 1879, p. 113. Ord (W. M.). Remarks on some points of interest in regard to the presence of Sugar in the Urine. " Brit. Med. Jour.," 18S9, II., p. 965. Pavy (F. W.). Introductory Address to the discussion of the Clinical Aspect of Glycosuria. " Lancet," 1885, II., pp. 1033 and 1035. Peiper. The Etiology of Diabetes. " Deut. med Woch.," 1887, No. 17. PoNiKLO (S. J.). Structural Changes of the Sympathetic Nerve in Diabetes. " Lancet," I., 1878, p. 268. PouLET (v.). Recherches experimentales sur les phenomenes chimiques de la respiration. " Arch, de Physiol.," 1888, I., p. 174. Prout (W.). An inquiry into the nature and treatment of Diabetes, Calculus, and other affections of the Urinary Organs, 2nd edition. London, 1825, p. 60 et seq. Redard (P.). On ephemeral Glycosuria in surgical practice. Revue de Chir.," 1886, No. 8. Note sur un cas de glycosurie transitoire au cours d'un absces chaud. "Arch. gen. de Med.," 1888, I., p. 474. Rendu. Quoted by Debove, Renzi (E. de). Studii di clinica medica compiuti durante I'anno scolastico 1879-80. "Ann. Univ.," Vol. CCLI. Reumont (A.). A case of Tabes Dorsalis complicated with Diabetes Mel- litus. " Berhn klin. Woch.," 1881, No. 13. Richardiere (H.). Glycosuria and Diabetes occurring in disseminated Sclerosis. " Revue de Med.," No. VII. 1886. Roberts (Sir W.). A practical Treatise on Urinary and Renal Diseases. 4th edition. London, 1885. Robertson. Quoted by Campbell. Roger (G. H.). Contribution to the study of Glycosuria of Hepatic Origin. " Revue de Med.," 18S6, p. 935. Rogers (P. F.). Case of acute Diabetes of unknown duration; death from Coma seventy-two hours after coming under observation. " Boston Med. and Surg. Jour.," Vol. CXI., 1884, p. 298. RoLLO. Op. cit. Scheuplein (C). Verletzung der Wirbelsaule, Diabetes mellitus acutus, vollstandige Heilung. "Arch. f. klin. Chir.," XXIX., p. 365. ScHMiTZ (R.). Meine Erfahrungen bei 600 Diabetikern. Neuenahr. "Pro- ceedings of the Med. Soc, 1884, p. 279. Kann der Diabetes mellitus ubertragen werden ? "Berlin. klin Woch.," 1890, No. 20. Scudamore (C). a Treatise on the nature and cure of Gout. London, 1S16, p. 5c. Seegen. " Berliner klin. Woch.," 1887. ETIOLOGY. 26 r Sinclair (W. J.). The Glycosuria of Lactation. " Med. Chron.," Vol. III., p. 276. Smith (R. Shingleton). Remarks on the Morbid Anatomy and Pathology of Diabetes. "Brit. Med. Jour.," 1S83, I., p. 657. Spencer (W. G.). Diabetes in Surgical Cases. " Westminster Hosp. Rep.," Vol. IV., 18S8, p. 89. Stern. Diabetes in Children. "Lancet," 1890, I., p. 1317. Tait (Lawson). Climacteric Diabetes in Women. "Practitioner," 1886. Trousseau (A.). Chnique medicale de I'Hotel-Dieu de Paris. Vol. II., p. 771. Clinical Medicine. " New Syd. Soc," Vol. III., 497. Tyson (J.). A treatise on Bright's Disease and Diabetes. Philadelphia, 1881. Weber (L.). Two fatal cases of Diabetes Mellitus in Children. " American Jour, of Obstetrics," 1884, p. 102. W HiTE (W. Hale). The Pathology of the Central Nervous System in Exophthalmic Goitre. "Brit. Med. Jour.," 1889, I., p. 699. Yarrow (H. C). Temporary Glycosuria, produced apparently by enforced sexual continence. " Philad. Med. and Surg. Rep.," Vol. XLVI., 1882. ZiNN. Ueber Mellituria nach Scharlach. " jahrb. f. Kinderheillc," N. F. XIX., 1S82. 262 Chapter XVI 1 1. MORBID ANATOMY. {TJ12 Bradshaw Lecture delivered before the Royal College of Physicians in London, August 18th, 1890.)* Mr. President, Fellows of the Royal College OF Physicians, and Gentlemen : — It is my first duty to express my gratitude to you, and my humble acknowledgment of the honour done to me and I hope I may say to the city to which I belong, in selecting me to deliver the lecture which, by the pious munificence of his widow, annually commemo- rates the birthday of the late Dr. Bradshaw, a former Member of this College, and a worthy and esteemed physician, who practised during his lifetime in the town of Reading. It is fitting also that I should express on behalf of the College our respectful recognition of this lady's appreciation of the character and aims of our ancient corporation, by founding this lectureship for the promotion of the study of medicine. I feel deeply conscious of my own inability to perform the task so generously entrusted to me in such a manner as to deserve your praise ; but by your courtesy I know I may expect a patient hearing, and from your indulgence I trust I may escape your censure if I fail to attain the high level of excellence which has characterised the discourses of my eminent predecessors in this chair. The subject I have chosen for your attention to-day is undoubtedly wanting in novelty, but I was induced to select it chiefly because it was a matter on which my thoughts were already engaged, and concerning which I possessed abundant materials for reinvestigation of the questions which have been raised in recent years, with the opportunity of studying them in the light of the most modern methods of histological research. If I have no new discoveries to announce, and if I must content myself rather with the humble position of a critic than that of a revealer of fresh facts or novel theories, I * This lecture has been throughout revised and in part rewritten. MORBID ANATOMY. 263 will at least ask you to believe that this has not been from any want of patient industry and careful thought, but because of the great difficulty of making new observations in a field which has engaged the close attention of so many competent observers. It is my purpose to lay before you an account of the changes observed in diabetes in the principal organs of the body and in the blood, concluding each description with com- ments upon points of interest on which my own observations seem to me to have thrown any light. THE NERVOUS SYSTEM. Brain. — Though no constant lesion has been observed in the brain, this organ is seldom normal. This statement is at variance with the .statistics of cases accumulated from all sources (WiNDLE), but is in harmony with recent observations. Out of twenty-seven cases of which I have records of ne- cropsies, the brain was stated to be normal in only five. The most common description given is that it was " oedema- tous and congested, with thickened membranes," eleven out of the twenty-two abnormal brains presenting more or less of these characteristics. It is less often described as anaemic. Atrophy of the convolutions has been stated to be common (Mackenzie) ; but this does not accord with my observations. These changes are, of course, not peculiar to diabetes, and cannot be considered to have any special relation to its pathology. In quite a minority of cases localised lesions are found, the value of which differs greatly, and in many instances is not easily appraised. Among the most important are tumours in the fourth ventricle and medulla, of which a relatively small number only have been recorded. Not a single instance has come under my own observation, and I have only found records of ten cases, of which three were published by Frerichs. Of the direct dependence of the diabetes upon the growth in many of these cases there can be no reasonable doubt. Instances have also been recorded of softening (LUYS) ; of the presence of corpora amylacea and colloid masses (ABRAHAM) ; of localised alterations in colour and congestion (Tardieu) ; and of enlargement of the peri-vascular spaces (DICKINSON). Of these the softening alone is of undoubted value. The congestion and dark colour of the medulla are interesting, but, taken by themselves, prove little ; while the enlargement of the peri-vascular spaces is too 264 DIABETES. common in non-diabetic brain disease, and too exceptional in diabetes, to count for much. The observations of Dr. Abraham are a valuable contribution to the histology of the diabetic brain, and possibly belong to the same class as other lesions, to which I shall refer immediately, which indicate failure of nutrition of the brain tissues, and are rather an effect than a cause of the disease. There is undoubtedly a tendency in the diabetic brain to the formation of cysts in the white matter. I have found such cysts in the frontal lobes, in the medulla, and in the pons ; while in another case a small focus of softening in each crus cerebri looked like an early stage in this process of cyst formation. These cysts are quite free from haematoidin staining. Some of them are so small as to be hardly worthy of the name of cysts, but others are as large as horsebeans. It seems probable that this condition is due to a failure of nutrition. The choroid plexuses also occasionally present abnormalities ; thus I have found cysts on the choroid plexus of the left lateral ventricle, and the same structure in the fourth ventricle was in one case hypertrophied, while in another case the plexuses of the lateral ventricles were of a dark-purple colour, as if from congestion. The lateral ventricles and the iter a tertio ad quarhnn ventricidum have been found dilated without any mechanical obstruction to explain it. Thiroloix has recorded a case of diabetes in which the pancreas was normal, but a patch of sclerosis existed in the floor of the fourth ventricle. Extensive haemorrhage into the brain substance is rare in diabetes. In Windle's tables there are only three examples in one hundred and eighty-four necropsies, or in v6 per cent. There has been no instance at the General Hospital for twenty years out of a total number of one hundred and twenty cases with twenty-nine deaths. Dickinson has, however, described minute hemorrhages as common. Finally, glycogen has been found in large quan- tities in the medulla oblongata and in the vessels of the cerebral cortex (FUTTERER). Zaleski found iron present, but we are still in doubt as to how far this is an abnormality. On careful microscopical examination I have not been able to detect, even with the most modern technical methods, any constant histological changes either in the cortex, the basal ganglia, or the medulla. The latter has been the subject of special investigation, but the only positive fact observed has been that the capillaries of the vagus nucleus in one case MORBID ANATOMY. 265 seemed to be abnormally numerous and full of blood. The specimen has been placed under one of the microscopes. I have looked for minute haemorrhages without finding them., and the absence of blood pigment in the cysts already alluded to is opposed to the view that these originate in that fashion. While not disputing its occasional occurrence, hsemorrhage is certainly not a constant or common form of lesion in the diabetic brain. Spinal Cord. — In a certain number of cases diabetes has followed the extension of diseased processes from the spinal cord into the medulla, as in locomotor ataxy and insular sclerosis, where the disease is unquestionably the result of the lesion of the medulla. Sandmeyer has published a case of diabetes in which a small patch of degeneration was found in Goll's columns occupying the anterior«half at the cervical en- largement and the anterior two-thirds in the upper cervical region. The pancreas was normal. Williamson has found in two cases pallor of the posterior columns very visible after hardening in Muller's fluid, and escaping the action of staining agents, but under the microscope very slight atrophic changes could be seen. I have been unable to confirm these observa- tions in the cords which have come under my notice. Again, diabetes has not infrequently followed injuries to the spinal column, though in one case where this occurred the cord was apparently uninjured. In connexion with these facts, it will be remembered that Schiff has produced artificial glycosuria by dividing the cord opposite the second dorsal vertebra ; but in cases where the diabetes is neither a compli- cation of a recognised disease of the cord nor a consequence of injury to the spine, this structure has been usually described as normal. Unfortunately, the number of cases in which it has been carefully examined is not large, but in these enough has been found to show that secondary nutritive changes, similar to those in the brain, are apt to occur in the cord ; these are dilatation of the central canal, enlargement of the peri-vascular sheaths, and localised softening. Tumours of the cord in connection with diabetes have been very rarely recorded ; the only case known to me is one of myxoma of the dura mater (Shingleton Smith). Glycogen has been found in large quantities in the spinal cord. Microscopical examination of the spinal cord, stained after Weigert's method, has been carefully carried out without any special change being noted. 266 DIABETES. Cerebrospinal Nerves.— Tumowrs situated on. or compress- ing the vagus nerve have been found associated with diabetes. Three such cases have been recorded (Harley, Henrot, Frerichs), and in each instance the right nerve was the seat of the lesion. In Frerichs' case the tumour encroached upon the floor of the fourth ventricle, but in the other two cases no such complication existed, the tumour being situated in the thorax. These observations are very interesting in connection with the recent experiments of Arthaud and Butte, who found that artificially induced neuritis of the central end of the divided vagus caused glycosuria, while a similar lesion of the peri- pheral end caused hunger, wasting, polyuria, and thirst. Lubimoff has found in one case of diabetes atrophy and pigmentation of the inferior ganglion of the vagus. Few pathological observations on the spinal nerves in diabetes are known to me, but it is noteworthy that Arthaud and Butte T-Q. 53. Right Median Nerve showing very advanced interstitial and parenchymatous neuritis. Osmic acid preparation. have produced glycosuria by setting up neuritis in the roots of the first dorsal pair of spinal nerves. Schiff, moreover, has shown that stimulation of the central end of any sensori-motor MORBID ANATOMY. 267 nerve, such as the sciatic, may be followed- by glycosuria. Clinical observation has revealed the existence of a secondary diabetic neuritis, which may be multiple (Leyden), or attack particular nerves (Althaus). In these circumstances it gives rise to the phenomena of paralysis, with wasting and loss of faradaic response of the muscles supplied by the affected nerves. In other instances we may meet with a general peripheral neuritis closely resembling locomotor ataxy in its clinical features, and, as we shall see, very hard to distinguish from it. There is a widespread interstitial and segmentary neuritis with great increase of the connective tissue. In the cord some swelling and pigmentation of nerve cells only has been observed. The accompanying drawing {Fig. 53) is from a case under my care which will be described further on. Sympathetic Net'ves. — Changes in this system of nerves in diabetes seem very early to have attracted the attention of pathologists. Thus Duncan, as long ago as 1818, found the sympathetic in the abdomen three times as thick as normal ; and Percy, in 1842, described the semilunar ganglia, the splanchnic nerves and vagus, as thickened and of cartilaginous hardness. Klebs and Ph. Munk, in 1870, found changes in the cceliac plexus with destruction of a number of ganglion cells, and Cavazzani has observed atrophy, pigmentation and necrosis of nerve cells with increase of the connective tissue, nuclei and fibres. Lubimoff has also found sclerosis of the sympathetic ganglia and atrophy of their nerve cells. In four of my cases the semilunar ganglia have been found enlarged, in two cases atrophied, with increase of connective tissue and atrophy of nerve cells, and in one, embedded in a dense mass of fibrous tissue. Hale White has recently des- cribed similar lesions in four cases of diabetes. On the other hand Shingleton Smith has made numerous observations on the state of the sympathetic ganglia without finding any uniform or definite change. In three of my cases the semi lunar ganglia were normal, and I have shown in a paper published in the British Medical Journal in 1883 that similar microscopical changes to those above described are met with apart from diabetes. Yet I have never seen the semilunar ganglia enlarged except in diabetes ; in some of my cases the right semilunar ganglion was quite twice the normal size. The importance of these facts depends upon the results of experiments which have shown that destruction of various sympathetic ganglia — for example, the superior and inferior DIABETES. cervical (Pavy), the first thoracic (Eckiiard), and the ab- dominal (Klebs), — and division or ligature of the splanchnic nerves (Hensen, Arthaud and Butte), are followed by glycosuria. Extirpation of the coeliac plexus is followed by wasting and death, with temporary glycosuria and acetonuria (LUSTIG, PEIPER). THE CIRCULATORY SYSTEM. Heaj't. — In about 40 per cent, of my cases the heart has been described as free from noticeable change ; while in about the same proportion it has been described as pale and soft ; Fig. 54. Heart muscle from a case o£ very advanced fatty and fibroid degeneration. Fat droplets Btaiiied black with osa.io acid. (Hartnack oc. 2, obj. 7. Tube drawn out.) more rarely, dilated or hypertrophied, or distinctly fatty. Pericarditis occurs occasionally, and, in one case of death from a carbuncle in a diabetic subject, the pericardium was full of fluid, fatty blood. Valvular disease is quite ex- ceptional, though Lecorche has described endocarditis as a complication of diabetes, and Maguire has recorded a case. It is said to occur in the later stages, and to affect usually the auricular surface of the mitral valve. The rarity of endo- carditis may be estimated from the occurrence of only one MORBID ANA 1 OMV 269 case of valvular disease out of the ninety-four cases collected in Windle's tables ; and in my twenty-nine cases there was valvular thickening in one only. Mayer has stated that out of three hundred and eighty diabetics seen at Carlsbad, eighty- two, or 24 per cent, showed signs of cardiac enlargement, and Schmitz, of Neuenahr, has made a still stronger statement as to the prevalence of fatty heart. Frerichs has drawn attention to glycogenic degeneration of the cardiac muscle, and suggests that this is the real cause of the cardiac debility of diabetes. Hypertrophy of the heart was present in 1 3 per cent, of cases examined in the Berlin Pathological Institute, and this accords very nearly with my experience. Fatty heart is probably much more common, if we are to judge by the fre- quency with which the muscular substance is described as pale and soft in reports of diabetic necropsies ; yet I should estimate it as occurring in less than 40 per cent, of all cases. The preceding illustration {Fig. 54) shows the appearance of the muscle in a very marked case. Glycogenic deposits in the Fig. 55. Heart muscle apparently healthy, except lor a few granules of glycogen lying within tho Bheaths ol the muscular bundles. (Hartnack, oc. 2, obj. 7. Tube drawn out.) wall of the heart have only been found by me in such small quantity that I cannot ascribe to them any serious pathological significance. The drawing {Fig. 55) shows a few granules of 270 DIABETES. glycogen deposited between the muscular bundles, but the muscular fibre appears healthy. Blood. — The blood of diabetics generally looks normal to the naked eye. It is sometimes described as dark, and is some- times very obviously loaded with fat, a white, cream-like layer rising to the surface when the blood is allowed to stand. Under the microscope the fat is seen to be at first in a state of molecular subdivision, but these molecules run together to form droplets after death, and this may produce the appear- ance of capillary embolisms. Occasionally the red blood- corpuscles are found broken down into a granular material (Foster, von Jakscii). In one of my cases the leucocytes were peculiarly large. Quantitative changes in the hsemocytes are common, these being generally reduced in number, with a corresponding reduction in the haemoglobin. Normal blood contains sugar in varying amounts. The following table gives the estimate of four observers • — Name. Parts per cent. Pavy ... Otto ... Seegen Frerichs 0*078 to o'oSi (dog). O-IO „ 0*14 „ 0*15 ., 019 (man). 0*12 „ 0-3 „ According to Seegen, the amount present in mild cases of diabetes does not exceed the normal, but in severe cases it may rise as high as 0"4 parts per cent. The alkalinity of the blood serum is reduced, owing to the presence of certain organic acids of doubtful identity, of which diacetic acid and y8-oxybutyric acid seem the most probable. The existence of acetone is disputed, as former reports of its presence are believed to be due to the breaking up of diacetic acid to form acetone and carbonic acid gas. In certain experiments con- ducted by me some years ago in the laboratory of Professor Tilden, at Mason College, I was unable to detect any acetone in the blood of a diabetic patient who had died of coma. THE RESPIRATORY SYSTEM. Lungs. — Pathological alterations in the lungs are the rule in diabetics, and perhaps no organ shows more constant changes. In my cases 17 per cent, only were free from disease. The MORBID ANATOMY. • 271 most common condition was congestion, or congestion and oedema. The next most frequent alteration was phthisis, which was present in 27 per cent. Small foci of softening were observed in one case, abscess in one, hsemorrhagic in- farcts in one, and gangrene also in one. Dreschfeld has ■described the following types of lung affection in diabetes : (\) Acute croupous pneumonia, very acute and fatal, but rare ; (2) acute broncho-pneumonia, which may terminate by gan- grene ; (3) chronic caseating tubercular broncho-pneumonia, the common form of diabetic lung complication ; (4) chronic non-tubercular broncho-pneumonia ; (5) gangrene of the lung. Fink recognises two forms of diabetic phthisis : (i) Tubercular and (2) fibroid. In the latter there are no tubercle bacilli in the sputa of lung, no caseous deposits, and the lung undergoes chronic induration. Non-tubercular phthisis is not so common as used to be imagined ; at least I have almost in- variably been able to find tubercle bacilli in the sputa, but an undoubted example, with most careful post morteni examina- tion has been placed on record by Roque Devic and Huguenenq. Pleurisy and empyema occur rarely. Fat embolisms have been described as playing an important part in the pathology of diabetic coma (SANDERS and HAMILTON), but it is doubtful if they are not post viorteni formations, due to the running together of the fat which was previously held suspended in a molecular state, and in any case they are not present in such numbers as to give rise to any symptoms (Saundby and Barling). The vessels of the lungs have been described as undergoing hyaline and fibroid thickening ; but this is not a primary change, or one in any way peculiar to diabetes. THE DIGESTIVE SYSTEM. Liver. — Great interest attaches to this organ, because of its physiological relations to sugar formation. An opinion was at one time held, and has been expressed by recognised authori- ties, that the liver in diabetes is usually healthy, and even a more than usually healthy appearance has been described as characteristic of it. In my experience this is a very erroneous view. The liver is generally enlarged, weighing from sixty to eighty ounces. In a smaller number it is small, pale, and soft. Fatty degeneration is very common ; congestion is often observed ; the consistence of the organ is sometimes abnormally firm. A certain degree of interstitial hepatitis is 272 DIABETES. frequently present, and occasionally this goes so far as to pro- duce distinct cirrhosis. This is attributed by Letulle to the effect of the abnormal destruction of haemocytes. Hanot and Schachman have also described this form of cirrhosis. The liver is sometimes smooth, at others granular and scarred. The lesion begins, according to these observers, around the radicals of the hepatic vein, but Brault and Gaillard point out, in my opinion rightly, that the new growth begins in both the hepatic and portal areas. A form of cirrhosis is associated with bronzing of the skin (diabete bronze). Some degree of interstitial hepatitis may, however, be seen without any evidence of pigmentary deposit in the liver or the integument {Fig. 56). This drawing shows very well marked commencing a=S»^9=^ Tig. 56. Section of liver sho-wing commencing interstlHal hepatitis in a portal canal. Two newly formed biliary oanalicull are seen near the edges of the acini. (Hartnack, oc. 3, obj. 1. Tube drawn out.) cirrhosis in a diabetic liver, Abscess of the liver is sometimes met with associated with diabetes. I remember one such case when I was a pathologist, and I believe it presented all the clinical phenomena of severe diabetes. The liver contained one large abscess and numerous smaller ones. A similar case was reported in the U.S. Navy Reports for 1878. It is permissible to believe that the abscess in these instances was really the cause of the diabetes. Dickinson has described thrombosis of the branches of the portal vein, and angeiomata formed of dilated capillaries near the radicals of the hepatic vein. In spite of its fatty appearance Weyl and Apt have not MORBID ANATOMY. 273 found the diabetic liver to contain an excessive amount of fat :— Normal liver - - - - 370 pts. per mille. Diabetic liver . - - - 375 „ „ Moreover, absence of fat from the liver cells has been observed by Beale and Frerichs. Quincke described excess of iron in the liver, deposited in the form of granules. Zaleski has not observed it in granular form ; he estimates the diabetic liver to contain 068 5 parts of iron per mille, but he points out that we have no data to enable this to be compared with the normal quantity. Spleen. — This organ is very frequently described as normal, but the most common naked-eye change is that it is small, pale and soft. It is more rarely enlarged and congested, and sometimes contains tubercle. It is said to contain excess of iron (Quincke), but, as already explained, data are wanting as to the amount present in health. Glycogen has also been found in it. Hyaline degeneration of the small arteries has been described, but I have not been able to perceive anything abnormal about them. Pancreas. — Dr. Baumel, in a paper published in the Montpellier Medical for 1881-82 was the first to contend that disease of the pancreas was the regular cause of diabetes, and in the same communication he recorded a case of diabetes without emaciation {diabete gras) in which this association existed. To him, therefore, belongs by right any honour that is due to the writer who first distinctly recognised the full sig- nificance of the pancreatic lesion in diabetes. But it was Lancereaux who drew general attention to the frequency with which the pancreas is atrophied in diabetes, and he went so far as to associate the clinical type of diabete viaigre with this lesion. The importance of these pathological observations first became manifest when the experiments of Minkowski, Lepine, and others showed that extirpation of the pancreas in animals is followed by diabetes. This organ is by no means so carefully examined by pathologists as it deserves to be, and there is wanting that familiarity with its ordinary naked- eye and microscopic appearances which gives value to their descriptions. In many cases no note of its condition has been made. The following table shows the state of the 18 274 DIABETES. pancreas in twenty-seven cases examined in the General Hospital : — Pancreas atrophied and fibrous - - . . n „ , „ soft .... 2 „ enlarged „„-■--■ i ,) 5 » hard 3 •f 11 - ' ' ~ ' J „ congested (mottled) i „ normal 6 so that it was normal in only 23 per cent. So far as my own observations go, I am disposed to agree with Lancereaux, as I have found the pancreas shrunken in all m}^ cases of typical wasting diabetes, but Lepine has seen atrophy of the pancreas in a fat diabetic subject. That the pancreas stands in some relation to diabetes is shown by the experience of Bull, of New York, whose patient died of diabetes after he had extir- pated the pancreas. Duffey and Dreschfeld have published cases of diabetes associated with cancer of the pancreas ; and a very well marked example of the same kind was under my care last summer. Churton has recorded a case of pancreatic cyst associated with diabetes. In a review article (August 2nd, 1890) the editor of the PJiiladelphia Medical News referred to a case of cystic disease of the pancreas from a case of diabetes exhibited by Longstreth in 1877, ^^d to one of multiple pancreatic abscesses with glycosuria re- ported by Prison in 1875 ; on the other hand, he stated that Langenhans had recently published a case of necrosis of the pancreas in which there was no sugar in the urine. Numerous collections of cases of pancreatic diabetes have been since published by Vaughan Harley, Williamson, J. G. Hoppe-Seyler, Hansemann, Fleiner and others. In the cases of pancreatic disease collected by Dr. Handfield Jones, and more recently by another distinguished Fellow of this College, Dr. Norman Moore, there is no mention of diabetes. It has been suggested, (i) that the pancreas supplies the liver with the fatty acids necessary to the formation of bile acids from glycogen, hence, in affections of the pancreas there is excess of glycogen with resulting diabetes (Popper) ; (2) ex- cessive production of glucose from diastatic ferments formed in the stomach and duodenum (Bouchardat) ; (3) the forma- tion of paraglucose by the action of modified pancreatic juice (Cantani); (4) the absorption of the pancreatic ferment, which, passing direct to the liver, changes the glycogen to glucose MORBID ANA TO MY. 275 (Baumel) ; (5) the suppression of a normal sugar-destroying ferment which should pass by the pancreatic lymphatics to mingle with the chyle (LfiPlNE) ; and (6) that the pancreas regulates in some manner the sugar-producing function of the liver (Kaufmann). Brault and Gaillard have described a pigmentary cirrhosis of the pancreas analogous to the pigmen- tary cirrhosis of the liver observed in diabetes. Pancreatic calculi may cause cystic degeneration or sclerosis, or complete adipose transformation. The drawing {^Fig. 57) is a low-power view of a portion of c a ^aa Fig. 57. Section of atrophic cirrhotic pancreas, showing great increase of connective tissue with n, hynline degeneration of glandular epithelium ; b, newly formed ducta, and c, ducts undergoing atrophy. (Hartnack, oc. 2, obj. 4. Tube drawn out.) pancreas, showing great increase of connective tissue with a new formation (?) of ducts and a hyaline condition of parts of the pancreatic glandular epithelium. The latter appearance shown in Ftg. 58, which was formerly thought to be a morbid change, is probably only a physiological condition of the cells 276 DIABETES. distended with secretion. It is evident that there is an increase of fibrous tissue with destruction of the gland analogous to Tirf. 58. — Highly magnified view of a group of pancreatic acini which have undergone hyaline transformation. (Hartnaclc, oc. 3, obj. 7. Tube drawn out.) cirrhosis of the liver. This process is undoubtedly inflamma- tion and not simple atrophy. In the earlier stages of the process the gland is swollen from abundant infiltration of its tissue with round cells. A section of such a swollen pancreas, obtained from a case of rather acute diabetes, is shown under one of the microscopes {Fig. 59). It has been suggested that the atrophy of the pancreas may be secondary to disease of the coeliac plexus ; but Lustig found that extirpation of this plexus was not followed by atrophy of the pancreas ; and this has been confirmed by Peiper. Stomach. — It is unfortunate that the stomach is often omitted in post viorteni reports. I have notes of its condition in only eleven cases, but it is significant that in only one instance was it found to present no morbid alteration. In three cases it was dilated, in three there were haemorrhages generally near the pyloric end, in two the mucous lining was congested, in one softened, and in one in a state of chronic catarrh. Windle speaks of " thickening " of the mucous membrane as not un- common, and also of distension of the organ by gas. Intestines. — The large bowel is generally found filled with hardened faecal^ masses, and congestion or catarrhal conditions of the mucous membrane are not uncommon. Haemorrhages MORBID ANATOMY. 277 similar to those in the stomach also occur in the duodenum. In two instances large masses of taenia medio-canellata were present. The mesenteric glands were twice found to be enlarged. Frerichs has described a dysenteric condition of •■■■■•-■:•■ '■•• ■.■■■■ v-'4.-5's-'r;Ssi i »»,''•■ ■;•. Fin. sn.— Section of enlarged pancreas showing commencing cirrhosis with infiltration of the con- nective tissue spaces by round cells. iHartnack, oc. 2, obj. 4. Tube drawn out.) the large intestine, and Ebstein desquamation of the epithelium lininsT the bowel. GENITO-URINARY SYSTEM. Kidneys. — In not one of my cases were the kidneys des- cribed as normal, though in many the changes were not of great importance. The most common condition appears to be a slight degree of fatty degeneration. This comes out in Windle's tables as well as my own. Such kidneys are gener- ally enlarged, and their capsules are often adherent. Less commonly the kidneys are enlarged and congested. Some- times there is thinning of the cortex, or distinct contraction of the organ. Tubercle and lardaceous disease occur occasionally, and the kidney may become gangrenous (TURNER). The above-mentioned fatty change has been described specially by 278 DIABETES. Fichtner, who regards it as characteristic of diabetes. But the most interesting histological fact in the diabetic kidney is the hyaline degeneration of the tubular epithelium, which was first described by Armanni. His observations were confirmed by Ebstein, who assigned the seat of the lesion to the descending limb of Henle's tubes ; but this was disputed by Ferraro, who, however, found the change nowhere outside the medullary portion of the kidney. This last observer attributed the changes to a primary lesion of the vascular walls. These changes in the epithelium and the co-existing hyaline changes in the vessels were well described by a distinguished Fellow of this College, Dr. Stephen Mackenzie, in opening a discussion at the Pathological Society of London in 1883. Ehrlich also described, " as characteristic of and peculiar to diabetes," a hyaline degeneration of the epithelium of that part of the kidney between the cortex and the pyramid — that is, the boundary zone ; and Strauss proved that this lesion is identical with that described by Armanni. Strauss found that it was only present in one out of three cases, but he agreed that it is absolutely characteristic of diabetes, and he attributed it to the osmosis of sugar into the cells. Ehrlich considered that the change was due to glycogenic infiltration of the cells, but Strauss, in a later paper, says that no glycogen may be visible, even when all Ehrlich's precautions are taken. With reference to its causation, Albertoni and Pisenti have investigated the changes produced by administering small doses of acetone to rabbits. They found the following lesions : (i) granular degeneration of the epithelium of the convoluted tubes, the nuclei still staining well ; (2) complete destruction of the epithelium with disappearance of the nuclei, and slight dilata- tion of Bowman's capsules ; the glomeruli and connective tissue were not affected. They suggest the possibility that the necrosis of the epithelium observed by Ebstein may be due to the action of acetone on the kidneys. Stokvis, too, found that artificial diabetes, produced by injecting grape sugar into the blood, caused albuminuria ; and he believes that this sets up a chronic nephritis. Both these are possible explanations of the fatty change already alluded to, which is entirely like that of slight chronic parenchymatous nephritis due to infective disease ; but they do not throw any light upon this peculiar and characteristic hyaline change. My observa- tions entirely confirm the existence of this hyaline degeneration and its restriction to the epithelium of Henle's tubes. It is MORBID ANATOMY. 279 well shown in the illustration {Fig. 60), and is quite different Fiq. 60.— rortion of Henl'3's looped tube, showing hyaline degeneration of the epithelium Armanni s lesion. (Hartnack, oc. 2, obj. 7. Tube drawn out.) Fin. 111.— Renal tubule Bho\rlng masses of glycogen within the epithelial cells or free. (Hartnack. oo. 3, obj. 7. Tube drawn out.i from the glycogenic infiltration which may also be present, as shown in the drawing {Fig. 6i), though this fails to bring 28o DIABETES. out the characteristic mahogany staining of the glycogen granules. The kidneys, like many other organs in diabetes, may present marked fatty degeneration {Fig. 62), droplets -^^>„^rO-:a^^. ^^- Fig. 62. — Portion of renal tubnle showing fat droplets, stained black with osmic acid, lying within the epithelial cells or free in the lumen. (Harcnack, oc. 3, obj. 7. Tube drawn out.) staining black with osmic acid being abundantly visible within the epithelial cells and free in the lumina of the tubules, the straight tubules being chiefly affected. Not uncommonly the kidneys present all the characteristic features of chronic diffuse nephritis, as is illustrated by one of the microscopic specimens. Bladder. — This organ is usually normal, but it is often dilated and hypertrophied. The mucous lining sometimes may be the seat of haemorrhages. Ovaries. — Israel has described a case in which there was gangrene of both ovaries associated with recent general peri- tonitis. These organs have also been described as cystic and atrophied, but these are common conditions, and not in any way specially associated with diabetes. Concluding remarks. — It is very plain that diabetes, far from having no morbid anatomy, has one of a very com- plicated kind, and one that cannot be without bearing upon its pathology. Definite changes in the medulla and vagi are undoubtedly causative, but are exceedingly rare. The most important common lesion is the wasting of the pancreas ; ot some significance, too, are the alterations in the abdominal sympathetic ganglia, though they are too inconstant to form the basis of a satisfactory theory. The liver changes are probably altogether secondary to a functional hyperaemia induced under nervous influence. The appearances in kidneys, lungs, heart, and brain are mainly the results of defective nutrition and of long-standing hyperglycaemia. MORBID ANATOMY. 281 BIBLIOGRAPHY. Abraham (P. S.). On some Microscopical Lesions from two cases ol Diabetes Mellitus. " Dub. Med. Jour.," Vol. LXXVII., p. 395. Albertoni and Pisenti. Azione dell' acetone e dell' acido acetacetico sui reni. " Arclji. per le Sc. Med.," 1887, Vol. XL, pp. 129 to 152. Althaus. Neuritis of the Circumflex Nerve in Diabetes. "The Lancet," Vol. I., 1890, p. 455. Armanni and Cantani. Le diabete sucre et son traitement dietetique. Paris, 1876. Baumel (L.). Pancreas et diabete. " Montpellier Med.," 1881-2. . Etiologie et pathogenic du diabete sucre, Montpellier, 1894. Brault and Gaillard. Sur un cas de cirrhose hypertrophique dans le diabete sucre. "Arch. gen. de Med.," Vol. I., 1888. Cavazzani. Morbid Changes in the Sympathetic System in Diabetes MeUitus. " Centrlbl. f. allg. Path.," July ist, 1893. Churton (T.). a case of Diabetes associated with pancreatic cyst. "The Lancet," 1894, Vol. I., p. 1374. Cyr (J.). Etude critique sur quelques travaux recents concernant I'anat- omie pathologique du diabete. Paris, 1880. Dickinson (W. H.). On Diabetes. London, 1877. Dreschfeld (J.). On the Pathology of the Lung Complications in Diabetes. "Med. Chronicle," Vol. I., p. 5. DuFFEY (G. t. ) On the Connection of Acute Diabetes with Disease of the Pancreas. "Trans. Acad. Med. in Ireland," Vol. II. Duncan. Clinicar Reports, 1888, case 28, p. 137. Ebstein (W.). Ueber Drusen-Epithelnekrosen beim Diabetes mellitus mit besonderer Beriicksichtigung des diabetischen Coma. " Deutsches Arch, f. klin. Med.," 1881, Bd. XXVIIL, p. 143. . Weiteres iiber Diabetes mellitus insbesondere iiber die Complication derselben mit Typhus abdominalis. Ihid., 1882, Bd. XXXI., p. I. Ehrlich. Ueber das Vorkommen von Glycogen in diabetischen und normalen Organismus. " Zeit. fijr klin. Med.," 1883, Bd. VI., p. 33. Ferraro (P.). Nuove ricerche sulle alterazioni degli organi nel diabete mellito. "II Morgagni," 1883, pp. 71 and 233, Fichtner (R.). Zur pathologischen Anatomic der Nieren beim Diabetes mellitus. " Virchow's Archiv," Bd. CXIV. Fink (H.). Zur Lehre von den diabetischen Lungenerkrankungen. "Mijnch. med. Woch.," 1887, No. 37. Fleiner. Zur pathologic des calculosen und artericsclerotischen Pankreas- cirrhose und der entsprechenden Diabetes formen. " Berl. klin. Woch.," 1894, Nos. I and 2. Foster (B. W.). Diabetic Coma — Acetonsemia. "Brit. Med. Jour.," 1878, Vol. I., p. 78. Frerichs (T.). Ueber den Diabetes. Beriin, 1884. . Ueber den plotslichen Tod und iiber das Coma beim Diabetes (Diabetische Intoxication). "Zeit. fiir klin. Med.," Bd. VI., Heft. i. Futterer (G.). Glykogen in der Capillaren der Grosshirnrinde beim Diabetes melUtus. " Cent. f. d. med. Wiss.," 1888, No. 88. GuiLLioT (O.). Glycosurie et inositurie; degenerescence graisseuse du pancreas. " Gaz. med. de Paris," 1881. Hanot and Schachmann. Sur la cirrhose pigmentaire dans le diabete sucre. "Arch, de Physiol.," 1886, Vol. I., p. 50. Hanot (V.). Diabete bronze. "Brit. Med. Journal," 1896, Vol. I., p. 206, Hansemann. The pancreas in Diabetes. Int. Med. Congress, " Brit. Med. Journ.," 1894, Vol. I., p. 796. 282 DIABETES. Harley (quoted by Roberts). Urinary and Renal Diseases. Harley (V.). The Pathogenesis of Pancreatic Diabetes MelHtus. "Brit. Med. Journ.," 1892, Vol. II., p. 452. Henrot. " Bull, de la Soc. Med. de Rheims," 1874, No. 13. Hoppe-Seyler (G. ). Beitrag. zur Kenntniss der Beziehungen der Erkrankung der Pankreas und seiner Gefasse beim Diabetes mellitus. " Deutsches Arch. f. k. Med.," Bd. 32, p. 176. HuGOUNENQ. Contribution a I'etude de la dyscrasie diabetique. "Rev. de Med.," 1887, p. 301. Israel (O.). Zwei Falle von Nekrose innerer Organe beim Diabetes mellitus. " Virchow's Archiv.," Bd. LXXXIII., 1881. Jaksch (R. v.). Ein Fall von sogen. Acetonamie. " Prag. med. Woch.," 1880. Jones (C. Handfield). Observations respecting Degeneration of the Pan- creas. " Med. Chir. Trans.," Vol. XXXVIII.. 1855. Klebs and Ph. Munk. Handbuchder Path. Anat.," Bd. III., 1870, p. 547. . " Tagebl. der Innsbruoker Naturforscher Vers.," 1869, p. 113. Lancereaux (E.). Notes et reflexions sur un cas de diabete sucre avec alteration du pancreas. "Bull, de L'Acad. de Med.," 2e. Ser., VI., 46, 1887. . Le diabete maigre et le diabete gras. " L'Union M^d.," 1880, XIIL, 16. Lecorche. De I'endocardite diabetique. " Arch. Gen. de Med.," 1882. — . Traite du Diabete. Paris, 1877. Lepine (R.). Le ferment glycolytique. Paris, 1891. Letulle. Deux cas de cirrhose pigmentaire dans le diabete sucre. " Soc. Med. des Hopitaux," 1885. Leyden. Die Entzundung der peripheren Nerven. Berlin, 1888. LusTiG (A.). Sugli effetti dell' estirpazione del plesso celiaco. "Arch, per le Scienze Med.," 1889, No. 6. LuYS. " L'Encephale," May, 1882. Mackenzie (S.). ■ Discussion upon the Morbid Anatomy of Diabetes." "Trans, Path. Soc," 1883. Maguire (R.). Roberts' Renal and Urinary Diseases. 1885, p. 271, foot note. Mayer (J.). Ueber den Zusammenhang des Diabetes mellitus mit Erkran- kungen des Herzens. " Zeit. f. klin. Med.," Bd. XIV., Heft 3. Moore (Norman). Cancer of the Pancreas. "St. Barth. Hosp, Rep.," Vol. XVII., 1881, p. 205. Norta. Observation du diabete maigre. " L'Union Med.," 1881. Otto (J. G.). Ueber den Gehalt des Blutes an Zucker und reducirender Substanz unter verschiedenen Umstanden. " Pfiiiger's Archiv," 1885, Bd. XXXV., p. 467. Pavy (F. W.). Croonian Lectures on Points connected with Diabetes. " The Lancet," 1878, Vol. I., p. 557. Peiper. Experimental Studies on the results of Extirpation of the Coeliac Plexus. "Miinchen. med. Wochen. ," April 29th, 1890. Percy (J.). Case of Diabetes Mellitus. " Med. Gaz.," 1842 to 1843, Vol. I., p. 49. PiLLiET (A.). Sclerose du pancreas et diabete. "Le Prog. Med.," 1889, No. 21, p. 391. PONIKLO (S. J.). Op. cit. Pryce (J. Davies). On Diabetic Neuritis with a clinical and pathological description of diabetic pseudo-tabes. " Brain," 1893, 416. Quincke (H.). Ueber Siderosis, Eisenablagerung in einzelnen Organen des Thierkorpers. " Fest. zum And. v. Al, v. Haller," Bern. 1877. MORBID ANATOMY. 283 RoQUE Devic and Hugounenq. Du coma diabetique. " Revue de Med.," 1892, p. 995. Sanders and Hamilton. Lipsemia and Fat Embolism in the Fatal Dys- rrnoea and Coma of Diabetes. " Edin. Med. Jour.," Vol. XXV., Part i, 1879, p. 47. Sandmeyer. "Centrlblt. f. k. Med.," 1890, No. 28. Saundby and Barling. Fat Embolism. "Jour, of Anat. and Phys.," Vol. XVI., 1882, p. 515. ScHiFF (J. M.). Untersuchungen ueber die Zuckerbildung in der Leber. Wurzburg, 1859. " Jour, de I'Anat. et de la Phys.," Vol. III., p. 369. ScHMiTZ (R.). On a Frequent and Noteworthy Complication of Diabetes mellitus. " Lond. Med. Record," Vol. IV., 1876, p. 200. Seegen (J.). Ueber die Zuckerbildung in der Leber. "Arch. f. Anat. und Physiol.," 1880. . Ueber dem Zuckergehalt des Blutes vom Diabetikern. " Wien. med. Wochen.," i885. No. 47. Smith (R. Shingleton). Remarks on the Morbid Anatomy and Pathology of Diabetes. " Brit. Med. Jour.," 1883, Vol. I., p. 657. Strauss (J.). Contribution a I'etude des lesions histologiques du rein dans le diabete sucre. " Arch, de Phys.," 1885, Vol. II., p. 322. . Nouveaux faits pour servir a I'histoire des lesions histologique du rein dans le diabete sucre. Ihici., 1887, p. 76. Tardieu (quoted by Roberts). Op.cit. Thiroloix (J.), Diabete bulbaire. " Gaz. Hebd.," 1892, No. 16. Turner. Necrosis of the Pyramids of the Kidney. " Brit. Med. Jour.," 1888, Vol. L, p. 1059. Weyl and Apt. Ueber den Fettgehalt kranker Organe. "Virchow's Archiv," Bd. XCV., p. 351. White (V/. Hale). On the Sympathetic System in Diabetes. "Path. Soc. Trans.," Vol. XXXVI., p. 67. Williamson (R. T.). Changes in the Posterior Columns of the Cord in Diabetes Melhtus. " Brit. Med. Journ.," 1894, Vol. I., p. 398. . The Condition of the Pancreas in fourteen con- secutive cases of Diabetes Mellitus. " The Lancet," 1894, Vol. I., p. 927. Windle (B. C. A.). The Morbid Anatomy of Diabetes Mellitus. "Dublin Jour, of Med. Science," Vol. LXXVI., 1883, p. 112. Zaleski (S.). Zur Pathologic der Zuckerharnruhr (Diabetes mellitus) und zur Eisenfrage. " Virchow's Archiv," Bd. CIV,, p. 91. Chapter XTX. CLINICAL HISTORY. SYMPTOMS. Diabetes Mellitus presents itself for clinical observation under two types, (i) acute, (2) chronic, in which the essential symptoms, wasting, thirst, polyuria and glycosuria are present in varying degrees of intensity. In the former these are all great, in the latter the first three especially are moderate, and the total excretion, though perhaps not the actual percentage of sugar, is also not excessive. It does not appear to be practicable to refer the majority of cases of diabetes to their anatomical cause, but exceptionally we may recognise the dependence of the disease on some affection of the nervous system, pancreas, or liver. In the acute type the patient is young, he looks ill, his face is pale or cyanosed, his expression is anxious, the hair rough, the skin dry, the lips parched, the tongue red and sticky or covered with a black coating. The pulse is weak, and the temperature sub-normal. The body weight falls rapidly to much below the normal standard in spite of an appetite which is often voracious ( Diabete maigre). Thirst is excessive and micturition is so frequent that broken nights add to the misery of his condition. The quantity of urine varies from 100 to 300 or more ounces in twenty-four hours, and the quantity of sugar ranges from 5 to 10 per cent. In the chronic type the patient is elderly, often florid and well-nourished without any special appearance of ill health, but he complains of unaccustomed weakness, thirst, frequency of micturition and some loss of flesh. Many of these patients have been very stout, so that the wasting is not so apparent {Diabete gras). The quantity of urine varies from 60 to 120 ounces, and the quantity of sngar from 3 to 10 per cent. Prout thought that diabetics were usually fair-skinned and red-haired, and Fagge has confirmed this impression. Such an opinion is of little value, as no one would pretend that all CLINICAL HISTORY. 285 fair-skinned persons are diabetic or that all dark-skinned persons enjoy an immunity from the disease. Babington believed he could always detect diabetics by their odour. We now know that the breath of diabetics contains acetone and ethylic alcohol at times, but many diabetics do not smell at all diflerently to healthy persons. The skin of diabetics is usually harsh, and the hair dry. The face may be flushed in a peculiar way as if the patient were blushing, or it may be pale, cyanosed, and the lips parched. The nutrition of the 7iails is often inter- fered with ; they become brittle and in some cases come off. The temperature is usually normal or sub-normal, but Skerritt has described a case of acute febrile glycosuria in which the temperature ranged for three days between 99° and 103°. The intellectual centres are as a rule unaffected ; but there is often irritability of temper and other evidences of enfeeble- ment of the controlling centres ; common sensation is usually unaffected ; motor paralysis is rare, but sometimes occurs as a consequence of diabetic neuritis. The knee Jerks are frequently absent, probably from the same cause. Sexual power is gradually lost ; as a rule this loss is permanent, but if the disease improves it may be regained. In females menstruation is generally deficient or absent. Vision is frequently affected, the most common derangement being due simply to weakening of the muscle of accommodation, but toxic amblyopia, retinitis, haemorrhages, and cataract may occur. Hearing is usually normal, though in one of my cases deafness came on at the same time as the disease, and aural complications are not uncommon. Smell and taste may be blunted. The appetite is usually good, and digestion easy, but constipation is very commonly present. The tongue is often red and sticky, and the patient usually complains of dryness of the mouth, which sometimes causes a difficulty in degluti- tion. The teeth are generally decayed and falling out, from atrophy of the gums. The abdomen is often retracted, but may present no unusual appearance, and the outline of the liver and spleen are commonly normal, though enlargement of the liver is a tolerably frequent occurrence. The stools are peculiarly foetid ; this was first pointed out by Hodgkin who ascribed it to deficient bi!e. In uncomplicated cases there is no cough or dyspnoea, and the position and outline of the heart are normal. The cardiac impulse is often feeble, and evidences of weak circulation are only too common, especially as the disease advances. Ejido- 286 DIABETES. carditis occurs rarely, but fatty degeneration of the muscular wall of the heart is a frequent change. In early cases, before the heart's wall has degenerated, the pulse preserves a good degree of tension, as illus- trated in Fig. 63, which shows a full tidal wave. But later on, the heart ■^»-^2- fails, the pulse fails too, and we get such a tracing as the following \Fig. 64). The pulse rate is not increased unless in consequence of some complication. It is usually regu- lar, without intermissions. A rapid pulse is one of the early signs of the onset of coma. ^'3- "^ The peculiar odour of the breath has been already alluded to and ascribed to the presence of acetone and ethylic ether. Lung affections, especially chronic phthisis, occur very com- monly. The symptoms are very latent, cough being slight and expectoration often absent. But such lung troubles are of the nature of complications and will be fully described in that section. The blood contains excess of sugar, and, as already noticed, its alkalinity is reduced in some cases as much as 50 per cent. Its serum is said to be poisonous to rabbits (ROQUE Devic). Bremer has stated that the red blood corpuscles in diabetes either do not stain or stain very pale yellow, with eosin, but I have not met with this change in the cases I have had examined for the purpose. Marked anaemia often occurs, in which the red blood corpus- cles may be reduced by half and the haemoglobin by more. Rollo showed that the blood of diabetics obtained by vene- section remained for days without undergoing putrefaction, the sugar acting as an antiseptic. The quantity found has varied in the case of different observers. According to Seegen in mild cases it does not exceed the normal, but in severe examples it may rise as high as 0*4 per cent. Sugar has also been found in the sweat, tears, and saliva. Very remarkable fluctuations of body weight occur during the course of this disease, a variation of two or three pounds being observable in the course of a few days. A patient sent me the following table of weights, and complained that her CLINICAL HISTORY. 287 medical attendant scarcely seemed to believe in its accuracy. As this experience has occurred to me many times in hospital practice, I do not hesitate to publish it as illustrat- ing a fact. June 30th 8 St. 13 lbs. J uly 7th 9 St. I >^ lbs. July 14th 9 St. ;^ lb. July 22nd 9 St. X lb. July 29th 9 St. X lb. August 9th 8 St. 12 lbs. August 14th 8 St. 10 lbs. August 2 1 St 8 St. 12 lbs. August 28th 9 St. o lbs. September 5tli 9 st. ^ lb. September 15th 8 st. iij^ lbs. September 1 8th 9 st. ^ lb. Between the 15th and i8th of September there was a gain of 3 5 lbs. These variations are probably to be attributed to the very great daily loss in water and solids, amounting to many pounds, by which the normal equilibrium of nutrition is deranged. The Urine. — The capital symptom of diabetes mellitus is the presence of sugar in the urine, and the diagnosis of the disease depends upon its detection. Is sugar ever present in quantity in the urine of healthy persons ? Physiologists tell us that minute traces can be found in normal urine, but the amount is far too small to be detected in the ordinary way. Flint has asserted that glycosuria, in obvious degrees, is present in one out of three hundred and seventy-seven healthy persons. This statement lacks confirmation, and is not borne out by my experience. The only healthy, or apparently healthy person in whom I have met with glycosuria was the following : — Case 37. — Glycosuria — no polyuria — no thirst — no loss of weight. Arthur M., thirty-two, metal roller, came to me in July, 1887, to be examined for life insurance. He was a very powerfully built man, 5 ft. 6 in. in height, and weighing twelve stone. There was no history of injury, or syphiHs, or any family history of diabetes. His knee jerks were present. There was no other evidence of disease but his urine, which was of sp. gr. 1029, and was loaded with sugar. The quantity was not increased. A second sample, examined a fortnight later, was just the same. He was sent again to me in May, i883, when I found no loss of weight had taken place, and no thirst or polyuria had come on, but the urine was still loaded with sugar, sp. gr. 1023. In order to be sure that there was no fallacy, the urine was fermented and the presence of sugar placed beyond doubt. 288 DIABETES. I saw him ao^ain on February i6th, 1895, when his urine still contained sugar; he weighed 12 st. 9 lbs., and considered himself in perfectly good health. Eating excess of sugar on an empty stomach causes tem- porary glycosuria in healthy persons ; but it has often occurred to me to ask whether such people are not really dangerously likely to become diabetic, if their power of assimilating sugar is so easily exceeded (FowLER, COLLINS, von JAKSCH, Grooz) ? In disease, apart from diabetes, sugar is occasionally found in the urine, but not so often as is sometimes asserted; Thus T, A. Mc.Bride, in a discussion at the New York Academy of Medicine, stated that it may be found in the urine of incipient phthisis, emphysema, chronic bronchitis, chronic pleurisy, heart disease, liver troubles, nervous troubles, cerebral haemor- rhage, fracture of skull, concussion of brain, and in psychoses. He had also met with it in cases presenting the following group of symptoms, — insomnia, neurasthenia, parsesthesia, hemi- anaesthesia, and paresis. It is very doubtful whether these statements are correct, except for nervous disorders. According to Chovstek alimentary glycosuria can be induced in five out of six cases of Graves' disease. Goodhart has published a number of examples of glycosuria connected with neurasthenia, and the occasional occurrence of this symptom in organic disease of the nervous system and in insanity and epilepsy is sufficiently attested to be indisputable. The quantity of urine in diabetes is generally greatly in- creased, from 200 to 300 ounces in twenty-four hours being a common amount, but in certain cases, especially in elderly persons, the quantity may not exceed lOO ounces, and where diarrhoea is present may not exceed or may even fall below the normal. The specific gravity is usually high, from 1030 to 1050, but again in elderly persons it may be below 1030, and even below 1020, being only 1013 in two of my cases. A low specific gravity is no proof of the absence of sugar, nor is a high specific gravity any proof of its presence. The colour is usually pale greenish yellow, or straw coloured, but gouty diabetics often pass high coloured urine, loaded with lithates. Diabetic urine is generally clear, but may be turbid from the growth of torulae or from lithates. The reaction is almost invariably strongly acid. It deposits very commonly a considerable amount of uric CLINICAL HISTORY. 289 acid, even in cases in which there is no gout. This is often due to the use of nitrogenous diet. Under the microscope uric acid crystals and torulae may generally be seen. Of the normal constituents of the urine there is an increase of water, chlorides (SENATOR^ sulphates, creatinin, and phos- phates. According to Toralbo the loss of lime in the form of earthy phosphates is so great that it may amount to 2*5 grms. daily. Butel has found that the phosphates stand to the urea as I to 10. The urea is increased, holding an approximate relation to the amount of sugar of i to 22 (HARRISON and Slater). The amount of ammonia is greatly increased (Hallervorden). Stadelmann attributes this to the enor- mous excess of acid in the blood, which in some way disturbs the normal mechanism for fixing ammonia. According to Weil nitric acid is formed normally in the body by synthesis of ammonia, and it is this process which is destroyed, leading to a diminution of nitrates and excess of ammonia. Of abnormal substances sugar is present in quantities varying from i to 12 per cent. It has been suggested that where vesical catarrh is present the sugar may be destroyed by a process of fermentation in the bladder, and F. Miiller has related a case of pneumaturia in which the bladder contained a mixture of carbonic acid, hydrogen, and nitrogen, derived, he believes, from fermentation of sugar which was present in the urine ; but as Teschemacher points out, if this were the case alcohol should be formed, and so far this has not been demon- strated. Glycogen is said to be constantly present (Leube), and leevulose in some cases (Seegen). For a time the sugar may be present intermittingly, as in the following curious case : — Case 38. — Diabetes Mellitiis — thirst— polyuria — intermittent glycosuria — rlieiimatic pains — lichen scrophulosorii7n — scaly eruption on scalp — amblyopia — ultimate death from c07/ia. George B., aged twenty-eight, was first admitted on July 24th, 1886, complaining of lumbar pains, thirst, and polyuria. History. — -The last two symptoms had existed for three months, but the pain for only three weeks. At Christmas he had rheujtiatic pains in feet and knees, but was not confined to bed, and had never been well since. He could remember no other illness, or any injury. His family history was good, and he knew of no other case of diabetes among his relatives. He had been under treatment by Dr. Foxwell as an out-patient for three months, before his admission. His urine averaged over 200 oz., sp. gr. 1040 ; urea o"9 per cent.; sugar, 8'o per cent.; he had lost 14 lbs. in weight. He was sent to the Suburban Hospital and afterwards re-admitted 19 290 DIABETES. from there on September 26th of the same year. He then complained chiefly of weakness. Conditioti on Admission. — He was a fairly well-built and well-nourished man, with a pale and anxious face. He weighed 8 stone 95 lbs. There was slight ptosis of the right eyelid which had always existed. His skin and joints were normal. Patellar reflexes present. Tongue clean. Bowels confined. No abnormal physical signs. Pulse, 66; Temp., 98°; Resp. 24. On ordinary diet he passed over 100 oz. of urine, but on being put on diabetic diet the quantity fell to 50 to 60 oz., while the sugar fell from 8 percent, to ri per cent. There was generally a faint haz of albumen present. Progress of Case. — He was treated with Clemens's solution, and under this treatment the urine kept low, the sugar was never more than 4 per cent., often much less, and he gained weight. On his discharge, Novem- ber 2nd, he weighed 8 stone I2ilbs. He was made an out-patient. Alter leaving the hospital he attended as an out-patient, continuing his diet as well as he could, and going on with cod-liver oil and iron. After this his urine was often free from sugar for months together, even though he ate bread. On November 13th the urine had a specific gravity of 1035, but con- tained so little sugar that it was analysed in order to find out what solid constituent was in excess, and 4*5 per cent, of urea was found to be pre- sent. He complained about this time of bleeding from the gums, which was stopped by a krameria mouth wash. On December 4th, he had an eruption of lichen scrophulosorum on the chest, which was soon cured by ung. hydrarg. ammon. Jan. 1st, 1889. His urine contained sugar, and continued to do so in varying amounts. In February he complained of a dry, brown scaly eruption on his scalp, which was greatly improved by washing with borax lotion. He began to complain of dimness of vision, and on May 28th he was sent to the Eye Hospital for a complete report upon his vision, which was as follows : — V. in R. eye is ^^ when corrected for error of refraction ; V. in L. eye is 2% badly. Both fundi are normal, and media clear. He smokes over 4 oz. of black twist tobacco a week, and has central scotoma for red and green, the defect arising no doubt from toxic amblyopia. Sees better in twilight, etc. This patient died of coma, on Nov. loth, 1891. His lungs were tubercular, and his blood very fatty ; his pancreas was atrophied and soft. When re-admitted he had well-marked physical signs of consolida- tion and excavation at the right apex. He looked anaemic and his blood showed — Red corpuscles, 2,700,000 ; White corpuscles, 8,000 ; Hcemoglobin, 50 per cent. Albumen is occasionally met with in the urine of elderly diabetics ; it is less common in young subjects. Maguire says he has always found it in the urine of cases of diabetic coma of KUssmaul's type. This is generally true, but there are exceptions to this rule. Indican and skatoxylsulphuric acid may be present in excess (Otto). CLIMCAL HISTORY. 291 Acetone, aceto-acetic acid, be ta-oxy butyric acid, and beta- crotonic acid have all been found in the urine, and stand in close chemical relation to one another. Much interest attaches to these bodies, as they are believed to be the poisons which give rise to Kussmaul's coma, and some of them give the well-known Burgundy red coloration with ferric chloride. This reaction is also occasioned by formic acid, which, according to Le Nobel, is present in diabetic urine. Oxalic acid and hippuric acid are also frequently present (Czapek). Tests for Sugar. — These will be found in full on p. 197, et seq., and need not be repeated here. Tests for Acetone. — (See p. 200.) The Fej-ric Chloride Reaction. — (See p. 201.) Prognosis. — As a general rule the prognosis of diabetes depends upon the age of the patient. Under forty it is a fatal, and usually a rapidly fatal disease. Over forty it is chronic, often intermittent, and sometimes curable. But in considering this very important question the etiology of the disease should always be carefully studied and duly considered. Marker's case of a child of two years of age, who recovered, was apparently due to excessive use of sugar with his food. A family tendency to diabetes, or to nervous affections, is a bad prognostic element. On the other hand, many recoveries have taken place where the disease has supervened after an injury, or some acute disorder, such as diphtheria. Probably the most favourable cases are those which are distinctly related to obesity or gout, especially where the glycosuria is intermittent, and the quantity of urine not very large. Climacteric diabetes is also held to be eminently curable. The third consideration that must always guide our prognosis is the progress already made by the disease ; the degree of emaciation, the quantity of urine, and the total quantity (not the percentage) of sugar excreted ; in other words the earlier the case comes under treatment the better. The fourth point is the influence that dietetic restric- tions are found to possess in controlling the excretion of sugar. Fifthly, much depends upon the conditions under which the patient lives, for in this as in so many other chronic diseases, freedom from care and anxiety, and the possession of the means to secure the most favourable advantages of climate, 292 DIABETES. residence and diet, count for much in prolonging life, even if a cure cannot be obtained. But diabetes under no circumstances can be regarded as free from danger. The elderly diabetic, whose symptoms can be easily controlled, is liable to die suddenly from some slight imprudence, and is never out of risk. The presence of albuminuria, acetonuria, or diaceturia is only a danger signal, and does not make the prognosis necessarily worse (SCHMITZ). Duration. — It is true, as a general statement, that diabetes runs a longer course in direct proportion to age. In other words, it is an acute and rapidly fatal disease in children and young persons, lasting only weeks or months, or perhaps a year or more. Nevertheless, I have met with cases in children that seem to run a very chronic course ; and Pavy has related instances lasting five, eight, and even more years. Agnes L. was seen last in 1894, and had then been ill eight years; she was fifteen, and looked like a child of six or seven. On the other hand, in elderly persons the disease lasts for years. Worms has given instances where it lasted from twelve to twenty-five years, and disappearance of the symp- toms is not uncommon. Termination. — Death occurs in many cases as a result of one or other of the complications to be described, of which pneumonia and pneumonic-phthisis are the most common. In very many cases the patient's strength is gradually reduced, and he dies quietly in a drowsy state without being actually comatose. But in a large proportion death is more or less sudden, the fatal symptoms supervening as the result of some slight occasioning cause, such as a walk too great for their enfeebled powers, a chill, excitement, etc. In these cases death is preceded by coma. This mode of death is so peculiar that it has attracted much attention, and will be described in a separate chapter. COMPLICATIONS. Integumentary System. — The skin of diabetics is gene- rally dry and harsh, with not uncommonly a tendency to desquamation of the epidermis. The circulation may be feeble, and there is often some cyanosis of the ears, nose, and cheeks, while the feet and legs are cold. Acne pustules, boils, and carbimcles occur not infrequently in elderly diabetics. Pigmentation of the skin, especially marked on the exposed CLINICAL HISTORY. 293 surfaces may occur in the type called bronzed diabetes. The most common skin affection is a form of erytJteina on the hands and arms, legs and feet. The patches are slightly raised, irregularly oval in shape, about half to three quarters of an inch in their longest diameter, and purple in colour. Case 39. — Diabetes Mcllitus — very slight polyuria — thirst — hiniger — erythematous eruption on extremities — cataracts — deafness — sciatica — diarrhwa. Elizabeth R., aged thirty-seven, shopkeeper, was admitted into the General Hospital on May 30th, 1889, complaining of weakness of the arms and legs, thirst, and polyuria, with pain in the back and abdomen alter food, and an eruption on the nape of the neck and on the feet ; also of failing sight. She had been quite well up to lour years ago, when, being pregnant for the second time, she suffered from thirst and swelling of the legs, which continued after her confinement, and she became weaker and thinner. She kept a mangle and a little shop up to four months ago, when her parents took her home to live with them. Family Histoty. — Her own mother died of phthisis, but she had a step- mother. Her father was alive and m good health, but very nervous. Two brothers and a sister were alive and well. Patient was a widow, her husband having died of bronchitis two years ago. She had had two children, both dying after a few weeks of life. State on Admission. — She was fairly developed, but greatly emaciated, skin dry, some patches of eczema with enlarged lymphatic glands in the nape of the neck, due to pediculi capitis. Skin of lower part of legs and feet roughened and mottled with irregular discoloured areas of congestion, varying in size front a sixpence to a shilling, which itched when warm. These had been coming out in successive crops for eighteen months. The spots when fresh were raised above the general surface of the skin. Temp., 97'6° ; pulse, 96; Resp., 20. Weight, 5 st. 82 lbs. She thought the quantity ot her water was about eight pints ; and a specimen examined was clear, acid, 1026, pale brownish-yellow, loaded with sugar, and containing a faint cloud of albumen. On June ist, three days after admission, the urine report was as follows: — 68 oz., 1020 acid, pale opalescent; urea, 0*9 per cent.; sugar, 2 per cent. ; albumen a very faint haze, blood in ti'aces. Under the microscope, red and white blood corpuscles and squamous epithelium. The blood and albumen were thought to be clue to the vaginal discharge. This was on milk diet with bread. Treatment. — She was then put upon the following diet : — Meat, green vegetables, a pint of beef tea, gluten bread, Vichy water and lemon juice. She was ordered, in addition, a teaspoonful of cod liver oil three times a day. July i6th. For the last three days there had been slight swelling of the eyelids with watery discharge, and there was some conjunctivitis with a small sub-conjunctival haemonhage in the right eye. This morning an extensive eruption broke out over the forearm and hands. It consisted ot rose-coloured elevated spots, as large as a split pea, thickly distributed over the elbows, fingers, and palms of the hands, and often coalescing iO as to produce red shiny blotches. Some of the larger spots had a tendency to become white and transparent in their 294 DIABETES. centres, lool-rino- something like nettle stings. This papular erythema gTadually faded until by the 22nd there was only a brownish-red motthng over the seat of it. Shortly after this she was made an out-patient (July 24th). Leroux has described the case of a child in whom a sym- metrical erythema in large elevated itching patches attacked the nose and chin. This was followed by an outbreak of psoriasis guttata. Later on the nails underwent a peculiar change, which led to their falling off, and finally, after copious sweating, a lichen-like papular eruption appeared, which was followed by numerous boils. Davies Pryce has described a condition which he has called erythematous oedema; he believes it to be dependent upon diabetic neuritis. It is characterised by very severe gnawing pains, with swelling and discoloration of the skin. Burning of the palms of the hands and soles of the feet (Marcet) may be complained of, while sweating in the same situations is not uncommon. Profuse general sweating sometimes occurs, as in a patient of mine, a male, aged thirty-nine, in whom it was checked by Dover's powder after atropine had been tried and failed. Bronzing of the skin, so as to suggest Addison's disease, is seen in association with a peculiar pigmentary cirrhosis of the liver, under which it is described {see p. 321). Eczema of the genitals is somewhat common, especially in women, and may constitute a serious trouble. It is undoubt- edly set up by the irritation of fungoid growths in the saccharine urine remaining on the parts, and in males a very little cleanliness will prevent this. Even in men, however, an eczematous balanitis may occur. In women the difficulty of keeping the parts thoroughly clean is greater, and eczema attended by great irritation, which spreads over the abdomen and thighs and renders life a misery, is too often seen. In some cases pruritus vulvas is complained of without any eczema being present. Purpura may occur in the earlier stages (Simon). Horden has recorded a case of pityriasis rubra in a diabetic. Kaposi has described an affection to which he has given the name oi papillomatosis diabetica. The patient was a Brazilian doctor, who had suffered from diabetes for twenty years, but was well-nourished and vigorous. The affection was limited to the left arm and forearm which were extensively swollen, and the backs of the fingers were covered with excrescences varying in size from a lentil to a sixpence, ulcerated in places, CLINICAL HISTORY. 295 the ulcers beine^ rounded or kidney-shaped, bordered by florid granulations, and discharging freely. On the elbow was a growth as large as the palm of the hand, raised over two centimetres above the level of the surrounding skin, deeply fissured and presenting a slightly bleeding surface covered with warty protuberances. Addison and Gull first described a peculiar eruption which is now called xanthoma tuberosum. A case was described by Dr. Bristowe in 1866. In his case the eruption consisted essentially of somewhat indurated tubercles of a dull reddish hue (but not much deeper in colour than the surrounding skin in their neighbourhood) and of roundish or obtusely conical form. Their margins passed invariably into the healthy skin around, and their apices were often of a pale yellow colour, as though containing a minute quantity of pus. Their size was not uniform; to speak roughly their horizontal diameter varied from a line upwards, and their vertical projection from a line downwards. The yellowness of their apices was found not to be due to any accumulation of fluid there; for this part, like the rest of the tubercles, was quite solid. The tubercles appeared from microscopical examination to consist essentially of a kind of dense fibrillated texture, studded more or less with oil globules of various sizes. It was the presence of such globules in great abundance that caused the yellowness just described. Marchal (de Calvi) quotes a case, perhaps of this nature, where the body of the patient was literally covered with great coppery pustules or hard vesicles, containing a material as hard as very dry cheese. They were harder and more elevated than variola pustules. Some were rounded, terminating abruptly in a point. Generally isolated, they were occasionally in groups. This eruption disappeared, leaving only minute cicatrices, and did not recur as the disease got worse. This tendency to disappear is true of xanthoma. Another peculiar eruption, in the form of circumscribed necrotic patches, has been described by Rosenblath. It occurred in the form of small round red spots the size of pins' heads, about the ankles and on the dorsum of the feet. Some of the spots were little vesicles containing watery fluid. At the autopsy they were found to consist of little centres of necrosis, and ulceration was found on the tongue and in the mucous membrane of the oesophagus, stomach, and intestines. The skin eruption appeared to commence in the sweat glands. 2g6 DIABETES. Celhilitis and gangrene are complications which are more apt to occur in diabetes as hfe advances, and are more common in men than in women, though Hunt throws doubt on this latter statement. Godlee thinks that gangrene in diabetes is due to two distinct causes requiring different treatment. In the first the condition depends upon arterio-sclerosis, and amputation should be performed high up, but in the second, where it is caused by neuritis, he counsels abstention from operative interference. Case 40. — Diabetes Mellitus — perforati7ig ulcers — gangre?ie of both lower extremities — successful aiiiputatio7i of necrosed parts. Joseph F., sixty-four, tailor, was admitted February 20th, 1889, with gangrene of right foot. History. — Father died at eighty-six; cause not known. Mother was killed. Three brothers alive; one brother died young. No histoiy of illnesses. About five years ago he came under Mr. Chavasse with what he called "corns" on the second digit of each foot. That of the left foot got well, and the toe on the right foot was amputated. At that time he h:id no suspicion of any illness. He had not complained of thirst or of weakness ; but on coming to the Hospital he was told he had diabetes. For some time he was only slightly troubled with sores on his toes, and about eighteen months ago he began to be thirsty. Twelve months ago last March all the toes on the left foot were taken off in the General Flospital, and he then went to the Suburban Hospital, leaving there in July. In January of this year the toes on the right foot began to be affected, and in February he came into the General Hospital again, and the third and fourth toes were amputated at different times. In April the ankle began to be bad, and on June 15th the leg was amputated. Latterly his health has not been so well. It is only in the last twelve months he has noticed lie has been passing a large amount of water. Has had no cough. No history of boils or other skin diseases. Whilst the urine was measured from April 3rd to 21st he was passing from 66 oz. to 109 oz in twenty-four hours, with an average of about 90 oz. Urine Report : — Acid Urea i'4 p.c. -,) '5 '8 „ 51 It 5 )) Feb. 25. — 1036. Mar. 29. — : 036. April I. 70 oz. 1034. „ 6. 88 oz. 1030. „ 15- 80 oz. 1036. June 17. — 1033- Sugar 8-3 p.c. Acetone none. ,^, 5-5 » „ present. >, 5-2 ,, )' )i „ 5-5 ,. -.1 '1 „ 5-0 „ ■>) „ 6.2 „ — Case 41. — Diabetes Mellitus — polyuria — thirst — albtcminitria — gangrefie of toes — knee jerks diminished — improvejiient on diet aiid opiuin. William F., aged fifty-seven, attended as an out-patient on October 26th, 1886, complaining of passing three to four quarts of water and of getting up very frequently at night for this purpose. He had been ill three years, when he got gangrene of three toes on the right foot, and his urine was found to contain sugar. He suffered from thirst ; his urine was pale, clear, sp. gr. 1022, and contained a cloud of albumen and a large quantity CLINICAL HISTORY. 297 of sii^^ar. The knee jerks in both legs were almost absent. On anti- diabetic diet and o|jium he lost his thirst, he was not disturbed at night to make water, and the quantity ot this secretion fell to 90 oz. daily, or little more than two quarts, of sp. gr. 1020. He was not seen after January 18th, 1 887. Kaposi has described a rare condition under the name of ^angrcBiia bullosa serpiginosa. The patient was a woman, aged fifty-one; on her left leg were three gangrenous patches, and over the neighbouring sound skin fifteen or twenty bullae vary- ing in size from a pea to a bean. The condition improved somewhat under treatment at Carlsbad, then got worse and the patient died. Several cases of per/orating ulcer of the foot in diabetes have been published (Kirmissen, Heusoner, Spencer). The ulcer is preceded by circumscribed anaesthesia, and an anaes- thetic zone surrounds the ulcer when formed. In Heusoner's case the ulcer preceded the symptoms of diabetes, and post mortem nothing abnormal was found in the medulla or pons. It is probable that this lesion is another consequence of disease of the peripheral nerves. Against this formidable catalogue of skin affections due to diabetes it is some comfort to set the fact that persons have been known to lose chronic skin affections upon the superven- tion of diabetes (Watson). Kaposi attributes all diabetic skin affections to impregna- tion of the skin with sugar. We have seen that in the case of eczema genitale, the sugar is undoubtedly the exciting cause, but its direct influence is doubtful in other cases. We know that all the tissues of diabetics are very prone to disease in consequence of malnutrition, but it is taking a somewhat narrow view to ascribe ever3^thing to the sugar circulating in the blood, which not unfrequently is not more than normal, the overplus being constantly excreted by the kidneys. Dropsy. — In a disease characterised by polyuria it is hardly to be expected that dropsy should occur. It is, however, sometimes present, evidently as a result of heart failure and is attended by a cessation of the polyuria. Ascites may be present as well as oedema of the lower or even upper extrem- ities (Roberts). Case 42. — Diabetes Mellitus — bronchitis — oedema of tt'itnk and lower limbs — recovery. Mary Ann M., aged thirty-nine, widow, metal button maker, was ad- mitted into hospital on January 8rh, 1887, complaining of cough, pain in the back, and swelling of the legs and abdomen. 298 DIABE TES. History. — She had been ill six weeks, the attack commencino with cough. A week ago she noticed her abdomen was swollen, and soon after the Ici^s began to swell. Her breath got very short, and she felt very ill and weak, but she went about until the day of admission. She had been quite strong, except that ten years ago she had rheumatic fever, and for the last five or six years had suffered trom a cough in the winter. Co?idition 071 Admission. — There was much cyanosis of the face, hands, and arms, with great oedema of the lower extremities and trunk, but no ascites or hydrothorax. She could not lie down in bed, and her breath was very short and wheezy. Pulse 114, Temp. 98°, Resp. 30. Trouble- some cough ; no dulness over lungs : breath sounds very wheezy, with moist rales and sibilant bronchi throughout; vocal resonance undiminished; heart's action regular, no murmur ; pulse very small and weak. She had not menstruated for two months, and the flow had been very scanty for some month-^. Urine 48 oz., acid, 1043, a faint cloud of albumen, 8*3 per cent, of sugar, no blood, no casts, squamous and pear-shaped epithelium in deposit. She was put on strict anti diabetic diet, with a little morphia for her cough. On this treatment she steadily improved, the sugar diminished rapidly, and the cedema disappeared. She left the hospital on February 2 1 St, free from dropsy and with no sugar in her urine, though this still showed a faint trace of albumen. Temperature.— The temperature in diabetes is usually normal or sub-normal, and in some cases may be very low indeed, as in the example given by Fagge, .where the thermometer marked only 93 '6. In the following case the temperature was irregular, being sometimes as high as 100°, sometimes as low as 95°. Case 43. — Diabetes Mellitus — polyuria — wasting — diar?Ji(£a — very low temperature — discharged unt elieved — subsequent deatJi. George H., forty-two, tailor, was admitted into hospital on Jan. 25th 1887, complaining of tingling of his tongue and the 1 oof of his mouth, with cramps in his legs. These symptoms came on about a week alter Christmas. History. — He had been losing weight since November. He had been pas ing more water than usual and had been thirsty. He had never been ill, except that when he was nineteen he spat a little blood. Father died aged thirty-five of "brain fe\er"; mother died aged seventy, of "diseased stomach." There was only one sister, who died when she was five, but he did not know the cause of death. He had never met with any accident or personal injury. Co?idition 071 Admission. — He was a poorly nourished man. Pulse 90, Temp. 100", Resp. 17. Physical examination revealed nothing, except some want of resonance and deficient breathing at the apices of both lungs, and his pulse was very weak. Urine 116 oz., sp.gr. 1035, acid, straw-coloured, no deposit; o"8 per cent, of urea, 5 "8 percent, of sugar, no albumen. Progress of Case. — He was dieted and treated with alkalies and cod liver oil ; alterwards with morphia. He had several attacks of diarrhoea which interfered with his progress, and his temperature was irregular, sometimes CLINIC A L HIS 7 OR V. 299 rising to nearly 100°, dui more often being siib-itofinal beini^ several times as low ill the mornijii^ as 95". The low temperature was not the result of the dianhoea, that is, it did not occur at the same time as the diarrhoea, or after those attacks. He never complained of feeling cold when it was at its lowest, and on being asked said he did not feel cold. He was ultimately discharged, and we heard died in a short time. Disappearance of Glycosuria. — In acute febrile diseases the sugar sometimes disappears from the urine, as in a case of enteric fever, reported on p. 322. It has also been observed to disappear iii relapsing fever (Simon), small-pox (Rayer, Pavy), febrile angina, dysentery (Andral), and pneumonia (Leube, Oliver). Dr. Noel Paton has shown that in animals glycogenesis is increased by diminished elimination of heat, but diminished by fever caused by the products of bacterial growth. Bernard noticed the absence of glycogen from the hvers of fever patients. Nervous System. — The connection between diabetes and grave diseases of the nervous system has been fully illustrated in the section on etiology, it is, therefore, not surprising if in this disease we meet with listlessness and depression of spirits, weakness and peevishness of temper (Watson), or even melancholia with suicidal tendencies (Legrand DE Saulle), or temporary mania (Pavy). In certain cases there seems to be an alternation between the mental disturbance and the glycosuria, the latter only appearing when the patient's mental state is relatively good (Madigan). In some cases there may be symptoms resembling those due to an intra-cranial growth, e.g., headache and giddiness, with epileptic or apoplectic attacks. Diabetic neuralgia is usually symmetrical, though it may commence on one side. It usually comes on suddenly, fre- quently in bed, and the pain is excruciating. Each attack lasts only a short time, but there may be three or four in twenty-four hours. The attacks appear to be aggravated by the warmth of the bed. The sciatic nerves are specially liable to be attacked (Cornillon). Case 44. — Bilateral Sciatica — glycosuria — albumijiuria — no polyuria or thirst. Ebenezer H., sixty-five, came as an out-patient on May 14th, 1889, complaining of paroxysms of excruciating pain in the course of the sciatic nerves. History. — He said the attacks lasted six to eight hour?, and that they had come on about once in three months for the last twenty years. For thirty years he had been subject to attacks of gout. He did not know of any case of diabetes in his family. 300 DIABETES. Condition on Admission. — He was a short, stout, florid man ; he had lost most of his teeth ; his bowels were confined. Physical signs normal. Urine, sp. gr. 1013, acid, a cloud of albumen, reduced Fehling moderately. He was dieted, and orclered to take the following : — J^i Sodii Salicylatis gr. xv. ; Itifusi Gentiancs gj- ; to be taken thrice daily. May 28th. — The urine was free from sugar, and there had been no more paroxysmal pain. Case 45. — Diabetes Mellitus — thif^st— polyuria — wastijtg — unilateral sciatica. Josiah W., fifty-six, came to the out-patient department on April ist, 1886, complaining of pain and swelling in the right leg, which he had been told was sciatica. He also complained of violent pain in the abdo- men, of great thirst, and of passing a large quantity of water, as much as three pints in the night alone. History. — He had been under treatment for six weeks, but the pain began a month earlier. He had been losing weight. He had usually enjoyed good health, but eighteen years previously he had " rheumatics," and was laid up five weeks, with pains which shifted about ; his knees were swollen at the time. He had bronchitis twelve years ago ; he had never had gout. Had a comfortable home ; said he was temperate, but drank two or three pints of beer daily. He used lead in his work to hold castings, but there was no lead dust. Father died, aged sixty-three, of apoplexy. Mother died, aged sixty-three, of dropsy. Of his thirteen brothers and sisters five were living in good health ; the others died in infancy, except one sister who died in childbirth. Condition on AdniisJon. — He was a big, stout man, with a florid face ; weighed 14 st. 3 lbs. No blue line on gums. Right leg pitted on pres- sure, but there was no obvious swelling, except some puffing over the instep. No cedema elsewhere. Pulse 88, Resp. 18, Temp. 98-8°. Physi- cal signs normal. Breath foul ; tongue red at edges ; suffered from wind ; bowels regular. Urine 76 oz., loaded with sugar, a cloud of albumen. Progress of Case. — He was put on diabetic diet with an alkaline mix- ture, and the sugar at once disappeared. The pain rapidly improved. On being allowed ordinary diet, the urme contained 2 per cent, of sugar, which disappeared again at once on the diabetic diet being resumed. The swelling and pain completely disappeared, and before he left he was allowed a little brown bread, without giving rise to any return of glyco- suria. He was discharged on May 5th, and made an out-patient. Florain has described a painful affection of the fingers, Hke the pricking of a pin, which occurred in a pregnant woman whose urine was loaded with sugar. Intense hypersesthesia of the soles of the feet has been described by Auerbach. Loss of sexual desire is an early and very frequent symptom. Paralysis may attack single groups of muscles, giving rise to ptosis, strabisvius, or paralysis of a limb. This is probably not due to central disease, but to peripheral neuritis, examples of which have been published by Althaus and Buzzard. CLINICAL HISTORY. 301 Mabboux thinks that conjugate paralysis of the ocular muscles is generally diabetic in origin. In other cases there may be complete paraplegia, affecting both upper and lower limbs, mobility, sensibility, and reflexes being all abolished, without paralysis of the sphincters (Strahan). This form is also evidently due to general peripheral neuritis. In some cases there may be symptoms closely resembling locomotor ataxy, and although the pupil reflex was said to be never lost (Fischer), Grube has shown that this is unfortunately not always true. The last author has also described gastric crises closely resembling those of tabes as occurring in diabetes. Salomonson has described a case in which, after violent exercise in skating, the patient complained of pains in the body and legs. Sensibility and gait were normal, and there was no loss of co-ordination, but the superficial reflexes were impaired, and the patellar reflexes on both sides were abolished. She could stand with her eyes shut, and the pupils reacted well to light. The right eye was healthy ; the left showed some opacity of the lens. There was great diminution of the galvanic excitability of the muscles and nerves. He regarded it as a case of peripheral neuritis due to diabetes. Davies Pryce has described three very good examples of this pseudo-tabes of diabetes ; they all occurred in elderly people with well-marked arteriosclerosis. Case 46. — Diabetic general neuritis. T. G., aged 60, engine driver, admitted into the General Hospital February iQlh, 1896. He had been suffering from diabetes, particularly from thirst and loss of flesh and strength for two years. Lately, his eyesight had grown dim from the formation of cataracts ; one eye was operated on unsuccessfully, panophthalmitis resulting. A fortnight before admission he found both arms painful and numbed, and every day they became more powerless. On admission, he was found to be passing three to four quarts of water of sp. gr. 1038, containing about 5 % of sugar; no reaction of acetone or with liq. ferri perchlor. His breath had a sweetish odour, and his mouth was dry. Except weakness of the heart's sounds, there were no noteworthy alterations in the physical examination of the thorax and abdomen. The muscles of the extremities were wasted and flabby, and he could walk with difficulty; he could raise the right arm from the bed, but not the left, and had no power of gripping in either hand. The hands looked puffy, smooth and shiny. He complained of numbness in his fingers and toes. Common sensation was g-reatly diminished in both arms and hands, and there was great blunting of the sense of pain in both arms and in both legs below the knees. Sensation of heat and cold was absent in the same areas, and over the rest of the body was delayed and imperfect. The knee jerks were entirely absent, ■502 DIABETES. but the plantar reflexes were increased and the other superficial reflexes were normal ; organic reflexes normal. In the right arm the flexor muscles did not respond at all to faradism, but the extensors contracted well to a strong current ; in the left arm no response was obtained to the strongest current from any muscle ; electro-sensibility was absent. Both arms failed to respond to the galvanic current. Below the knees there was no faradic or galvanic response, but above the knees the muscles reacted well to a strong faradic current. There was some tenderness over the trunks of the musculo-spiral nerves in both arms, but none over other nerve trunks. He was dieted and carefully nursed, but grew worse. His urine had to be drawn off by a catheter and became purulent and ammoniacal. He passed his fteces at times in bed — apparently from mental dulness. He was at times delirious, and wanted to get out of bed at night. On the afternoon of March 2nd, he had a rigor ; his tem- perature rose to ioo°, and his pulse became almost imperceptible. He died the same night. The post 7nortem examination showed the body to be much wasted, and the muscles of the legs, upper arms, and forearms very flabby ; there were ,^;iS/:^-B. Fig. 65. — Eight Median nerve, Bhowing very advanced interstitial and parenchymatous neuritis. Osmlo acid preparation. bed-sores on the ankles, trochanters and sacrum. The pericardium was adherent to the heart by fine fibrous tissue ; the myocardium was pale, tough, and in parts had undergone fibroid degeneration ; the coronary arteries were narrowed and calcified, and the mitral and aortic valves were thickened and rigid. The hmgs were adherent, emphysematous, and CLINICAL HISTORY. 303 engorged. The stomach was dilated ; the liver weighed 80 oz., was enlarged, brown, soft and fatty. The pancreas weighed 6 oz., was indu- rated and gritty on section ; the kidneys were enlarged, together weighing 17 oz., dark red, cortices broad, pyramids atrophied at their apices, calyces and pelves dilated and catarrhal; iho. bladder showed traces of cystitis. The suprarenal bodies were enlarged and degenerated ; the spleen was soft and pulpy. The brain weighed 46 oz. ; its cortex was atrophied, sulci widened, pia mater and arachnoid thickened and opaque. The carotids showed extensive atheroma, and the basilar was filled with clot which could not be squeezed out. The spinal cord showed no naked eye changes, but under the microscopes the cells of the anterior cornua were swollen and pigmented. The peripheral nerves were partially examined ; the right median nerve showed {^Fii^. 65) extreme interstitial neuritis with great increase of connective tissue forming broad bands in which no nerve substance was visible, and the nerve fibres themselves showed an advanced degree of segmentary degeneration of their myelin sheaths; the same description applies to the state of the left median nerve, the right radial, bot.i anterior tibials, and in a less degree to both sciatics. Lepine and Blanc have described a case of hemiplegia with only microscopic lesions in the motor convolutions. Apoplexy occurs sometimes, but is not common. Case 47. — Diabetes Mellitus — no polyuria — wasti7tg — vertigo — albu- minuria — apoplexy — death. Mr. W., fifty-six, was seen in 1885, as a candidate for life assurance, when sugar was found in his urine. He was brought to me on Nov. 29th, 1886, by Mr. F. W. Underbill, of Moseley, complaining of giddiness and temporary attacks of loss of consciousness. His eyesight was good ; there was no hemiopia, or double vision ; his optic discs were normal. There was no obvious hypertrophy of the heart ; the pulse was rather empty. The urine was not increased in amount ; he did not rise at night to pass it; it was acid, sp. gr. 102 1 ; contained a little sugar, and gave a haze of albumen on boiling. I heard that he got much better on the treatment employed ; but on Feb. 3rd, 1887, he had some friends to dinner and drank champagne. The following day he was seized with deafness, inability to speak, and progressive stupor. When seen late that night he could not speak, his pupils were contracted, his pulse hard, and he was restless ; but there was no paralysis of the limbs. He was bled to i6oz., and afterwards expressed himself by signs as feeling better. However, he died the following night from cedema of the lungs. Coma occurs frequently as the termination of diabetes, and will be described separately. Epileptic Fits occur occasionally. Finlayson has described a case in which repeated fits alter- nating with furious mania occurred for seventeen hours before death. The urine was quite free from albumen, and on post mortem examination there was nothing to account for the convulsions. 304 DIABETES. Loss of Knee Jerk has been observed very commonly in diabetics ; it is attributed by Strumpell to degeneration of the peripheral nerves. Dreyfous has met with an example of exaggeration of the knee jerk in a diabetic woman aged sixty-eight. According to Bouchard it was absent in nineteen out of sixty-six cases, or in 29 per cent. Of those in which it was absent 6 or 31 "5 per cent, died, while of the others only 2 or 4*2 per cent, died, which suggests that absence is of very bad prognostic significance. Still it is said that the jerk may reappear if the symptoms improve (MARIE and Guinon). Rosenstein does not agree in regarding the loss as of grave import, as he found that it bears no relation to the amount of sugar or to the acetone or ferric chloride reaction-giving substances in the urine. He points out that it cannot be reproduced by subcutaneous injections of strychnine, as in alcoholism. Grube also disputes the significance of loss of knee jerks. He examined 1 13 cases ; of these, the knee jerks were — Normal in - - - - 113 • Increased ,, - - - - 5 Diminished „ ----- 13 Of the last there were — Severe cases 4 Slight „ 9 so that he concludes that the absence is of no importance, and in this I agree with him. Barnes has described a case in which the symptoms of diabetes and exophthalmic goitre came on simultaneously. The patient was a domestic servant, aged thirty-four ; she died after being under observation about three months, but unfortunately no examination of the body could be obtained. Eye Affections.-— The table on the next page of one hundred and forty-four cases, collected by Galezowski, shows the relative frequency of various eye affections in diabetes. He thinks of these, cataract, retinitis, amblyopia, hemiopia, and muscular paralysis, alone, are to be regarded as really dependent upon diabetes ; the others are merely accidental complications. Deutschmann has found in diabetic eyes swelling and softening of the pigment layer on the posterior surface of the iris. In the deepest layers of the lens he found leucocytes containing myelin, with irregular lumps of albuminous material lying between the lens fibres and fine granulation and vacuo- CLINICAL HIS TOR Y. 305 DISEASES. CASES. I'ERCENTAGE. Conjunctivitis and ) Disturbance of accommodation J Keratitis .... Iritis - - . . Choroiditis gummatosa Cataract _ . . . Retinitis .... Amblyopia - - - - Hemiopia - . . . Paralysis of ocular muscles Detached retina ... Atrophy of optic nerve 5 4 7 4 46 27 31 4 10 3 3 3-5 2-8 4-9 2-8 31-0 i9'o 217 2-8 7-0 2T 3-1 lation in the peripheral fibres, the epithehum of the anterior capsule stained irregularly, with granular degeneration of the nuclei both at the equator and the periphery. He thinks the changes in the lens depend rather upon the general mal- nutrition than upon the presence of sugar. Diabetic Cataract is bilateral, developing and ripening quickly ; it occurs in younger persons than ordinary cataract, and is attended by severe symptoms of diabetes. It was noticed by Mackenzie and Duncan, but was first clearly described by France in a paper in the OphtJialmic Hospital Reports for 1859. These cataracts are usually soft, but not always (Graefe, Wilde), and they may disappear spon- taneously (Nettleship). Operations for their removal are generally undertaken on young subjects, but these are not free from danger, as there have been several cases of death from coma following this operation (Spencer), and the healing process is liable to disturbance by attacks of iritis, etc., (Samelsohn). Diplopia is mentioned in a case recorded by Willan and quoted by Rollo ; it is due to paralysis of the external rectus on one side. A more common condition is amblyopia, de- pending upon paralysis of the muscle of accommodation, with loss of converging power, which Trousseau was the first to point out as an early symptom of diabetes. It may be only temporary, passing -off after a time (WALLACE ANDERSON). Case 48. — Diabetes Mellitus — brozeght on by an attack of iitfiuejisa — amblyopia fi-oin failure of accommodative power— ^prurittes viilvcB. O. M. B., aged twenty-two, single, housemaid, was admitted into Hospital on April 15th, 1890, complaining of great hunger, thirst, and 20 3o6 DIABETES. polyuria. Her illness had lasted about three months. Just before Christmas she went to the Eye Hospital on account of inability to read. History of Present Illness. — Some time betore last Christmas she had an attack which she called influenza ; it lasted about a fortnight, and left her very weak. Soon after this she noticed that she was thirsty and had to pass water more frequently, while she began to lose flesh. Towards the end of February she began to have hysterical fits two or three times a day, and there was a vaginal discharge with much itching and irritation of the vulva. For this complaint she attended the out-patient department of the Women's Hospital. She always had a bad appetite till five weeks ago, since which time she had a constant desire to eat. Prese7it Co?iaition. — Patient was a pale-faced brunette ; she said she used to be quite stout, even up to Christmas. She weighed 6 stone I if pounds. No jaundice, cedema, or cyanosis. Pulse 60; Temp. 98"; Resp. 24. Alivie7itary System. — Many teeth were decayed, but she had not had toothache. Mouth dry ; tongue dark red, clean, moist ; hunger and thirst were constant. Had some pain in back, and occasional nausea after meals. Bowels confined for two days. Abdomen hard, retracted, and rather tender. Liver 4 inches in V. M. L. Spleen \\ inch in M. A. L. Circulatory System. — No palpitation or dyspnoea. Heart's impulse in 5th I. S. one inch internal to V. M. L. Area of dulness not increased. Sounds rather weak and prolonged. No murmur. Pulse 66, regular, tracing shows distinct evi- dence of increased tension, though the curve is small. {See Fig. 66.) Respirato7y System. — N ormal. Integumentary System. — There were a few patches of brown pigment on the abdomen near the umbilicus. No eczema. Urinary System. — She had to rise three or four times at night to make W'ater. Urine 106 oz., pale straw colour, acid, sp. gr. 1042; urea i"i per cent. ; sugar 10 per cent. ; no albumen ; no blood. There was at times a faint haze of albumen, which was probably due to admixture with vagina', discharge, as it always coincided with the presence of leucocytes and squamous epithelium in the deposit. There was a marked ferric chloride reaction, but no acetone. Vision. — Her eyes were carefully examined by Dr. Young, who found that vision corrected by glasses equalled f in each eye, and that there was no reduction of the field of vision or any ophthalmoscopic change. He reported that her inability to read was " purely due to weakened accominodation and a certain amount of retinal asthenopia arising from her weak state." All the muscles of the eye may be affected by paralysis. Fienzal has related a case of sudden facial^ paralysis with cor- neal ulceration which ended in complete recovery. There was no history of syphilis or rheumatism, but the urine was loaded with sugar. Keratitis and iritis are not uncommon. Diabetic Retinitis. — Diabetic retinitis was first described in CLINICAL HISTORY. 307 1856 by Edward Jaeger, afterwards in 1858 by Desmarres, but until recently it has attracted little attention, the writers of special works contenting themselves with very brief refer- ences to it, while the general body of the profession is at most only aware that such a condition exists. This neglect has been no doubt due chiefly to the rarity of its occurrence ; diabetes itself is one of the less common diseases, its average annual mortality being only two per 100,000 of the population, and the retinal changes occurring in only a small fraction of diabetics. But, in addition to this, an opinion prevailed formerly even among specialists that it was merely a variety of retinitis albuminurica. This was founded on the facts that the urine in most of the reported cases contained albumen as well as sugar, and that there is a general resemblance in the ophthalmoscopic appearances, though, as we shall see, more careful study has established well marked characteristic differ- ences ; while the cases recorded by Noyes, Desmarres, Eales, and others have proved that the presence of albuminuria is by no means constant. Diabetic retinitis is invariably met with in elderly persons, and only in those in whom the disease has existed some time, although the derangement of the general health may have been so slight that diabetes has frequently been unsuspected, and has been first discovered by the appearances of the fundus leading to an examination of the urine. Two well-marked varieties have been described (HlRSCH- BERG) : — 1. Retinitis centralis punctata diabetica, in which there is a characteristic inflammation of the central portion of the retina, causing small, bright spots arranged in groups, and often accompanied by hsemorrhages {Plate III). 2. Retinitis hcenwrrhagica diabetica, in which retinal hsemor- rhages occur, followed by inflammatory and degenerative changes (Plate IV). 3. Cases presenting the characters of both the above types or mixed forms are met with. Retinitis centralis punctata diabetica, or central diabetic retinitis, is a truly characteristic affection. It occurs in persons of middle or advanced age who have been for some time the subjects of glycosuria, but its symptoms may be so slight that it is only discovered by an ophthalmoscopic exam- ination. It is generally bilateral, but may supervene gradually or suddenly. The patients complain of dimness of sight, or of 3o8 DIABETES. a mist before the eyes, or of difficulty in reading, although they may preserve good vision for ordinary purposes. The external appearance of the eyes is perfectly normal, but visual acuity may sink to one-half or even one-twentieth of the normal, u^hile there is a dark spot in the centre of the visual field (HiRSCHBERG). The media of the eye are usually quite clear, although it is always possible that some opacity of the lens may be present, due to diabetic or senile changes, but not enough to account for the defect of vision. Serious cloudiness of the vitreous does not occur in this disorder. The chief causes of the visual disturbance are groups of small, clear, bright specks, situated in the structures of the retina in and around the central part, between the upper and lower divisions of the temporal branches of the retinal artery, also near the disc and on its nasal side. As the spots in the centre of the retina grow larger, small streaks or crescents are formed, but they never assume the radiated appearance met with in retinitis albuminurica. There is never any pigmentation in or around the specks. Fine streaks and minute points or small spots of haemorrhage occur around the bright spots, and occasionally in or upon them, and such haemorrhages may be observed nearer the periphery than the white spots. Haemorrhages are seen in all forms of retinal degeneration, but in this they appear never to exceed a certain size. Such small haemorrhages may disappear by ab- sorption, and new ones take their place ; nor are the white spots quite permanent, though it is doubtful if they ever com- pletely disappear. As a rule, they increase in size and number, and the visual disturbance, which may improve temporarily, remains stationary or gets worse. It is especially noteworthy that there is no affection of the optic nerve, and neither diffuse retinitis nor marked vascular change. These characters suffice to differentiate it from any of the forms of albuminuric retinitis at the first glance. Nettleship thinks that the so-called white spots are also somewhat yellower than those seen in albuminuric retinitis ; but this is not always the case. Leber, de Wecker, and M'ackenzie be- lieve that there is a much greater tendency to large haemor- rhages into the vitreous in diabetic than in albuminuric retinitis ; and Nettleship has recorded a case in which the retinitis was complicated by the formation of blood vessels in the vitreous. " Over the whole of the central region," he CLINICAL HISTORY. 309 writes, " the retina is (^edematous and hazy, in some parts densely cloudy. Near the yellow spot are some densely opaque yellowish-white clumps of deposit, such as have been described in other cases of diabetic retinitis. The retinal veins are considerably distended, and in various parts are a few scattered blood spots. Close to \ki& fovea centralis two or three vessels of medium size suddenly appear in the retina ; they cannot be followed to the optic disc, but have every appearance of springing from the choroid directly into the retina. The largest of them (seen at its apparent emergence from the choroid with + 2"5 D), followed upwards and out- wards, is found to divide into a network of minute vessels, which project forwards in the form of fine loops into the vitreous, where the most prominent of them are seen with -|- 6 D. On a few of these loops an appearance of small swellings, perhaps capillary aneurisms, can be distinctly seen." The following case was under the care of Mr. Eales, who sent her to me at the General Hospital. Case 49. — Diabetes Mellitus — thirst — glycosuria — wasting — reti7iitis centralis punctata diabetica. Flora M., aged 49, married, was admitted into the Gen':'ral Hospital on Nov. 1st, 1892, complaining of thirst, pain in the left shoulder and in the chest, rising in the throat, inability to see clearly, everything looking like shadows, itching generally over the body, but chiefly in the palms of the hands and soles of the feet. Family history. — Father dead, aged 61, paralysed ; illness lasted a year. She says he suffered in some way from his water, but she was too young to know about it. Mother dead, aged 40, from " inflammation of brain " a month after the death of the father. There were five sisters and one half-sister, of whom three are dead, including the last ; of three brothers one is dead, but patient knows of no case of diabetes or phthisis in the family. She has had eleven children, all of whom are delicate ; her eldest son suffers from some chronic chest complaint, which he has been told is bronchitis. Previous health. — Her general health has been fairly good, but she had croup several times when a child, and typhus (?) fever at the age of 14. She suffered much from flooding at her confinements, and was operated on ten years ago by Mr. Lawson Tait for a swelling in the right iliac region. A year ago she suffered from pain and throbbing on the top of her head, which, after poulticing, ended by a discharge of blood and matter down her nose ! Last Easter she was ill for a month with vomiting and a burning pain in the stomach. Her general surroundings at home have been very comfortable, her habits have been temperate, but she has been in the habit of drinking about a pint of beer daily. History of present illness. — For three or more years patient has had to get up at night to make water, and for about the same time she has 3 Id DIABETES. suffered from thirst, but she thinks her sight has been failing for about five years. ^tate 071 Admissiojt. — Patient is a sparely-nourished little woman, dark hair, sallow complexion, evidently a Jewess. No cyanosis, jaundice, or oedema. There is a linear scar in the middle line above the symphysis pubis. Height, 4ft. g^in. ; weight, 6st. 2lbs. ; T., 97-4 ; P , 102 ; R., 18. Alimentary system. — Appetite poor, mouth dry and parched, a good deal of thirst, throat dry, burning and rising in throat, weight and fulness after eating, pain at epigastrium going through to back, acidity and flatulence, also nausea at times, but no vomiting. Lips a good colour, teeth very deficient, tongue pale and slightly furred, stomach not dilated, bowels very constipated, there is a large prolapsus ani, liver dulness in V.M.L. 4i in., splenic dulness in M.A.L. n't in. Circulatory system. — Pain and palpitation in przecordia ; she often feels faint. Form and appearance of prascordia normal, apex beat in 5th I. S. \ in. internal to V.INI.L. Heart's area of dulness not increased ; sounds normal ; pulse full, moderate tension. Respiratory system. — No cough or expectoration. Chest expands well, but she complains of pain below the left breast, on taking a deep breath. Percussion note and breath and voice sounds normal ; no friction. Genito-Urinaty System. — She has not menstruated for five years. Micturition is frequent, sometimes difficult, but never painful. The quantity of urine has varied, but never exceeded 64 oz. ; sp. gr., 1029, acid, a faint haze of albumen (at times). Urea, 2*9 per cent. ; sugar, 4 '8 per cent. ; no blood or bile ; reaction with nitro-prusside of sodium and ammonia well marked, also with ferric chloride, but the patient is taking sodium salicylate. Nervous system. — Patient complains of numbness and tingling in the palms of the hands and soles of the feet. Patellar reflexes absent ; all other reflexes diminished. No loss of motion or sensation. Ophthalmoscopic appearances in the right eye are as follow : — Optic nerve a little pale, edge quite distinct ; in the outer quadrant of the retina large patches of a bright white colour, over the surface of which the retinal vessels can be traced ; no haemorrhages. Left eye : disc clearly defined ; very similar white patches in the corresponding part of the retina with a punctiform haemorrhage in one of them. The pathology of the retinal affections of diabetes is un- doubtedly the dyscrasia which gives rise to nutritive changes in the blood vessels and tissues of the body. The histological changes of this form have been very well worked out. In a case recorded by Dr. Stephen Mackenzie the eyes were examined microscopically by Mr. Nettleship, who found the following changes : — I. The retina was thickened in all its layers, the change being greatest in the nerve fibre layer, where there were numerous varicose swellings ; the disc was slightly swollen and its nerve fibres converted into an intrcate network of fine threads, the meshes being for the most part empty, but some- times filled by swellings like those in the retina. The CLINIC A L HIS TORY. 3 1 1 ganglion cells and the granule layers were well preserved, and indeed more readily seen than usual, their elements having been, as it were, dissected apart by the effusion of fluid between them. The bacillar layer was wanting, and its place in some parts occupied by a layer of albuminous effusion. In the intergranule and molecular layers were round spaces filled with faintly refracting albuminous granules. The vienibrana limitans interna was much thickened in parts and thrown into abrupt folds, which, when deep, resembled papillae. There were no distinct haemorrhages in the retina, only one or two small patches of rusty granules near the disc. 2. The vitreous of the left eye contained a quantity of blood, the source of which could not be traced. 3. The choroid was unaltered at the margin of the disc, but was greatly thickened in other parts. This was due to great distension of the vessels, and to a collection of a faintly granular albuminous substance in the stroma between the vessels and in the elongated spaces of the meinbrana siipra- choroidea. 4. The trabecular tissue of the subvagi?ial lymph space of the optic nerve was much increased in bulk by thickening of the individual strands and by increase in their number. 5. The optic nerve showed no very marked alterations, but its connective tissue nuclei were increased in number in and just behind the lamina cribrosa. 6. The ^r^m^i", especially the central artery and its branches, showed thickening ol their coats, chiefly due to a deposit of hyaline material between the endothelium and the fenestrated membrane. In places,' the thickening was fibrous. The whole vascular wall was swollen. The veins were, as a rule, merely distended. The capillaries were distended, and in the retina formed minute aneurisms, which usually contained reddish brown granules ; their walls were not thickened. In a case of Mr. Nettleship's, exarnined by Mr. Lawford, there was interstitial neuritis affecting the optic nerve, attri- buted to plugging of the central artery, which was present. The choroidal and retinal arteries showed hyaline thickening in places, with aneurismal dilatations and haemorrhages. Large masses of " waxy " and granular material were ob- served in both granule layers, while others of smaller size could be seen in the nerve fibre layer. The microscope therefore shows thickening and dilatation of the retinal vessels, capillary aneurisms, and a considerable 312 DIABETES. exudation of granular material between the two granule layers. ' It is probable that the condition is a true inflammation commencing around the vessels and attended by exudation of inflammatory products into the retinal substance, which presses upon and destroys the nervous tissues and finally undergoes fatty degeneration. Hczniorrhagic diabetic retinitis, or the second type of this disease, differs from the preceding in the fact that the haemor- rhages constitute the essential part of the process as observed with the ophthalmoscope, and that any white patches which appear are merely due to inflammatory or degenerative changes in the damaged tissues and in the effused blood. It may, and not uncommonly does, begin in one eye. The haemorrhages are usually punctiform, but occasionally striated, and are situated all over the retina, by no means being con- fined to the region of the disc. Their source is not the superficial retinal vessels, and their rounded shape indicates that they are situated below the nerve fibre layer. There may be some haziness of the retina pointing to some degree of oedema, and crystals of cholesterine may be visible in the vitreous. Nettleship has described a case in which " a venous branch of considerable size passing upwards from the main upper division of the vena centralis showed a number of small dilatations which gave the vessel an imperfectly beaded appearance." Case 50. — Diabetes Mellitus — polyuria — wasting— pruritus inclvce — heredity — phthisis — retinitis hcemorrhagica diabetica — acetonuria. Amelia M., fifty-seven, housewife, was admitted into the General Hospital on November 15th, 1889, complaining of weakness of sight, pain in the back, loss of strength, and irritation of the pudenda. Her symptoms had been coming on since the climacteric period, which commenced with her four years ago, though there was nothing more definite than weakness and wasting until the last six months. She had had no thirst, and polyuria had occurred only lately. The attacks of pudendal irritation had, however, troubled her from time to time for the past ten years, especially when pregnant. Previous History. — She had enjoyed a comfortable home and good food, with half a pint of beer daily. She had had erysipelas twice, twenty-four and twelve years ago. She had small-pox at twelve years of age ; could recollect no accidents or injuries. Had been married thirty- eight years, and had borne seventeen children besides five miscarriages. Ten of the children were alive and well ; the others died young. Family History. — Father died, aged sixty-four, of bronchitis ; mother died, aged seventy-three, of "cancer of the face." One s'sterhad died of phthisis and a brother of diabetes. Another sister died of fever in America. The others (eight) were alive and well. She knew of no cases CLINICAL HISTORY. 3'3 of gout, rheumatism, or insanity, and of no other cases of diabetes or phthisis. State on Admission. — She was a well-developed stout woman, with a florid face, moist skin, and great varicose dilatation of the veins of the legs. No oedema. Temp. 98°, Pulse 96, Resp. 24. Alimentary System. — Appetite poor ; no thirst ; no discomfort or pain after food. Teeth very defective ; tongue clean. Bowels confined; liver dulness in V. M. L., ^\ inches: splenic dulness in M. A. L., I inch. Circulatory System. — Area of cardiac dulness not increased. Heart's apex in fifth I. S. internal to V. M. L., sounds normal. Pulse 96, lull, incompressible, regular. Respiratory System. — Appearance of chest normal. Above right clavicle percussion resonance diminished, vocal resonance increased, ex- piration prolonged. Ophthalmoscopic Appearajtces. — Right eye : Numerous punctiform haemorrhages round disc, and many glistening white patches, varying in shape, and some of considerable size. Left eye : One small haemorrhage on the inner side of disc, and in yellow spot region a large area of white glistening patches with numerous punctiform haemorrhages. Genito-urinary System. — Had not menstruated for three and a half years. There was no eczema about vulva ; the pruritus had existed for three months. Urine 56 oz., sp. gr. 1035, acid, yellow, urea i'8 per cent., a trace of albumen, sugar 6 per cent., acetone present. Treatmettt. — House diet, no sugar ; Ext. Cascarce Liq. "Ix. ; Aquce 5j- ; thrice daily. October i8th. — Diet : Meat, green vegetables, potatoes, one slice of toasted bread with each meal. Milk, two pints. Tea or coffee. The dose of fluid extract of cascara was increased to twenty minims. October 29th. — Ordered, Haiist. Magft. Carb. ; thrice daily, and to be made an out-patient. Her eyes were in the same state on her discharge. There had been no complaint of the pruritus during her stay in the hospital. The following table shows the state of the urine during her stay in the hospital : — DATE. URINE. SP. GR. URBA. SUGAR. Nov. 17th ,, 24th „ 26th 56 46 38 1035 1040 1040 1-8 p. c. 17 p. c. 6 p. c. 6 p. c. 5-8 p. c. We are somewhat in the dark as to the actual anatomical changes in this condition, but the lesions are known to consist primarily of haemorrhage, and secondarily of inflammation and fatty degeneration of the areas injured by the effused blood. I can find no account of any microscopical report on the eye in this type, but we may infer that there are degener- ative changes in the arteries and capillaries very similar in 314 DIABETES. kind to those already described, and which are met with in many other parts of the bodies of diabetic persons. The symptoms of the disease in both forms are due to failure of vision, which may be more or less sudden, and vary in amount. The patients often appear to complain of a mist or haze before their eyes, or of sparks, dark spots or muscae, whilst in some cases disturbance of colour vision has been noticed. The course of the disease may be irregular, a succession of attacks of partially disturbed vision may occur, between which sight may be in a great measure restored (Mackenzie). But in the course of time the lesions are pro- gressive, and so far as we know they never end in recovery. From the description already given, we learn that these appearances, when well marked, are fairly characteristic. They differ from the retinitis of Bright's disease not only in their general appearance, but in the following special points : ^i. The patches are irregularly distributed around the centre of the retina, not specially near the macula, and are met with on the nasal as well as on the temporal side of the disc. 2. The patches are never arranged in a fan shape. 3. They are never associated with papillitis or diffuse retinitis. 4. The haemorrhages are, as a rule, punctiform, and not stri- ated. 5. Haemorrhages into the vitreous are common. These lesions can hardly be confounded with syphilitic retinitis, which is a choroido-retinitis, is seldom free from pigmen- tary disturbance, and never presents the unpigmented white shining infiltration of the true retinal tissues seen in diabetes; Haemorrhages /^r j-^ are of course not distinctive, but when hsemorrhage occurs into the vitreous we may lay it down as a rule that the urine should be examined for sugar. The diagnostic significance of these changes, when well marked, is therefore very great ; but it is never prudent to rely only upon the ophthalmoscopic changes when it is so easy to confirm the diagnosis by examining the urine for sugar. The importance of the discovery of the occurrence of these changes for prognosis is undoubted, for there can be no question that they indicate advanced tissue degenerations and a more or less speedy break up of the constitution. In a case of otherwise mild diabetes with retinal changes I should form a very grave opinion of its future ; and I have no hesitation in saying that such a view, though not supported by any statistical evidence, is based on sound pathological principles CLINICAL HISTORY. 315 Jaeger has recorded a case of diabetic retinitis where the swelHng was so great as to hide the outlines of the disc, and was accompanied by numerous haemorrhages and yellow patches. There was a marked central scotoma. Such central scotomata explain the occurrence of one form of diabetic amblyopia. There is loss of vision in the central part of the retina, just as in tobacco amblyopia ; but cases have been ob- served in diabetics who were not tobacco smokers (GOWERS, Jensen, Nettleship and Edmunds), though they generally are. According to Samelsohn the scotoma may be sometimes peripheral. Atrophy of the Optic Nerve may be caused by (i) effusion of blood within its sheath ; (2) descending degeneration from brain lesions, or (3) ascending degeneration after destruction of the retina by hjemorrhages (Samelsohn) ; Nettleship and Edmunds have described a case in which the atrophy appeared to be primary, but the man was a large smoker of tobacco, so that it was not an uncomplicated case in its etiolog}^ Smell and Taste. — Jordao has recorded a case of blunt- ing of taste and smell, but this may have been due to some cerebral complication. Ear Affections. — Deafness is generally due to inflamma- tion of the middle ear, but it may be caused by oedematous swelling of the Eustachian tube (MiOT). Diabetic otitis media (Griesinger, JordAo, KiJLz, Raynaud, Toynbee), has been described as an acute inflammation of the middle ear not dependent upon any external cause(?). The disease is character-' ised by intense pain localised in the mastoid region, and is accompanied by tinnitus and intense deafness. There is redness and swelling of the auditory canal with some muco- purulent secretion, and the tympanum is congested, swollen and dull. There is purulent inflammation of the mastoid cells. The disease comes on very suddenly, without any cold or coryza. The osseous tissue is extensively destroyed, and according to Raynaud the disease begins in the bone. Kirchner has described a case of double purulent otitis in a diabetic patient in v/hich there was entire absence of fever. These cases call for special local treatment on exactly the same principles as in non-diabetic cases, and although the prognosis is not favourable, they may heal very well. In some cases deafness appears to be purely nervous in its origin, and may supervene at the same time as the commence- ment of the diabetes. 3i6 DIABETES. Respiratory System. — The late Warburton Begbie met with a case of membranous infiaininatio7i of the larynx and trachea in a male patient, aged thirty-nine, under treatment in the Royal Infirmary of Edinburgh for diabetes. The compli- cation proved rapidly fatal, causing suffocation, but it was in all probability merely a case of diphtheritic inflammation occurring incidentally in a diabetic. The lungs may be affected by catarrh^ but the most common pulmonary trouble is chronic pneumonic phthisis with or without the presence of tubercle bacilli.* It comes on very insidiously, often with little cough or rise of temperature, and when dis- covered there is often a considerable area of lung invaded. Case 51. — Diabetes Mellitus — phthisis — wasting — thirst^polyuria. Walter J. B., aged thirty-four, brass worker, was admitted into the General Hospital on July i6th, 1890, complaining of thirst and polyuria. His illness had existed for seven months. Family History. — Father living and healthy. Mother died, aged thirty- three, of enteric fever. Had two brothers and one sister hving, and in good health. There was no history of fits, cancer, diabetes, gout, rheu- matism, or insanity in the family. Previous History. — Patient had diphtheria when he was twenty-three years of age. He had never met with any injury. Present I/Ittess. — At Christmas, 1889, he found that he was passing an increased quantity of water of pale colour, which left a white deposit when it dried. He was also troubled with thirst, and noticed that he was losing flesh. There was also some irritation about the glans penis. He was under medical treatment for a week. Six weeks ago he began to suffer from cough and pain in his chest, and latterly he spat up some thick yellow phlegm, occasionally tinged with blood. There had been no night sweats. Appetite not increased. Bowels confined. At Christmas, 1889, he weighed 9 st. 10 lbs. State on Admission. — He was a well-developed but spare man, weighr ing 7 St. 7 lbs. No jaundice or oedema. Temperature 97*8°; Respiration 28; Pulse 108. Alimentary System. — Lips red and moist ; teeth sound ; tongue fiss- ured, dry, and coated with yellow fur. Appetite good, but not excessive. No pain or nausea after food. Bowels very constipated. He complained of pain without tenderness across the abdomen below the umbilicus and round to the back. Liver dulness in V. M. L., 4 in, ; splenic dulness in M. A. L., I in. Circulatory System. — Apex beat in 5th L S., internal to V. M. L. Heart not enlarged ; sounds normal. Pulse regular and fairly strong. Respiratory System.— W& had a slight cough with scanty expectoration, containing numerous tubercle bacilli. There was flattening above and below both clavicles, and he complained of pain over the manubrium, which was increased by coughing or forced respiration. The percussion * Out of five cases of diabetic phthisis recently under my care, in two no tubercle bacilli were found. CLINICAL HISTORY. 317 note was impaired at the right apex in the supraspinous fossa behind, and as far down as the second rib in front. The breath sounds were harsh, expiration was prolonged, accompanied by moist riles, and vocal reson- ance and vocal fremitus were increased. Urinary System. — Urine 126 oz., pale straw-coloured, acid, sp. gr. 1031, urea 1*3 p.c, sugar 6"2 p.c. ; no albumen. In some instances gafigrene of the lung takes place, from rapid sphacelus of parts affected by the inflammatory pro- cess. Case 52. — Diabetes Mellitus— phthisis — gangrene of lung — death — autopsy. James B., twenty-nine, wire drawer, admitted June 27th, 1885, com- plaining of general weakness, wasting, and thirst. History. — He had been ill eighteen months, the first symptom noticed being loss of weight. He used to weigh 13 st. His work was in an ill- ventilated shop, exposed to acid fumes ; he drank about eight quarts of beer daily. His previous health had been very good. His father and mother and five of his brothers and sisters were dead, but he could furnish no precise information as to the causes of death. Three of his sisters were alive and well. Early symptoms of his illness were thirst and pass- ing a very large quantity of water ; his appetite had latterly been good, but he had got weaker. For a month past he had had a feeling of tight- ness of the chest and a cough. His eyesight had been unaffected. Condition oft Ad/nission. — He was rather pale, hollow-cheeked and emaciated, weighed 9 st. His cough was frequent, expectoration about \\ oz. daily, nummular, greenish grey. Chest flat and hollow below the clavicles. On the right side there was dulness at the right apex with bronchial breathing, metallic crepitations and whispered pectoriloquy ; on the right side resonance at apex impaired, breathing harsh with a few crepitations. Pulse 108 ; Respiration 24 ; Temperature 101° ; urine 298 oz., pale, clear ; sp. gr. 1040 ; faintly acid ; very faint cloud of albumen ; 6'89 per cent, sugar ; 07 per cent, urea ; acetone reaction ; ferric chlor- ide reaction. Progress of Case. — He was dieted and treated by extract of opium (gr. i.) thrice daily, and Vichy water. His urine fell to about 100 oz., sp. gr. 1031, sugar 5"8 per cent., but on July 15th, eighteen days after admission, at 9.40 p.m., he was found very weak, with quick pulse, laboured respira- tion and dilated pupils. He was conscious and lay quite quietly, but occasionally the right side of his mouth was drawn down by a spasmodic twitching of the platysma myoides. He died at 11 p.m., but he was still conscious shortly before the end. The post 7no7'te7!i examination was made by Dr. Bull. The bodv was emaciated ; there was no peculiar smell on opening the body, and the blood did not contain excess of fat. The left lung was free, osdemat- ous and congested. No fluid in the pleura. Right lung adherent at upper part, which was converted into a large abscess cavity containing thick sanious fluid, which escaped on removing the lung. The inner sur- face of this cavity was rugged, dirty green, and a large piece of black gangrenous lung tissue hung by a shred from the posterior wall. Bands of tissue crossed the cavity. Its walls were very soft. It had no very offensive smell. The lower lobe was congested and oedematous, and 3i8 DIABETES. contained numerous patches of lobular pneumonia, some breaking down. The bronchial glands were greatly enlarged. There was no other special change noted in any other organ, except that the liver and kidneys were very large. Circulatory System. — Valvular disease of the heart, as a consequence of endocarditis occurring in the course of diabetes has been described by Lecorche. According to his statement it usually affects the mitral, rarely the aortic valve. Maguire has met with one or two examples. It is undoubtedly very rare, as in my pathological experience I have only met with this complication once. Affections of the wall of the heart are common, of which the most serious are fatty and fibroid degeneration, which may be attended by attacks of angina pectoris (Vergeley), but too often attract little attention until death occurs suddenly from syncope. Digestive System. — Affections of the gums are very common, the most frequent being a form of atrophy in which the teeth loosen and come out ; but there is often more or less inflammation present, and the gums may be spongy and bleeding. Case 53. — Diabetes Mellitus — thirst— polyuria — wasting— family his- tory of diabetes — giftg/vitis—faihcre of strict diet to remove sugar— some improvement in ge7teral condition. Thomas C, aged thirty-six, engine-fitter, admitted to the General Hospital on July i6th, 1889, complaining of thirst, polyuria, weakness and wasting. He had been ill four months, his illness having begun with a shght cold and sore throat, for which he attended the hospital as an out- padent for two months without getting better, when he became very thirsty, his water increased to seven pints daily, he lost his appetite, his tongue was blistered, and his teeth grew loose. He lost weight very rapidly — seven pounds in one week — and had continued to waste ever since. He had been very weak in the legs lately, but the thirst and quantity of water had been less. Familv History.— Yath&r died aged seventy. Mother died aged sixty, of bronchitis. One brother died of diabetes and phthisis. Was married, but wife died eighteen months before of inflammation of lungs. Three children alive and well. No history of gout in family. Previous History. — Could remember no illness except occasional colds, and a crop of boils twelve years ago. Gonorrhoea eighteen years ago ; no history of syphilis. State on Ad7)2ission.—VsX\&nt was a well-developed sparely nourished man ; skin moist ; face pale ; lips a good colour. Temperature 98° ; Pulse 58; Respiration 16. Weight 9 st. 5 lbs.; used to weigh 11 st. 2 lbs. Alimentary System.— T^^t^h bad and loose, gums sore ; tongue large, white, rather dry. Appetite fair ; bowels confined. Liver dulness began in sixth interspace and extended two fingers breadth below the costal border. Splenic dulness normal. CLINICAL HIS TORY. 319 Resfiiratory System. — No cough or pain in chest, but some dyspnoea on exertion. Percussion and auscultatory signs normal. Circtilalo>y System. —No palpitation or pain ; heart's area not enlarged ; apex Ijeat in 5th I. S. inside V. M. L. ; sounds normal. Pulse regular, not easily compressible. Ncrz'otcs System. — Knee jerks present. Special senses normal. No neuralgic pains or abnormal sensations. Complained of lecling very irritable since illness began. Genito-iirinary System. — Total loss of sexual desire. Urine 92 oz. ; sp. gr. 1040, acid, pale amber ; urea \'^ per cent., a very faint haze of albumen ; sugar 7*4 per cent. ; under microscope only bacteria visible. Treatment. — Diet: Mutton, beef jelly, milk two pints, Vichy water (Haute Rive) and lemon juice. He had no medicine except an occasional aperient. His stay in hospital was only troubled by toothache, which occurred o;i July 22nd, and lasted some days. He was made an out- patient on September 12th, having been in hospital about two months. The followinKf table shows the result of treatment. Date. Urine. Sp. sr. Urea. Sugar. \Vt. u 1 Palieiu. July 17th... 92 oz. 1040 1-5 p.c. 7"4 P-c. 9 St. 5 lbs. „ 23rd... 96 oz. 1035 28 pc. 6"2 p.c. 8 St. 13 lbs. „ 30th .. 68 oz. 1037 2-8 p.c. 4-6 p.c. 8 St. I2.Ubs. .•\ug. 6ih... 90 oz. 1037 4-8 p.c. 9 St. lbs. „ 14th... 100 oz. 1032 2'2 p.c. 3-6 p.c. 9 St. 2 lbs. „ 19th... 80 oz. 1030 2-4 p.c. 2-6 p.c. — — „ 22nd... 96 oz. 1036 2-8 p.c. 5"4 P-c. 9 St. 2 lbs. „ 25th... 106 oz. 1036 — 4-6 p.c. — — „ 29th... 96 oz. 1036 2'0 p.c. 5-1 p.c. — — Sept. 1st... 90 oz. 1037 — • 57 P-c. — — 5th.., 96 oz. 1040 1-8 p.c. 5-4 p.c. — — „ 8th... 98 oz. 1039 2-5 p.c. 5-4 p.c. — — „ nth... 106 oz. 1036 2-1 p.c. 4-0 p.c. 9 St. 92 lbs After becoming an out-patient he continued to gain weight, until he reached 10 stone. He passed about five pints of water daily. In Dec. he complained of profuse sweating. He was treated with various drugs — opium, cocaine, and phosphorus — without any very definite effect ; but on the whole he had made progress up to the time he was last seen (April 29th, 1890). The mouth is generally dry, but salivation may be profuse (ROLLO). Occasionally complaint is made of hot sour risings into the mouth, causing the teeth to feel as if they were set on edge (ROLLO). Pavy has described a sense of emptiness at the pit of the stomach. Rosenstein states that the gastric juice often contains no free hydrochloric acid, which may be due to nervous causes, but where permanent is the result of atrophy of the glands from interstitial gastritis. Gans has 320 DIABETES. examined the stomach in eleven cases of diabetes and found the digestive capacity and mobility of the stomach always normal. On the other hand Honigmann found out of seven cases free hydrochloric acid absent in three. In my cases I have observed absence of free hydrochloric acid, with no deficient digestive action in the filtered gastric contents or loss of motor power, but I have not examined many cases. Heller has stated that the gastric juice contains sugar, but Ponomaroff denies this. Ulceration of the stomach and intestines may occur, giving rise to vomiting and diarrhoea. The bowels are generally constipated, but diarrhoea is sometimes present, generally depending on catarrh. Case 54. — Diabetes Meltitics — rheumatic fains— polyuria — thirst — emaciatioi — improvement on diet and opium — diarrhoea — failure 0/ jambol. Mary P., aged fifty-three, attended as an out-patient on May 4th, 1886, complaining of pains in the back and legs, thirst, loss of flesh, and of pass- ing a great quantity of water. She had been ill four years. The quantity of water in twenty-four hours was about nine pints, sp. gr. 1030, loaded with sugar. She was treated by anti- diabetic diet, extract of opium (gr. i.) three times daily, and allowed saccharin as a sweetening agent. On this treatment the quantity of urine fell rapidly to four pints in twenty- four hours, and thirst was lessened. The following year she began to suffer from repeated diarrhoea. Jambol Avas tried as a substitute for opium, with some temporary rise in the quantity of water. The diarrhoea had to be kept in check by the use of chalk and opium ; the urine re- mained about the same, four pints, sp. gr. 1039, when last seen in Sept. 1887. Edwards has related the case of a child, aged seven, who after suffering from symptoms of diabetes for three or four months, was seized suddenly with pain and tenderness over the abdomen. Examination showed a considerable quantity of ascitic effusion. The temperature was 102°. Misdiagnosis was acute peritonitis with effusion. Death occurred the same night, but no autopsy appears to have been made. Hirschfeld has described a type of diabetes in which assimi- lation of albumen and fats is deficient; it is characterised by early attacks of colic which do not occur later, by absence of polyuria, and sometimes by whitish faeces though no lumps of fat are visible. He suggests the very probable explanation that the colic is pancreatic, and that the disease is due to calculi in the pancreatic duct setting up atrophy of the gland. Jaundice may occur as an accidental complication, and on its supervention the sugar as a rule disappears from the urine, CLINICAL HISTORY. 321 but this is not always the case, as shown in Case 28 (page Cirrhosis of the Hver is more of a pathological than a clinical complication, but enlargement of this organ can be not uncommonly detected on physical examination, and is due to a process of interstitial inflammation which in a certain number of cases leads to atrophy. In some cases, as already mentioned, the cirrhosis is of a peculiar character, and gives rise to the type called by Hanot diabete bronze, of which the following case is an example: — Case 5 5 . — Bronzed Diabetes— glycosuria — -polyuria — thirst — wasting — enlarged liver — pigmentation of skin. Henry S., ostat 47, admitted March 6th, 1891, complaining of thirst and loss of flesh. He had been ill only two mon hs. Family History. — Father died of consumption at the age of 36 ; mother died aged 77., but he cannot say from what cause. Two brothers are said to "suffer from their livers," one is in America, the other at home, both have dark complexions and have got darker of late years. Three sisters are alive and in good health ; they are not particularly dark skinned. Perso7ial History. — Patient is married, the father of six healthy children : in addition, his wife has had six miscarriages. He has a comfortable home and surroundings. He is by trade a glass cutter, and he worked at it up to the age of thirty-two, when he took a public house which he held for eleven years ; then he tried to resume his trade but found that his eye- sight had become weak, so that he became a grocer's shopman. He has enjoyed very good general health until recently ; he has never met with any serious injury ; there is a doubtful history of syphilis in youth, viz.., a sore not followed by any constitutional symptoms ; six years ago he had typhoid fever : he denies having been intemperate, but admits that he had been takmg a little spirits every day. Present Illness. — About six weeks ago he noticed there was a dull aching pain in the lower part of his back, his friends told him he looked thinner, his thirst became insatiable, and his urine was pale and abundant. State on Admission. — Patient is a well developed, sparely nourished man, 5-ft. 8-in. in height, weight lo-st. 4-lbs. ; he was ii-st. a few weeks ago. His complexion is a very dark olive ; but the skin becomes abruptly paler near the root of the hair ; the rest of the body is not so dark as the face ; the conjunctivae are very dark and injected. He says that he has been getting darker since he was about thirty years of age. Temp. 37'6°, Pulse 54, Resp. 20. His lips and gums are dark in colour, and the latter bleed easily : his teeth are worn down evenly (gouty.'') but fairly sound. Tongue dry and furred in centre. Bad taste in mouth in morning ; appetite good ; no discomfort after meals, nausea or vomiting ; bowels confined. There is tenderness on palpation below the costal margin and the ^i.'g^ of the liver can be felt below the ribs. The liver dulness in the vertical mammillary line is 5 inches ; splenic dulness \\ inch. The circulating and respiratory systems are normal. He complains of pain before passing water, and of too frequent micturition ; he has to get 21 322 DIABETES. up two or three times in the night. Quantity 140 oz., sp. gr. 1036, pale straw colour, acid, a very faint haze of albumen, sugar 8 per cent.,' urea 07 per cent., acetone present, no ferric chloride reaction. Later in the case this reaction was constant. His blood showed corpuscles 91 per cent. ; haemoglobin 60 per cent. On his attention being drawn to his liver he told us that ten years ago his doctor had treated him for "enlarged liver," but he could not say whether he was cured. He was discharged on April 1 8th, unrelieved. Marie has written a ver}-^ good account of this condition, which he prefers to regard as a distinct morbid entity apart from diabetes. Enteric Fever. — There seems to be a more than ordinary Habihty in diabetics to suffer from enteric fever. Numerous cases have been recorded by Rayer, Griesinger, Bamberger, Gerhardt, Ryba and Plumert, Seifert, Ebstein, etc. The sugar may disappear during the course of the fever. The prognosis is said by Ebstein to be unfavourable. Bernard noted the absence of glycogen from the livers of fever patients. Noel Baton says that in animals diminished heat elimination increases glycogenesis, but in fever pro- cesses due to the growth of micro-organisms, this function is diminished. Case 56. — Diabetes Mellitus — polyut ia — thirst — -wasting — interciirrent pyrexia reseinbli?tg typhoid. Agnes L., eight, school girl, was admitted into hospital on February 7th, 1S87, complaining of thirst, hunger, headache, and passing a large quantity of water. History. — Her mother had noticed that these symptoms had been coming on for six months, as she was constantly drinking water and losing flesh. She had been previously pretty well, but never strong since she was four years old. Her sister was with her in the hospital with diabetes, and another child had died of the same disease at the age of eleven. Six others and the father and mother were alive and well. Nothing was known of any other cases of diabetes in the family. Conditio7t on Admission. — She was a small, ill-nourished child, of strumous appearance. Temp. 98^, Pulse 96, Resp. 18. Her tongue was dry and clean ; the only abnormal signs were deficient resonance and feeble breath sounds at the left apex. Urine 58 oz., sp.gr. 1013, acid, contained 3 per cent, of sugar ; no albumen. Pr ). Pryce (T. Davies). a certain cutaneous affection occurring in Diabetes. "Lancet," 1888, II, p. 59. On Diabetic Neuritis, with a clinical and pathological description of diabetic pseudo-tabes. " Brain," 1893, p. 416. Robinson. Xanthoma Diabeticorum und seiner Verwandschaft mit gewohnlichem Xanthom. " Monatshefte f. prakt. Dermat." 1890, XII, No. i. RoQUE Devic and Hugueneng. Du coma diabetique. "Revue de Med." 1892, p. 995. Rosenblath (W.). Ueber multiple Hautnekrosen und Schleimhautulcera- tionem bei einem Diabetiker. " Virchow's Archiv," Bd. CXIV. Rosenstein (S.). Ueber das Verhalten des Kniephanomens beim Diabetes mellitus. "AUgem. med. Centralzeitung," 1885, No. 28. Salomonson. Over het ontbreken van den patellair-reflex bij. diabetes mellitus. "Weokbl. van het Nederl. Tijdschr. voor Geneesk." 1890. Samelsohn. Diabetic diseases of the Eye. " Deutsche med. Wochenschr." 1886. Saundby (R.). The Middlemore Lectures on the Retinal affections of Bright's Disease and Diabetes. " Birm. Med. Review," 1892, I. ScHMiTz (R.). Prognose und Therapie der Zuckerkrankheit. Bonn, 1892. Seegen. Ein Fall von Levulose in diabetischen Harn. " Centrlbl. f. d. med. Wissensch. " 1884, No. 43. Seifert (O.). Ueber Acetonurie. " Verhandl. der physik,-med. Ges. in Wurzburg." N. F. 4, 1882. Ein Fall von Diabetes mellitus mit Typhus abdominalis. " Wien. med. Wochenschr." Bd. XXXI, 1881. Simon (J.). Note sur le diabete sucre chez les enfants. " Revue Medicale," 1S85. bKERRiTT (E. Markham). Acute febrile Glycosuria. " Brit. Med. Jour " 18S5, II> P- ^^052- CLINICAL HISTORY. 32Q Spencer (W. G.). Diabetes in Surgical Cases. " Westminster Hospital Reports," Vol. IV, 1888, p. 89. Stadelmann. Ueber die Ursachen der pathologischen Ammoniakausschei- dung beim Diabetes mellitus und des Coma diabeticum. " Archiv f. exp. Path." XVII, p. 419. Strahax (J.). A case of Diabetes with remarks. " Dublin Jour. Med. Sci." Vol. LXXXI, p. 29S. StriImpell Text-book of Medicine, p. 915. Te.schemacher. Ueber wirkliches und scheinbares Aufhoren der Zucker- ausscheidung bei Diabetes mellitus. " Internationale klinische Rundschau," 1S88. ToRALBO (— .). " Centrlbl. f. k. Med." 1890, p. 19. Tuffier. Diabete at neoplasmes. " Arch. Gen. de Med." 1888, Vol. II. Vergeley (P.). De I'angine de poitrine dans ses rapports avec le diabete. "Gaz. Hebd." 1883. Watson (SirT.). Lectures on the principles and practice of Physic. 4th Edition, 1857, Vol. II. Weyl anJ Citron. Ueber die Nitrate des Thier und Pflanzekorpers. " Virch w's Archiv," Bd. CI. 1885. Willan, quoted by RoUo, Op. cit. Wilson (T. S.). Notes on Friedreich's Disease. " Birm. Med. Review," 1S93. Vol, XXIV, p. 193. Worms. Le diabete a evolution lente et son traitement. " Le Progres Med." 1SS9, No. 20, p. 377. Chapter XX. DIABETIC COMA. ProUT wrote that diabetics may be considered as existing .on the brink of a precipice, and since Prouts time the very precarious tenure by which they hold their hves has come tc be very generally recognised. We are all aware of the great risks to which they expose themselves in travelling, probably on account of the unavoidable annoyances, as well as fatigue, which travellers even in these days m^ust put up with. Violent mental emotions and bodily fatigue are well known dangers which we cannot be too careful to warn our diabetic patients to avoid. It is understood that diabetics are more liable than other persons to the usual sort of accidents that befall any one occasionally : thus a diabetic is more likely to have an attack of pleurisy or pneumonia, and such inflammations not unfre- quently pass on to breaking down of the lung, or even to gangrene of the inflamed part. But besides this special pre- disposition to inflammatory diseases, there is a complication of diabetes which has something characteristic and peculiai in it, so that of late years it has received a good deal of attention from some of the best clinical observers. It differs from those already alluded to by the alarming rapidity with which death may supervene in the midst of apparent good health. This it is to which the name of Diabetic Coma has been given, from coma being the final and most constant phenomenon. As is well known, diabetic coma was described by Kiiss- maul, in 1874. His paper did not meet with the attention it deserved, in this country, until public interest in the subject was aroused by Sir W. Foster's graphic description of two cases which had come under his observation, in a paper read at the Manchester meeting of the British Medical Association, in 1877. Since that time, many other cases have been recorded, and the general clinical history of the condition has been elaborated by many writers. DIABETIC COMA. 331 Etiology. — The frequency with which deaths from this cause occur, ma}' be inferred from the statement of Mackenzie, that of the instances of fatal ch'abetes collected by him from the registers of the London Hospital, all those under the age of twenty-five, with only one exception, had died of coma. The statistics of Guy's and the London Hospital, show very clearly the greater frequency of this mode of termination of diabetes in young persons, so that yoith appears to be a predisposing cause. Sex has no special influence that has been yet made out, nor does such an influence seem probable. Condition of life also appears unimportant. Constipation has been a marked feature. It occurs most commonly in acnte cases, and, as proved by the post mortem examination of the intestines, has existed to a far greater extent than had been suspected during life, so that I rate it highly in the list of predisposing causes. That the intestines are the seat of numerous fermentative and putrefactive pro- cesses is now well known, and it is easy to understand that constipation acts unfavourably in two ways : (i), by diminish- ing elimination of effete matter by one of its ordinary and most important channels, and (2), by affording time for the development of fermentative processes giving rise to the formation of toxic substances which may be absorbed into the blood. It is only too true that the life of a diabetic hangs by a thread, and we cannot be too careful or too persistent in our warnings. Above all we should not allow cases of advanced diabetes to travel ; too many of those who go to foreign health resorts in the hope of finding a cure, die of coma very soon after their arrival. This fact was insisted on by Prout, and is well illustrated by examples related by the physicians at the French and German spas frequented by diabetics. Clinical experience has suggested the dangers of imiscnlar fatigue^ 7ie7'voiis shocks and exposure to cold. Bond and Windle in their remarks on a fatal case of diabetic coma which occurred at the General Hospital, say that the change from ordinary diet to richly albuminous lood has been present as a factor in this and one other case under their obser- vation. While not doubting the influence which great and sudden changes in diet can produce in the system, it is note- worthy that in the case published by my colleague, Dr. Rickards, the patient was taking ordinary diet. 33^ DIABETES. Pathology. — Our knowledge of the pathology of this subject has been much widened, and our view of it has gained much in comprehensiveness from the writings of Senator, who has sought to establish the existence of a self-infective pro- cess, dependent upon the formation of toxic substances in normal or pathological cavities of the body, which, occurring in many other conditions besides diabetes, gives rise to pheno- mena essentially identical with those described by Kiissmaul. He has recorded seven such cases ; two of chronic cystitis, two of gastric cancer, and three of pernicious anaemia. In none did the urine contain any sugar, or give a reaction with ferric chloride. Riess has described eight cases in anaemia, five in anaemia with renal disease, and four in gastric and hepatic cancer. Von Jaksch has published a case of " com.a carcinomatosum," in a patient the subject of gastric cancer, the urine containing acetone and aceto-acetic acid but no sugar. Litten has described one case which occurred under what he calls "dyspeptic conditions," and which terminated in recovery, but the patient was a boy convalescing from scarlatina, and suffering at the time from albuminuria. I am, therefore, disposed to accept the view that Kiissmaul's coma, if I may be permitted to use this convenient term, is not restricted in its occurrence to cases of diabetes, but may be met with in several other diseases, especially in those in which the state of the blood has undergone profound patho- logical alteration. This is proved by the case of Harriet B., which is pub- lished at length at page 62. In that case, the cause of the coma Avas pyonephrosis with renal calculus, and there was no glycosuria, but the type of coma corresponded to Kiiss- maul's description. Various theories have been brought forward to account for the symptoms. As is well known, Kiissmaul adopted the view that the phenomena depended upon poisoning of the nerve centres by acetone. Acetonceinia was not altogether a new idea in pathology, as Fetters, as long ago as 1857, had found acetone in the blood, expired air, and urine, of a severe case of diabetes. Later on Kaulich noticed an acetone-like smell in the urine of patients suffering from variola, typhus, and pneumonia. The presence of acetone in diabetic urine was subsequently confirmed by Cantani, Kaulich, Rupstein, and Fleischer. There is very little doubt that acetone is frequently present in the urine of DIABETIC COMA. 333 diabetics, but it is met with in many other diseases ; thus Bull, who investigated this point at my request, found it present in five out of twenty-one cases of pneumonia, in acute chorea, intestinal colic, tonsillitis, fractures, burns, and contusions. The blood of Sarah L. (Case 60) was distilled very care- fully, but no acetone could be detected in the distillate. These investigations were conducted in Prof Tilden's labora- tory, where I had the great advantage of his kind assistance and co-operation. Moreover, Dr. MacMunn could find none in the blood of F. R. W. (Case 58). Another difficulty in the way of accepting the view that acetonaemia is the cause of these toxic symptoms, is that it has not been proved that acetone is capable of giving rise to similar physiological effects. Kiissmaul obtained results which were of a not very decided character, but more recently Salomon and Brieger have shown that acetone in large doses produces no effect on animals or men, even when diabetic. The urine of the subjects of these experiments had no smell of acetone, gave no reaction with ferric chloride, nor any of the chemical reactions of acetone, so that it must have been destroyed in the body Similar experiments by the same observers with aceto- acetic acid, caused acetone to appear in the urine, where it announced its presence by its smell, the iodoform reaction, and its characteristic combination with bisulphide of soda, but in no case did the urine give the ferric chloride reaction. Very large doses were without any noticeable effect ; neither dyspnoea nor somnolence was produced ; after the doses had been continued for many days, there was some loss of appetite, and the breath acquired a peculiar aromatic smell. Penzoldt has stated that when excretion through the lungs is retarded, the introduction of large quantities of acetone into the circulation of rabbits, is followed by intoxication, hebetude, and coma, and he contends that when the lungs are disabled from any cause, these results will follow acetonjemia in man. Unfortunately for the application of these facts to the explanation of the cases under consideration, the absence of pulmonary complications has been specially noted in the majority of them, and has even formed the basis for an aphorism, viz., " that when pulmonary disease is absent or 534 DIABETES. slight, the occurrence of coma is more to be feared, especially the younger the patient and the more acute the disease." (Mackenzie.) Senator in the paper already alluded to suggests that tri- methylamine may be the toxic agent, but advances little evidence in favour of this hypothesis. Minkowski has discovered the presence in the blood of diabetics of large quantities of an acid, which he believes he has identified as ^-oxybutyric a id, one of the isomeric series of butyric acids, and has introduced a new theory by calling attention to the toxic influence of large quantities of acids when introduced into the body. Von Noordcn believes that this acid is the essential cause of the coma. He points out that its presence may be inferred when the urine is dextro- tatory after the glucose has been removed by titration with Fehling, or precipitation by basic acetate of lead and ammonia. Walter, in the course of some researches into the effects of acids on the animal organism, noticed that in rabbits the introduction into the stomach of large quantities of diluted phosphoric and hydrochloric acids was followed by "dyspnoea, depression of the heart's action, and death by collapse." Post mortem examination showed in some cases erosion of the mucous membrane of the stomach, and the coagulation of the blood was delayed. The objection that the symptoms might have been due to the local action of the acids on the stomach, was disproved by the effects of subcutaneous injec- tions of alkalies, which prevented or cut them short. From his investigation, he arrived at the conclusion that the de- alkalisation of the blood by the introduction into the body of excess of acids, causes first stimulation, and later on paralysis of the respiratory centre. It is important to notice that ^-oxybutyric acid is capable of breaking up to form di-acetic acid, which yields on decom- position acetone and carbonic acid, so that this substance must be regarded as being nearly allied to acetone. Binz has found that sodium butyrate produces coma in cats. Latham has suggested the following theoretical explanation of the production of a toxic substance in the blood. He f OH thinks that the second cyan-alcohol C2H4 \ ^^ is converted by hydration into lactic acid, which if not completely DIABETIC COMA. 335 oxidised into CO., and H._,0 would first form aldehyde, thus ; — C= H' { 80OH + O = { cSh + CO^ + "^O- Lactic Acid. Acetic Aldehyde. Then by condensation : — 3 Co H, O - Cg H12 O3 Paraldehyde. This is a hypnotic, and would cause drowsiness. Or he suggests that the third cyan-alcohol C3 Hr \ OH might be hydrated into oxybutyric acid. \ CN In spite of the negative results of most post mortem exam- inations, an attempt was made by Sanders and Hamilton to find a structural basis for these symptoms. Their view, as is well known, was that the respiratory and nervous pheno- mena are caused by fat embolism of the pulmonary and cerebral capillaries. They based this theory on the results of the post mortem examination of one case of diabetic coma, in which the blood was very fatty, and fat embola were found in the lungs and kidneys. It is curious that Kiissmaul's first case had also fatty blood, and the lungs presented numerous small infarcts respecting which he remarks, " perhaps we might attribute to the lipsemia and fat embolism the numerous small lung infarcts, at least another source of embolism was not to be discovered /;/ no case could the fearful terminal dysMuva have originated in tJies^ small infarcts, the greater part of winch were of far older date." Thus this theory had not escaped the notice of KUssmaul, although he merely noticed it to dismiss it. Lipaemia is only exceptionally present in diabetic coma, and even when it exists, fat embolism may not occur (TAYLOR, Dreschfeld); in two cases with lipaemia, examined by Mr. Barling and myself, the fat in the vessels had assumed rather the appear- ance of post mortem thrombi than of embolism, and was less than we found in many cases of fracture where it had given rise to no symptoms at all during life. Although Stockvis and even Ebstein, maintain the uraemic origin of the coma, they have found few supporters; clinically, it differs from the classical type of uraemia, in which convul- sions play the leading role ; etiologically, neither albuminuria nor suppression of urine nor diminution in the normal urinary solids is a constant phenomenon ; finally, the doctrine 336 DIABETES. of uraemia rests on quite as uncertain a basis as that of acetonsemia. In concluding this part of the subject, I may express my own opinion, that, while at present we are unab e to determine positively the nature of the toxic substance, or the determin- ing causes of the sudden explosion of the fatal terminal symptoms, these phenomena are toxaemic, and in diabetes depend upon the presence in the blood of some substance nearly allied to acetone. There has never been any dispute that Jieai't failure is the obvious explanation of a certain number of cases of sudden death in diabetes. This is said by Schmitz to be due to fatty degeneration of the heart, which is a common form of cardiac degeneration in diabetes. Frerichs has suggested that the muscular fibres of the heart undergo a " glycogenic degenera- tion," in which their power of contractility is lost, but it is doubtful if the deposit of glycogen injures the heart's muscle. Symptoms. — The premonitory symptoms vary very much. Sometimes the attacks begin with maniacal excitement ; more commonly abdominal pain or headache is complained of; a sudden fall in the sp, gr. and sugar contents of the urine has been sometimes noticed, but this is by no means always a cause for alarm. Lepine attaches much importance to the rapidity of the pulse as a trustworthy prodromal sign. The urine usually gives a Burgundy red colour on the addition of a solution of the perchloride of iron, the colour disappearing on heating the mixture. This reaction is cer- tainly present in diabetic urine apart from coma, and has been met with in other diseases. Thus Von Jaksch has met with it in many acute disorders, especially measles, scarlatina, and pneumonia. He has also observed it in a case of gastric cancer terminating fatally by coma. Hoppe-Seyler has des- cribed it in a case of sulphuric acid poisoning as occurring during the time no food was taken. Senator observed it in a case of atropine poisoning which died comatose. Windle has observed it in pneumonia, Bright's disease, scarlatina, and several other pathological conditions apart from diabetes. It cannot be therefore regarded as in any sense a pathogno- mionic sign, and it was absent in Case 65. Acetone is present in the urine, as indicated by a rose-violet coloration with a solution of nitro-prusside of sodium and ammonia. So far as I am aware, this is constant ; the DIABETIC COMA. 337 amount present varies greatly, but it may be due to the diet, and disappear when carbo-hydrates are allowed (HiRSCH- FELD). a trace of albumen is very commonly to be found. Another symptom which is very striking, but not always present, is the peculiar odour of the breath, which has been variously described as like sour beer, apples, hay, chloroform, and acetone. The patient gradually becomes more drowsy, the respiration acquires a deep sighing character, the surface of the body grows cold, the pulse is weak and rapid, complete un- consciousness supervenes, and in this state he may remain several hours ; death is sometimes preceded by convulsions ; the temperature is usually subnormal, but in rare cases is raised. Frerichs attempted to give greater precision to our study, by classifying cases of sudden death in diabetes into three groups. In the first group he placed those which suddenly, and usually after previous exertion, become prostrated, with cold extremities, small failing pulse, drowsiness, and loss of con- sciousness, and terminate fatally in a few hours ; these he called death from heart failure. In the second group the duration is longer, and there is a prodromal stage which may be either general prostration, gastric disturbance, vertigo, vomiting, constipation, or a local disease, such as a dental abscess, pharyngitis, an abscess with a tendency to gangrene, bronchitis, or catarrhal pneumonia. The attack itself commences with headache, restlessness, de- lirium, anxiety, sometimes with maniacal outbursts, dyspnoea, characterized by frequent deep respiration with free entrance of air into the lungs, sometimes with cyanosis, sometimes without it, feeble rapid pulse, low temperature, drowsiness and coma. The breath has a peculiar smell like fruit or chloroform, or acetone. Such cases may recover temporarily, and in some rare instances the attack may pass away. The duration of the symptoms may be from twenty-four hours to three or four days, or even longer. He attributed this type to a peculiar unknown poison, perhaps acetone, acting on the respiratory centre. In the third group he placed cases which present no dyspnoea or anxiety, have moderately firm pulses, and are fairly well nourished. The attack is characterised by headache, a feeling of intoxication, disordered gait, sleepiness, and gradual coma, 22 338 DIABETES. from which they do not awaken. The breath has the charac- teristic smell. This was believed by Frerichs to be the con- sequence of a poison which affected the nervous system like alcohol. In the first group the symptoms are those of collapse, coma occurring only at the end, and the duration of the whole attack is very short. In the second group we have Kiiss- maul's typical complex of symptoms, with dyspnoea, peculiar odour of breath, and coma. In the third group there is no dyspnoea, the symptoms more closely resemble alcoholic in- toxication, but the breath has the characteristic smell, and coma is present. I cannot recall a case of mine in which deep breathing, or the so-called dyspnoea, was not present, but examples have been recorded (Frerichs, Prescott Roberts). The following cases illustrate the usual pathological and clinical features of diabetic coma as I have observed it: — Case. 58. — Diabetic coma — deaiJi — atUopsy. F. R. W., an engine driver, aged forty-one, unmarried, was admitted on May 17th, 1884 ; he had been attending as an out-patient since the previous December. His own account of himself was that he had always been a healthy man ; he came of a g'ood stock, his mother and several brothers and sisters being ahve and well, and his father having died of smallpox at the age of fifty-four. About a month before he was tirst seen, he was leaning over the strap of the fly-wheel, cleaning his engine, when his foot slipped, and he fell so as to contuse his abdomen and strain his back. He came at once to the hospital, and was treated surgically for the strain, but got weaker, and was eventually transferred to my care. At that time he had lost a good deal of flesh, he complained much of weakness, and passed a large quantity of water, which was loaded with sugar, but contained no albumen, and gave no special colour reaction with ferric chloride. On modified diet and treatment he im.proved some- what : that is to say, the quantity and sp. gr. of the urine were reduced ; but he continued to lose weight, and became so very anaemic and weak, in spite of iron and cod liver oil, that he was admitted into the hospital. He had slight signs of phthisis at the left apex. After admission he im- proved a little, gaining 5^ lbs. in weight by June 14th. His bowels were very obstinately constipated, and towards the end of June he had some gastric trouble for which all his medicines were stopped except an occasional purgative dose of jalap. On July 4th, he complained of faintness ; as we were on the look out for the supervention of coma, his urine was tested with ferric chloride and found to give a marked colour reaction which disappeared on heating. On July 8th he went out to see his mother who lived in the town ; the next day he complained of feeling very tired and did not eat his food. On that day also the ferric chloride reaction was present. DIABETIC COMA. 339 On the evening of July loth he said he was feeHng very tired, and com- plained of sharp pain in the left side of the chest with difficulty of breath- ing. This was relieved by hot fomentation. The following day he was still tired and drowsy ; his hands and feet were cold. Towards evening Jiis respiratiotis became deep, and sii^lnng, he was cold and drowsy, but could be roused, and answered questions intelligibly. He died quietly at 7 a.m. The post vi07-teiii examination was performed the same day by Dr. Foxwell. The brain weighed fifty-nine ounces ; there was a cyst the size of a horse bean in the white matter of each frontal lobe, and the lateral ventricles were dilated and contained clear fluid. At the apex of the leit lung were two small cavities, and the lower lobe was in a state of recent pneumonic consolidation. There was no unusual smell on opening the body, but the blood which ran out as the organs were removed was of a milky purple colour. On standing it looked like black currant juice on which cream was floating. Under the microscope the cream-like layer consisted of finely molecular matter, entirely soluble in ether. Some of the blood was distilled by Dr. MacMunn, but no acetone could be detected in the distillate. The liver weighed 81 02., it was soft, friable, and its cut surface was mottled with yellow patches. The spleen weighed 5 oz., and appeared nornial. The pancreas weighed i^ oz., it was only 4 inches long", and very friable. The kidneys weighed together 18 oz., they were coarse, pale, and soft, their capsules stripped off" readily. The supra- renal capsules were healthy. The semi-lunar ganglia were much en- larged, and of dense consistence. The large intestine was stuffed full of solid faeces. The semi-lunar ganglia were hardened in picric acid and examined microscopically. The sections showed great increase of connective tissue which was swollen and hyaline, and crowded with lyinphoid cells. The nerve fibres were abundant, and their nuclei well marked. The ganglionic cells were loaded with pigment but otherwise unchanged. The lungs, liver, and kidneys were examined microscopically for fat embola. The lungs presented no branching embola, but in some cases the capillaries contained droplets of fat large enoug"h to occlude the lumina of the vessels. The liver capillai^ies contained numerous similar droplets. The connective tissue of the liver around the ducts showed some infiltration with round cells. The kidneys were very slightly fatty, some tubules contained hyaline casts, and there was an increase of con- nective tissue around the larger veins. The capillaries contained veiy few fat droplets on the whole ; by far the largest amount of fat was seen in the capillaries of the liver, and this to such an extent as to suggest very strongly that it was formed there. I examined the heart very carefully for glycogen, following Frerichs' directions, but the muscular fibre, though showing a considerable degree of pigmentary or brown atrophy, was otherwise free. Case 59. — Acute Diabetes — coma — death — autopsy. F. W. A., seventeen, jeweller, presented himself as an out-patient at the General Hospital, on Thursday, Oct. 19th, 1882, complaining that he was rapidly losing strength and flesh, and passing a very large quantity of urine. He looked very ill, and his uririe, on examination, contained a large quantity of sugar, was of sp. gr. 1040, but gave no reaction with ferric chloride. He was recommended for admission, and the following 340 DIABETES. history was obtained. There was no known instance of diabetes in the family ; his mother died of phthisis three months ago, and this circum- stance had been a source of great grief to him. His previous heakh had been good, with the exception of biHous attacks, to which he was subject. Five weeks ago, he began to feel ill and to pass water during the night, and for the last fortnight he had been passing very large quantities both in the day and night, altogether, he estimated, about two bucketsfui of what he described as "hay-smelling '' urine. For the last two weeks he had suffered from constant frontal headache, and great thirst ; his appetite had continued good, but not inordinately so. His bowels during the same period had been open every other day. Five days ago he vomited, and had to give up his work. His penis became a little sore, and he noticed that his urine left a sticky stain on his shirt. He had been taking medicine from a chemist for four days before admission. Present Co7idition^ October 20th, 11 a.m. (the day after admission): — Patient complained of frontal headache, weakness, constant desire to pass water, and great thirst. He was an emaciated looking lad, with dilated pupils, and dark rings under his eyes ; his alas nasi were working, but his lips were of a good red colour. Expression anxious ; skin dry and rough ; Temp. 98° ; Pulse, 112 ; Respirations, 24. No oedema of legs. Teeth glazed ; gums red and slightly spongy ; throat covered with thick mucus ; fauces reddened ; tongue very dry, and its centre coated with a grey fur ; appetite fair, no vomiting. Bowels were opened on the day before admission (October i8th). His breath smelt sweet ; there was no cough ; breathing deeper than in health. The circulatory organs appeared normal. During the night he passed a large cjuantity of urine, which was acid, sp. gr. 1040, contained \ column of albumen, and a large quantity of sugar. The urine passed in the morning was acid, clear, greenish coloured, sp. gr. 1035, contained ^ column of albumen, a large quantity of sugar, and gave an unmistakable deep vinous-coloured reaction with ferric chloride. His eyesight was unaffected. On the day of admis- sion the patient took ordinary diet, but since then diabetic diet. The detection of the ferric chloride reaction at once suggested the fear that toma might be imminent, and as the bowels had not been moved for forty-eight hours, two scruples of pulv. jalapse co. were administered at 12.30 p.m., and he was ordered to be carefully watched. 3 p.m. — Patient became very restless, and complained of great pain in his abdomen ; his respirations were deeper, and his pulse quick and feeble. The pain in the abdomen was relieved somewhat by hot fomen- tations. The bowels had not been moved. 5 p.m. — Pulse 156, feeble ; Resp. 34. Ordered a teaspoonful of brandy every half-hour. 5.30 p.m. — No cyanosis : respirations deep and sighing ; pulse very feeble ; complained of no pain. Not restless, seemed rather drowsy. Ordered three teaspoonfuls of brandy at once, and a teaspoonful every ten minutes. 7 p.m. — Patient quite comatose : thirty minims of ether injected subcu- taneously did not rouse him, nor did he appear to feel the operation of having a drop of blood taken from his finger. After a little he roused sufficiently to put out his tongue and to say that he felt short of breath, but no pain. There was no cyanosis ; breathing was very deep, 41 ; pulse (before the ether) 174, extremely feeble. Pupils were dilated, but reacted to light. Breathing very harsh : heart sounds scarcely per- DIABETIC COMA. 341 ceptible. The blood on examination did not contain any fat globules, but the leucocytes appeared slightly increased. An enema of one ounce of brandy and a drachm of ether, in two ounces of water, was then adminis- tered, and he was enveloped in a hot pack. 9 p.m. — Patient had been very violent, tossing himself about in the bed : radial pulse not to be felt ; pupils dilated and insensible to light. Breath- ing- deep ; no cyanosis. He was deeply comatose and could not be roused. Later on his father managed to rouse him by repeated shouting, and on his father saying, " Do you hear me ?" patient replied, " Yes ! I hear you," II p.m. — Patient died ; eight hours after the onset of the more serious symptoms. The nurse reported that he turned "bluish'" and struggled very violently before his death. No urine was passed after 6 p.m. ; but ten ounces were passed during the previous hour ; this was examined by Dr. Windle, and he reported it to have been pale yellow, clear, acid, sp. gr. 1030, containing a trace of albumen, i"6 per cent, ot sugar, '95 per cent, of urea; chlorides diminished ; no trace of indoxyl ; a deep vinous red reaction with ferric chloride. The total quantity of urine passed in the twenty-four hours, from 5 p.m., October 19th, to 5 p.m., October 20th, was 160 ounces. The temperature on the evening of the 19th was 100° Fahrenheit, but fell gradually, being 98" on the morning of the 20th, and 97" at 7 p.m., four hours before his death. Autopsy. — The -post mortem examination was performed by Dr. Windle, on October 21st, fifteen hours after death. Exterjial Appea7-ances. — The body was that of a young male, somewhat emaciated ; cadaveric rigidity and hypostatic congestion were well marked. The Spinal Cord presented no abnormal naked eye appearance. Head. — The cranial bones were very thin ; the dura mater was ex- tremely adherent ; there was no clot in the superior longitudinal sinus. There was increase of the Pacchionian bodies on the arachnoid along the longitudinal fissure. The brain substance was firm, slightly hypercemic throughout, with numerous puncta cruenta ; a small amount of reddish serum in the lateral ventricles. Thorax. — The cavities of the heart contained some dark fluid blood, and a very few soft clots ; the valves were normal ; the heart substance was rather pale. The lungs, when squeezed, emitted a peculiar sour acetone-like odour, which was also observed on section of them. Their substance was slightly hypersemic, but otherwise normal. Abdomen. — The stomach and intestines were much distended. There was no unusual smell detected on opening this cavity. The diaphragm- atic concavity reached as high as the upper edge of the fifth rib. The liver was slightly enlarged, and on section pale in colour. The gall bladder was almost empty and collapsed. The bile ducts were pervious. The spleen was small and soft. The kidneys were rather large, their capsules stripped readily ; substance pale. The supra-renal capsules were normal. The pancreas was small and shrunken in appearance. The stomach was full of pultaceous food ; its mucous surface showed patches of hypertemia. The intestines were loaded with fasces, the sigmoid flexure and rectum being stufi'ed full of hard grey masses, quite uncoloured by bile. The small intestine was full of pale yellow soft 342 DIABETES. fasces. There was a large mass of taenia in the colon. The solar plexus and cervical sympathetic ganglia appeared normal. The blood nowhere presented any abnormal appearance. On microscopical examination the liver, spleen, kidneys, and lungs were quite normal. There were no fat embola or any traces of fat in the vessels of the lungs and kidneys, or in the renal tubules. The medulla was also normal, though the perivascular spaces were slightly enlarged. The cells of the pancreas were badly defined, and their contents cloudy. The sympathetic ganglia were unfortunately lost. Dr. Norris, who examined the blood, reported that the leucocytes were peculiarly large, and the red corpuscles and granular matter slightly in excess, but there was no excess of fat. The clinical phenomena presented by this case are of great interest. In the first place, the diabetes was apparently pro- duced by nervous shock, the profound grief induced by the death of a near relative, a fact which is in accordance with many previous observations, and which goes with them to support the view of the purely nervous origin of the disease. Secondly, the course of the disorder was remarkably acute and rapid. Tliirdly, we were able to trace the development of the whole of the terminal symptoms. Among the earliest of the premonitory signs was the altera- tion of the respiration : in the morning note we find that the breathing was " deeper than in health." Throughout the report of the clinical symptoms we have repeatedly the note, " no cyanosis," and until just before death, when according to the nurse he turned " bluish," there is not the slightest evidence of any alteration in the function of blood aeration. Undoubtedly cyanosis has been described in other cases, but as it is not constant, when present it is probably due to some complication. Its absence indicates that the dyspnoea is purely nervous in origin, and the result of stimulation of the respiratory centre, rather than of any local change in the lungs, and this afifords an additional argument against the theory of Sanders and Hamilton. T\\.Q pulse at the morning visit was 1 12, and soon rose to be extremely rapid and feeble ; this symptom is of great value as an early indication of the onset. Abdominal pain was complained of first at 3 p.m., and may have been partly the effect of the purgative ; but it is, however, known to be a very constant and early sign in these cases. Drowsiness was first noticed at 5.30 p.m., and by 7 o'clock he was quite comatose. Death was preceded by convtclsions. Senator speaks of twitchings as sometimes supervening, but n another case DIABETIC COMA. 343 under my care as in this, actual convulsions occurred. Con- vulsions have also been observed by Minot and by Buhl Cyr considers that the absence of convulsions affords a diagnostic distinction between this form of coma and that from uraemia, but this, it is obvious, cannot be maintained. Among the premonitory signs presented by this case, were the gradual fall in the sp. gr. and quantity of the urine, and consequent diminution of the amount of sugar excreted, which was far too great to be accounted for by the change of diet. In the last sample of urine examined the quantity of sugar was only about seven grains to the ounce, an amount which must have been greatly surpassed in the previous day, when the sp. gr. was ten degrees higher. A sample of the urine, some days old, was distilled by Prof Tilden, F.R.S., at Mason College, for acetone, but none was found. The percentage of urea was low, being under one per cent., but considering the large quantity of urine passed, the total amount excreted during the final twenty-four hours of life must have been quite seven hundred grains. This disposes of the suggestion that the toxic phenomena were due to non- elimination of urea. No urine was passed after 6 p.m., but this coincided with the supervention of the coma. This case illustrates the prognostic use that may be made of the ferric chloride reaction, for although it is not uncom- monly found in diabetes without being followed by coma, and is often present in the urine of other disea^-^es, yet its sudden appearance, especially in young subjects and in acute cases of diabetes, should be regarded as a sign of grave moment, and should direct attention to the state of the bowels, the respiia- tion, the pulse, and the other prodromata which have been described. The teuiperatuTe as a rule is normal, or subnoimal, but it may rise to a considerable height (Case 63). Case 60. — Diabetes Mellitus — intra-venoiis injection — death from coma •with hii^h temperature. Sarah L., nineteen, tailoress, was admitted on August 22nd, 18S5, complaining of thirst and of passing a great quantity of water. Condition on Adniission. —She was poorly nourished, but the physical signs were normal. The urine was 136 oz., sp. gr. 1039, acid, clear, a cloud of albumen; sugar 7'6 per cent.; urea o'65 per cent.; acetone and ferric acid chloride reactions both well marked. Temp. gS'S", Pulse 108, Resp. 24. She was placed on house ditt and ordered a simple enema. Progress of Case. — On the evening of the 23rd she had an enema, and 344 DIABETES. felt faint after it. She vomited just before midnight, and again at 4 a.m. At 5 o'clock she cried, and complained of great pain ni the small of her back. The matter vomited gave a distinct acetone reaction with the nitro-prusside test. Hot fomentations were applied, and at 8 a.m. she had a grain of extract of opium, and a second was given at 10 o'clock. At the visit at 10 a.m. she was still complaining of the pain ; her respira- tion was panting, 32; pulse 132; temp. 98'5°; bowels had been moved freely; tongue red and dry. She had passed no water since 4 a.m., so at 1 1 a catheter was introduced and 10 oz. of urine drawn of, which was pale, clear, sp. gr. 1040, acid, with a cloud of albumen, sugar 5*9 per cent., urea 0*9 per cent., acetone and ferric chloride reactions well marked. She was becoming unconscious, and by 11.30 was lying on her back comatose, with contracted pupils. At 1 1.30 thirty-six oz. of sulphate of soda solution were injected into the veins. She improved during the operation, the pulse became stronger, she was less drowsy, and she com- plained of the tightness of the bandage which had been applied to her arm. At 2 p.m. she could not swallow, so three-quarters of a pint of water were administered by the bowel. At 3.30 the pulse was 165, very feeble, eyes turned up, respiration sighing. At 4 p.m. a second enema of about a pint of acidulated water was given. The pulse improved a little and respiration was quieter. At 5.30 sixteen oz. of urine were drawn off, which did not differ materially, except that it was of sp. gr. 1031, and contained only 4 per cent, of sugar and o'3 per cent, of urea. An enema of acidulated water was given every hour; but at 7.30 p.m. the noisy deep breathing began again, and the enemata were discontinued as they were not retained. At 7 p.m. the temp, was 130°, and at 9 p.m. it had risen to 103*5°. Resp. 22 ; Pulse 169. No other change took place. She died quietly, without any convulsion, at 11.10 p.m. At the autopsy the body was covered with a thick layer of fat. There was no peculiar smell on opening the body. The blood appeared normal. All the internal organs were congested but healthy, though the brain presented some excess of cerebro-spinal fluid. Diagnosis. — I do not think anyone can find a difficulty in diagnosing diabetic coma, when he has once grasped its salient features. The peculiar dyspnoea, which is so characteristic, at once arrests attention. This is regarded by Senator as a pathognomonic symptom, and our present knowledge justifies his view. But it is not so easy, and, if possible, it is of greater practical importance to recognise those prodromata which foreshadow the approach of these formidable and almost invariably fatal symptoms. The first warning of their supervention has been, in two cases of my own, the discovery of a very marked ferric chloride reaction in the urine. In Case 58, it was very remarkable that this reaction, which had been repeatedly looked for, was never noted till just before his death. I think, therefore, that restricting this statement to cases of diabetes, the sudden occurrence of this reaction should DIABETIC COMA. 345 always serve as a warning. Stadelmann attaches much prognostic importance to the increase of the ammonia in the urine. Rapid disappearance of sugar from the urine has preceded the attack, but this is exceptional, as is also any marked alteration in the quantity of urine. Of more certain value than any of the foregoing is epigastric pain. This often pre- cedes by some hours any other symptom. Next to this, in chronological order, is rapidity and feebleness of the pulse. But most significant of all is the altered respiration. Inspira- tion and expiration become prolonged, and the respiratory rhythm is quickened, but air enters freely into the chest ; the lips and cheeks retain their former colour. Sooner or later the patient becomes drowsy^ but it is easy to awaken him from this somnolent state. Convulsions may appear, usually towards the termination of the case ; and before death cyanosis may be present, from failure of the circula- tion than from any difficulty in the oxygenation of the blood in the lungs. The peculiar odour of the breath is so far from being a constant phenomenon that Kussmaul did not mention it in his description, and I believe it to be present only in a minority of cases. Prognosis. — The prognosis of these cases is most grave, but although the serious disorders so generally present almost preclude recovery, it is right to remember that four cases have been recorded in which death did not take place (QUINCKE, Gamgee, Reynolds). The two following examples show that epigastric pain, drowsiness, and even sighing breathing, are not necessarily followed by fatal coma. Case 6 1 . — Diabetes Mellitics — polyuria — thirst — wasting — temporal y attaclcs of drowsiness — early loss of sexual desire — urethral pain —no benefit from treatment — discharged at own request — death soon after. Charles S., thirty-six, chaser, was admitted into the General Hospital on December 12th, 1889, complaining of polyuria, thirst, loss of flesh, and pains in the back and thighs. These symptoms began twenty-five weeks ago with frequency of micturition, followed in a week or two by pains between the shoulders, for which he consulted a doctor, who told him he had diabetes, and put him on a diet under which the quantity of his water became less, the frequency of micturition was diminished, and the pain in the back disappeared. In fact, he was so much better he was allowed to take bread and potatoes ; but this was only for one day, as the doctor stopped them again. Latterly he had begun to get very low ; his 546 DIABETES. urine had increased again in quantity. He left off work and seemed to improve, but again became worse. On October 21st, he attended as an out-patient, and for the next month improved, gaining" weig^ht and passing less water; but he relapsed, and continued to get worse until admission. In the course of his illness he had several attacks of drowsiness, which passed off in two or three days. Sexual power disappeared very early, but returned for a short time at the end of six weeks. Frcviotcs History. — He attended the Queen's Hospital when eleven years of age with a cough, and at twenty-eight he had a Cjuinsy. He also had small-pox and measles when a child. He could remember no accidents or injuries. State on Admission. — He was a well-developed but spare man, with some varicose veins in his legs. No jaundice or oedema, or skin erup- tions. Complained of lumbar pain on admission, Avhich disappeared after twenty-four hours' rest in bed. Skin dry, weight 8 st. 3 lbs. Alimentary System. — Lips dry, with teeth decayed, tongue moist and pale. Appetite good but not excessive, thirst great. Mouth dry and sour in the morning. No pain or tenderness in abdomen. Liver dulness in V. M. L. 25 inches. Circulatory Systein. — Heart's area not increased ; apex beat in fifth LS., internal to V. M. L. Heart-sounds weak but clear. Pulse fairly strong and regular. Respiratory System — Respiratory muscles wasted, showing fibrillary contraction when tapped. Movements normal. No cough. Physical signs normal. Genito-icri7iary System. — Sexual desire absent ; no irritation of geni- tals. Urinated once every hour and a half, with sharp pain in the middle of urethra, which lasted about three minutes. Stream good but twisted. No history of gonorrhoea ; no difficulty in passing wa'er. Urine 188 oz., acid, straw colour ; urea 1*27 per cent., no albumen ; sugar 47 per cent. ; acetone present. Nervous System. — Aching pain in thighs, worse in bed. Eyesight and hearing good. Sleep unimpaired. Treatment. — Diet : meat, fish, fowl, green vegetables, i^ pints of milk, I pint of beef tea. Medicine: Ext. jainbolaiuz liq. (Christy) 3ij. ; tr. opii III XV. ; aquam ad. 5j. ; thrice daily, with ext. cascarce liq. 5ss. ; glycerini 5ss. ; aqttani ad. oj- ; at bedtime as an aperient. Dec. i6th. Complained of pain in epigastrium and bitter taste in mouth, with drowsiness. 17th. Drowsiness, pain, etc., had gone. 31st. He went home at his own request, and we heard that he died very soon after. The following table shows the effect of treatment. DATK. UNINE. SP. GR. URBA. SUGAR. \VT. OF I'ATIENT. Dec. 13th.... „ 1 6th.... ,, 19th.... „ 25th.... 188 OZ. 136 oz. 160 oz. 168 oz. 1032 1030 1028 1035 I "27 p.c. 1-5 p.c. VI p.c. VI p.c. 47 p.c. 4-0 p.c. 37 P-c. 5-5 PC. 8 St. 2 lbs. 8 St. i^^lbs. 8 St. 2% lbs. DIABETIC COMA. 347 Case 62. — Diabetes Mcllitiis — polyuria — ilurst — ruasiing — thf-eatening coma averted by sponlaucous diarrhwa. William S., aged twenty one, engine cleaner, was admitted into Hos- pital on March 27th, 1887, complaining of thirst, loss of flesh and polyuria. History. — His illness began six weeks before with thirst. He had a "low fever" three years ago, and formerly suffered from some kind of urticaria when working as a brass filer. He had always been temperate, and had a comfortable home. Father and mother and ail his brothers and sisters alive and well ; no history of diabetes in his family. Condition on Admission. — He was rather deaf, especially in the left ear. He was wasted, and looked ill. Except some dulness and deficient breathing at the lelt apex posteriorly, the physical signs were normal. Urine 250 oz., sp. gr. 1037, acid, pale straw colour, no deposit, o'8 pen cent, of urea, 6'2 per cent, of sugar, a faint trace of albumen, a i&w squamous epithelial cells and crystals of oxalate of liine. Progress oj Case. — On March 31st he was dieted and treated with alkalies. His urine fell to half the quantity. On April 3rd he complained of pains in head and abdomen, seeined drowsy, and had sighing breathing. His bowels, which had been acting once daily, were moved spontaneously four times, and the condition passed otit'. He left at his own request on April i8th, and we heard in July that he had died. Treatment. — Prevention is proverbially better than cure, but I need not repeat what has been already said respecting the predisposing and exciting causes, and will assume that all possible means will be taken to guard against them. In addition, two plans of treatment by drugs suggest themselves as theoretical prophylactic measures. The first is to check the fermentative processes by means of antiseptic or antizymotic drugs. For this purpose Foster recommended thymol, but I am not aware that he has ever given it a trial. Salicylate of soda has been used very extensively in diabetes, but in spite of it these symptoms have supervened. Nevertheless, in selecting new remedies we should bear in mind that this action of the salicylate is one among other reasons for its employment. The other plan is the use of alkalies This mode of treat- ment has received the sanction of the highest authorities, yet it is at present in some danger of falling into disfavour. A high degree of acidity of the urine should be regarded as an indication for its use, Vichy water being as good as any other mode of administration. Is there any remedy which can arrest the attack, when it has commenced ? Frerichs regards all therapeutic measures hitherto suggested 348 DIABETES. as useless. Injections of ether, camphor, and similar stimu- lants have been tried without advantage. Kussmaul tried transfusion of blood with only temporary results, and inhalation of oxygen was also without effect. Bence Jones employed peroxide of hydrogen and stimulants with no better result. Hilton Fagge and Taylor injected a weak solution of phosphate of soda and sodium chloride into the veins, in one case with benefit for some hours, but after a dose of codeia the coma returned and proved fatal. In another case no result followed. Re3molds recommended, and published two cases of recovery after the administration of a dose of castor oil followed by thirty to sixty grains of citrate of potash every hour in copious draughts of water, the patient being encouraged to drink about a gallon. None of these has proved itself worthy of our confidence. Rest in bed should always be insisted on when any threatening symptoms appear. In the early stages I recom- mend energetic evacuation of the bowels, and the administra- tion of stimulants and alkalies by the mouth or rectum. These three cases further illustrate the results of various remedies. Case 63. — Diabetes Mellitus — polyuria — thirst — ei7taciation — coma — use of strych7titie — high te7nperature — death — autopsy. Arthur P., forty-three, nailer, was admitted into the General Hospital on October 20th, 1886, complaining of thirst, weakness, and of passing a large quantity of water — he thought as much as six or seven quarts a day. History. — His illness began six months ago with pains in his legs, which his doctor called rheumatism. A month later it was discovered that he had diabetes, but no change was made in his diet. He continued to get worse, and having been to Rhyl without benefit he came to the hospital. His previous health had been good, except for rheumatic pains in his hands. His father and mother were alive, as well as all his brothers and sisters, and, except that his mother suffered from rheuma- tism, no pathological incident could be discovered. Condition on Admission. — He was a small, emaciated man ; height 5 ft. 3 in. ; weight 8 st. \\h. He used to weigh 10 st. Temp. 98° ; Pulse 72 ; Resp. 14. Teeth irregular and decayed, tongue red and beefy, flatu- lent eructations after food, bowels regular, liver and spleen normal. Complains of giddiness, and is short of breath on exertion. Heart's sounds normal ; no cough ; some impaired resonance, harsh breathing, prolonged expiration, and slight crepitation at the right apex. Urine 264 oz., sp. gr. 1035, acid, clear, urea 07 per cent., very faint cloud of albumen, sugar 6'9 per cent. Progress of Case. — On Oct. 22nd he was put on six pints of skim milk daily. Oct. 23rd. He grumbled about his diet. DTABETIC COMA. 349 Oct. 24th. Complained of feeling low ; bowels open ; tongue still raw and beeiy. Urine 2160Z., sp. gr. 1033, acid, pale, straw colour, white flocculent deposit, urea o"9 per cent., a cloud of albumen, sugar 6'25 per cent., a trace of blood, and a few red and white blood corpuscles seen with the microscope. At 7.30 p.m. he complained again of feeling low, and of a pain in his bowels which he attributed to the milk, Oct. 25th. In the morning he made the same complaint, and said he was cold. His pulse was feeble, and his tongue dry, brown, and cracked. At 10 a.m. he was drowsy, and his respiration was rather deep. At 1 1.30 a.m. Pulse 160; Resp. 20; there was pain in the stomach and bowels; no urine passed since 8 a.m. He was ordered an enema to empty the bowels, a bottle of Vichy water to be taken with lemon juice in the course of the day, an alkaline injection {Sodii bicarb, gi-, ad. aq. Oss.) to be given by the bowel as soon as the rectum had been cleared out, and the following mixture every hour : I^. Etheris sulpkieris nixx ; Potassii hicarbonaiis gr. x ; Aqiiam ad. gi., M. In the course of the day the rectum was well cleared out and scybate removed, but he got worse, and at 8.45 p.m. I saw him again. Temp. 99° ; Resp. 24. He lay apparently asleep, but could not be roused. His breathing was very deep, but there was no special odour about him. His urine gave a well-marked acetone reaction. He was ordered liq. strychninse tii v. sub cute every fifteen minutes until muscular twitchings were produced. After three injections he spoke, and drank some Vichy water. At 9.25 he had another alkaline enema, containing one ounce of bicarbonate of soda. After this the strychnine injections were given irregularly at 10. lo, 10.40, 11. 10, 11.55, 1.50 a.m., and then not till 9 a.m. 26th. At 9.30 a.m. I saw him again. No physiological symptoms had been produced by the strychnine, so ten minims were ordered to be injected every half-hour. Pulse 128 ; Resp. 26 ; Temp. 99°. He was decidedly better, answered when spoken to, took beef tea very well. The knee jerks were absent. The strychnine was again neglected ; after I left it was given only every hour. His temperature had begun to rise. At 11.30 it was 102°; at 12.30, 103°; by 2 p.m. he was comatose again. Three ounces of urine were drawn off from his bladder; it was acid, sp. gr. 1023, and free from albumen and sugar. At 5 p.m. his temperature was 105^, and at 6 p m. reached 106"^. At 6.30 he was plainly dying ; the face was a little drawn to the left, and the right pupil was larger than the left. He died at 6.40 p.m. without any other change taking place. Autopsy. — A spare subject, somewhat emaciated, faint sweetish ethe- real odour emanating from cadaver, p.m. rigidity slight, hypostasis chiefly posterior. Brain Membranes. — Excess of serous fluid in subarachnoid space and in ventricles ; arachnoid very oedematous, cerebral convolutions well defined, no change to naked eye. The corpora striata and optic thalami showed no change on section except the "pin holes" described by Dickinson; these were certainly evident and scattered chiefly in the white substance of the internal and external capsule. Medulla : no change recognisable by naked eye ; it was kept for microscopic investigation. Pons normal. Heart — 8 oz., normal. Lungs. — Left upper lobe solid with caseous pneumonia ; the inter- lobular peribronchial fibrous connective tissue was likewise thickened. Pleura over upper lobe thickened and adherent ; lower lobe congested 350 DIABETES. and oedematous. Right Litiig : one or two small foci of caseous pneu- monia at apex. Liver. — 59 oz., surface of a dark reddish brown colour. Section : the organ was generally hypersemic, of a dark red colour, but scattered here and there in an irregular fashion were small yellowish patches corres- ponding to two or more lobules, where the liver cells microscopically were very fatty. Kidneys. — 10 oz., capsules stripped easily, both very dark from hyper- asmia, the streaky and punctiform distribution of which was very obvious.; the glomeruli appeared as minute red points, slightly elevated above the surface ; the medullary cones were of deeper hue. There was a faint sweetish ethereal odour emanating from the viscera. No mention of the condition of the pancreas or semi-lunar ganglia. Case 64. — Diabetes Melliiics—fainily history of phthisis — acetonuria — coma — strychnine i?ijections — oxygen i7ihalaiio7is — and intra-peritoneal alkaline injections — death — autopsy. Mary Ann M., aged thirty, screw-maker, was admitted into the General Hospital on September loth, 1889. complaining of great and increasing weakness, excessive thirst, and increased secretion of urine. These symptoms came on gradually four years a.^o, accompanied by low feelings, fainting fits, sickness, and shortness of breath. Her hunger was at that time so great that she could not get enough to satisfy herself, and she began to lose flesh, to sweat a great deal at night, and to suffer from a troublesome itching of the skin, which was worse at night. During the whole time her bowels had been very constipated, having been open only once or twice a week. Micturition had been very frequent and attended by smarting. For the last month there had been some pain and discom- fort after food ; and her ankles had got swollen after she had been standmg. Three days before admission she had felt so low that she had gone to bed, and had remained there ever since. Family History. — Father alive, but suffering from phthisis. Mother and seven brothers alive and well. Seven other children died young. Patient had been married ten years, but had had no children. Previous History. — Could remember no other illness. State on Admissio7i. — Patient was rather a spare woman with a flushed face. Temp. 99"5°; Pulse 88. Weighed 7 st. 5 lbs.; former weight 11 st. 4 lbs. There was a peculiar sweet smell emanating from her. Alime7itary Syste7n. — Teeth decayed posteriorly ; gums bled readily ; subject to toothache ; teeth were loose, but had got firmer ; a nasty taste in the mouth, worse in the morning ; mouth dry ; great thirst ; appetite voracious. Tongue large, dry, cracked transversely, and covered with thin dirty fur on dorsum. Some pain and discomfort after food. Stomach dilated, reaching nearly to umbilicus, with splashing sound on palpation. Liver dulness 4 inches in V. M. L. Splenic dulness not increased. Circ7elatory Syste77i. — No pain or palpitation ; some dyspncea. Area ot cardiac dulness not increased ; apex beat in fourth 1. S., inside the V. M. L. Sounds clear; pulmonary second accentuated. Pulse 96, not easily compressible. Res{>irato7y Syste7/i. — No cough, pain, or dyspnoea ; percussion note deficient in resonance at right base. Urinary Syste77i. — Urine 90 oz., sp. gr. 1034, acid, pale amber ; urea n per cent., a very faint haze of albumen ; sugar 5"4 per cent. DIABETIC COMA. 35' Treatment. — Diet: Mutton, meat jelly, milk two pints, cold meat two portions, Vichy water with lemon juice. Medicine : Ext7-acti bclladonnce gr. \ ; extract i aloes gr. iij. ; cuo/iyinini gr. j. ; in pill at bedtime. July 15th. Complained of feeling very sick ; ordered an enema, which brought away a motion containing a lot of hard lumps. Urine 1025, highly acid ; contained a haze of albumen, gave a deep Burgundy red coloration with ferric chloride, and a moderate rose-violet coloration with nitro-prusside of sodium and ammonia. At ?too/h face flushed, epigastric pain, pulse 132, tongue dry, respiration 24, sighing. Ordered, liqtions strycJmincE iflv., sub cute quartis Jioris j and to continue the Vichy water without the lemon juice. Later in the day her extremities got very cold. July i6th. 4 a.m., was conscious ; 8.30 a.m., pulse scarcely percep- tible ; hands not cold ; unconscious ; passed water in bed. Respirations irregular, but not Cheyne-Stokes' type. Pulse 128; Resp. 32. 10 a.m., extremities cold. 10.30, passing plenty of water in bed ; swallowing difficult. Strychnine to be injected every half-hour. This was done legularly until 4.35 p.m. inclusive, except at 3.30. 11.30. Oxygen was administered by means of a nitrous oxide gas apparatus. During the inhalation the pulse became weaker. The whole of the oxygen contained in a cylinder was given, but without the slighiest benefit. 3.30 p.m. A solution of bicarbonate of soda (two oz. of the salt dissolved in two pints of water at 100° F.) was slowly introduced into the peritoneal cavity. 4.15 p.m. No result having followed the first injection, two pints more were introduced. The patient seemed better. She took some milk and beef tea ; and just as there seemed a ray of hope that at least temporary improvement had been secured, she quite suddenly looked worse, there was a slight spasm of the muscles of face and left arm, and she died in spite of the prompt injection of a syringeful of ether. Autopsy. — A spare but fairly nourished woman. Abdomen distended, and on opening it a large quantity of yellowish tinged fluid escaped. The retro-peritoneal cellular tissue was much infiltrated with fluid, also the deep fascia and inter-muscular connective tissue of the lower part of right side of thorax. Brain. — 46 oz., anaemic, nothing abnormal recognised with naked eye. Pons and medulla preserved. Heart. — 8J oz., L. V. was firmly contracted and appeared thicker than normally, measuring nearly j-^ inch. No valve lesions, heart otherwise quite healthy. Lungs. — 2 lbs., both congested ; hypostasis of the bases. Liver. — 65 oz., much engorged with blood. Veins dilated. Colour of parenchyma a dark reddish brown, but mottled here and there with yellowish patches. Kidneys. — 15 oz., large, capsules tense, slightly sticky. On section both looked fatty. Cortex increased and variegated by deep red striae alter- nating with an opaque yellowish grey labyrinth, both considerably congested. Pa?tcreas. — 2% oz., small, gland substance looks shrunken, consistence generally tough and fibroid, cuts with perceptible resistance to knife's edge. Semilunar ganolia. — Looked small, weighed together 57 grams. Stomach. — Much distended, partly with a dark brown grumous fluid ; mucous membrane pale but remarkably mammillated. 352 DIABETES. Case 65. — Diabetes Mellitus— heredity — vertigo — diarrhcea— aceionuria — sickness — coma — 7io ferric chloride reaction — intra-periio7teal injections — death — autopsy. Amelia P., aged thirty-seven, domestic servant, was admitted into the General Hospital October 23rd, 1889, complaining of hunger, thirst, wasting, and polyuria. These symptoms had existed for ten months. Previous History. — She could remember no previous illness or injuiy ; her health had been good, but she was subject to frontal headaches. Six years ago she had an " abscess " over the left eye, and the pain had been worse in that spot ever since. She had worn spectacles since she was twelve years of age, and had supported herself since she was thirteen. The work had been hard, and she had had a good deal of worry, but had always plenty to eat. She had been accustomed to take very little beer, about one glass for supper. Family History. — Father died of bronchitis, aged fifty-three. Mother died of diabetes, aged thirty-seven ; in the latter part of her illness she had many "fits." One brother died in the General Hospital after an accident ; two others were living in good health. She did not know of any insanity or phthisis or any other case of diabetes in the family. State 071 Ad77iissio7t. — A small, slightly developed woman. Weighed 6 St. 10 lbs., but used to weigh 8 stone or more. She looked wasted. Her face was a peculiar brownish yellow colour, which she said was a recent change ; her cheeks were flushed and her lips red. Eleven days before admission she had a fit of giddiness in which she fell down and abraded the skin on the bridge of her nose. She believed that she lost conscious- ness completely. Temp. 97°, Pulse 84, Resp. 18. Alime7itary Syste/n. — She was very hungry, craving food every two hours, and her thirst was also great. Bowels regular. Tongue pretty clean, furrowed, dry. Teeth defective, decaying. Flatulence after eating, but no pain or tenderness. She had had one or two severe attacks of diarrhoea. Abdomen not distended. Liver dulness in V. M. L. 3^ inches. Splenic dulness in M. A. L. i^ inches. Circulatory Syste7ii.- — Heart's area not increased. Apex in fourth I. S. in V. M. L. Sounds normal. Pulse 84, regular, small and soft. Respi7'at07y Syste7n. — Chest movements normal, no cough. Percussion and breath sounds normal. Ge7iito-uri7tary Syste7n. — She had not menstruated since November (12 months) ; no vaginal discharge. Frequent micturition. Urine 244 oz., sp. gr. 1035, acid, pale yellow ; urea o'8 per cent., no albumen ; sugar 57 per cent., acetone present, no deposit. Treatment. — Diet: Meat, beef jelly, fish, chicken, two eggs, no bread or vegetables, toast-water, Vichy water and lemon juice. Medicine : Ext. opii gr. j. ; twice daily. Progress of Case. — Oct. 26th. Between 3 and 4 a.m. she had a seveKe attack of diarrhcea, followed by a feeling of sickness, and was drowsy and heavy all day. Complained of being hot and feverish, but temperature was 98-5°. Oct. 27th. Complained of sickness and a sinking feeling ; ordered half a pint of milk, an effervescing mixture, and some gluten bread. Oct. 28th. She would not eat the meat alone, so was allowed green vegetables, and as no gluten bread had arrived, two small slices of toast were allowed. DIABETIC COMA. 353 Oct. 29111. Sick a.qain in ihe morning. Respiration sighing at times towards evening. Oct. 30th. Was restless and moaning all night. Between twelve and one she was delirious, screaming and trying to get out of bed. Respira- tion was sighing, 20. Pulse 96. Hands and feet cold; not conscious. No water had been passed since 9 p.m. 1 1 a.m. she was lying quietly, respiration sighing, face pale, extremities cold ; no pecuUar odour of lireath. Urine, drawn off by catheter, 7 oz., pale, greenish, clear, acid, sp. gr. 1017, a cloud of albumen, loaded with sugar, faint acetone reaction with nitro-prusside of sodium, no reaction with ferric chloride. 11.45, almost pulseless ; a syringeful of ether was injected subcutaneously. 12.15, two pints of the following solution, at the temperature of the body, were injected into the peritoneal cavity : — Sodii sulphatis ; sodii bicar- bonatis aa 5j. ; aquce biillientis Sviij. ; solve ; adde aquse distillatse, Oj. This was followed by no improvement, and she died at 2.15 p.m. the same day. Autopsy. — Height, 60 inches ; circumference of chest, 27 inches ; rigidity well marked ; puncture seen in linea alba midway between umbilicus and pubes. Thorax. — Heart 7 oz. ; large milk spot over right ventricle ; much fat over right ventricle externally. Left ventricle, heart substance slightly fatty ; mitral valve normal ; aortic valve normal and competent, com- mencing atheroma at the beginnmg of the aortic arch. Right ventricle contained very dark p. m. clot; tricuspid and pulmonary valves competent and normal ; auricles normal. Left lung : 8 oz. ; substance healthy ; no bronchitis ; was bound down to chest wall by few adhesions. Right lung : 10 oz. ; normal. Abdo7nefi. — Liver; anterior surface adherent to the diaphragm. On section, consistence rather tough. Groups of lobules appeared trans- lucent surrounded by yellow streaks. Gall-bladder collapsed; on squeezing it yellowish-green bile exuded. Right kidney: 6 oz. ; capsule slightly adherent, taking away a little kidney substance ; cortex pale yellow ; interpyramidal cortex the same, streaked with translucent yellow lines ; malpighian bodies very prominent through the whole cortex, arranged in rows ; pyramids lightish red, streaked with yellow. Left kidney: 6^ oz. ; same condition as right. Brain. — 3 lbs. ; subarachnoid fluid over both hemispheres. Section showed brain substance slightly congested. Right semilunar ganglion somewhat larger than left. Conclusions. — The following conclusions summarise brief- ly the most important facts contained in this long chapter : — 1. Diabetic coma is specially apt to supervene in acute cases in young persons. 2. Diabetic patients and their friends should be warned of the danger of constipation, muscular fatigue, nervous exhaus- tion, and cold, as probably predisposing causes of death by coma. 3. The discovery of the ferric chloride reaction in the urine should be taken as a warning against the premonitory symp- toms of coma. 354 DIABETES. 4. Deep respiration, rapid pulse, and abdominal pain are the earliest premonitory signs of this condition. 5. Cyanosis is absent in spite of the dyspnoea, but may appear just before death. 6. Convulsive seizures are not an uncommon occurrence just before death. 7. The temperature is usually normal or sub-normal, but may be considerably raised. 8. Diabetic coma, with all its classical symptoms, occurs independently of any excess of fat in the blood, and the patho- logical value of lipaemia, when present, is yet undetermined. 9. The toxaemic theory, e.g.^ poisoning by acetone, or yS-oxybutyric acid, or some nearly allied substance or sub- stances, affords the best explanation of this remarkable group of symptoms. 10. Recovery is possible from the prodromal symptoms, and even, from some degree of drowsiness, but from actual coma it is at least very rare. 11. Great benefit may ensue in the early stages from speedy evacuation of the bowels by a brisk purgative. Treatment in the later stages seems always unavailing. BIBLIOGRAPHY. BiNZ. Pathology of Diabetic Coma. " Cong, fiir inn. Med. Wiesb.," ,i885. Bond and WiNDLE. Diabetes terminating by Coma. "Brit. Med. Jour.," 1883, I., p. 908. Buhl, Ueber diabetisches Koma. " Zeit. f. Biol.," Bd. XVI., 1880. Bull (G. C). A preliminary Report on the presence of Acetone in the Urine. " Birm. Med. Rev.," Vol. XVII., 1885, p. 211. Cantani (A.). Der Diabetes mellitus. Berhn, 1887. Charcot (J. M.). The Causation of Diabetes. " Journ. de Med.," April, 1883. Cyr. De la mort subite on tres rapide dans le Diabete. " Arch. Gen. de M6d.," 1-877, II- and 1878, I. Dreschfeld (quoted by Gamgee, A.). A Text-book of Physiological Chemistry of the Animal Body. London, 1880. Dreschfeld (J.). The Bradshaw Lecture on Diabetic Coma. "The Lancet," 1886, II., p. 369. Ebstein (W.). Ueber Drusen-Epithelnekrosen beim Diabetes mellitus, mit besonderer Beriicksichtigung des diabetischen Coma. " Deutsches Archiv f. klin. Med.," Bd. XXVIII. , 1881, p. 143. Fagge (C. Hilton). Op. cit. Fleischer (R.). Beitrag zur Chemie des diabetischen Harns. " Deut. med. Woch. ," 1879, No. 18. Foster (B.). Diabetic Coma — Acetonsemia. " Brit. Med. Jour.," 1878, 1., p. 78. Foster and Saundby. Diabetic Coma. " Birm. Med. Rev.," Vol. XIII., 1883, p. I. DIABETIC COMA. 355 Frerichs. Plotzlicher Tod und Coma bei Diabetes. " Zcit. fiir klin. Med.," Bd. V.. Heft i. 1883. Hesse. Coma benefited by intra-venous injection of 4 per cent, solution of Carbonate of Soda. " Berlin, klin. Woch.," No, 19, 1888. HlKSCIIFELD (F.). Op. cit. Hoppe-Seyler (G.). Uebsr das Auftreten acetonbildender Substanz im Urin nach Schwefelsaurevergiftung. " Zeit. f. klin. Med.," Bd. VI., p. 478. Jones (H. Bench). On Animal Chemistry, in its application to Stomach and Renal Diseases. London, 1S50. KOssMAUL. Zur Lehre vom Diabetes mellitus. " Deut. Archiv f. klin. Med.." 1874. L.\THAM (P. W.). Pathological relation between Diabetes, Gout, and Rheumatism. "Brit. MeJ. Jour.," 18S5, H., p. 105s. Le Nobel (C). Ueber einige neue chemische Eigenschaftsn des Acetone und verwandter Substanzen und deren Benutzung zur Losung der Acetonurie- frage. " Archiv f. exp. Path.," Bd. XVHI., Heft i and 2. Lepine (R.). Sur la pathog^nie et le traitement du coma diab^tique. " Revue de Med.," Vol. VII., 1SS7, p. 224. LiTTEN (M.). Ueber einen eigenartigen Symptomencomplex in Folge von Selbstinfection bei dyspeptischen Zustanden (Coma diabeticum). " Zeit. f. klin. Med.," Bd. VII. Mackenzie (S.). The Pathology of Diabetes. "Brit. Med. Jour.," 1883, I., p. 655. Minkowski (O. ). Ueber das Vorkommen von Oxybuttersaure im Harn bei Diabetes mellitus. Ein Beitrag zur Lehre von Coma diabeticum. "Arch. f. exp. Path.," Bd. XVIII., 18S4. Minot (F.). Sudden Death in Diabetes. " Boston Med. and Surg. Jour.," Jan. 19th, 1888. MoTT (F. W.). Four cases of Diabetic Coma. " The Practitioner," Vol. XL., p. 420. NOORDEN (C. VON). Op. Clt. Penzoldt (F.). Ueber den diagnostichen Werth d. Harnreaktion mit Dia- zobenzolsulphosiiure u. iiber deren Anwendung zum Nachweis von Trauben- zucker. " Berlin, klin. Woch.," Bd. XX., 18S3, p. 14. Prout (W.). On the Nature and Treatment of Stomach and Renal Diseases. Fifth edition. London, 1848. Quincke (H.). Ueber Coma diabeticum. " Berl. klin. Woch.," Bd. XVII., 1880. Reynold (E. S.). On the Treatment of Diabetic Coma. "Med. Chron.," 1891, p. 338. RiCKARDS (E.). A case of Diabetes, terminating suddenly with milky blood. " Birm. Med. Rev.," Vol. XL, 1882, p. 271. Roberts (Prescott). A case of Diabetic Coma. " Brit. Med. Jour.," 1882, II., p. 1058. Roberts (W.). Urinary and Renal Diseases, Fourth edition. London, 1885. Roque Devic. Op. cit. Salkowski and Leube. Die Lehre vom Harn. Berlin, 1882. Salomon and Brieger {vide Frerichs). " Plotzlichen Tod und Coma." Sanders and Hamilton. Lipaemia and Fat Embolism in the Fatal Dyspnoea and Coma of Diabetes. " Edin. Med. Jour.," Vol. XXV., 1879, p. 47. Saundby (R.). Diabetic Coma. " Birm. Med. Rev.," Vol. X., 1881, p. 193. and Barling. Fat Embolism. " Jour, of Anat. and Phvs.," Vol. XVI., 18S2, p. 515. Sudden Death in Diabetes. " Birm. Med. Rev.," Vol. XV., 1884. p. 148 356 DIABETES. Saundby (R.)' Kiissmaul's Coma. Ibid., Vol. XVII., 1885, p. 49. ScHMiTZ (R. W.). On a frequent and noteworthy Complication of Diabetes IMellitus. "Berlin, klin. Woch.," Jan. 31st, 1876. . Zur Behandlung des Coma diabeticum. " Berlin klin. Woch.," 1890. Senator. "Ziemssen's Cyclopaedia." Vol. XVI., p. 916. . On self-infection by the products of abnormal processes of de- composition within the body, and the resulting (Dyscrasia) Coma (Kiissmaul's Diabetic Coma). " Zeit. f. klin. Med.," Band VII., Heft 3. Stadelmann. Coma diabeticum und seiner Behandlung. " Deut. med. Woch.," 1889, No. 46. " Deut. Archiv f. klin. Med.," Bd. LXXXVI., Heft 6. Stockvis and Hoffmann. Zur Pathologie und Therapie des Diabetes mellitus. "Cong, fiir inn. Med. Wiesb.," 1886. Taylor (F.). On the fatal termination of Diabetes : with especial reference to the death by Coma. " Guy's Hosp, Rep.," 3rd S., Vol. XXV., 1881. Von Jaksch (R.). Ueber Coma carcinomatosum. " Wien. med. Woch.," 1883, Nos. 16 and 17. — . On the red colour produced in Diabetic Urine on the addition of Chloride of Iron. "Zeit. f. Heilk.," Bd. III. . On the presence of Aceto-acetic Acid in the Urine. " Zeit. f. phys. Chem.," Bd. VIII., Heft 6, 1883. Walter. Untersuchungen fiber die Wirkung der Sauren auf den thierischen Organismus. "Arch. f. exp. Path.," Bd. VII. Windle (B. C. a.). On the Ferric Chloride Reaction in Urine. " Livsi. Med. Chir. Jour.," Vol. IV., 18S4, p. 34. 357 Chapter XXI. TREATMENT OF DIABETES. The treatment of diabetes has fortunately been evolved independently of those physiological controversies respecting the pathogenesis of the disease which seem to be as far as ever from an end. The meat diet of Rollo and the gluten bread of Bouchardat were introduced years before CI. Bernard made his discoveries, and owe nothing to him or his successors, and we ought to be very unwilling to admit the right of either side in this dispute to dictate to clinicians in this department at least. Our modern treatment is based upon two sound clinical observations, viz., the value of nitrogenous diet and of opium or its alkaloids in controlling the symptoms of the disease. But experience has modified the conclusions to be drawn from these observations, and although they constitute the ground-work of every modern system for the treatment of diabetes, we follow neither in its original simplicity. Diet. — We have learnt that while strictly nitrogenous diet is by no means always able to remove all the sugar from the urine, every diabetic retains the capacity to assimilate a certain amount of carbo-hydrates ; moreover while a strictly nitro- genous diet is badly borne by most patients and can rarely be enforced for more than a short time, a suitable addition of carbo-hydrates improves the general health, makes it possible to secure conformity to dietetic rules for any desired time and does not aggravate any of the symptoms of the disease. There has been during the present century a gradual tendenc}' in this direction, and at the present time our differences in practice are not nearly so great as our differences in theor>'. The orthodox diabetic dietary, as set forth in most text- books, is very varied and liberal when compared with Rollo's exclusive meat diet, and if we venture to-day to go a step further and claim for each diabetic as much liberty as experi- ence shows he may be safely allowed, it is only in harmony with those general principles which we admit when we declare that we try to treat, not the disease, but the patient, and lo adjust our remedies and our doses to his individual wants. 333 DIABETES. When a case comes first under observation and the diag- nosis has been made, it is very desirable to find out the effect of diet ; for this purpose the strict anti-diabetic diet should be ordered (see page 359). Of course there may be occasions, as in acute disease, extreme weakness or impending coma, where such an investigation would be out of place. But in most cases this should be done, and the patient be requested to adhere closely to the diet for seven days ; he may be encouraged to do this by the promise that these rules will be gradually relaxed as his condition permits it. At the end of a week the urine must be collected for twenty-four hours and the total daily amount of sugar calculated in grains. We may then make an addition of some carbo-hydrate, and I know nothing safer or more agreeable to the patient than a large baked potato to be eaten at dinner. Laevulose, in quantities up to i| oz. daily, is much appreciated, especially by children. When these have been shown to be tolerated, we may in all but the most severe cases try the effect of permitting bread in the form of thin, very dry toast, of which I \ oz. may be allowed three times a day. The effects of each of these additions must be ascertained by careful estimation of the total daily quantity of sugar eliminated at least once a week. The following examples illustrate this method of proceeding and show that patients who pass a large quantity of sugar on an ordinary diet may pass very little when taking a properly limited amount of bread and potatoes. Case 66. — Mr. T. S. W., aged 55, is engaged in large commercial transactions ; a moderate case of diabetes in an elderly man. On ordinary diet, urine 84 oz., sp. gr. 1025, contains 2016 grs. of sugar; on strict diet, urine 78 oz., sp. gr. 1018, contains a mere trace of sugar. On adding to this diet one large baked potato and 4^ oz. of toast, estimated to contain about 1500 grains of starch, the urine contained only 2^ grains of sugar per ounce, or not more than 250 grs. of sugar at the outside. Case 67.— Mr. D., setat 50, a slightly more severe case of the same type ; on ordinary diet passed 3360 grs. of sugar ; on strict diet 576 grs., and on the same with the addition of toast and potato, as described, 672 grs., that is the addition of 1500 grs. of carbo-hydrates caused an increase of less than 100 grs. of sugar 1 Case 68.— Mrs. B., setat 49 : — On ordinary diet On strict diet - - - - Urine. 70 OZ. 50 oz. Sugar. 3360 grs. a trace „ ,, with one potato - 4i oz. of toast added - - - 42^ j> >j » ' 50 oz, 50 oz. 28 grs. 360 grs. 55 oz. 242 grs. TREA TMENT. 359 Such cases are of course readily amenable to treatment, but the following are more serious examples : — Case 69 — E. C, aged 33, ill ten months, has lost two stone in weight, under strict treatment. Uiine, 130 oz., sp. gr., 1028, contains 1872 grs. of sugar. On adding first one then two baked potatoes to his daily diet he improved in health and the sugar fell to 1056 grs. daily. Case 70. — K. j\I. C, aged 8, a tolerably acute case of diabetes with considerable loss of strength, irregularly dieted. On strict diet, kept up with difficulty, daily sugar excretion 1872 grs. ; with two baked potatoes daily she gained 7 lbs. m weight, and passed only a trace of sugar. Several of these cases show that the addition of carbo- hydrates caused some increase of glycosuria, when compared with strict diet, but in every instance it is obvious that the in- crease only represents a small part of the carbo-hydrate ingested, the balance having been used up in the body. The effect of strict diet in controlling glycosuria is a very valuable measure of the severity of the case and an indi- cation how far we may safely go in adding carbo-hydrates. That is to say, the less the effect, the smaller room is there for any such addition and the greater the need for caution in proceeding. Strict Diet. — By this I mean a dietary which is by no means free from sugar-forming substances, but one as free as it is desirable to insist upon. I give my patients a printed slip of paper upon which the following list is printed : Meat soup, beef tea, fish of all kinds, butcher's meat, poultry, game, eggs, green vegetables, seakale, celery, salad, milk (i pint), cream, custard, butter, cheese, cream cheese, jelly, isinglass blanc mange, Irish or Iceland moss, Callard's brown loaf or almond biscuits, tea, coffee, claret, still moselle, hock, brandy, whiskey, mineral waters ; and a footnote points out that no sugar must be employed in the preparation of any of these articles, but saccharin may be used if desired. Fat of any kind, fat bacon, butter, cream, or even cod-liver oil may be allowed with advantage on the strictest diet, although unhappily in severe cases the power of assimilating fat is often greatly diminished. It is a most important and difficult question how to supply diabetics with a suitable bread substitute when they are unable to assimilate a minimum quantity of ordinary wheaten bread. There is no lack of articles purporting to supply this want, but they vaiy as the following analyses show, and some, as the Lancet has pointed out and I have unhappily too often observed, are neither more nor less than frauds, while the best ^6o DIABETES. are very expensive, so as to be quite beyond the reach of the poorer classes. Analysis of Glutem Bread. French. Moisture Sugar Fat Insoluble carbo-hydrates Gluten Ash Samples dried at 21: Gluten ... ... ... ■.. ...I Insoluble carbo-hydrates... ... ...' 9-30 2-50 2-50 33-28 49-62 2-80 5471 56-60 Engli.sh. 9-0 ro 14-3 27-4 55-5 1-8 55-5 27-4 I have quite given up the use of gluten bread as the best contains nearly 30 per cent, of starch; it is always unpalatable and relatively to its dietetic value absurdly dear. In those cases where I wish to try the effect of strict diet 1 recommend Callard's starchless brown loaf and biscuit food, or biscuits made with almond flour or cocoa-nut flour, to which a little gluten flour or aleuronat flour* may be added. Analyses of Callard's Brown Loaf and Biscuit Food. Moisture (212° F.) „ Mineral matter Fat Starch Nitrogenous matter Cellulose P.rown Loaf. Biscuit Food. 39'5o7o 3'30 34-00 675 1 16-45 8-4% 2.5 12-5 6-6 66-6 3-4 The following directions may prove useful to patients who wish to make such biscuits or cakes at home : — (i,) Almond Cakes. One pound of ground almonds, four eggs, two tablespoonsful of milk and a pinch of salt are required. Beat up the eggs and stir in the almond flour, divide into cakes and bake in a moderate oven for forty-five minutes. * Aleuronat is the patent name of a gluten flour obtained as a by- product in a starch factory. It is strongly recommended by Prof. Ebstein and can be obtained from the diabetic food shops. TREA TMENT. 361 (2,) Cocoa-nut Cakes. Three-quarters of a pound of dried cocoa-nut, one quarter of a pound of ground almonds, six eggs, and half a teacupful of milk. Mix as before and bake for twenty-five minutes. (3,) The same. Half-a-pound of dried cocoa-nut, half-a-pound of aleu- ronat, tour eggs, and a little water sweetened with saccharin. Mix, divide mto cakes and bake (Williamson). Any of these cakes can be sweetened with saccharine or glycerine. It is of importance that the cocoa-nut and almond flour should be tested by the addition of iodine for starch and by boiling with Fehling for sugar before it is used, as adulterations are common. Certain writers have ventured to recommend Semolina and " Florador " as suitable for diabetes, but the untrustworthiness of the advice is shown by the following analysis : — Moisture Mineral matter Fat Carbo-hydrates Nitrogenous matter Semolina. Florador. 12-2% V\ 07 74-5 11-5 1 1 '00% 0-8 0-25 75-55 12-40 The use of "Soy" beans was advocated some few years ago by Dujardin-Beaumetz. These resemble the haricot bean, and are obtained from Soya Hispida, a plant originally brought from China and Japan, but now cultivated in Austria. When originally introduced it was recommended on the ground that it contains only 2 per cent, of starch, but this statement is very misleading, as is shown from the following analysis by Professor Kinch, given in Professor Frankland's " Agricultural Chemistry," which I have had verified : — Analysis of Soy Beans: — Water - - - •• - ii'3 Nitrogenous matter - - - 37"8 Fat ------ 20-9 Carbo-hydrates - 24*0 Fibre ----- 2'2 Ash - - - . - 3-8 This great discrepancy is accounted for by the presence of a mucilaginous substance, convertible into sugar, and therefore equally obnoxious to. a diabetic. Articles made from this bean should not therefore be allowed to patients on strict diet ; but those on a modified diet may take them if they like. Some of my patients have disliked the flavour and in others their use has been followed by relaxation of the bowels. 362 DIABETES. Modified Diet. — In severe cases it is necessary to be ex- ceedingly cautious in the addition of starchy food. Lcevulose, which was recommended by KUlz in 1874, has only recently become available as an article of food. It is now sold in two forms: (i,) as a white, coarse, granular powder, slightly sweet, and perfectly agreeable, the laevulose of Schering and Glatz ; (2,) Haycraft's laevulose, a treacle-like substance pre- pared by Allen and Hanbury. They are equally good and supply carbo-hydrate in a form which diabetics appear able to assimilate in limited quantities {\\ oz.). Testimony to its utility and harmlessness has been borne by several writers as well as by myself, and I think it decidedly preferable to saccharin. The following table from de Nedats, quoted by Dujardin- Beaumetz, shows the amount of starch in various vegetable substances : — Rice ... Maize Wheat flour - Wheat meal - Rye flour Millet Buckwheat - Wheat bread Oatmeal Peas - - - Rye bread Haricots Jerusalem artichokes Potatoes Potatoes therefore occupy the first place from this point of view, and I have already quoted several cases which show their effects. The three following cases were all severe, two proved subsequently fatal, and the other was quite unable to eat toast, yet they all bore the addition of potatoes well. Case 71. — H. G., astat 36. 74*io per cc 65-90 5> 63-00 >» 59-60 :» 59-84 It 57-90 )> 50-00 )> 42-70 5J 39-10 5> 37-00 11 36-25 r» 36-00 11 i6-6o 11 15-50 11 Average Average Diet. Duration. Urine. Sugar. Weight. Strict 4 days 135 OZ. 5872 grs. 6 St. 13 lbs. With potatoes 15 5) 132 oz. 3455 grs. 7 St. 4 lbs. Strict 13 11 136 oz. 4283 grs. 7 St. 4 lbs. With potatoes 9 11 127 oz. 4141 grs. 7 St. 2 lbs. Case 72.— A. J. With potatoes II 11 87 oz. 2376 grs. 5 St. I lb. Strict 57 11 84 oz. 2498 grs. 5 St. 5 lbs. With potatoes 15 11 ^^ oz. 1625 grs. 6 St. I lb. TREA TMENT. 363 Case 73 — A. M., netat 21. Diet. Duration. Avge. Urine. Avge. Sugar. Weight. Strict - 12 days 91 oz. 2053 grs. 9 st. 2 lbs. With I potato 6 „ 63 oz. 1989 grs. 9 st. 5 lbs. „ 2 potatoes 26 „ 77 oz. 1798 grs. 9 st. 10 lbs. DaJilia tubers have been suggested as vegetables, and have been shown to be of service (Hale White), but are not ordinarily available. This difficulty does not apply to Jeru- salem artichokes, which may be tried in definite quantities. Milk may always be allowed, but i-^- pints daily should not be exceeded. The skim milk treatment which was at one time in vogue cannot be recommended. But milk is well known to be a valuable article of diet ; it contains a certain amount of fat, milk sugar, and lime salts. Toralbo has drawn attention to the great loss of lime salts in diabetes, and Grube has suggested that milk may be useful to com- pensate for this waste. Some authors insist on the use of alcohol as a substitute for carbo-hydrate, but I have little experience of its actual utility. Most patients wish to take some, and when no contra-indication exists, such as gastritis or albuminuria, I am in the habit of allowing whiskey, unsweetened gin, brandy, Rhine and Moselle wines, Bordeaux claret, and "sans Sucre " champagne ; of course in limited quantities, such as half a bottle of wine, or from two to four ounces of spirits daily. In very mild cases Bass's beer which contains only a very little sugar, may be permitted, but it must be given with caution, not more than a pint daily, and its effect on the urine determined. Purdy recommends Budai, a Hungarian wine, and the Diatetischer Rothwein as being quite free from sugar. But no restriction should be placed on non-alcoholic beverages which do not contain sugar. It is cruel to interfere with the craving to satisfy thirst, which is the result of the withdrawal from the body of large quantities of water. All mineral table waters are permissible, and those which contain alkaline carbonates do good by helping to keep up the alkalinity of the blood. They may be suitably taken with wine or spirits at meals, or where no alcohol is taken, with lemon juice or a slice of lemon. Hot water poured on a slice of lemon makes a drink which many persons like. Climate and Mineral Waters. — No one would be so bold as to contend that the climate of every part of these islands is at all times of the year the best that can be obtained by those who have the means to live where they 364 DIABETES. please, so that although diabetes is not a disease which is influenced specially by soil, altitude or temperature, some patients may enjoy much better general health and derive real benefit in other places than their own homes. I am strongly of opinion that life in the open-air is of the utmost importance ; diabetics should therefore, if possible, live where they can be a great deal out-of-doors. But severe cases stand the fatigue of travelling very badly, and there are many others who would be imprudent to leave the comforts of their own homes, the affectionate care of their relatives, and the wise ministrations of a well-tried medical friend, to exchange these for li''e in hotels or lodgings, and the attend- ance of strangers. No diabetic should leave home who is not in fair health, and in possession of sufficient means to procure all necessary comforts. In winter such a patient may find a more genial climate than that in which his home is situated at one of our own south coast watering-places, or in Madeira, the Canaries, the Riviera, Algeria or Egypt He must travel by easy stages and take with him proper food supplies to maintain his dietary while on the journey. If he is a good sailor he will find it better to go all the way by sea, than to travel overland. In the summer he may go to one of the spas where diabetes is made a special subject of treatment. The nearest of these is Neuenahr, close to the Rhine and only a short distance from Cologne. In this pretty little town he will find him- self amongst pleasant health-giving surroundings, in a district which affords innumerable charming walks and excursions, and at the same time he will be able to obtain excellent treat- ment for his malady. The waters, whose chief constituents are chloride of sodium and the carbonates of iron and sodium, are highly charged wiJi carbonic acid gas, and are not un- pleasant to drink. The hotels and gardens are good. The season is from May to October, but July should be avoided on account of the great heat. The district abounds in mineral springs, the celebrated ApoUinaris well being only a few miles away, and this as well as many others afford a great variety of good table waters. But diabetics may and do go to many of the other Rhenish watering-places, and I see no reason why diabetes should not be treated as well, for example, at Homburg as at Neuenahr. Almost identical waters are found at both, the climatic conditions are much about the same, and English TREA TilIENT. 365 people may prefer a place where they may meet plenty Oi'" their acquaintances, and where the hotels conform to Enc,^lish ideas ; but after all it is mainly a preference for the local doctor that determines our selection. Carlsbad, in Bohemia, has a great reputation for the treat- ment of diabetes, which seems to me to be due in a great measure to the very able physicians who come there during the season to attend the crowds of patients who flock to this favourite Austrian spa. The chief constituent of the waters is sulphate of sodium, and the different springs vary only in the quantity the}- contain. The place is well situated, the season is the same as at Neuenahr, and a visit there may be made very enjoyable, but the journey is a long one, the regimen is strict, the mode of living German, and prices arc very high. Marienbad, its neighbour, is a little Carlsbad, with the same waters, but over-shadowed by its fashionable rival. Carlsbad is eminently the place for diabetes associated with obesity, gastritis or liver disease. Vichy (Departement Allier), the most famous of all French watering places for the treatment of diabetes, is not so popular as it was formerly with English doctors and patients. This is possibly due to the great advances which German medicine has made during the last fifty years, which have deprived France of her former place of proud pre-eminence on the Continent, or it may be that fashion has changed. Vichy is still as charming as ever, its etablisseiuent as well managed, its waters as suitable, and it is certainly more accessible. The Vichy waters have for their principal con- stituent bicarbonate of soda, and are highly charged with carbonic acid gas. The season is from April 15th to October 15th, but the great heat in July and August renders these two months unsuitable. La Bourboule and Chatel-Guyon, both in the department of Puy de Dome, are not very far from Vichy, and have com- paratively modern reputations for the treatment of diabetes. The former is a small village 2790 feet above the sea level. Its waters contain chiefly chloride and bicarbonate of sodium with traces of arsenic, to which last ingredient great importance is attached in the treatment of diabetes. Chatel-Guyon is a small town, 1300 feet above the sea. Its waters resemble those of Carlsbad, but are weaker and highly charged with carbonic acid gas ; they vary in temperature from 82° to 95° F. Contrexeville in the Vosg-es is a somewhat fashionable 3G6 DIABETES. resort for diabetic and gouty patients ; the waters contain bicarbonates and sulphates of hme, magnesia, and iron ; the different springs vary somewhat, some containing more of certain constituents than others ; traces of arsenic are said to be present. It cannot be said that the specific effect of any of these waters has ever been demonstrated satisfactorily, but patients who go to these places find themselves able to spend the whole day in the open-air ; their meals are served in gardens or on terraces ; they get up earl}^, live temperately, enjoy a very unwonted amount of sunshine, drink only light wines, in many places the growth of the neighbourhood, and take under medical advice draughts of, for the most part, innocuous waters. No doubt the waters at some of these places are not to be trifled with, notably those of Carlsbad, and are not to be recommended to weakly or nervous patients. To stand the Carlsbad cure a patient should possess a good margin of strength and stability, and many would do well enough at Neuenahr or Homburg whom a course at Carlsbad might injure. Patients who are unable to visit these places may try the effect of the waters at home, but from what has been said above, divorced from their surroundings they do not promise much benefit. The waters of La Bourboule, Vichy, and Contrexeville may be used as table waters to mix with wine or lemon juice ; and Carlsbad water or Carlsbad salt or the water of Chatel-Guyon may be employed as aperients when such remedies are needed. Exercise and Fresh Air. — Although I have already expressed my opinion of the great importance of these for the maintenance of health in diabetes, it is desirable to emphasize it by a separate paragraph. Sedentary modes of life seem most favourable to the development of diabetes, while those who labour in the open-air rarely suffer. Open-air life must therefore be insisted upon, but the amount and nature of the exercise may vary. In particular we must enjoin abstinence from pursuits or exercises requiring strenuous exertion or involving great effort. In all cases the exercise should be regulated so as to avoid fatigue. The evil effects of over- exertion in precipitating fatal coma have been already com- mented upon and illustrated, but apart from such tragic results, excessive exercise may cause loss of strength and weight which is never res^ained. TREA TMENT. 367 Baths. — Diabetic patients often derive great comfort from bathing. A hot-water bath is the simplest, and most suit- able for severe cases. Fat diabetics may use the Turkish bath with benefit. The Russian or vapour bath is also valuable. This treatment is specially indicated where the skin is dry and irritable. Massage has been strongly recommended by Finkler, as not only causing a general improvement in health and strength, but as leading to diminution of sugar, which in one case entirely disappeared. i\ye has more recently published a case in which considerable benefit followed this mode of treatment, so that he was able to give up his dietetic regimen and discontinue the use of opium. The plan is worthy of adoption, but we must not expect too much from it. Drugs. — We may now pass to the important subject of the specific treatment of the disease by drugs. Two things are aimed at by their use — the limitation of the urinary secretion, and the diminution of the amount of sugar. Of many remedies suggested there are four which claim the chief share of our attention. Opium is the oldest, and still retains the first place ; next, its alkaloids, morphine and codeine ; then salicylic acid or its salts ; and lastly, salts of bromine. The difficulty of carrying out strict comparative experi- ments with drugs is very great, because over and above the time and labour involved it is oftentimes impossible to secure the necessary conditions for their success, viz., that the other factors of the experiment shall remain undisturbed — diarrhoea, a severe attack of toothache (to which diabetics are very liable), inability to continue the same diet, and other accidents interfere with the course of the experiment, and oblige us to reject cases as untrustworthy upon which a good deal of time has been spent. The following table shows the effect of opium as compared with diet alone and with other drusjs. The other drujjs used ORDINARY DIET. DIABETIC DIET. WITH OTHER DRUGS. WITH OPIUM. Total c„ „r Urine. ^^■^'■ Sugar p. c. Total c„ „, Urine. '^P" &■•• Sugar p.c. Total Urine. Sp. gr. Sugar p.c. Total Urine. Sp. gr. Sugar p.c. 244 1040 10 200 1034 i 8 170 1030 8 176 1030 6-6 36S DIABETES. were arsenite of bromine, salicylate of sodium, bromide of potassium, lithia, codeine, salicin, boracic acid, and uranium nitrate. The case was that of A. P., aged twenty-five, already quoted (Case 65). This man took two grains of extract of opium three times a day, a much larger dose than usual. The next case, E. H., aged twenty-seven, shows a more striking result, but the only drug with which opium was com- pared was salicylate of sodium. ORDINARY DIET. DIABETIC DIET SALICYLATE OF SODIUM. OPIUM. Total Urine. Sp.gr Sugar p. c. Total Urine. Sp. gr. Sugar p.c. Total Urine. Sp.gr. Sugar p.c. Total Urine. Sp.gr. Sugar p.c. 186 1042 5-8 158 I03I 476 no 1038 476 58 1034 4-5 I'he dose was one grain of extract of opium twice daily. Opium is especially valuable for the influence it appears to exert in diminishing the amount of urine. An opium pill often gives an undisturbed night to patients who without it have to rise frequently to pass water. Villemin recommends the combination of belladonna with opium. MoT-phine acts equally well, but codeine, when given even in much larger doses than are suggested by its principal advocates, is com- paratively inert. Case 74. — Diabetes Mellitus — cured by diet a?td opium. Henry H., aged fifty-seven, collier, attended as an out-patient on Jan. 4th, 1887, complaining of thirst and of passing a large quantity of water, seven pints daily. He was put on extract of opium (gr. ]) three times a day, and anti-diabetic diet. By March 22nd the quantity of urine had fallen to two-and-a-half pints, sp. gr. 1015, and the sugar had disappeared. He was allowed to take modified diet, viz., bread and potatoes, and on April i^th the absence of sugar was confirmed. Case 75. — Diabetes Mellitus — temporary disappearance of sicgar under dietetic restrictions and opium. George E., aged sixty-one, attended as out-patient on Dec. 6th, 1887, complaining of thirst and of getting up a dozen times at night to make water. Quantity of urine five pints, pale, clear, sp. gr. 1027, contained a moderate quantity of sugar. Weight of patient 218 lbs. He had been ill two years. On anti-diabetic diet and extract of opium (gr. j) three times a day, by May 8th the quantity of water had fallen to three pints, of sp. gr. 1018, free from sugar. He then began to eat bread freely, and the sugar returned, though the quantity of urine remained low. Jambul and aniipyrin were tried without effect on the su^ar. TREA TMENT. 369 I have treated many cases with and without opium, and the strong impression left on my mind by these cases, is that in opium we possess the most valuable drug for the treatment of this disease, but I do not use opium in every case or continue it after it appears to have done its work. Salicylate of sodium as an alkali may be of some service, for I am strongly in favour of the alkaline treatment of diabetes, but I have never observed it to produce any specific effect on the quantity of water or the amount of sugar, although Sympson has published a very good case of the disappearance of sugar in a boy of seventeen, under the use of this drug in ten-grain doses every four hours, combined with strict diet. A?'se?iite of bromine, whether used pure or in the form of Clemens' solution* has never in my hands justified the praises it has received in some quarters ; I have used it in many cases without being able to observe any specific effect. I have given it in doses of \ gr. of the pure drug, and up to ten minims of the solution. Another form in which arsenic may be given is that known as Martineau's specific.f Bromide of potassium does not deserve the name of a specific, but is, in my opinion, the best routine remedy to employ in conjunction with the use of opium. It is suitably given in a mixture combined with a little bicarbonate of potassium and some bitter infusion, and very satisfactorily allays the nervous irritability so often present. Teissier has found it very useful in the treatment of the dia- betes of elderly women in doses of thirty to forty-five grains daily ; but we know that this is a mild form of diabetes, with a natural tendency to amelioration or cure. The relation of the pancreas to diabetes mellitus, and the success attending the employment of raw thyroid gland or extract in the treatment of myxcedema, naturally led to great hopes from pajicreatic remedies. But Minkowski found that dogs rendered diabetic by extirpation of the pancreas were * Liquor dementis. — According to Hager its composition is as follows : — Acidi Arseniosi, Potassii Carbonatis, aa gr. jss. Place in a test tube and add five drops of distilled water, and warm so as to form a clear solution. Dilute this with distilled water till the quantity weighs 153 grains. Then add 6-2 grains (4 drops) of bromine and set aside for one day. The fluid is then ready for dispensing. A modified formula is frequently employed now. f Carbonate of Lithium, 20 centigrammes (3 grains), added to a tablespoonful of the following solution : — Arseniate of Sodium, o'20 centigramme (-/^ grain); Distilled Water, 500 centigrammes (80 minims) ; the mixture to be placed in an ordinary soda-water machine (Briefs apparatus), and this quantity to be used daily with and between meals, as a drink, alone or mixed with wine. 24 370 DIABETES. not benefited by being fed with fresh pancreas, or by the hypo- dermic injection of fresh pancreatic emulsion, and numerous clinical experiments with all sorts of preparations of the gland administered in the most varied way, have alike been fruitless. Lepine, following in the line of his theory of pancreatic dia- betes as being dependent upon the absence of a glycolytic fer- ment, recommends a glycolytic ferment which he prepares by digesting five grammes of malt diastase in a litre of water to which one gramme of sulphuric acid is added, the mixture to be kept at from 35^ to 1'^° C. (95° to 100-4^ R), for three hours ; it is then neutralised with bicarbonate of soda. It should be made fresh every day, and this quantity (i litre) is the daily dose. He reports three cases in which the quantity ■of sugar fell, under the use of this remedy. Among other remedies recommended are antipyrin in 15 grain doses thrice daily (GERMAIN See) ; sulphide of calcium, in doses of \ to \ grain, three or four times in twenty-four hours (Cauldwell, Draper) ; creasote, 4 to 10 drops daily (VALENTINE) ; pJienacetin and exalgine (DujARDIN- Beaumetz); c-^w/Z/or (Peyraud); zc^(e^rm (Moleschott); jiitro-glycerine (KENNEDY) ; salicin, in doses of from 2 to 18 grammes (30 to 270 grains) daily (Dornbluth); carbonate of soda, \ oz. to 2 ozs. daily, with citric acid (Stadelmann) ; 5 to 6 ozs. daily of a 10 per cent, infusion of the bark oi syzygium jainbolanwn (QUANJER) ; sidpho-carbolate of soda, 5 to 30 grains for a dose (MONCKTON) ; pilocarpine (^V grain), with i grain of sulphate of potash, three times daily (EAGER) ; nitric or nitro-hydrocJdoric acid, with tincture oinux vomica (WiLKS); cocaine (\ grain), three times a day (OLIVER) ; pepsin, 10 grains three times a day (GARDNER) ; jambul (powdered bark of eugenia jambolana), in doses of 3 to 5 grains, thrice daily (KiNGSBURY) ; ouabain, in doses of tooo of a grain three or four times a day (Gemmell) ; phosphorus, in perles containing each -^q of a grain, of which three and then six were taken daily (Balmanno Squire) ; tiranium nitrate, up to 30 grains daily (West) ; ergot, the liquid extract 5ss three times a day (Dougall) ; benzosol, 4 to 5 grammes (60 to 75 grs.) daily (PlATKOWSKi) ; strontium bromide 30 grains daily (SOLIS Cohen) ; permanganate of potash and mate (MONIN) ; piperazin (HiLDEBRANDT). fambul. — This drug was originally recommended by Banatvala of Madras, and spoken of in terms of highest praise. More recently Quanjer in Java has had an equally favourable TREA TMENT. 37i experience of it. Both of these writers mention the syzygium jr-inbolanum as the source. Kingsbury, who drew the attention of the profession in this country to its use by the recital of some successes he had met with, speaks of the plant as eugenia jambolana. On consulting Messrs. Christy, I am informed that these plants are the same. In my observations the drug was administered in the form of Christy's jambul perles, or liquid extract prepared from freshly imported jambul seeds. Case y6. — A. J., aged eighteen : — Diet. — Meat, greens, Bonthron's gluten bread, and one pint of milk. This was not chancjed throui^ihout. DOSE. DURATION. URINE. SUGAR. BODY WRIGHT. Morphine — ^ grain thrice daily Jambul — 7 days 85 oz. 9 per cent. 5 St. 43^ lbs. 6 perles daily 3 days 100 oz. 7*6 per cent. 9 perles daily 6 days 100 oz. 6'8 per cent. 12 perles daily 6 days 104 oz. 8 per cent. 5 St. 6)4 lbs. Ext. Opii— 3 grains daily 7 days 76 oz. 5*4 per cent. 5 St. 10 lbs. Case yy. — W., aged thirty-three : — Diet. — Meat, greens, Bonthron's gluten bread, potatoes, one pint of milk. DOSH. DURATION. URINE. SUGAR. BODY WEIGHT. Morphine — }{ grain daily 6 days 167 OZ. 9 per cent. 8 St. 5X lbs. Jambul — 6 perles daily 6 days 205 OZ. 5'2 per cent. 8 St. s>(lbs. 9 perles daily 5 days 285 OZ. 5 "8 per cent. 12 perles daily 4 days 394 oz. 7"6 per cent. 8 St. 3 lbs. Ext. Opii — 3 grains daily 7 days 200 oz. 6"6 per cent. 8 St. 8;< lbs. In another case as many as thirty-six perles were given daily without effect, and a liquid extract also supplied by Messrs. Christy was given in several cases in doses gradually rising to 13^2 ozs. daily. It was tried in every case under treatment about the same time, and in no single instance was any distinct benefit 372 DIABETES. observed to follow its use. Minkowski found jambul absolutely useless in experimental pancreatic diabetes. During the administration of ouabain for whooping-cough, sugar was observed to disappear from the urine of one of the cases on which it was tried (Gemmell). Messrs. Christy kindly supplied me with a sample of liq. ouabaini prepared by them, which I administered to several diabetics without observing any benefit. The dose was carried as high as nine drachms daily, beyond which I did not venture to go. Ouabain is an alkaloid having the following composition : — CgoH^^O^o ; it is obtained from the ouabais plant which is used as an arrow poison by the Somalis on the East Coast of Africa. Phosphorus, which was recommended by Balmanno Squire because he had observed the sugar disappear during its use from the urine of an elderly man suffering from eczema, has had an extensive trial without any evidence being obtained that it possesses the power to control any of the important symptoms of diabetes, and exactly the same may be said of cocaine, which was recommended by Oliver on theoretical grounds. Benzosol, 1 5 or 20 grains three or four times a day, is being largely used at present in Germany, sometimes with good results. Grube has drawn attention to the improvement in the general health w^hich followed the use of a heaped up teaspoon- ful of powdered egg-shell, by two patients. The remedy is a bit of folk-lore, but Grube thinks it fulfils the indication afforded by the great loss of lime from the bod}^ and suggests the use of a teaspoonful daily of a powder consisting of 93 parts of carbonate of lime and 7 parts of phosphate of lime. It has no influence on the glycosuria. Treatment of Symptoms. — Neuralgia. — In many in- stances, as in cases quoted, diabetic neuralgia ceases when the disease is checked by general treatment. But to afford relief we may give antipyrin, 1 5 or 20 grains for a dose, or exal- gine, 3 to 4 grains for a dose, or opium or morphia, by the mouth or hypodermically. The following ointment may be used locally : I^ Moithol, gr. xv ; Cocaine, gr. v ; Chloral Hydratis, gr. iij ; Vaseline, 5j ; Fiat Unguentuni. Sig. — To be rubbed gently over the seat of pain. Thirst depends on the great drain of water from the body, and the rational treatment of it is to lessen the polyuria. In TREA TMENT. 373 the meantime no gc)od purpose is served by placing restric- tions on the quantity of fluid to be drunk, as this can only augment the patient's suffering without any benefit. Sucking ice, or the use of lemon or bitartrate of potash water as a drink, may check it. With the object of promoting a flow of saliva and so relieving the dryness of the mouth, hypodermic injections of pilocarpine (grain 2V to j--) have been frequently used, and with good results. McAvoy recommends for the same purpose 5 minim doses of glycerinum acidi carbolici. Constipation appears in some cases to increase thirst. A subordinate but nevertheless highly important detail of treatment is the regulation of the bowels. All, or almost all, diabetics are constipated, whatever they may say. I have seldom made a post-mortem examination of a subject of this disease without finding the colon stuffed with hardened masses of fieces. Therefore, it is usually necessary to give a purga- tive twice a week. We may use any of the favourite or fash- ionable remedies^ avoiding only such preparations as contain sugar, but one of the most certain is Rubinat water. The ccdeuia of diabetes generally disappears very rapidly on rest in bed and appropriate general treatment. Dickinson thinks large doses of perchloride of iron (30 to 40 minims of the tincture three or four times a day) act as a specific. Mass- age should be tried in all obstinate cases. Pruritus. — This may be treated by careful cleansing with a sponge dipped in some antiseptic fluid after micturition. Lawson Tait speaks very favourably of the use of a lotion containing hyposulphite of soda, an ounce to a quart of water, and of an ointment containing 10 grains of sulphuret of potassium to the ounce, combined with the use of opium. A warm fresjily-made saturated solution of boracic acid may be used with confidence that it will give relief, and after carefully drying the parts, zinc ointment should be applied freel}% but it is right to say that the condition, possibly from want of care on the part of the patient, is sometimes very intractable. Routh recommends the following remedies : — Put a tea- spoonful of borax into a pint bottle of hot water, add 5 drops of oil of peppermint and shake well. Bathe the affected parts freely with a soft sponge. If rawness or eczema is present, apply olive oil to which iodoform has been added in the pro- jDortion of 5 grains to the ounce. Sweating. — This is a rare affection, and according to Schmitz, is a favourable symptom, so that it may not be always desir- 374 DIABETES. able to check it. But where this is the case I have found that Dover's powder, taken as a substitute for the opium preparation previously in use, has proved very useful. BIBLIOGRAPHY. Armitage (W. S.). Semolina in Diabetes. " Lancet," 18S3, Vol. I., p. 859- Aye. Gymnastic Treatment of Diabetes. " Berlin, klin. Woch.," 18S9, No. 30. Banatvala. The Use of the Syzygium Jambolanum in Diabetes. " Mid. Med. MiscelL," 1S83. Cauldwell (C. M.). Calcium Sulphide in the Treatment of Diabetes Mellitus. " New York Med. Jour.," 1884, Vol. I. Defresne (M. Th.). Essais sur le mecanisme du diab^te maigre. " Gaz. des Hopitaux," 1890, No. 59. DoNKiN (A. S.). The Skim-milk Treatment of Diabetes and Bright's Dis- ease. London, 1871. DoRNBLiJTH (O., Junr.). Ein Beitrag zur Theorie und Praxis der Arzneibe- handlung des Diabetes mellitus. " D. Archiv f. klin. Med.," Bd. XXXVIL, Heft I and 2. Dougall (J.). Ergot in Diabetes Mellitus. "Glasgow Med. Jour.," Vol. XXXIX., p. 96. Draper. Sulphide of Calcium in Diabetes. " New York Med. Jour.," 1884, Vol. I., p. 380. Dujardin-Beaumetz. Du regime alimentaire dans le diabete. " Bull, de Therap.," Vol. III., p. 385. Eager (T. C). A case of Diabetes treated by Pilocarpine. " Lancet," 1884, Vol. II., p. 275. FiNKLER. The Treatment of Diabetes by Massage. " Fifth Congress for Internat. Med.," Wiesbaden, 1886. Gardner (E. B.). Pepsin in Diabetes. " Practitioner," 1886, Vol. XXXVIL, p. 448. Gemmell (W.). On Ouabain in Whooping Cough. " Brit. Med. Jour.," 1890, Vol. I., p. 950. GR.UBE (K. ). On the Treatment of Diabetes Mellitus, especially of its more advanced forms. "The Lancet," 1893, Vol. II., p. 1613. Einige Beobachtungen, iiber die Bedeutung des Kalkes bei Diabetes mellitus. " Miinchener med. Woch.," 1895, No. 22. Hager. Composition of Liquor dementis. " Wiener med. Blatt.," 1883. HiLDEBRANDT. Ueber eine Wirkung des Piperazins und seinen Einfiuss auf dem experimentellen Diabetes. " B3rlin. klin. Woch.," 1894, No. 6. HiRSCHFELD (F.). The Indications and Contra-indications of Alcohol in Diabetic subjects. " The Medical Week.," 1895, P- 9^- Kennedy (R. A.). Nitroglycerine in Diabetes. " Canada Med. Record," Jan., 1S88. Kingsbury (G. C). Jambul Seeds in Diabetes. " Brit. Med. Jour.," 1S87, Vol. I., p. 617. Lepine (R.). a, new Treatment of Diabetes. " The Med. Week.," 1895, p. 259. Leo (H.). Ueber die Stickstoffsauscheidung der Diabetiker bei Kohlehy- dratzufuhr. " Zeitschr. f. k. Med.," Bd. XXII., Heft 3, p. 225. McAvoy (J.). Glycerinum Acidi Carbolic! in Diabetes Mellitus. "Lancet," 1885, Vol. I., p. 376. TREA TMENT. 375 MoLEscHOTT (J.). Iodoform gegen Diabetes mellitus. " Wein. mad. Woch.," Bd. XXXII., 1882. MoNCKTON (F. A.). Sulphocarbolate of Soda in Diabetes Mellitus. " Aus- tralasian Metl. Gaz. ," 1884. Nkdats (He). Quoted by Dujardin-Beaumetz, op. cit. Oliver (T.). Cocaine in Diabetes. " Lancet," i88g, Vol. II., p. 735. PiATKOwsKi. Ueber die therapeutische Wirkung des Benzosols bsi der Zuckerharnruhr. " Wien. med. Woch.," 1892, No. 51. PoRTEOUs (J. L.). Diabetes Mellitus : Skim-milk Treatment. " Edin. Med. Jour.," Vol. XXX., Part I., p. 508. QuANjER. Use of the Bark of Syzygium Jambolanum in Diabetes. " Weekbl. v. h. Nederl. Tijsche voor Geneesk," 1888, Vol. I., p. 251. Saundby (R-). A case of Diabetes treated by Lsevulose. " Internat. Clin.," Vol. IV., Series 3, 1894. See (Germain). Antipyrin in Diabetes Mellitus. "Brit. Med. Jour.," 1889, Vol. I., p. 1472. SoLis CoHEX (S.). Laevulose and Strontium bromide in the treatment of Diabetes Mellitus. " Internat. Clinics," Vol. IV., Series 3, 1S94. Squire (Balmanno). A case of Diabetes benefited by Phosphorus. " Brit. Med. Jour.," 1889, Vol. II., p. 1216 ; 1890, Vol. I., p. 293. Teissier. Sur le traitement du diabete sucre. " Bull, de Therap.," Vol. CVIII.,p. 332. Valentine (P.). Le creosote centre le diabete. " L'Osservatore," Jan. 5th, 18S9. Villemin. Traitement du diabete aigu. " Bull, de I'Acad. des Sciences." "Arch. gen. de Med.," 1887, Vol. I., p. 364. White (W. Hale). On the effect of giving Lasvulose and Inulin to patients suffering from Diabetes Mellitus. " Guy's Hosp. Rep.," Vol. L. , p. 132. WiLKS (S.). Cases of Diabetes treated with Nux Vomica and Mineral Acids. "Med. Times and Gaz.," 1884, Vol. I., p. 320. Williamson (R. T.). A bread substitute for Diabetic Patients. "Brit. Med. Jour.," 1895, Vol. I. p. 922. 576 Chapter XXII. DIABETES INSIPIDUS. In spite of the discovery of Willis, in 1670, of the presence of sugar in the urine in certain cases of diabetes, it was not till the end of the eighteenth century that the formal dis- tinction into diabetes mellitus (verus) and diabetes insipidus (spurius) was made by Cullen. Diabetes insipidus, according to Senator, is the name applied to every case of chronic morbidly increased secretion of urine, free from sugar, which is caused by no profound structural alteration of the kidneys, and which constitutes either the sole or at least the most prominent and primary inorbid phenomenon. According to this definition it is the polyuria which causes the thirst, but there are cases in which the thirst is primary, so that it is preferable to define the disease simply as characterised by the two symptoms, thirsty and polyuria, with absence of glycosuria. Synonyms for this condition 2sq polyuria, polydipsia, hydruria, etc. ETIOLOGY. Bernard caused simple polyuria by puncture of the floor of the fourth ventricle near th«e spot injury of which is followed by glycosuria. Eckhard produced similar results in rabbits, by injuring the posterior lobe of the vermiform process of the cerebellum. Peyrani induced the condition by electrical stimulation of the cervical sympathetic; and it is said to follow section of the splanchnic nerves. Predisposing Causes. — The age at which the disease occurs is illustrated in the followins; table :^ Agr. ROBRRTS. Strauss. Van der Heijdhn. Under 5 yrs. 7 9 2 5—10 15 12 5 10 — 20 13 r 19 20 — 30 16 '' 23 30—40 — 19 40—50 15 I 9 50 — 60 7 6 60 — -JO 4 — 4 70 85 87 DIA BE TES INSIPID US. 3,77 This shows tiiat the greatest frequency is during adolescence, early manhood and middle life, infancy and old age being comparatively exempt. The male sex seems decidedly more liable than the female in the proportion of nearly three to one : — NAME. MALES. FKMAI.KS. Roberts Van der Heijden 55 71 0^ 25 126 47 The influence of heredity is well known. Weil has published a very remarkable history of a family in which no less than twenty individuals out of a total of ninety-one, in four gener- ations, were attacked by the disease. Males and females were attacked in equal proportions, and no age appeared exempt. There was no evidence of scrofula or tubercle in the family ; all the males were well developed and had performed their military service. It seemed to have no influence on their vitality, the diabetic ancestor having lived to be eighty-three, his daughter to seventy-four, and two living members, also affected, had attained the ages of sixty-seven and seventy- six respectively. In Lacombe's case, a mother, her four children, and her brother and his children were all affected. It has been supposed that the tnbercidar diathesis is a predisposing cause, and although in Weil's family, just quoted, there was no evidence of such a taint, R. H. Clay has recorded the cases of three children, two brothers and a sister, suffering from diabetes insipidus, in whose family four other children had died of consumption. SypJiilis is undoubtedly a cause, but in this case the effect is generally due to the formation of a gumma in the brain. Gout is probably to be reckoned as a predisposing factor, and so is insanity. Among the exciting causes, severe contusions in various parts, but particularly the head, occupy a well-defined place. One of Matthews Duncan's cases was apparently caused by a blow of great severity on the back of the head. Flatten has reported a case in which a blow from the trunk of a tree on 378 DIABETES, the left side of the neck and occipital region, was followed in seven days by great thirst and polyuria, accompanied by com- plete paralysis of the left external rectus oculi muscle, and a slight paresis of the corresponding muscle on the right side. He thinks the blow caused a circumscribed hsemorrhagic softening on the level of the point of exit of the abducens nerves in the hindermost part of the pons or the anterior part of the medulla. Drummond, of Newcastle, has described a case in which the disease came on suddenly in a man who had been roughly throttled by a fellow workman, and in the discussion which followed Oliver mentioned the case of a man who fell into a dock and was rendered unconscious for ten or twelve days ; on recovering consciousness he drank greedily, and from that moment polydipsia and poly- uria existed. A case came under my observation several years ago, where a fall from a train in motion was followed by temporary glycosuria and by polyuria which has per- sisted. Nothnagel recorded the case of a man aged thirty-four, who was kicked in the left side of the abdomen and fell with the back of his head on a hard floor. He suffered from pain with a sense of compression in the occiput, and his pupils were much contracted. Soon after, he was seized with thirst and passed a large quantity of water. These symptoms gradually disappeared, and eighteen days after his accident he was dis- charged cured. The influence of pregnancy is also not to be doubted, but the condition appears to be temporary. Thus in Hughes Bennett's case the disease came on at the fifth month and dis- appeared two days after delivery; in Matthews Duncan's case it disappeared a month after delivery, and in Esterle's the disease appeared in two successive pregnancies, but dis- appeared in the interval. Westphal has published a case which he attributed to the loss of blood at the confinement. Senator has recorded a case which after lasting several years disappeared on the supervention of pregnancy. Possibly in close alliance with the last-named cause, in their mode of origin, are those cases in which abdominal tumours have been associated with this disease. Ralfe had met with it in two cases of aortic aneurysm, and Haughton in a case of uterine fibroid, with enlargement of the mesenteric glands and faecal accumulation, Ralfe believed the aneur3^sms pressed upon the vagus. DIABETES INSIPIDUS. 379 Somewliat allied, too, is the case described by Kuster, which followed the incision and drainage of a pancreatic cyst, but there may have been injury to the splanchnic nerves or vagi. Among other exciting causes are exposure to cold and drinking cold fluids when heated, infective diseases, i>iuscular effort, exposure to a Jiot snn, and mental emotion. As illustrations of the effect of musc2ilar effort may be quoted Frank's case of a boy who strained himself by pushing the wheel of a cart which was sunk in the mud; and Jarrold's of a girl who slipped, but saved herself from falling by a very great exertion. Jacobi has recorded a case which was cured by the removal of a taenia medio-canellata; but in a case of Lunin's, removal of the worm was not followed by any benefit to the specific symptoms. Acute alcoholic intoxication is stated by Dickinson to be an indubitable exciting cause ; in his own words " a person gets what is vulgarly called dead drunk"; on regaining conscious- ness he is polyuric and so remains. Finally, lesions of various parts of the nervous system are direct exciting causes of the disease, but these are better des- cribed under the heading of morbid anatomy. MORBID ANATOMY. Nervous System. — Various lesions of the brain have been observed, such as fracture of the base of the skull, with contusion of the anterior lobes ; yellow softening, inflam- mation and degeneration in the floor of the fourth ventricle. Tumours, tubercle, glio-sarcoma, gummata, and exostoses in various positions ; carcinoma of the pineal gland. Lesions have also been found in the semi-lunar ganglia and splanch- nic nerves. The ganglia showed the atrophy of nerve cells associated with increase of connective tissue and dilatation of vessels, which is seen in so many diseases. The nerves showed fatty degeneration of their axis cylinders, with granular degeneration and dilatation of the vessels of the neurilemma (SCHAPIRO). The Blood. — According to Strauss, the solids of the blood are increased : — First Observation. Second Observation. Water 7779 per cent. 77'937 per cent. Solids 22'2i per cent. 22'o63 per cent. 3So DIABETES. The solids in the second case consisted of: — Fibrin :-.... o"467 per cent. Haemoglobin .... 1172 per cent. Other Albuminoids - - - - 7*44 1 per cent. Extractives- .... i '301 per cent. Ash- ...... I "1 34 per cent. The serum contained : — Water 88712 per cent. Albumen - . . . . 9-062 per cent. Extractives .... 1 '012 per cent. Ash - - - - - - I '2 14 per cent. Alimentary System. — The mucous membrane of the lar^e intestine may be ulcerated and ecchymosed (SCHAPIRO), or there may be tubercular ulceration (ROBERTSj. Dickinson has observed cancer of the liver in one instance. Respiratory System. — Where, as has several times happened, the disease is connected with tubercle, there may be more or less extensive pulmonary phthisis. Lobular pneumonia was present in one case (Neuffer). As a rule the lungs are normal. Urinary System. — The kidneys appear normal or may be congested, the Malpighian bodies especially appearing as well marked hyperaemic points. Secondary changes in the kidneys are not uncommon. Thus Neuffer describes a case in which the renal tubules were dilated, some being stripped of their epithelium, others stuffed with fatty debris ; Beale observed similar changes, together with increase of the peri-vascular connective tissue. In some cases the kidneys are sacculated, the cavities containing urine or pus, and the bladder and ureters are also thickened and dilated (see Case 80, p. 384). Pathology. — There can be little doubt that the disease is a neurosis which depends upon changes in the nerve centres, or upon peripheral irritation acting through those centres. The channel for the transmission of the morbid influence appears to be the vagus nerve, and the mechanism consists in relaxing the tonus of the renal arterioles and permitting a very free af^u.x of blood to the Malpighian bodies. SYMPTOMS, AND CLINICAL HISTORY. As has been already stated, the cardinal symptoms are thirst and polyuria. In certain cases thirst is the first symptom noticed ; in others, and perhaps in the majority, polyuria is the primary affection. DIABETES INSIPIDUS. 38 1 The following case illustrates very well the type in which thirst precedes polyuria : — Case 78. — Diabetes Insipidus — thirst — polyuria — ^outy history — im- provement. John P., forty-nine, came as an out-patient on April loth, 1S83, com- plainino of thirst and passing a large quantity of water. He said that his illness began quite suddenly six years before. He was out for a walk one Sunday when "a great thirst came on him, so that at every house or brook he came to he must be drinking." He was in perfectly good health, and had not met with any accident. He had worked as a stamper in Birmingham, and had always enjoyed good health. The only illness he could recall was "stoppage of the water'' eighteen years before, but he soon recovered. He was a married man, but had no children living. Two were born dead and his wife had had several miscarriages, but he could give no history of syphilis, sore throat, or skin eruption, though he admitted having had gonorrhoea when he was nineteen. He had no knowledge of any similar case in the family. He had had gout several times. He was a well-nourished man; there was a depressed scar over the right frontal eminence, which was caused by a fall in early childhood before he could remember. He weighed 12 st. 7 lbs. His tongue was furred posteriorly, and he suffered from pain and wind, after food. His bowels were regular; liver and spleen normal. He complained of severe cough and spit, and shortness of breath, but he had no palpita- tion or oedema of feet ; his heart and lungs appeared normal. Pulse 120. He said that he passed a chamber-pot full of water in the night and more in the day. The urine was clear, pale yellow, sp. gr. looi, faintly acid, no albumen or sugar. Ophthalmoscopic signs negative. He had no headache, giddiness, or vomiting'. He was treated by colchicum, car- bonate of magnesia, and sulphate of magnesia, and under these remedies his polyuria and thirst greatly diminished. As will have been noted, this disease does not necessarily involve weakness or loss of flesh, but is consistent with good general health. In some cases, there is wasting and evident ill-health, in others obesity (VOSS). The flow of saliva may be greatly increased (KUELZ), and there are often pains in the back and loins. The bowels are generally confined. The temperature of the body is normal, in some cases it is sub-normal. When it comes on early in life it affects the growth of the individual. The following is a good example of this type of case : — Case 79. — Diabetes Insipidus — neurotic family history — stunted growth — -polydipsia. Frederick S., sixteen, jeweller, was admitted into the General Hospital on June 19th, 1890, complaining of thirst and of passing large quantities of water. 382 DIABETES. Family History. — Father died aged thirty, from "diseased bowels." Mother ahve, aged forty-two, had been an inmate of a kmatic asyhun for three years. She suffered from fits before becoming insane. Two brothers Hving — one died in infancy. No history of phthisis or diabetes. Previous History. — Patient was always weak. He had measles at six years ot age. Ever since his infancy he had passed water in large Cjuantities, and had suffered from thirst. For the last three years he had been in the habit of drinking quite a quart of water during each night. His appetite had never been excessive. Present Conditio/i. — Patient was fairly well nourished, very small for his age ; weight 4 st. 6 lbs. : height 4 ft. 7f in. No jaundice, oedema, or special dryness of skin. He seemed very lively and intelligent. Pulse 80; Resp., 16; Temp.,98-5° Alime7itary System. -There was a red line along the margin of the gums. Tongue moist and furred. Appetite poor. Thirst marked ; he drank 63 pints of fluid yesterday, and one pint in the night. No pain after food, or vomiting. Bowels rather confined. Liver dulness in V.M.L., 3 in. Splenic dulness in M.A.L., i^ in. Circulatory System. — There were some dyspnoea and palpitation on exertion ; cardiac impulse obscure, in 5th I.S., in V.M.L. Cardiac dul- ness was bounded above by the 3rd C.C. to the right by the right edge of the sternum, and to the left by the V.M.L. Heart sounds rather feeble ; pulmonary second sound reduplicated ; no murmur. Pulse regular, fairly strong, easily compressed. Respiratory System. — No cough. There were some dilated veins over the upper part of the front of the thorax. Sternum rather convex. Vocal fremitus feeble; percussion note resonant ; breath sounds vesicular; vocal resonance normal ; no adventitious sounds. Urinary ^y^/t'/;?.— Micturition frequent ; usually about three times in the night. No scalding or pain. Urine 104 ozs., sp. gr. 1002, neutral, pale opalescent straw colour ; white deposit consisting of bacteria, mucus, leucocytes and triple phosphates ; urea 0-65 per cent. ; a haze ot albumen, no sugar or blood. Analysis of another specimen showed total solids to be only o'bb per cent. These were made up as follows : — Organic substances — Urea - - - 0-324 Albumen and mucus 0-040 = 0-364 per cent. Inorganic substances — Chlorides - - 0-023 Sulphates - - 0-044 Soluble phosphates - 0-060 Insoluble phosphates 0-020 Magnesia, Lime, Soda, and Potash - - 0-149 = 0-296 per cent. There was a disposition for his temperature to be subnormal, ranging from 97-5 to 98°. He gained no weight while under treatment, nor was the ur'.ne affected by the drugs employed, viz., a mixture of dilute hydrochloric acid with a bitter infusion, given well diluted with water as a drink, and 3 grains of ergotin daily, in the form of pills, containing each I grain. DIABETES INSIPIDUS. 3S3 The following table shows the quantity of fluid ingested and the quantity of urine passed in corresponding periods of twenty-four hours, during his stay in hospital. DATE. URINE IN 1 FLUID INf.ESTED IN OUNCES. OU.N'CKS. June 22 104 130 „ 23 no 120 M 24 126 100 ., 25 106 ICO „ 26 116 120 „ 27 108 120 „ 28 122 140 » 29 118 130 » 30 136 150 July I 160 150 » 2 140 140 ., 3 120 130 ,. 4 128 no „ 5 130 no „ 6 120 130 „ 7 122 no „ 8 128 120 » 9 100 no These patients suffer a good deal from dryness of the skin, and dry mouth and fauces. There may be a good deal of gastric disturbance, especially when the kidneys are becoming disorganised. According to Lowinsky, boils, originating in inflammation of the sweat glands, may occur. The bladder may become very irritable, and oedema of the feet may super- vene in the later stages. Great intolerance of alcohol has been observed, which is the more remarkable as it must be excreted very rapidly, w^hile Trousseau has recorded a case in which great tolerance existed, the patient being able to drink twenty litres of wine and a litre of brandy at a sitting. Hunger may be present in a very marked degree, and Trousseau speaks of these patients as the terror of the keepers of restaurants a prix fixe. The Urine is always greatly increased ; it may be faintly acid, alkaline, or neutral ; it is always of low specific gravity, and as a rule free from albumen. It contains no glucose, though cases in which diabetes insipidus appears to alternate with diabetes mellitus have been observed. Inosite, or muscle 384 DIABETES. sugar, has been frequently found to be present (SCHULZEN, Strauss), but it is not constant. It is detected by evaporat- ing the urine to dryness, tlien moistening with ammonia and a sokition of calcium chloride, and evaporating again. If inosite is present a ruby red colour makes its appearance (SCHERER). The polyuria is occasionally intermittent (Fagge). The urea is greatly increased until the kidneys become dis- organised, when it diminishes to belov/ the normal amount ; under these circumstances pus or albumen may be present. The uric acid is probably normal ; kreatin and kreatinin are said to be diminished (StrauSS, PRIBRAM) ; hippuric acid is present (Bouchardat) ; the chlorides are increased (Senator); and so are the phosphates. Case 80. — Diabetes insipidits — with sacculated kidneys — iircsmia. Alfred W., aged 26, a sieve-maker, was admitted into Hospital on September 12th, 1894, complaining of intense thirst, frequent micturition, and the passage of a large quantity of uiine. This was the third occasion on which he had been an inmate of our wards for practically the same symptoms. He had suffered from thirst all his life, but he believed he had gradually got worse. For the last ten years he had been subject to attacks of pain in the abdomen, and when in hospital for the fiist time, four years ago, there was some tenderness on palpation in the right lum- bar region. On the second occasion, tenderness in the abdomen was noted "over both kidneys, but no marked enlargement of either " ; this was in 1891. He contracted gonorrhoea about four years before his final admission, probably before he came to the hospital at all, and he has since suffered from a persistent gleet. His family history reveals no in- stance of a similar condition nor any evidence of diathetic disease, except in the person of an uncle, who suffers from gout. The patient was a slenderly-developed, badly-nourished man, looking younger than his age; he weighed 8 St., and as in 189c he weighed 8 st. 3 lbs., and in 1891 7st. 1 1 lbs., we niay take it that he has been about the same weight for some years, although he stated on admission that he had recently been losing flesh. His skin was very dry, and his face flushed; T. 97'5°, P. 78, R. 16. His appetite was very poor, but his thirst was constant, disturbing his bleep. His tongue was furred and furrowed. He vomited nearly every morning, the vomited matter consisting of watery mucus for the most part. He had lived in a beershop and had all his life been accustomed to drink large quantities of beer to relieve his thirst. His abdomen was tender, especially over the left kidney ; liver and spleen not enlarged ; bowels confined. He suffered from pain at the prsecordia, with frequent attacks of dyspncea, but the heart sounds, though weak, were pure, and this organ was not obviously altered in size ; lungs normal. He stammered in his speech, and had some com.plaint of numbness in his fingers and toes ; but in other I'espects his nervous system presented no anomaly. The urine on each occasion of his stay in hospital measured between five and six pints ; but he told us that when he was going about it was more, and his thirst was greater ; its sp. gr. was about loio, and its reaction was gener- DIABETES INSIPIDUS. 3S5 ally alkaline. This time it contained a very little albumen due to pus ; there was no sugar ; the urea was diminished, beiny little over 200 grains in twenty-tour hours ; no casts were ever found, but some pus cor- puscles were constantly deposited. Analysis of the Urine. — Total urine 178 oz. ; Sp. gr. 1005 ; Total solids o*9 ; Organic matter 0'596 ; Urea 0*55 ; Albumen traces ; Sugar none ; Inosite none ; Inorganic matter o'304 ; Chlorides o'023o ; Phosphates o'o446 ; Sulphates 0-0782 ; Lime and magnesia 0-0250 ; Potash and soda 0-1332 ; Water 99-1. . He was treated, mainly for his stomach symptoms, by light diet, chiefly milk, bismuth and alkalies, and saline aperients. At first he improved, but in a few days he began to complain very bitterly of pains, neuralgic in character, in his legs ; these were not relieved by salicylate of soda. On the 26th he was given a hypodermic injection of three minims of the Pharmacopoeial hypodermic solution of morphia. After this he slept heavily all through the 27th and 2Sth, dying on the 29th of September. During this time he could be roused and answered sensibly, but when left alone he fell asleep again. He passed very little urine during this semi- comatose period. The post mortem examination was made on the 29th. The only noteworthy changes were some cedema of the lungs, slight hypertrophy of the left ventricle of the heart, a certain amount of enlarge- ment and fatty change in the liver, but the kidneys require detailed description. Both these organs were in a state ot hydronephrosis and they have been mounted for permanent preservation. The right kidney presented a large cyst which bulged forwards under the peritoneum. On removing' the organ, this cyst was found to be the greatly dilated renal pelvis. From the corte.x to the hilum it measured three inches, and its length was the same. On section, the pyramids and cortex were much atrophied ; the capsule was partially adherent ; the ureter, which was much dilated, opened from the most depending part of the pelvis, and was not obstructed. The left kidney was small and its pelvis was dilated, though not to the same extent ; it contained a concre- tion about the size of a hemp-seed. The ureter was also somewhat dilated, but not obstructed. The cortex was atrophied, and the capsule adherent. The weight of the two kidneys taken together was twelve ounces. The bladder was enlarged and its walls thickened, but the orifices of the ureters and their lumina were quite patent. There was no prostatic disease or urethral stricture. I may add that the brain looked anaemic, but otherwise appeared normal, and that the medulla oblongata, exam- ined microscopically, showed no morbid change. It IS well known that in this disease the excretion of urea is generally greater than normal, and may be enormously in excess. But in this case the amount of urea excreted daily was very little over 200 grains — a figure which, even on milk diet, is dangerously below the normal for an adult person. When he was in hospital in 1891 he excreted 480 grains of urea, so at that time he evidently possessed an adequate amount of healthy kidney substance. We must therefore watch the urea excretion in all cases of 25 3S6 DIABETES. diabetes insipidus, and be on our guard against a fatal ursemic termination whenever this becomes persistently reduced below the physiological proportion, although this varies at different ages. Dr. Ralfe gave the following table : — At 5 years i8o grains. 12 „ V~o „ 21 „ 535 „ 4° „ • ••• 555 „ But I am accustomed to teach that these figures are too high for a patient in bed on milk diet. I believe the case is safe so long as the daily amount exceeds 300 grains. Intercurrent infective diseases usually produce a diminution in the quantity of urine. This has been observed in small-pox (Lacombe, Charcot, Kuelz), typhus (Pribram), pleurisy (Desgranges), acute rheumatism (ROBERTS), pneumonia and erysipelas (SENATOR). But Dickinson has recorded a case in which an attack of scarlatina was attended by no dim- inution. Affections of the eye do not form any part of the proper symptoms of this disease. Cataract is rare, and such condi- tions as double optic neuritis, atrophy of the optic nerve (GOWERS), retinal hemorrhages (Galezowski), and staphy- loma posticum (Laycock), are either the consequences of some cerebral lesion, or accidental coincidences. The knee jerks may be exaggerated apart from cases following injury. Prognosis. — The duration of the disease is very indefinite, as it may exist the whole of a long lifetime, and does not appear to have any essential tendency to cause death. Many instances of spontaneous cure have been recorded ; thus a case that had existed eighteen years was cured by an attack of acute rheumatism, another by a pleurisy treated by blistering, and one already alluded to, by the removal of a tapeworm. A little patient, seen by me, was apparently cured by an attack of measles. Brunton has recorded a number ot cases among European children in India, attributed to expo- sure to the sun, which all got well in a few weeks or months. Garnerus has recorded the case of a child who soon after birth suffered from polyuria with progressive emaciation, and during the second month sugar appeared in its urine. This dis- appeared later on, but the polyuria did not improve till the child was fed on milk from which the sugar was removed by fermentation, sweetened with glycerine and mannite and diluted with boiled water. After three months of this diet DIABETES INSIPIDUS. 387 ordinary milk was given it without any relapse following, and the child remained well. The prognosis as to life is not unfavourable, as has been already shown in Weil's cases. The cause must determine this to some extent ; obviously if there is reason to believe in disease of the central nervous system, the prognosis must de- pend on the curability of this condition. Where there is a history of syphilis a cure may be hoped for. We have seen that after injuries the condition may be temporary, and in pregnancy it terminates as a rule, at or soon after delivery. While the disease may exist for years without apparent alteration of health, when kidney changes set in, the patient eventually dies with symptoms of chronic uraemic poisoning; therefore evidences of renal affection, and especially diminu- tion of urea, must be regarded as unfavourable. Treatment. — In the majority of chronic idiopathic cases drugs are of little use. Where there is a syphilitic history mercury and iodide of potassium should have a prolonged trial. One of the most highly recommended remedies is valerian, given either in the form of extract, in drachm doses, or valeria- nate of zinc, up to 15 grains, three times daily. Ergot, in the form of the liquid extract, 10 to 30 minims, three times a day, or ergotin, in doses of i, 2 or 3 grains, three times a day, have also been successful. Eichhorst has cured a case with tincture of the acetate of iron, and another with 5 grammes (75 grains) of antipyrin, daily. The latter drug has been also successful in the hands of Laplane, Zenner, and Opitz. Galvanisation applied to the nape of the neck (Altiiaus, Clubbe) has been strongly recommended. Voniovitch has cured a case by 3^ gramme doses of anti- pyrin, eight to twelve times daily. Clarke has reported con- siderable improvement after feeding with fresh supra-renal glands. Kennedy has urged the use of nitric or nitro-muriatic acid in doses of from i to 5 drachms daily. Libby has em- ployed with advantage spirits of turpentine, 15 to 20 drops, three times a day. Murrell observed benefit in a traumatic case from a combination of ergot with belladonna, and Brunton used belladonna in all his successful cases. Roberts recom- mends a blister to the pit of the stomach. It is useless and unnecessarily cruel to attempt to limit the quantity of fluid drunk. The dryness of the mouth may be 388 DIABETES. relieved by pilocarpin, or by sucking ice, or lemon, or glycerine lozenges. Opium or morphia may be tried to diminish the polyuria, but obviously the general condition of the patient must be our guide as to the extent to which we should push active treatment. While the general hygienic surroundings of the patient should be as satisfactory as they can be made, there is no reason to make him more of an invalid than he need be, and his diet, while wholesome and sufficient, should not be restricted. The dryness of the skin may be relieved by frequent steam or hot water baths, and there is some advantage in anointing the skin after the bath with olive oil, scented by the addition of a few drops of rosemary or bergamot. BIBLIOGRAPHY. Althaus (J.). Diabetes Insipidus treated by Galvanisation of the Medulla. " Med. Times and Gaz.," 1880, Vol. II., p. 617. Bennett (J. Hughes). The Principles and Practice of Medicine. 5th Edition, p. 996. Brunton (J.). Diabetes Insipidus in children, caused by hot weather. " Brit. Med. Jour.," 1892, Vol. II., p. 735. Clarke (W. F. ). A case of Diabetes Insipidus treated by ingestion of supra- renal glands. " Brit. Med. Jour.," 1895. ^o^- I-- P- 1086. Clay (R. H.). Three cases of Diabetes Insipidus in one family. "Lancet," 1889, Vol. I., p. 1188. Clubbe (C. p. B.). Diabetes Insipidus treated by Electricity. " Lancet," 1881, Vol. II., p. 749. Drummond. Proceedings of the Northumberland and Durham Medical Society. " Brit. Med. Jour.," 1889, Vol. II., p. 928. Duncan (J. Matthews). On Diabetes Insipidus in Pregnancy and Labour. ■' Obstet. Trans.," Vol. XXIV. p. 308. Eichhorst. Praktische Erfahrungen liber die zuckerige und einfache Harnruhr. " Corresp. Blatt. fur Schweizer Aerzte," 18S8, No. 13. Esterle. Quoted by Tarnier and Budin. " Traite de I'art des Accouche- ments, " Paris, 1886, p. 51. Fagge (C, H.). The Principles and Practice of Medicine. Vol. 11. , p. 347. Flatten. Beitrag zur Pathogenese des Diabetes insipidus. " Arch. f. Psych.," 1882, Bd. XIII. Garnerus. Combined Diabetes Mellitus and Insipidus in a new-born child: cure. " Deut. med. Woch.," Oct. 23, 1884. Haughton. Uterine Tumour with Enlarged Mesenteric Glands, " Dub, Quar. Jour.," 1863, p. 323. Jacobi. Diabetes Insipidus. " Arch, of Pediatrics," Nov. 1888. Kennedy (H.). Cases of Diabetes Melhtus, and the Treatment found Successful. "The Practitioner," 1878, Vol. XX., p. 94. KuELZ. Studien iiber Diabetes mellitus und insipidus. " D. Archiv f. klin. Med.," Bd. XII., p. 248. KusTER. Zur Diagnose und Therapie der Pancreascysten. " Deut. med.. Woch.," 1887. Bd. Xill. DIABETES INSIPIDUS. 389 Laycock (T.). Beneficial use of Jaborandi in cases of Diabetes Insipidus or Polydipsia. " Lancet," 1S75, Vol. II., p. 242. LowiNSKY (J.). Furunculosebei Diabetes insipidus. " Cent. f. klin. Med.," 1890. LuNiN. Ueber Diabetes Insipidus. "Jahr. fiir Kinderheil.," Bd. XXI., Heft 4. MuRRELL (W ). On a case of Diabetes Insipidus treated by (i,) Belladonna, and (2,) Ergot. " Brit. Med. Jour.," 1876, Vol. I., p. S. Neuffer. Ueber Diabetes insipidus. " Diss. Tubingen," 1856. NoTHNAGEL. Durst uud Polydipsie. " Virchow's Archiv," 18S1, Bd LXXXVI. Opitz (M.). Antipyrin in Diabetes insipidus. " Deut. med. Woch.," Aug. 8, 1S89. Ralfe (C. H.). Two cases of Aortic Aneurysm, with Increased Secretion of Urine. " Lancet," 1876, Vol. I., p. 308. Saundby (R.). Diabetes Insipidus. " The Practitioner," 1895, Vol. LIV., P- 39- ScHAPiRO. Zur Lehre von der zuckerlosen Harnruhr. " Zeitschr. f. klin. Med.," Bd. VIII., p. 191. Strauss. Die Einfache zuckerlose Harnruhr. " Prager Vierteljahrsch.," 1871, Bd. CXIII., p. I. Trousseau (C). Clinique Medicale de I'Hotel-Dieu de Paris. Quatrieme Edition, p. 808. Voss (A.). Uber Diabetes insipidus und adipositus. "Berlin, klin. Woch.," 1891, No. I. Weil (A.). Ueber die hereditare Form des Diabetes insipidus. "Virchow's Archiv," Bd. XCV., p. 70. Westphal (A.). Ein Fall von Diabetes insipidus. " Berlin, klin. Woch.," 1889. Zenner (P.). A case of Diabetes Insipidus with favourable termination. "Cleveland Med. Gaz.," Sept., 1889. 390 Section IV. MISCELLANEOUS RENAL DISEASES. Chapter XXIII. STONE IN THE KIDNEY. STONE in the kidney, or renal calculus, is a condition attended by very varying indications. It may cause any degree of pain in the region of the kidney, from a dull aching to an intense agony which tries the strongest man; there may be blood or pus in the urine or albumen only, or nothing abnormal; the urine may be increased in quantity and frequency, or diminished or totally suppressed; and, finally, each or all of these symptoms may be present when the kidneys are quite free from stone. This disease is very common in most parts of England, occurring at all ages and in both sexes, though more usually after middle age and in males. It is most often associated with a personal or family tendency to gout, and the most usual forms of calculi are composed of tmc acid or oxalate of lime; more rarely we meet with stones formed mainly of phosphate of lime, generally with an organic nucleus, or of cystin, or of old and altered blood clot (Martin). Phosphatic concretions may form around any foreign body lodged in the kidney; for example, on a nucleus of uric acid or oxalate of lime, or on a sewing needle (Kendal FRANKS), or on a bristle (Steven). Such phosphatic stones are usually associated with suppuration in the kidney and are probably always dependent upon decomposition of the urine. Cystin calculi are always associated with the presence of cystin crystals in the urine, which can be easily recognised by their hexagonal shape. {See page 195.) Recent researches point to the possibility that cystin is in som.e way dependent upon abnormal putrefaction of the intestinal contents. STONE IN THE KIDNEY. 391 We know very little respecting the conditions under which blood clots become so altered and hardened as to form calculi, but they originate without doubt in haemorrhage resulting from some injury to the kidney substance, such as might be inflicted by a blow or a crush. Stone is particularly frequent in England in Norfolk and Suffolk; in Scotland in Fife and Aberdeenshire; while Hereford, Dorset and Durham are singularly free. Plowright has sought to establish a relation between the prevalence of stone and a low mean annual rainfall, but Durham is an exception to this rule. Cider drinking is supposed by some to be a preventive of stone, but it probably acts only by taking the place of beer which favours the uric acid diathesis. Hard drinking water is a factor in the production of stone; or at least there has been a very sensible diminution of the disease in South Staffordshire since the surface wells were closed and softer tap water introduced. Both uric acid and oxalate of lime calculi appear to be dependent upon the uric acid diathesis, perhaps in different degrees, and under certain not understood variations of the conditions, as the same person may at different times pass both kinds of stone. The formation of a stone in the kidney may be due to abnormal positions of the organ, such as floating kidney or congenital displacement. Calculi, others than those formed from blood clot, are com- posed of minute crystals or particles united by an organic cement substance, and increase in size until they may form a complete cast of the cavity in which they lie. They may be present and even grow to an extreme size, without giving rise to any subjective symptoms, though the kidney atrophies, until it forms merely a capsule of fibrous tissue or more rarely of true fat (RiCKARDS). In other cases the stone passes into the bladder, and perhaps out from the urethra without pain. More commonly, it gives rise to pain and other troubles while in the kidney or during its passage into the bladder. A stone resting in the kidney may cause (i,) pain, (2,) haemorrhage, and (3,) inflammation. The pain is usually referred to the loin, and there is often tenderness just outside the edge of the erector spinae muscle. It is a dull aching pain, which radiates round the hip or towards the inner side of the thigh; some- times down the leg, or to the front of the abdomen or into the hypogastrium. It has been mistaken for lumbago, sciatica, the gastric crisis of tabes, intestinal colic, or even labour, and 392 MISCELLANEOUS RENAL DISEASES. may be attended by persistent vomiting. The pain may be constant or intermittent; and in the latter case may be brought on by prolonged walking or standing ; on the other hand it is usually relieved by rest, especially rest in bed, although in some instances it is worst at night (JACOBSON). Sooner or later as a rule hczinorrhage occurs, generally moderate in amount, but enough to make the urine bloody and not merely smoky. Under the microscope the blood discs are usually seen to be accompanied by pear-shaped epithelial cells, pus cells and crystals, the last being generally of the same nature as the stone. There may also be a few hyaline casts, but no renal blood casts, as the blood comes from the renal pelvis and not from the substance of the kidney. Cylindrical blood-casts of the ureter, half-an-inch to an inch in length, are occasionally found in the urine. More or less inflainmatton always attends the prolonged stay of a calculus in the kidney. This may reveal itself by great tenderness in the loin, indicating inflammation of the perinephric connective tissue, and may go on to the formation of perinephric abscess ; or pus in quantity may appear in the urine from pyelitis cr suppurative inflammation of the lining membrane of the renal pelvis ; or suppurative interstitial inflammation, with the formation of abscesses of various size, may attack the kidney substance itself. The formation of abscesses may be attended by all the phenomena of septic fever — rigors, high temperature and sweating ; while true pyaemia may develop with secondary abscesses in other organs. In addition there may be irritation of the skin, particularly in the epigastrium, urticaria, jaundice, or herpes zoster. If both the kidneys are affected uraemic symp- toms appear, and occasionally when one kidney was found post mortem to be fairly healthy, there has been complete suppression of urine from reflex inhibition (GODLEE). When a perinephric abscess has formed, it causes pain, tenderness and swelling of the part ; there may be bulg- ing between the last rib and the crest of the ilium ; or a tumour can be felt in the hypochondrium. If not opened such an abscess usually bursts externally, leaving a sinus through which pus is discharged. But when the stone becomes engaged in the ureter on its way to the bladder, it causes a very striking group of symptoms called renal colic, viz., (l,) pain, (2,) shivering, (3,) vomiting and diarrhoea, (4,) hsema- STONE IN THE KIDNEY. 393 turia, and (5,) suppression of urine; but all of these are not present in every case. As already stated, a stone may pass into the bladder unnoticed and without pain, but as a rule this process is one of the most intense suffering-; so much so that patients look back upon such an attack with horror. The immediate cause is often some unusual exertion or strain, jolting in a cart over a rough road, etc. One of my friends was getting into his carriage when the horse moved on, and he was thrown on to the back seat so as to give himself, as he thought, a twist in his loins. Pain came on at once, and in the course of the night he passed a stone. A young man who was the subject of cystin calculi brought on an attack by carrying his uncle in boyish fun upon his back. The pain is most excruciating; it starts from the kidney and shoots downwards and forwards to the groin ; it is often accompanied by retraction of the testicle on the same side. In his agony the patient rolls about, clutching at the bed-clothes, and cannot restrain himself from groaning or shouting. It is said to have given rise to all the symptoms of labour (Salzmann). At the beginning there is often s/iiveriiig, and as the attack proceeds the body may be covered with sweat. Voviitiiig is common, diain'ho3a may occur, and there may be hcBvwrrhage from the rectum. H(Einaturia is constant, except when the ureter is com- pletely blocked. There is great frequency of micturition from reflex excite- ment of the bladder, so that any blood voided is bright coloured. In most cases the attack terminates after a few hours by the passage of the stone into the bladder, whence it is . usually voided with the urine. But it may block the urethra and require to be extracted, or remain in the bladder, increase in size, and require removal by crushing or cutting, or it may stick in the ureter and cause complete or incomplete obstruction of that duct, or, lastly, it may fall back into the pelvis of the kidney. In the first and last cases when the attack is ended some tenderness may remain, but the patient soon resumes his ordinary mode of life. When the stone remains in the bladder it may not give much trouble for some time, and then develops a new group of symptoms which do not form part of my subject. If the calculus becomes impacted in the ureter it obstructs the outflow of the urine, which continues to 394 MISCELLANEOUS RENAL DISEASES. be secreted until the pressure within the tubules is equal to the blood pressure, when it of necessity ceases. Where the obstruction is incomplete the urine accumulates, and in course of time distends the kidney, causing JiydronepJwosis. Where it is complete, the kidney atrophies. If there is only one kidney, a condition which was present ten times in 3,108 post viorteni examinations, and must be relatively much more common in persons who have already suffered from calculus, total anuria occurs. The same result may follow from the simultaneous blocking of both ureters, a remarkable coinci- dence which has been several times recorded (Haehner, Reich). Absolute suppression does not always take place even in fatal cases of anuria, the irritated bladder ejecting from time to time a drachm or two of pale water-like or bloody fluid, containing very little of the normal urinary constituents. The general symptoms of anttria are distress, sleeplessness, vomiting and muscular twitchings, terminated by coma and death. The coma may be marked by the occurrence of deep sighing respiration, and by other phenomena resembling coma diabeticum (see Case i, page 62). The diagnosis of stone in the kidney is very difficult in many cases, and in these days of energetic surgery it has often happened that the kidney has been opened, or even excised, without any stone being found. Pain may be the only symptom present, as in a case recorded by Mr. Butlin where a calculus had existed for eight years without blood or pus appearing in the urine. Surgeon-Major G. H. Young has recorded a case of malarial nephralgia, presenting attacks of renal colic with retraction of the testicle, but normal urine, which was eventually cured completely by quinine. Dr. Nestor Tirard has reported a case in which the pain, which resembled that of calculus, appeared to be caused by firm cicatricial adhesions between the colon and the kidney. When in addition blood or pus, or both, are present in the urine, the diagnosis may appear more certain, but Dr. Ralfe has furnished an example where these were associated with paroxysmal pain in the right kidney and retraction of the kidney, but the patient was cured of all his troubles by opening an abscess which lay between the rectum and the bladder, and communi- cated with the bladder cavity. HcEinatiiria alone may be the only indication of a calculus, but even when its renal origin can be determined beyond doubt, as in these days is possible by means of the cystoscope, it may be due to malignant bTONE IN THE KIDNEY. 395 disease of the kidney, epithelioma in the renal pelvis, or as in a remarkable case recorded by Senator, which he calls renal haemophilia, the kidney after excision may appear perfectly healthy. Even when associated with pain hematuria does not necessarily point to the presence of a stone, as a slightly displaced kidney ma}^ give rise to these symptoms. The difficulty of diagnosis is very great. I had under my care for some years a young woman, whose attacks of pain and haematuria came on first after being struck in the loin by the angle of a wall. The pain and haemorrhage ceased after rest in bed, and for some years she seemed to get relief from the use of a pad and bandage, but at last her troubles returned in such an aggravated form that I recommended nephror- rhaphy, or stitching the kidney to the loin. She went under surgical treatment for this purpose, but when the kidney was exposed it was explored, and an oxalate of lime calculus as large as a blackbird's Qgg found and removed! Pus in the urine, when undoubtedly of renal origin, points to pyelitis, and although pain in the loin and irritability of the bladder may be present, yet on opening the kidney no stone may be found! We require therefore, in addition to pain and the presence of blood or pus in the urine, a history of the previous passage of a calculus to make the diagnosis of stone in the kidney a pretty safe one. In the absence of such a history our diagnosis must rest upon a very careful examin- ation of the patient, and upon the exclusion of other possible causes for the symptoms. An exploratory operation is often justified by the result and may be undertaken : — (i,) Where a perinephric abscess has formed. (2,) Where there is a renal tumour, with fever, and pus or blood in the urine. (3,) Where pain is so persistent or so frequently renewed, in spite of medical treatment, that the patient's health and comfort are seriously impaired. (4,) Where there is persistent haemorrhage from the kidney. (5,) When suppression of urine has occurred. A man was admitted into hospital some years ago, supposed to be suffering from spinal caries. There were several sinuses which led down to a rough body, believed to be a sequestrum ; it was removed and proved to be a renal calculus. The man made a perfect recovery. Plicque relates the case of a woman who suffered from severe pain in the left side of the abdomen, radiating into the 396 MISCELLANEOUS RENAL DISEASES. hip, vulva and rectum, while a painful oval tumour as large as a nut could be felt by vaginal examination in the left para- metrium. Left salpingitis was diagnosed and treated by morphine injections and poultices; next morning she passed two small stones in the urine, and only a little tenderness remained at the site of the tumour! The prognosis of stone in the kidney is not as a rule unfavourable, but it is grave when : — (i,) The urine is suppressed. (2,) The functions of both kidne3^s are seriously impaired, as indicated by great diminution of the urea excretion. (3,) When a large perinephric abscess has not been recog- nised until septic fever has produced serious wasting and loss of strength. Suppression of urine though grave is not always fatal, and recovery is possible even after it has lasted many days. My late colleague, Dr. Russell, recorded a case in which the suppression passed away after twenty days' duration, and the patient lived for more than two years. Renal failure, if correctly determined, must prove fatal before long, and the importance of ascertaining definitely the daily excretion of urea cannot be too strongly stated. In the third case there is room for hope, but the sooner the operation is performed the better, and the risk of failure must not be overlooked. When undertaken early the opening of a perinephric abscess is as favourable as any similar surgical procedure can be, and it is to be hoped that these unhappy cases, recognised too late, may in future be seldom seen. Very rarely the presence of a stone in the pelvis of the kidney appears to be the starting point of malignant disease, such cases having been reported by Norman Moore and others. It has been suggested that tuberculosis of the kidney is also favoured in the same way, and although it is not common, it may possibly be true at times; more commonly tuberculosis of the kidney originates independently of calculus. The treatment of stone in the kidney must be considered under (i,) prophylaxis ; (2,) medical and (3,) surgical means for removing the stone ; and (4,) management of renal colic. Prophylaxis. — From what has been said of the causes of stone, it may be judged that we do not possess the ground- work for a scientific prophylaxis. The most common forms of stone, uric acid and oxalate ot lime, are associated with the uric acid diathesis, and it is STONE IN THE KIDNEY. 397 certain that the precipitation of uric acid depends upon diminished alkaHnity of the blood. Such persons should be dieted by being warned to eat very sparingly of butchers' meat, and to eschew sugar, vinegar, sweet wines and malt liquors; they should live mainly on vegetables, fruits, farin- aceous food, game, poultry and fish, drinking light dry Moselle, or Bordeaux wine, or good whisky well diluted with aerated alkaline water. If the water of the district is hard, they should drink aerated distilled water to which potash or soda may be usefully added, and distilled water or boiled and filtered rain water should be used for making tea, coffee, etc. Exercise and cold baths, or the Turkish bath must not be omitted. Steady adherence to an absolute milk diet has often cured an inveterate tendency to stone, but most patients require to suffer much before they accept such a regimen for the remainder of their lives. Yet there have been sufferers who were glad to find relief even on this fare. The prophylactic treatment of cystin calculus should be by the regular administration of sulphate of magnesia or sulphate of soda as an aperient, together with salol (gr. x), or /3-naphthol (gr. v) in cachets two or three times a week. The medical treatment of stone in the kidney is of two kinds: (i,) solvent; (2,) expulsive. The solvents in common use are alkalies, or alkaline mineral waters. It is best to give a full dose of alkali at bed time: for example, forty grains of citrate of potash, or ten grains of citrate of lithia in half a tumbler full of potash water at bed time. I do not think the alkaline mineral waters effect very much by themselves, but they may help. The persistent use of distilled water, originally recommended by Murray, has answered very well in certain cases, but it is absolutely necessary that it be the sole vehicle employed for all beverages including tea and coffee. It may be obtained as potash, soda, or other mineral waters, and may be mixed with whisky or light wine. An extended trial of piperazine and lysidine, reputedly powerful solvents of uric acid, has left me doubtful of their value. The action of solvents is probably little marked except on uric acid stones, although Christison used to point out that the insolubility of the crystalline basis of a calculus was not proof of its impregnability to the attacks of drugs, as the 398 MISCELLANEOUS RENAL DISEASES. integrity of the calculus depends upon its organic cement which may be loosened by chemical means. The expulsives in use are turpentine, belladonna, and oil of sandal wood. Ralfe gave turpentine in ten minim doses in capsule; Murray recommends twenty minims of tincture of belladonna ever}' hour until the calculus is expelled or physio- logical symptoms of belladonna poisoning result; Philbert uses four ordinary capsules of oil of sandal wood for a dose. These remedies, if effectual, bring on an attack of renal colic, so that the patient must be warned of their possible effect, and he must be a bold man who does not hesitate to persevere in this line of treatment. The surgical measures to which we have recourse are : (i,) manipulation; (2,) incision. Manipulation was successfully performed by Mr. W. H, Bennett, who managed to feel a stone in the kidney and manoeuvre it down the ureter into the bladder ; but this great achievement has not been repeated to my knowledge. Incision, or nephrolithotomy, must be the only means of removing large stones, and in all cases when the kidney has been exposed it should be opened and explored, as a stone may otherwise easily escape detection ; in fact this has happened even after opening. Renal colic being one of the most painful maladies from which human beings suffer, anodynes must stand first in our list of remedies. The first thing to do is to give ^ grain of morphine hypodermically, except where there is good reason to believe the kidneys are badly diseased, and then we must rely on hot fomentations or the application of dry heat, or chloroform inhalation. Large doses of belladonna may be tried for the purpose of relaxing the ureter. The patient should remain in bed until all the pain has disappeared. Impaction of the stone in the ureter, with or without suppression of the urine, can only be treated by surgical means. The lateral abdominal operation advocated by Mr. Knowsley Thornton is to be preferred, as it gives better access to the whole length of the ureter. BIBLIOGRAPHY. Anderson (W.). Two cases of Renal Exploration for suspected Calculus. "The Lancet," i88g, I., p. 775. BuTLiN (H. T.). A case of Renal Lithotomy. "Trans. Clin. Soc," Vol. XV., 1S82, p. 113; Vol. XX., 1857, p. 22. STONE IN THE KIDNEY. 399 Bennett (W. H.). Manipnlatiin without Incision as a possible treatment in certain cases of Stone in tiie Kidney, "Tiie Lancet," 1887, Vol. I., p 1026. Franks (Kendal). Renal Calculus. "Dub. Jour. Med. Sci.," Vol. LXXXIX., 1890, p. 165. GoDLEE (R. J.). Case of Obstruction of one Ureter by a Calculus. " The Lancet," 1S87, Vol. I., p. 625. . — • Reflections suggested by a series of cases of Renal Calculus. "The Practitioner," Vol. XXXIX., 1S87, p. 241. Jacobson (W. H. a.). Four cases of Nephrolithotomy. "Trans. Clin. Soc," Vol. XXII , 1889, p. 198. Martin (C). Renal Calculi. (In Report of Meeting of Queen's College Medical Society.) "Birm. Med. Review," Vol. XXVII., 1890, p. 303. Moore (N.). Primary Cancer of Kidney with Calculus. "Path. Trans.," Vol. XXXIII., 1882, p. 129. Murray (W.). On the removal of Renal Calculi by toxic doses of Belladonna. "Prov. Med. Jour.," Vol. VIII. , 1889, p. 582. Plicque. Note sur I'exploration de I'uretere par le toucher vaginal et le toucher rectal. "Le Progres Med.," Vol. IX., 2 S., 1889, p. 235. Plowright (C. B.). On Calculous Disease. "The Lancet," 1886, Vol. II., P- 434- Ralfe (C. H.). On certain Nephralgias simulating Renal Calculus. "Brit. Med. Jour." 18S8, Vol. I., p. 182. On the use of Turpentine in the Treatment of Renal Calculi and Gall-Stones. "The Lancet," 1891, Vol. XL, p. 1271. Richards (E.). Remarks on the Fatty Transformation of the Kidney. " Brit. Med. Jour.," 1883, Vol. II., p. 2. Russell (J.). Case of complete obstructive suppression of Urine for twenty days. " Med. Times and Gaz.," 1879, Vol. I., p. 474. Salzmann (F.). De la frequence des calculs vesicaux en Finlande, et quelques mots sur leur traitement. " Finska lak. Handl., Helsingfors," Vol. XXIX., 1887, p. 115. Senator (H.). Ueber renale Hsemophilie. "Berlin klin. Woch.," 1891, No. I. TiRARD (N.). Some cases of Renal Colic. The "Lancet," 1892, Vol. I , p. 1 5. 400 Chapter XXIV. HYDRONEPHROSIS, PYONEPHROSIS, PYELITIS. The name hydronsp/wosis was originally invented by Rayer, to denote those cases of cystic kidney, in which the cysts are large, the contents water-like, and the apparent cause some obstruc- tion to the outflow of urine. The enlargement affects first the pelvis, afterwards the Calyces, and expands these at the expense of the kidney substance, which is stretched over them and converted by interstitial inflammation into fibrous tissue. Out of 3108 post mortem examinations, I met with 38 cases of hydronephrosis, or in V2 per cent. In 19 of these the affec- tion was bilateral, and of the remainder in 12, or 63 per cent, the left kidney only was involved. In more than half, the cause was obstruction to the urethra from stricture, or enlarged prostate or phimosis. Next, most commonly it was due to the pressure of some growth, e.g., cancer, aneurysm or hydatids, upon the ureter, or to occlusion of the ureter by the traction of procidentia uteri. Much more rarely it was due to calculus in the bladder, although in one instance double hydronephrosis originated in this way ; or it was the consequence of an injury, displacement of the kidney, congenital malformation or malposition of the ureters. Both ureters have been found bent twice upon themselves, while on the right side a constriction existed at the second curve (Livingstone) ; or the ureter opens into the pelvis of the kidney above its lower extremity, or at too acute an angle, or is guarded by valves (HARRINGTON Sainsbury), or the ureter may be compressed by a branch of the renal artery crossing it. Mobility of the kidney may give rise to hydronephrosis by kinking the ureter, and it is especially in these cases that we get the symptoms of intermittent hydronephrosis to be described further on. Among the rarer causes is that described by Knowsley Thornton, where the ureter was obstructed by a papillomatous HYDRONEr/fROS/S, PYONEPHROSIS, PYELITIS. 401 growth the size of a pea, capped by an oHve-shaped dark- brown calculus. The renal opening of the ureter has been found to be only a mere pin-point. Obstructions in the urethra and bladder would, presumably, cause double hydronephrosis, but there are curious exceptions to this rule. A boy with congenital stric- ture of the urethra was found to have hydronephrosis of one kidney, and granular contraction of the other (HUMPHREYS). It may be thought that stricture of the urethra being a somewhat remote, although common cause, is not capable of causing more than moderate expansion of the kidney. Un- doubtedly it is not associated with the largest tumours, but it may convert the kidney into a multilocular cyst with an outer wall not more than a quarter-of-an-inch thick. A rare cause of hydronephrosis is diabetes insipidus (see p. 384), where the condition is undoubtedly induced by the quan- tity of urine secreted exceeding the rate of outflow and so causing retention, which in course of time gradually expands and destroys the kidney. Mobility of the kidney is not a common appearance in the post inortem room, perhaps because the renal fat when cold holds the kidney more firmly than it did during life. It is perfectly certain that some cases of hydronephrosis have presented no visible obstruction to the outflow of urine. Kiister suggests that these cases may have been originally due to catarrh of the pelvis of the kidney. He says that it is not conceivable to have such a catarrh without some swelling of the mucous membrane by which the opening of the ureter becomes narrowed. During abundant secretion of urine, especially after drinking large quantities of fluid, a disproportion must ensue between the amount secreted and that leaving the kidney, and retention follows. When the intra-renal pressure is increased the swollen mucous membrane which is movable on the submucous layer, slips down in the direction of the stream, just as the mucous membrane of the bowel does in a hernia, and a fold is formed which constitutes a growing obstruction to the outflow of urine. When the dis- tension reaches a certain degree, it produces a change in the position of the kidney (SiMON), and causes complete occlusion of the ureter. Whether the secretion is more or less purulent depends upon the degree of suppuration which previously existed. The anatomical causes of hydronephrosis having been suffi- 26 402 MISCELLANEOUS RENAL DISEASES, ciently described, it only remains to discuss the resulting changes in the kidney itself. The distension of the organ varies in degree, in its minor forms amounting to more or less dilatation of the pelvis and calyces with flattening of the renal papillae ; but in the more pronounced cases the dilatation of these cavities increases until the kidney forms a lobulated sac, varying in size from a small cocoa-nut to a cyst filling half the abdominal cavity. On section the cyst is multilocular from the persistence of the walls of the calyces. It is lined through- out with a smooth mucous membrane, and there may be no trace of renal tissue recognisable by the naked eye. The change in the true kidney substance is due to interstitial inflammation, which destroys the tubules and glomeruli, re- placing them by indifferent connective tissue. Hydronephrosis, as already stated, is very often bilateral, but one kidney may be more advanced than the other, or one may be hydronephrotic and the other granular and contracted. It has happened more than once that one half of a horse-shoe kidney has become the subject of hydronephrosis, while the other remains healthy. From what has been said it is plain that the obstruction in hydronephrosis is never complete or permanent, at least in the earlier stages, and where complete closure or obliteration of the ureters is found, post utortem, this must have supervened after the development of the sac. Hydronephrosis occurs so frequently as a complication, or result of other more obvious conditions, that it is not uncom- mon for it to pass unsuspected or at least undiagnosed during life. Its earlier stages give rise to no symptoms, but later on there may be some pain or tenderness in one or both hypo- chondria, with vomiting, and perhaps shivering. In some cases severe vomiting, diarrhoea and abdominal pain, have been such as to recall the gastric crises of locomotor ataxy. The urine is rarely normal ; it usually contains a little albu- men and a few pus cells, while in the more advanced cases the amount of urea becomes greatly reduced. Ura^mic coma is the usual termination. The cases that are distinctly recognised during life are those in which hypochondriac pain leads to the discovery of a renal tumour. When large and distinctly fluctuating the diagnosis is easy, but in small cysts this sign may be absent, and the nature of the tumour can only be determined by aspirating some of its contents and testing for urea, although in old sacs this HYDRONEPHROSIS, PYONEPHROSIS, PYELITIS. 403 may have disappeared. As a rule renal tumours have the colon in front of them, and do not move on respiration ; but on the right side the colon may not have this relation to any appreciable extent, and movement on respiration may take place (FuRBRlNGER, KUSTER, ISRAEL). Hydronephrosis in a movable kidney is also an exception to this relation to the colon. The chief difficulty is to differentiate such a tumour from an ovarian cyst, but on vaginal examination no drawing-up of the uterus is found. The sac may discharge spontaneously through the ureter and never refill, or it may rupture into the peritonaeum, or even through the diaphragm into the lung, or it may suppurate and become pyonephrosis. Much attention has been lately directed to intermittent liydronephrosis, where the contents of the sac are discharged through the ureter from time to time, the tumour disappearing temporarily, but returning again. The usual history of these cases is that the patient goes about with a gradually increas- ing dragging pain in one side of the abdomen until forced at length to go to bed ; after a few days' rest the symptoms disappear and the patient gets up again. When under observation it is noticed that as the pain increases the urine diminishes, and a tumour forms in one or other hypochondrium. After going to bed, the urine be- comes greatly increased and the tumour disappears. These cases were first explained by Landau, and by him attributed to mobility of the kidney, and kinking or twisting of the ureter. From the description given by Kiaster of the mode in which hydronephrosis is brought about, when no anatomical obstruc- tion exists, it may be understood that position plays an important part in the process, and it is easy to realise the sequence of events which gives rise to this form. Case 81. — Jane , 47, was admitted on July 21st, 1888, complain- ing of a tumour in the right side of the abdomen. Eleven years before, about a week after a confinement, she had noticed a tumour, the size of a hen's &'g'g, just under the costal arch. There is no doubt that this was a floating kidney ; it was present for a day only and did not return for about three months, but she noticed it after this three or four times a year. It was a little painful but was not tender. Two years ago she observed a tumour in the right iliac region which gradually increased in size, rising higher up in the abdomen, and gradually disappeared after about three weeks. Six weeks later it returned, and continued to come and go in the same way at intervals of three, four, or five weeks. Then for a time the intervals became longer, but in April 1888 she grew worse, and went into the Workhouse 404 MISCELLANEOUS RENAL DISEASES. Infirmary, when she was told she had a "phantom tumour." On admission under my care, an oval smooth tumour could be felt in the right hypo- chondrium. It did not fluctuate, was painful and tender, and it did not move on respiration. The urine was very scanty, only lyi oz. being passed in sixteen hours after admission, and this contained a little albumen with leucocytes and squamous epithelium. The following day she had passed 52 oz. of urine and the tumour was much smaller. After a few days she was allowed to get up and the tumour returned, she was then sent back to bed and it disappeared. I was absent from home at the time of her ad- mission and when I saw her there was no tumour to be felt, and as she felt quite well she was discharged. On September 29th, she was re- admitted with pain, vomiting, and a large rounded swelhng in the right side of middle line of the abdomen. The swelling was movable and could be manipulated into the right hypochondrium when she was under an ansesthetic. It was aspirated, and bloody fluid drawn off which contained after removing the blood and albumen, 07 per cent, of urea, and gave crystals of nitrate of urea. The next day she had passed 27 oz. of bloody urine and the tumour was gone ! It did not return, and the patient was discharged, after the nature of her ailment had been explained to her ; but she was advised to go to bed whenever it troubled her. In addition she was provided with a well-fitting belt and pad, by which she kept fairly comfortable, and in June 1889, she was seen to be going on very well, having had only one relapse. This condition is much more common in women than men, in the proportion of 4 to i, and occurs more often on the right side than the left, in the ratio of 3 to 2, this being apparently dependent upon the greater frequency of mobility of the right kidney in women. The pregnant uterus may so compress the ureter as to prevent the recurrence of these attacks, or it may make them more frequent and more painful. On the other hand the presence of hydronephrosis places the pregnant woman in danger of abortion or premature confinement, of ursemic convulsions, or of death from suppression of urine. Intermittent hydronephrosis may become permanent in consequence of fibrous adhesions forming around the sac and strangling the ureter. Infection of the sac may take place at any time while the ureter remains open, converting the condi- tion into pyonephrosis, accompanied by more or less septic fever. Some cases of parovarian cyst may present these phenomena of temporary disappearance followed by increased secretion of urine owing to rupture of the cyst wall and discharge of its watery contents into the abdominal cavity, but the differential diagnosis is not difficult. The treatment of hydronephrosis may be {\^ palliative, or (2,) radical. Palliative treatment is only available in inter- mittent cases, where a pad and bandage may keep the kidney in place and prevent recurrence, or in very old standing cases HYDRONEPHROSIS, PYONEPHROSIS, PYELITIS. 405 where the health of the patient, or the great probabiHty of adhesions, may make extirpation out of the question, and a belt the only resource. Radical cure may be effected in the early stages of inter- mittent hydronephrosis by stitching the kidney in its place. Where mobility is not in question the kidney may be (i,) opened and drained, or (2,) extirpated. Although the former operation has effected a cure, as in a case reported by Tuckvvell and Symonds, as a rule a urinary fistula remains and extirpa- tion is to be preferred, but before this operation is sanctioned, we must be sure that the patient has a sufficiently sound kidney on the other side. We should be guided in our decision by the absence of pain, tenderness, or tumour on the presum- ably sound side, and above all by the elimination of a sufficient quantity of urea. Where pyonephrosis exists, extirpation is all the more urgently indicated, but it is too often impossible from the presence of adhesions ; it may be desirable to make an incision to let out pus, but such an operation is rarely attended with any satisfactory results. Rupture of the sac into the peritonaeum must be treated by prompt abdominal section, an operation which may save the patient's life, as was accomplished by my friend Mr. J. VV. Taylor, of Birmingham. Pyelitis is suppurative inflammation of the pelvis of the kidney. It was present in 35 instances out oi '^lo'^ post vior- tein examinations, and of this number it affected both kidneys in 28, or 80 per cent. Where one kidney only was affected, this was commonly the left — L. 5 ; R. 2. Its most common cause is cystitis, which accounts for fully half the cases. Next in frequency, but only accounting for about one sixth, is stone in the kidney. The other causes are tubercle, acute infective processes, such as enteric fever, pneu- monia, scarlatina, diphtheria, pyaemia, small-pox, infection in association with pressure upon the ureters, cancer of the bladder, etc. Th& pathogenesis of the condition is not always the same ; where it occurs in connection with diseases of the urinary passages, it is no doubt set up by infection through the ureters, but in the infectious processes the microbes reach the kidney through the blood. The most common symptom of pyelitis is pain in the loin, which may extend to both sides, and radiate down the leg. Pus is found in the urine. There ma}' be shivering, yawning, vomiting, and frequency of micturition ; in fact, the last 4o6 MISCELLANEOUS RENAL DISEASES. symptom may be the most serious trouble, and may be present when there is no cystitis, but giving rise to all the phenomena of irritable bladder. If the pyelitis is uncompli- cated by calculus or cystitis, the urine is acid and contains no crystals. Its differential diagnosis from calculus has already been considered. The condition may remain stationary, or go on to pyelonephrosis, or to perinephric abscess, or may subside and become cured, but its course depends very much upon the cause. The cases which are mosi; favourable are those which have originated in connection with infective pro- cesses, and are not complicated by any disorder of the lower urinary tract. The treatment of these cases is by rest in bed, milk diet, and the internal administration of alkalies and sandal-wood oil. Rest has a remarkable effect in alleviating the pain. Where other conditions exist which have excited the inflam- mation, these must receive appropriate treatment, which is mainly surgical, but simple cystitis improves greatly under this treatment. I generally order : — ^ Liq. Potassse - - - - 5ij Ol. Santal. flav. - - - 5ij Aq. Cinnamomi ad. - - - gviij M. Sig. — Two tablespoonfuls three times a day. Surgical treatment by drainage is absolutely useless, and incurs great risk of a urinary fistula. In mild cases, which we call pyelitis, a more serious operation is not justi- fiable, but in pyelonephrosis extirpation is the only means of cure, and if it is to be successful, must not be delayed long. Where the pyelitis causes constitutional symptoms which cannot be controlled by rest, surgical interference is both proper and necessary. BIBLIOGRAPHY. Coats (J.1. Cases of Hydronephrosis of unusual origin. " Glasgow Med. Journ.," Vol. XXXV., 1891, p. 342. Griffiths (J.). The Histological Changes in Hydronephrosis. "Path. Trans.," Vol. XL., 1889, p. 161. Humphreys (F. R.), Case of Congenital Stricture in a boy, where one kidney was hydronephrotic, the other granular. "The Lancet," 1891, Vol. I., p. 885. Knox (J. J.). Traumatic Hydronephrosis. "The Lancet," 1891, Vol. II., p. 1384- HYDRONEPHROSIS, PYONEPHROSIS, PYELITIS. 407 Landau (L.). Ueber intermittirende Hydronephrose. "Berlin, klin. Woch.," 1888., pp. 941 and 968. Livingstone (B.). On double Hydronephrosis from abnormal pending of the Ureters. " New York Med. Record." March 24, 1883. Lucas (CI.). The relation of movable kidney to Hydronephrosis. "Brit. Med. Journ.," 1891, Vol. II., p. 1343. Renvers. On gastric crises and intermittent Hydronephrosis. "Berlin, klin. Woch.," Dec. 31, 1888. Sainsbury (H.). Valvular obstruction of ureter ; Pyonephrosis. " Path. Trans.," Vol. XXXVII., 1886, p. 296. Saundby (R-). Case of intermittent Hydronephrosis. " Birm. Med. Review," Vol. XXVI., 1889, p. 155. Schede(M.). " Meine Erfahrungen iiber Nierenextirpationen." Hamburg, 1889. Schuchard (C). Ueber die Wichtigkeit geringer Verjinderungen der unteren Harnwege fiir die Entstehung von Hydronephrose. " Deutsche Ztschr. f. Chir.," Vol. XV., 1881, p. 610. Sonnenburg (E.). Beitrag zur Nierenextirpation wegen Pyonephrosis calculosa. "Berlin, klin. Woch.," Vol. XXI., 1884, p. 747. Steven (J. L.). The Pathology of Suppurative Inflammations of the Kidney. "Glasgow Med. Journ.," Vol. XXII., 1884, p. 161. Terrier and Baudouin. De I'hydronephrose intermittente. Paris, 1891. Thornton (J. K.). Hydronephrosis due to papilloma and calculus. "Path. Trans.," Vol XXXVI., 18S5, p. 269. 4o8 Chapter XXV. H.EMATURIA, H.EMOGLOBINURIA. The presence of blood in the urine is a symptom common to a number of pathological conditions, differing essentially in their seat, nature and relationships. It may appear in a corpuscu- lar or non-corpuscular form ; the former is called Jiceinaturia, the latter, hcBmoglobinuria. Blood may be mixed with the urine as it leaves the body, for example during menstruation, or whenever there is vaginal or uterine haemorrhage, or sometimes by bleeding from the rectum due to piles, etc. Haemorrhage from the urethra may be caused by villous growths or depend upon local congestion or injury. The blood is bright coloured, it may appear independently of micturition or at the beginning or end of the act, and is often accompanied by local pain and other symptoms pointing to its source. Haemorrhage takes place from the bladder when this is the seat of inflammation, ulcer, villous growth, cancer, stone, prosta- tic congestion, parasites, etc. These conditions have their own special symptoms, but the diagnosis of diseases of the bladder has acquired greater precision since the introduction of the cystoscopy Haemorrhage from the kidneys is due to numerous causes : — (i,) Local lesions : External injury, twisted or movable kidney, calculus,- tubercle, cancer, syphilis, embolism, parasites, congestion, inflammation (Bright's disease). (2,) Syniptoviatic : Blood diseases (purpura, scurvy, leucocy- thaemia, haemophilia), specific fevers. (3,) Toxic: Turpentine, cantharides, garden rhubarb (Boyd). (4,) Nem'otic or vicarious: Hysteria, insanity, asthma, men- struation, haemorrhoids. Blood from the renal substance is generally moderate in amount, altered in colour, and under the microscope is seen in the shape of casts of the renal tubules. Blood from the pelvis of the kidney may be more profuse, and form casts of the ureter, but never casts from the tubules. When blood has HALMATURIA, H.EMOGLOBINURIA. 409 been mixed with urine for some time its bright red colour becomes changed to dirty brown, and the urine may present all gradations of tint from a deep porter colour to mere smoki- ness. This change is due to conversion of the blood colouring matter from oxyh^emoglobin to methaemoglobin. Unaltered blood in the urine, even when present in small amount, may be recognised by its characteristic dichroism, that is, by reflected light it appears red, while by transmitted light it is green. The various tests by which the presence of blood in the urine may be detected are described in the chapter on the Clinical Examination of the Urine. External Injury causes laceration of the kidney substance, which if extensive may call for extirpation of the organ ; in most cases the wound heals and recovery takes place. The diagnosis presents few difficulties, and the treatment must depend upon the amount of haemorrhage, which, if great, will cause a tumour in the flank from eflusion into the neighbour- ing tissues. The treatment must be rest, an ice bag to the part, ergotin subcutaneously, and in the last resort extirpation. Case 82. Hematuria after Injury. — William C, aged 35, stone-mason, was admitted into the General Hospital on December loth, 1886, com- plaining of pain on the right side under the short ribs. A week ago he was crushed between a stone and some scaffolding just in the seat of pain ; and the next day there was pain on passing his water, which was "muddy" looking. His personal and family history were good ; he was well built and muscular, his heart sounds were feeble, his teeth were defective, his tongue dry and furred, and he complained of want of appetite with a foul taste in his mouth. When he first came to the hospital on December loth, he brought a specimen of urine which was red with blood, and in which there was a clot rather flattened in shape, about three-quarters of an inch in length, and three-sixteenths of an inch in diameter, probably a cast of the ureter. On microscopical examination the fluid contained "masses of granular matter, probalDly fibrinous, enclosing leucocytes and indistinct red blood corpuscles." Urine examined four hours and a half after it was passed contained numerous red cells, while the fibrinous masses were few and small. With rest in bed and a pad and bandage, the blood gradually disappeared, there being none on his discharge on January ist. Movable Kidney. — Closely connected with the foregoing are cases of persistent or intermittent ha^maturia dating from a blow or fall. It is supposed that the organ is partially dis- placed and rotated on its horizontal axis, so as to twist the vessels at the hilus, thus compressing the vein and causing passive congestion. The following case shows how severe, as well as persistent, such cases may be. 4IO MISCELLANEOUS RENAL DISEASES. Case 83. HcB7naturia from Displaced Kidney^ following a Fall. — A. R. B., aged 23, clerk, was admitted into hospital on November 2nd, 1886, complaining of hsematuria and pain in the loins, chiefly on the left side, aggravated by exertion. Four years before he had a bad fall from a bicycle, which was ioUowed by ha^maturia. This passed off", to return in March, 1886, after working at a forge in a metallurgical class at the Midland Institute. Finally, a few weeks later he was nearly run over, and in springing out of the way he seemed to strain his back. Since that time the haematuria persisted, in spite of rest in bed for fourteen weeks on milk diet. The quantity of urine was at no time diminished, and there was never any dropsy. His previous health had been good. On admis- sion there were no physical signs of disease or high arterial tension. The ophthalmoscopic appearances were normal. The urine was always suffici- ent in quantity, and contained a normal amount of urea. Blood casts were constant, but hyaline casts were rare, and an epithelial cast was only seen once. Mr. Langley Browne, of West Bromwich, under whose care he was, examined his bladder with negative results. The hseinaturia persisted, but for three weeks during the summer there was an intermis- sion. His general state was fairly satisfactory, but he was depressed and anaemic. He was treated unsuccessfully for a long time by a pad and bandage, and all kinds of htemostatic drugs, but ultimately got quite well. The next case has no history of injury, but probably belongs to this class, as the haematuria was relieved by rest and cured by a pad and bandage. Case 84. Hcsmaturia due to Re7ial Displacement: Temporary. — B. B., aged 18, warehouse boy, complained of pain in left lumbar region, which had existed for five or six years. He characterised the pain as dull and aching, worse when walking than while sitting. His previous health had been quite good, but his bowels were very confined. His urine was pale, clear, and contained a trace of albumen but no blood. With rest and attention to his bowels the pain left him, but on returning to his duties the pain returned, and the urine contained blood. He was then ordered to wear a pad and bandage, and a fortnight later was quite free from pain and the urine free from blood. Six weeks later this improvement was maintained, though there was still a trace of albumen. The diagnosis in this case depends mainly on the results of treatment, as there was no history of a IdIow or fall ; but it is supported by the disappearance of the haemorrhage during rest. The employment of an efficient bandage is of the utmost importance for the successful treatment of these cases. Calculus. — A medical friend of gouty habit and a great sufferer from oxaluria was getting into his brougham one day, when his horse started and flung him on the back seat in such a way as to bring on an acute pain in the left loin as if he had strained a muscle. Later in the day he vomited, and the pain was so great at night that he took opium to relieve it. The urine became bloody. In the course of twenty-four hours he passed a small oxalate of lime calculus, and his troubles ceased. This case shows that haematuria after a strain or blow may be caused H^.MATURIA, HA£MOGLOBINURIA. '411 by the displacementof a calculus which had formerly occupied some position in which it gave rise to no symptoms. Had the stone not passed the cause of the haemorrhage would have remained obscure or it might have been put down to partial displacement of the kidney. The symptoms of renal colic are tolerably characteristic. The pain shooting down towards the groin, with vomiting, and retraction of the testicle, are not met with in any other condition. It is noteworthy that the pain in biliary colic does not pass downwards to the abdomen, but radiates round the thorax, and is especially localised at a spot below the right shoulder blade. A medical friend whom I recently attended for biliary colic tells me that the worst pain of all was a feeling as if three or four vertebrae were being gripped by a pair of pincers. Confusion between these two conditions is impossible if hasmaturia is looked for and relied upon, as I believe it may be, as a constant symptom of renal colic, but it may not always be present in quantity sufficient to reveal itself to inspection with the naked eye. Conversely I hold that the diagnosis of calculus in the kidney is incomplete until hsematuria has occurred. The following case, probably also an example of renal twist or displacement, illustrates the difficulty of diagnosis of calculus from the symptoms of pain and haematuria alone. Case 85. Hcp.maturia due to Renal Twist. — Mrs. M., aj^^ed 43, was sent to me by Dr. Lycett, of Wolverhampton, with the history that she had been ill for four or five years, and had been told by her previous medical attendant and a physician in Birmingham that she had Bright's disease. Her symptoms were pain at the bottom of the back, worse on the left side, shooting down towards the groin, with albumen in the urine. She was a very stout woman, who had had six children very rapidly. At the time of her marriage she was very thin, but got stout during each pregnancy, becoming thin again after the first and second confinements She was never strong. There had never been any dropsy. The urine had been dark at times, but never like porter. Dr. Lycett had found that the urine was normal in amount and specific gravity, that the urea exxretion was not diminished, that there were never any renal casts, that the albumen was very small in amount and was frequently accompanied by blood ; oxalates and uric acid crystals were very abundant. As she made extreme complaints of the pain incapacitating her from all her duties, an exploratory incision was made by Mr. Tait, but no calculus could be found. The wound healed perfectly, and she left Mr. Tait's hospital quite free from pain and hfematuria, but these came on again in a i&\\^ weeks. I recommended an abdominal belt and pad, and this she wears, but still complains of pain. Her abdomen is very large, and the walls are very relaxed, so that it is difficult to apply pressure efficiently to the kidney. She is, however, no doubt much better than she was, and is certainly not the subject of Bright's disease. 412 MKCELLANEOUS RENAL DISEASES. It may be contended that the negative results of operation do not absolutely exclude calculus. In a case treated at one of our hospitals I believe a stone was passed per vias naturales after an exploratory incision had been made without success, so that we must allow that even surgeons are fallible, and we know that a stone of small size may give rise to marked symptoms without getting into the infundibulum. Tubercle. — Haematuria in tubercle is accompanied by pus and shreds of renal tissue. Tubercle most commonly causes pyelitis, and there is much more pus than blood in the urine. The diagnosis of tubercle depends largely on the constitu- tional condition and on family history. Cancer. — Haematuria is not always present in cancer ; when it is, it is very profuse. The diagnosis in some cases is easy, as a tumour may be felt, and deposits in other organs can be made out. Microscopic examination may show "cancer" cells, but these cannot be relied upon. In some cases the differ- ential diagnosis from calculus is very difficult The haemor- rhage is, perhaps, more profuse and persistent. The subjects of cancer may last a long time in fair health ; one patient of mine had suffered from haematuria for four years before I saw him, and lived quite two years afterwards. Mr. Chavasse made an exploratory incision under the belief (which I shared) that he had a calculus He recovered from this and died some time afterwards,. the post mortem examination, at which I was not present, showing cancer of the kidney and liver. Syphilis. — Gummatous deposits in the kidney are well known in the post mortem room, but their clinical phenomena have not been fully made out. In this respect the following case of syphilitic ulceration of throat accompanied by haemat- uria is of interest. Case 86. Syphilitic Sore Throat: Hcematiiria. — A. H., aged 19, an inmate of the Edgbaston Asylum, for the Bhnd, was admitted into hospital on March loth, 1887, complaining of her water being high-coloured and scanty and of deafness. Three years ago she sufifered in the same way. She had been blind from her birth, and since nine years of age had been an inmate of schools for the blind. Her mother was dead, but she could not tell the cause of her death. Her father and the rest of the family were living and healthy. She was a well-nourished girl, rather delicate looking. Cheeks flushed ; both cornea^ disorganised and staphylomat- ous ; no oedema anywhere ; thoracic and abdominal physical signs normal ; temperature 98'6° ; pulse 96 ; respiration 2J. Urine the day after admis- sion 32 ounces, specific gravity 1022, acid, turbid reddish in colour ; deposit consisted of red and white blood-corpuscles, urates, and squamous epithe- lium. On boiling there was a thick cloud of albumen, and the chemical HrEMATURIA, H/EMOGLOBINURIA. 413 reactions for blood were present. A very few hyaline casts were seen on only one occasion. The haematuria persisted for several weeks, but nine days after admission she began to complain of her throat, and liquids tended to come back through her nose. The pharynx and tonsils were very congested and covered with sticky muco-pus. Two days later a sloughy eroding ulcer appeared in the soft palate to the left of the uvula, which I have no doubt was syphilitic. In answer to inquiries she stated that her throat had been sore ever since the previous August. The ulcer was treated by the application of acid nitrate of mercury, and the patient took a mixture containing the perchlonde of mercury, combined with the perchloride of iron. The throat got slowly better, and on April i8th was nearly well, while at the same time the blood is noted to be "much less." On April 30th the liEematuria had entirely disappeared, and she was discharged cured. Embolism. — Embolism of the kidney is not an uncommon accident in heart disease, especially in vegetative endocarditis, also in pyaemia. Hsematuria occurring under these conditions may safely be attributed to embolism. Parasites. — Hydatid cysts in the kidney cause hsematuria, and can only be recognised by the passage of fragments of hydatid membrane in the urine. Bilharzia hsematobia, which generally attacks the bladder, may occur in the pelvis or sub- stance of the kidney, and manifests itself by the characteristic ova and embryos in the urine. Cojtgestion. — -Congestion may be active or passive. Active congestion is often only the initial stage of acute inflammation, a condition which very rarely attacks healthy kidneys, except during the course of acute specific diseases ; for example, scar- latina, diphtheria, tonsillitis, typhoid fever, etc. But such congestion also occurs when the functions of the skin are seriously interfered with, as by extensive burns, or more com- monly by chilling of the surface as in bathing, exposure to cold, etc. A few years ago a young man consulted me, saying that he believed he was passing blood. He had been to a swimming bath, and after returning home, noticed his urine was bloody. This was on Saturday, and on Monday, when I saw him, the urine contained only a trace of blood. By Wednesday the urine was normal. This patient told me that his brother had consulted Dr. A. H. Carter for haematuria following exposure to wet after playing football. The following case of persistent haematuria appears to me due to a special susceptibility to chill. These cases show that corpuscular blood may be passed as the result of chill. 414 MISCELLANEOUS RENAL DISEASES. Case 87. HcBmaturia due to Chill. — S. A., aged 19, came to me in December, 1886, complaining that his urine had been bloody for the last three weeks. Eighteen months before, in June or July, he first passed coffee-coloured urine for one day after playing cricket. He could not remember any blow or fall having preceded it. He had no shivering fit, and felt quite well. His previous health had been good, but he had been very subject to chilblains on his feet in summer as well as in winter, and his hands and feet easily get cold. He was a well-developed, fairly well nourished lad, with no objective signs of organic disease, but his face and hands had a congested and cyanotic look. He suffered no pain or uneasi- ness, had never had syphilis, jaundice, or dropsy, and had never been out of this country, but he had been at Cambridge for the last two years. The urine was dark amber, acid, 1018, with brown, flocculent deposit, composed of red and white blood corpuscles, spermatozoa, blood casts, a few hyaline casts, and granular matter. The quantity of urine was 50 ounces, and the excretion of urea 300 grains ^^r ^z>;;z. The quantity of albumen was not more than was accounted for by the blood. In spite of careful clothing and staying indoors, the hematuria persisted. At the beginning of the May term he went back to Cambridge, and kept much the same, well in himself, but the urine persistently bloody, though never very bad. It was no better in the very hot weather than it has been since it has turned colder. He has been playing tennis, and taking other exercise freely. I saw him again on October 8th, and found no change except an occasional intermission in the pulse, which was rather small. The urine was amber, acid, 1014, contained blood, and one-twelfth column of albumen. The deposit consisted of blood, oxalates, a few blood casts, and hyaline casts with blood corpuscles sticking to them. He has since entirely lost his liability to these attacks, and he now looks a strong man. Passive Congestion. — Venous engorgement, consequent upon liver, heart, or lung disease, may cause slight hsematuria. The condition is easily understood, and readily recognised. BrigJifs Disease. — In acute nephritis, more or less haemor- rhage occurs, and persists throughout the acute stage. The diagnosis depends upon the other evidences of Bright's dis- ease — for example, dropsy, and the presence of epithelial casts in the urine. In chronic Bright's disease, haemorrhage is not constant, but may occur at any time. The amount is usually moderate, but, in rare instances, may be alarmingly profuse and fatal. The recognition of the nature of the case depends on the presence of casts in the urine and other confirmatory signs — such as polyuria, low specific gravity of urine, cardiac hypertrophy, high arterial tension, albuminuric retinitis, etc. Syniptoniatic Hcematuria. — Haematuria occurring in connec- tion with specific diseases, such as yellow fever, malarial fever, and cholera, or in the course of blood diseases, such as purpura, haemophilia, scurvy, and leucocythaemia, depends for its correct diagnosis on the recognition of these diseases, each of which possesses well marked symptoms and definite clinical relations. HEMATURIA, H.^MOGLOBINURIA. 415 Case 88. Purpura Hceinorrhagicaj Hematuria; Recovery. Harold N., cCtat. 3, admitted into hospital May 27th, 1888, with purpuric rash and hasmaturia. He came of a healthy family with no evident tend- ency to rheumatism, htemorrhage or bruising. A year ago he had measles but had been quite well since. He had never previously had any spots on his skin, nor had his mother noticed that he bruised easily, or had ever passed blood before in his urine ; he had been well fed, mostly on bread, pudding and potatoes with green vegetables about twice a week, but not much meat. For some time he had had a little cough in the morning. Six days before admission he seemed ill and did not play as usual ; this con- tinued all the week, and on the day before admission his mother noticed when washing him that there were a few spots on his skin which she took for flea bites. In the afternoon he began to pass blood in his urine, which was quite red ; at night there were no more spots, but on the morning of admission she noticed spots all over his body and limbs, and his urine was still bloody. There had been no nose-bleeding, but on two mornings there was a thin line of dried blood on his lips. The motions had not been black or mixed with blood. Patient was a well-nourished, rosy-cheeked, well-cared-for child. The spots varied in size from half an inch in diameter down to pins' heads, and were circular in shape and of a purple colour ; they were most num- erous on the right side of the abdomen, but were present more or less over the entire surface. There were two marks like bruises on the back. A little patch of dried blood was on the upper lip. The tongue was pale, bowels open, motions free from blood ; temp. 99°, pulse 1 12, r. 28. There were a few rales and rhonchi over the chest and a little cough. The urine passed soon after admission was bright red in colour, and looked like pure blood ; it was acid, and under the microscope there were numerous blood corpuscles. The blood taken by puncture from the skin contained a normal number of hasmocytes, but the haemoglobin was reduced to 40 per cent. At noon he was given a draught containing half an ounce of tur- pentine and half an ounce of castor oil ; he vomited a little at 3 p.m., and his bowels were open at night ; the motion was free from blood. The next day the htematuria was quite as great. May 29th. — Hsematuria persisting ; still blood on lips in morning ; a fresh crop of spots noted on the left side of the body. At 1 1.45 a.m. he had ergotin, gr. j. subcutaneously. Blood again examined, and found to contain 120 per cent, of red corpuscles ; from one to three leucocytes in the field at once. In the evening, as the hasmaturia was unchecked, the injection of ergotin was repeated. At 9 p.m. he vomited and passed more bloody urine. His temperature ran up to ioo'6, p. 144, r. 30, and he complained of thirst and cough. After midnight he slept well, and his temperature came down. The next morning (May 30th) the urine was only smoky. On the 27th Dr. Crooke examined the blood for micro- organisms, and attempted to make a gelatine cultivation, but the results were negative. There was no enlargement of the liver or spleen. The ergotin was repeated, as the urine continued to be smoky, till late in the evening, when it was free from blood. xAfter this date (May 31st) there was no more hjematuria, but a few fresh spots were noted on June 2nd, and on the same day there was slight epistaxis, the amount of blood lost not exceeding one drachm. The injections of ergotin were stopped on June 5th, and the same quantity, on pain, being given by the mouth for 4i6 MISCELLANEOUS RENAL DISEASES. two days longer. He was then ordered Parrish's syrup, and on the llth was made an out-paiient, but remained quite well and was discharged. Toxic HcEinaturia. — Haematuria may follow the application of a fly blister or the internal administration of cantharides. The latter is seldom practised, but the drug has been recom- mended on quasi-homoeopathic principles by Dr. Sydney Ringer for nephritis, and in that condition I have seen it even in one-minim doses cause distinct hsematuria. When given for criminal purposes the dose is usually large, and the haematuria is accompanied by strangury, vomiting and symp- toms of irritant poisoning. Turpentine does not generally cause hsematuria, though the readiness with which the violet odour appears in the urine shows that it is absorbed and excreted by the kidney. I have had one very interesting example of haematuria due to this cause in a varnish maker who was sent to be examined for life insurance. He seemed a perfectly healthy man, but after he had gone I examined his urine, and found it contained a little albumen. I then noticed the odour of violets, and closer examination showed that the albumen was due to the presence of blood. There were no other evidences of renal disease, but there was certainly some special suscepti- bility to the action of turpentine, as this gentleman informed me that he was not personally engaged in the manufacturing processes, though he was much about the factory. I tried to follow up the case, but could not, as he abandoned the proposal. The influence of garden rhubarb in causing haematuria was well attested by a quite voluminous correspondence in the Lancet a few years ago, many of the writers giving their own personal experience ; the young forced vegetable seems to be free from this inconvenience. It is generally attributed to the production of an excessive quantity of oxalates, but this ex- planation has not been demonstrated. Neurotic and Vicarious Hceniaturia. — I have no personal experience of these conditions. Laycock mentions haematuria as not uncommon in hysteria, but I have never recognised a case, though I have certainly met with one or two cases of haematuria in women which I have not ventured to class. Sir W. Roberts mentions menstruation, haemorrhoids, and asthma as conditions in which vicarious or supplementary haematuria occurs, but I can only leave the matter without further com- ment, as I have never met with such cases. Dr. G. H. Savage states that h;tmaturia may occur spontaneously in acute mania and general paralysis. H/EMATURTA, HEMOGLOBINURIA. ^17 HAEMOGLOBIN URIA. — This condition depends upon the dissolution of the red blood corpuscles in the body, and the presence of free haemoglobin in the liquor sanguinis. Under these circumstances the haemoglobin escapes through the Malpighian tufts, and appears in the urine. The determining causes of this change are not clearly known. Certain organic and inorganic poisons have this property of breaking up the blood corpuscles by direct action upon them. In many septic and infective processes, puerperal fever, pyaemia, etc., haemo- globinaemia occurs. Physiologists now believe, but it is not formally established, that the red blood corpuscles are broken up and converted in the liver into bile pigment. It is supposed that in disease this process is interfered with, the destruction taking place in excess of the power of conversion, or the l^rocess stopping short at the stage of destruction. Paroxysmal Hczinoglobinuria differs essentially from the above. Practically nothing was known of it until twenty years, when Dr. George Harley published two cases under the title of intermittent haematuria, and it was almost simul- taneously described by Dr. Arthur Hill Hassall as intermittent or winter haematuria. Later on Pavy called it paroxysmal haematuria. As it came to be recognised that blood colouring matter, and not blood corpuscles, was present in the urine it acquired the name of paroxysmal haematinuria, and in 1872 this was changed by Lebert to paroxysmal haemoglobinuria in consequence of the discovery by Gschleiden that the spec- troscope showed the colouring matter to be not haematin, but haemoglobin or methaemoglobin. Mesnet, in 1881, suggested the title of haemoglobinuria a frigore, which suggests its true pathogeny. It is most common in young adults, but affects all ages, and both sexes, although it is very much less common in females. The exciting cause is unquestionably a chill. An interesting apparent exception was published by Rosenbach, in the case of a boy whose attacks were more common in summer than in winter, but it turned out that he was kept in a warm room in the winter, while in summer he was allowed to go out and play. It has often been observed that patients are specially liable to be attacked when, or after, making consider- able muscular exertion. Nothing is known definitely about the predisposing causes, except that a history of syphilis has been obtained in some cases and good results have been alleged to follow antisyphilitic treatment in some of these. It is closely allied to Raynaud's disease and is sometimes associated 27 41 8 MISCELLANEOUS RENAL DISEASES. with it. There is no doubt that the blood corpuscles are broken up during the stasis of the blood in the peripheral parts exposed to cold, — the hands, ears, nose, etc. It has been pro- duced at will, in susceptible persons, by plunging their hands into cold water, and free haemoglobin may be found in the blood serum (Hayem). The attacks are sometimes preceded by a distinct rigor, or by yawning, formication, or headache ; the temperature may fall below normal, in one example as low as 96'!° in the axilla, with lividity of the hands, feet and ears. These premonitory symptoms are followed by lassitude, weak- ness, pains in the back and limbs, and a desire to make water ; on voiding urine the patient is astonished to see that it con- tains blood. The temperature may rise during the attack to a considerable height ; the attack may last a few hours or several days. The skin and conjunctivae have been observed to become a peculiar dusky colour ; some patients have been described as jaundiced. There is often profuse sweating, sometimes confined to certain localities as the forehead or hands. Case 89. Paroxysmal HcEinoglobinitria. — K. G., aged 28, a labourer, was admitted into hospital on February 22nd, 18S6, complaining of shiver- ing, pain in the back and legs, and bloody urine, which had lasted since the previous morning. He had been subject to these attacks for the last three winters ; the first came on while working in a cold wind in the early winter of 1881. There was no history of ague or residence in a malarial district. He had had syphilis, a chancre followed by a skin eruption ten years before. He fell from a scaffold in 1879, a-i^d had a blow on the head three years ago ; but these were not in any way related to his attacks.- While in hospital he had a well-marked attack, which I will relate in detail. On March 4th, his temperature was normal ; he passed 40 ounces of urine, which was quite normal in every respect. March 5th was a clear but very cold day, and he went into the yard between 9 and 10 a.m., for twenty minutes. At 10.30 he began to shiver ; temperature 98^. At 10.45 he passed urine, which contained a trace of albumen, and gave a faint haemoglobin reaction. At i i.o his temperature was 100°. At 11.15 h^ passed 2 ounces of urine, which looked like pure blood ; this was at once examined microscopically, and showed no blood corpuscles, but a few round cells, much granular matter, granular casts, and oxalates. The spleen was distinctly enlarged, reaching 2 inches below the costal border. 11.30, Temperature 105*; five minutes later he vomited. 12 noon. Temperature 106° ; pulse 124 ; respiration 44. 12.30, Temperature 105*' ; sweating profusely ; complained of rushing noises in his head as soon as he began to get warm, and pain in his back when the attack came on, but these have now left him. i.o p.m. Temper- ature 105° ; copious faintly acid sweat ; complains again of pain in the back. 2.0, Temperature 104" ; urine like tawny port, faintly acid, 1015 ; deposit under the microscope does not differ from that previously des- HEMATURIA, H HEMOGLOBINURIA. 419 cribed ; tested for indican with HCl and CaClo gives a rose pink colour, indigo red. 3.0, Temperature 102° ; pulse 116. 4.0, Temperature 101°. 5.0, Temperature loo'^. 6.0, Temperature 100'' ; has stopped sweating about half an hour ; no pain in the back ; pulse 88; difficulty in com- mencing to pass water ; urine amber, 1014, faintly acid ; deposits a brownish cloud, which gave the haemoglobin reaction, and, under the microscope, was composed of granular matter. 6.30, Temperature gg''. 9.0, Temperature 98°. ii.o, Temperature 98'5°; urine pale amber, 1017 ; deposits a mucous cloud, acid ; gives hccmoglobin reaction. March 6th. — 8.10 a.m. Temperature 98°; pulse 80 ; urine 1023, acid, amber ; very little granular deposit ; slight reaction with guaiacum ; spleen cannot be felt. The urine passed later in the day contained only a faint trace of albumen ; bowels confined. March 7th. — Urine free from albumen; complains of headache; tongue foul ; bowels open. He had another slight attack before leaving hospital, and was finally discharged on March 31st, but has been in hospital since. The next case differs from the preceding in the absence of pyrexia. Case 90. Paroxysmal Hcemoglobiniiria. — J. E., 86, boiler-maker, was admitted into hospital on October i8th, 1886, complaining of chills, and passing bloody urine. He said that thirteen years ago, on a cold day in early winter, he was hard at work, when his feet suddenly became cold, and the next urine he passed contained blood. Since then he has been liable to these attacks every month or three weeks throughout the cold weather. He had never lived further than eight miles away from Birming- ham, had never had ague or syphilis, but had drunk a good deal of beer. He was a stoutly-built, florid-complexioned man. Physical signs normal. Temperature on admission 99°, afterwards generally below 98° ; urine 1024, acid, brownish red ; urea 2'6 per cent., contained albumen, haemo- globin, hyaline casts, yellowish brown granular matter, oxalates, no blood corpuscles. He said that he has occasionally pains in his back preceded by a chill, which commences in his feet and passes upwards ; the muscles of his legs twitch. The chill lasts about two hours, and when he gets warm he passes a large quantity of dark coloured urine, and the pain in his back goes away. He attributed his present attack to getting wet the day before. His conjunctivse were slightly yellow, and he says when he is very bad his eyes are very yellow. An attempt was made to get some blood serum by means of a blister, but this did not rise. The urine became normal by the 21st, and he left the hospital on November ist. The colouring of the conjunctivae is evidence of free colour- ing matter in the blood. The observations in Case 89 made on the urine directly it was passed disprove the statement that blood corpuscles are always present in the urine at that stage; but there is a strong resemblance between these cases and those of hasmaturia due to chill (see Case 87). It is worth bearing in mind that albuminuria is occasionally persistent in these cases, and Dr. Ralfe believed that this is due 420 MISCELLANEOUS RENAL DISEASES. to a permanent inability to dispose of the albuminous material set free by the destruction of the red blood corpuscles. But if this were true, the albumen excreted should be globulin, not serum albumen, a suggestion already made some years ago by Sir William Gull. I have endeavoured to test the truth of this hypothesis, but my analyses always showed that serum albumen was present as well as globulin. These attacks are not dangerous to life, but end in recovery after a longer or shorter time, and except for some anaemia and the liability to relapse, the patient enjoys good health. In some cases the predisposition ceases abruptly, but in others it persists throughout life, and in one notable case was not benefited even by residence in a tropical climate (Madras). It is doubtful whether remedies have any decided effect, on account of the tendency which the condition has to disappear spontaneously, but Begbie thought scruple doses of chloride of ammonium cured his case. After the attacks the administra- tion of iron is indicated. Susceptible persons should avoid chills by suitable clothing, and when circumstances permit, the winter should be spent in a warm climate. BIBLIOGRAPHY. Begbie (J. W.). Hsematinuria. "Edin. Med. Journ.," Vol. XX., 1875, p. 1005. Boyd (F. D.). Oxaluria and Hasmaturia. "The Lancet," 1891, II., p. 927. Druitt (R.). Two cases of Intermittent Haematinuria. " Med. Times and Gaz.," 1873, I., pp. 408, 461, 489. Gull (W. W.). A case of Intermittent Haematinuria, with Remarks. " Guy's Hosp. Rep.," Vol. XII., 3 S., p. 381. Harley (G.). Intermittent Haematuria. " Med. Chir. Trans.," Vol. XLVIIL, 1865, p. 161. Hassall (A. H.). Intermittent or Winter Hcematuria. "The Lancet," 1865, II., p. 369. Laycock (T.). Nervous Diseases of Women, p. 229. Lebert. Ein Fall von Hamoglobinurie. " Berl. klin. Woch.," May 13th, 1872. Mesnet. De I'hemoglobinurie a frigore. "Arch. gen. de Med.," 1881, I. P- 513- Pavy (F. W.). Paroxysmal Hasmaturia. " The Lancet," 1866, II., p. 33. RosENBACK (O.). Beitrag zur Lehre von der period ischen Hamoglobinurie. ■' Berl. klin. Woch.," XVII., 1880, p. 132. Saundby (R.). The diagnostic significance of Haematuria. "Brit. Med. Journ.," 1887, II., p. 1320. Purpura: a clinical study. " Birm. Med. Review," Vol. XXVI., 1889, p. 65. Paroxysmal Haemoglobinuria. " Birm. Med, Review," Vol. XL. 1882, p. 97. Senator (H.). Ueber renale Haemophilie. "Berlin klin. Woch," iSgij No. I. 421 INDEX. 272 253 201 332 200, 333, 336 Abadie, p. 75 ; Abeles, 225 ; Abraham, 263, 264 ; Addison, 295 ; Albertoni, 278 ; Almen, 229 ; Althaus, 387 ; Anderson, 75, 195, 305 ; Andral, 30, 299; Apt, 272; Aretaeus, 219; Arthaud, 192, 226, 228, 231, 266, 268 ; Arthus, 228 ; Auerbach, 246 ; Aufrecht, 39, 98 Abscess of the Rver Abscesses as a cause of glyco- suria Aceto-acetic acid Acetonseraia Acetone — in blood . . . . . . 270 Acid albumen . . . . . . 8 — blood 68 — phosphate of soda . . . . 185 Acne pustules in diabetics . . 292 Acromegaly associated with en- larged thyroid and diabetes . . 255 Acute and chronic infective dis- eases . . . . . . . . 92 — diabetes . . . . . . 284 — febrile glycosuria . . . . 285 — infective nephritis, blood in 100 complications of . . 102 — — — diagnosis of . . . . 102 — — — dropsy in . . . . 99 — duration of . . . . 102 — — — heart in . . . . 100 — — — histology of . . . . 98 — ■ illustrative cases of .. 103 — — — morbid anatomy of . . 98 oedema of the conjunc- tiva in . . . . . . . . 100 of the lungs and glottis in . . . . . . 100 — ophthalmoscopic ap- pearances in . . . . . . loi prognosis of . . . . 102 — — -- pulse in .. .. 100 — — — symptoms and course of 99 — — — temperature in . . 100 — treatment of . . . . 106 — — — urine in . . . . loi PAGE Acute nephritis, dropsy of . . 26 — oedema of lungs in Bright's disease . . . . . . . . 161 — peritonitis — rheumatism as cause of dia betes 320 256 — tonsillitis as cause of diabetes 249 Adventitia, thickening of Afferent vessels African and Mongolian races immunity of Age in diabetes Albumen Albuminuria . . . . 170 — of adolescence — cyclical . . — following paroxysmal hasmo globinuria — food ■ — • functional — hasmatogenous — mechanism of . . — neurotic — parenchymatous theory of — pathology of . . — remittent — vascular theory of Albumose . . Alcapton . . Alcohol and lithaemic kidney effects of . . 92, 363 — intolerance of . . — tolerance of . . Alimentary system in Bright disease . . Alkali albumen Alkalies Almond cakes America, diabetes in Ammoniacal urine Amorphous phosphate of lime . — urate of soda . . Anaemia in diabetes Analyses of foods . . Anatomy of the kidney . . Angina pectoris . . Antipyrin . . 78 4 242 244 203 290 14 14 419 16 8 22 15 22 I- 23 14 20, 23 9 196 120 379 383 383 164 8 173 360 241 184 187 193 286 360 318 370 422 INDEX. Aortic second sound, accentuation of 129 Appetite in diabetes . . . . 285 Arao-saccharometer . . . . 200 Armanni's lesion in diabetes 278, 279 Arsenite of bromine . . . . 369 Arterio-capillary fibrosis 49, 85 Arterioles, tonic spasm of ■ • 47 Artichokes, Jerusalem . . . . 363 Articular gout and nephritis, connection between .. ..119 Ascending nephritis . . . . 140 Aspergillus niger . . . . ■ . . 212 Atrophic changes in retina sec- ondary to inflammation . . 70 Atrophy of optic nerve . . • • 315 pancreas . . . . 274, 275 Ayur Veda 218 Babington, p. 285 ; Bamberger, 22, 44, 49, 85, 90, 98, 322 ; Barie, 154; Barling, 271, 335; Barnes, 304 ; Barreswil, 16 ; Bartels, 25, 26, 28, 29, 36, 47, 50, 58, 65, 85, 126, 127, 190 ; Baumann, 220 ; Baumel, 273, 275 ; Beale, 195, 273 ; Beck, 225 ; Belfanti, 9, 213 ; Bennett (Hughes) 256, 378 ; Bennewitz, 256 ; Berlioz, 189, 212 ; Ber- nard (Claude) 22, 220, 223, 225, 322, 357, 376 ; Bertillon, 237, 245 ; Biernocki, 164 ; Binz, 334 ; Black-Milne, 93 ; Black- all (of Exeter), 83 ; Blanc, 303 ; Bluhm, 97; Bock, 31 ; Bodeker, 196; Boinet, 154, 214; Bond, 255; 331 ; Bordier, 325 ; Bos- tock, 50 ; Bouchard, 9, 67, 68, 97, 186, 214, 304 ; Bouchardat, 220, 274, 357, 384 ; Bouillaud, 50 ; Bourneviile, 157 ; Brault, 272, 275 ; Braun, 67 ; Bremer, 286 ; Breusing, 214 ; Brieger, 154. 333; Bright, 46, 53, 66, 83, 84; Brissaud, 156; Bristowe, 295 ; Broadbent, 54 ; Brown- Sequard, 16 ; Briicke, 17, 222 ; Brush, 152 ; Brunton (Lauder), 16, 34, 205, 386, 387; Buhl, 49, 53 ; Burton, 229 ; Butel, 289 ; Batlin, 394; Butte, 192, 226, 228, 231, 266, 268 Bacillus pyocyaneus . . . . 213 — tuberculosis . . . . . . 212 Bacteruria . . . . . . . . 212 Baths and bathing 169, 367, 388 Bechamp's " nephrozymose " Beer as a cause of diabetes . 214 ,. 247 370, 372 •• 334 . . 201 . . 201 . . 201 . . 201 . . 169 .. 280 •• 383 .. 68 .. 36 378 4 100 207 377 286 253 292 Benzosol in diabetes /S-oxybutyric acid . . Bile acids . . — pigment Bilirubin . . Biliverdin . . Black Forest Bladder in diabetes — irritable Blood, acid — casts — loss of, as a cause of diabetes — vessels . . — in acute nephritis — — chronic nephritis . . . . iii — — ■ diabetes . . 270, 286, 379 — — lithsemic nephritis . . 127 the urine Blows as exciting causes of dia- betes Body weight, fluctuations of Boils as a cause of glycosuria . . — in diabetics Boundary zone of medullary layer Bournemouth Bowels, regulation of the Bowman's capsules Bradshaw lecture . . Braemar Brain in diabetes . . — substance, haemorrhage into Bright' s disease, acute, more common in children Bright's ■ priority of dis- covery of . . . . . • 83 chronic, increase of . . 88 classification of . . 83, 86 — — complications of chronic 148 — — deaths in England and Wales from . . . . . . 87 — — exciting causes of . . 92 general etiology of 83, 87 — — history of . . . . . . 83 in Holland, Denmark, Scandinavia . . . . . . 89 — — more frequent after middle life . . . . . . . . go obstructive causes of . . 94 occupations liable to . . 92 predisposing causes of 87, 92 — — tendency in, to attack members of the same family . . 91 treatment of . . . . 167 in the United States . . 8g 169 373 2 262 169 263 264 90 INDEX. 423 Bromide of potassium as a cause of diabetes . . . . . . 249 in diabetes . . . . 369 Bronchitis in Bright's disease . . 162 Bronzing of tlie skin . . . . 294 Burns as a cause of glycosuria . . 253 Butcher's meat, excessive use of 120 Buxton . . . . . . . . 169 Calmette, p. 250 ; Cantani, 274, 332 ; Carr, 157 ; Carter (Bru- denell), 77; Carter (W.), 17, 65, 68, 177; Cauldwell, 370; Cavazzani, 267 ; Cayala, 325 ; Celsus,2i9; Chantemesse, 156; Charcot, 22, 85, 119, 156, 386; Charles (Duke), of Bavaria, 72 ; Charrin, 97 ; Chauveau, 225, 22S ; Chevers (Norman), 240, 246 ; Chovstek, 288 ; Christison, 16, 30, 50, 58, 65, 66, 12S ; Clarke, 387; Clubbe, 387; Cohen (Solis), 370 ; Cohn- heim, 28, 29, 34; Colasanti, 194; Coldstream, 243 ; Collins, 75, 80, 288 ; Cook, 192 , Copeman, 2og ; Cornillon, 299 ; Cornish, 239 ; Cotunnius, 83 ; CuUen, 219, 376 ; Cyon, 226 ; Czapek, 291 Calculi, pancreatic . . . . 275 Calculus . . . . . . . . 410 Calices . . . . . . . . 6 Callard's brown loaf and biscuit food, analysis of . . . . 360 Camphor in diabetes . . . . 370 Cancer as a cause of glycosuria 253 — of kidney .. .. .. 412 — — the pancreas . . . . 274 Cantani's theory . . . . . . 234 Capsule of the kidney . . . . i Carbonate of lime . . . . 187 — — soda in diabetes . . . . 370 Carbuncles in diabetics . . . . 292 Cardio-vascular changes . . • • 43 Carlsbad . . . . . . . . 365 Casts, varieties of . . . . 36, 209 Cataract, diabetic . . . . 305 Catarrh of the stomach . . 164, 276 Catarrhal laryngitis in Bright's disease . . . . . . . . 161 Cellulitis in diabetes . . . . 296 Cerebro-spinal nerves . . . . 266 Ceylon, prevalence of diabetes in 239 Changes observed in the retina Chatel-Guyon Chemical composition of urine — theory of uraemia 70 365 184 64 PAGE Cheyne-Stokes breathing . . 152 Chill, influence of. . .. 89,379 China, diabetes in . . . . 240 Chlorides . . . . . . . . 184 Chloroform as a cause of diabetes 249 Cholesterin . . . . . . 203 Choroid plexus, cysts on . . 264 Choroidal haemorrhage . . . . 78 Chronic Bright's disease, compli- cations of . . . . . . 148 — catarrh of stomach . . . . 276 — diabetes . . . . . . 284 — heart, lung, and liver diseases 92 — infective nephritis, blood in., iii — ■ diagnosis of .. .. iii — — — dropsy in .. ..no — duration of .. ..112 etiology of . . . . 108 heart in . . . . . . no — illustrative cases of . . 112 — — — morbid anatomy of . . 108 — ophthalmoscopic ap- pearances in .. .. ..Ill — — — prognosis of . . .. 112 — pulse in.. .. ..in — symptoms and course no treatment of .. ..114 — — — urine in .. ..in — pachymeningitis in Bright's disease . . . . . . . . 160 Chyluria .. .. .. 181,202 — endemic . . . . . . 202 Cider as a cause of diabetes . . 247 Circulatory system in diabetes 268, 318 Cirrhosis of liver . . . . 272, 321 pancreas . . . . . . 275 Classification of Bright's disease 86 Clemens' solution . . . . 369 Climacteric diabetes . . . . 257 Climate in Bright's disease . . 168 diabetes . . . . . . 363 Clothing . . . . . . . . 169 Cocaine in diabetes . . . . 370 Cocoa-nut cakes . . . . . . 361 Codeine . . . . . . . . 368 Cohnheim's experiments. . . . 29 Cold as a cause of diabetes 254, 379 — bathing. . . . . . . . 169 — climates . . . . . . 254 — fluids, effect of drinking . . 379 Colic, pancreatic . . . . . . 320 — renal . . . . . . 392, 398 Collecting tube of kidney . . 3 Colloid casts . . . . . . 38 — degeneration of vessels of choroid . . . . . . . . 78 424 INDEX. PAGE Colour of urine in diabetes . . 288 Coma, diabetic . . . . . . 330 — treatment of . . . . . . 177 Complexion in diabetes . . . . 284 Congestion of kidney . . . . 413 — passive . . . . . . 414 lungs in Bright's disease. . 161 Connective tissue of kidney . . 6 Contrexeville . . . . 170, 365 Contusions as a cause of diabetes 377 Convulsions . . . . . . 342 — treatment of . . . . . . 176 Cortical layer . . . . . . i Creasote in diabetes . . . . 370 Croupous inflammation of larynx in diabetes . . . . . . 316 Crystalline phosphate of lime . . 186 — urate of soda . . . . . . 193 Cyst, pancreatic . . . . . . 379 Cystin . . . . . . . . 195 Cysts on choroid plexus . . . . 264 Dale, p. 252; Dalton, 223; Dastre, 223 ; Davenport, 257 ; Deane, 244 ; Debove, 249 ; Decker, 252 ; Denissenko, 72 ; Desgranges, 386 ; Desmarres, -07; Deutschmann, 304; Devic (Roque), 271,286; Devoto, 9 ; Dickinson, 43, 117, 120, 127, 258, 263, 264, 272, 373, 379, 380; Dieulafoy, 118, 153, 154; Dobrowolsky, 70 ; Dobson, 219; Dommergues, 153; Don- ders, 28 ; Dornbllith, 370 ; Dougall, 370; Douglas, 8; Downie, 153 ; Draper, 370 ; Dreschfeld, 253, 271, 274, 335 ; Dreyfous, 249, 304 ; Drum- mond, 378 ; Duckworth (Dyce), 256 ; Duffey, 274 ; Dufour, 222 ; Dujardin-Beaumetz, 361, 362, 370 ; DuncaTi, 267, 305 ; Duncan (Matthews), 257, 377, 378 ; Durham, 252 Dahlia tubers 363 Deposits of crystals of urea on 151 V5 284 284 284 292 292 237 237 the skin Detachment of retina Diabetes, acute — chronic . . — clinical history of — complications of - — duration of — etiology of — geographical distribution of — history of PAGE Diabetes, pancreatic, cases of . . 274 — pathogeny of . . . . . . 231 — predisposing causes of . . 237 — prognosis of . . . . . . 291 — termination of. . .. .. 292 — treatment of . . . . . . 357 of symptoms . . . . 372 — in America . . . . . . 241 — — China . . . . . . 240 Japan . . . . . . 241 Mauritius . . . . . . 241 — — Persia . . . . . . 241 Singapore . . . . . . 240 — insipidus . . . . . . 376 — — duration of . . . . . . 386 — — ■ etiology of . . . . . . 376 exciting causes of . . . . 377 heredity in . . . . . . 377 morbid anatomy of . . 379 — — pathology of . . . . 380 — -- predisposing causes of .. 376 — — prognosis of . . . . 386 — — symptoms and clinical history of . . . . . . 380 treatment of . . . . 387 — mellitus . . . . . . 218 age in . . . . . . 244 — — beer as a cause . . . . 247 cider as a cause . . . . 247 climacteric. .. .. 257 contagious . . . . . . 249 — — excessive use of sugar and starchy food as cause . . . . 247 exciting causes of . . . . 248 frequency of, among Jews 243 — — heredity in . . . . 246 — — incidence of, in India . . 239 — — morbid anatomy of . . 262 — — mortality from, in Euro- pean Countries and British Colonies . . . . . . 238 mortality from, in Paris . . 238 principal cities of Europe . . . . . . 237 obesity as cause . . . . 247 — — prevalence of, in England and Wales . . . . . . 242 — — prevalence of, in Ceylon. . 239 relation of, to tubercle . . 247 sex in . . . . ■ • 245 social condition in . . 245 Diabete bronze . . . . 272, 321 — gras . . . . . . . . 284 — maigre . . . . . . . . 284 Diabetic cataract . . . . . . 305 — coma . . . . . . . . 330 conclusions respecting . . 353 INDEX. 425 •• 344 •■ 331 ■ 332 ■• 345 •• 336 •• 347 .. 299 267, 3 I 315 316 306 201 320 177 118 169 357 271, Diabetic coma, diagnosis of etiology of . . pathology of prognosis of — — symptoms of — — treatment of — neuralgia — neuritis . . — otitis media — phthisis — retinitis. . Diacetic acid Diarrhoea in diabetes — treatment of . . Diathes bri^htique Diet in Bright 's disease — in diabetes Diffused opacity of retina, from cedema . . — retinitis .... Digestive system in diabetes 271, 318 Diphtheria as cause of diabetes 249 Diplopia in diabetes . . . . 305 Distal convoluted tubule . . 3 Drinking water .. .. ..170 Dropsy of acute nephritis 26, 99 chronic nephritis . . . . no — in diabetes — due to heart failure . . — • of hydraemic plethora lithaemic nephritis — — obstructive nephritis — pathology of . . — treatment of . . Drugs in Bright's disease diabetes Dupuy tren's contraction . . Dysenteric condition of large in testine Dyspepsia and lithaemic kidney Eager, p. 370; Eales, 71, 76, 78, 79, 307, 309; Ebstein, 119, 196, 232, 252, 255, 277, 278, 322, 335 ; Eckhard, 225, 226, 268, 376; Edlefsen, 26: Ed- munds, 77, 315; Edwards, 255, 320 ; Ehrlich, 185, 232, 278 ; Eichhorst, 47, 118, 153, 387 ; Eisenlohr, 109 ; Ernst, 39 ; Esterle, 378 ; Ewald, 43, 49, 54 Ear affections in diabetes Eclampsia . . Eczema in Bright's disease — of genitals in diabetes. . Efferent vessels Egg-shell powdered 297 26 32 132 143 25 175 170 367 325 277 120 315 142 149 294 4 372 PAGE Embolism of kidney . . . . 413 retinal arteries . . . . 78 Embolisms, fat . . . . 271, 335 Endarteritis obliterans .. ..121 Endemic chyluria . . . . 202 Endocarditis . . . . . . 285 Engadine . . . . . . . . 169 Enteric fever as a cause of diabetes . . . . . . . . 251 — • — in diabetes . . . . 322 Epileptic fits in diabetes . . 303 Epistaxis, treatment of . . . . 177 Epithelial casts .. .. 37,211 Ergot 370 Erysipelas as a cause of diabetes 249 — in Bright's disease . . . . 149 Erythema in Bright's disease 149 diabetes . . . . . . 293 Esbach's test . . . . . . 206 Etiology of Bright's disease . . 87 Exalgine . . . . . . . . 370 Exercise . . . . . . 169, 366 Exophthalmic goitre and dia- betes, connection between 256, 304 Extractives as causes of Bright's disease . . . . . . • • 93 Eye affections in diabetes . . 304 Fagge,;!'/. 243, 284, 29S, 348, 384; Feitelberg, 35 ; Ferraro, 243, 278 ; Feltz, 67 ; Fichtner, 278 ; Fienzal, 306 ; Fiessinger, 93 ; Finlayson, 212, 303 ; Flatten, 377 ; Fleiner, 274 ; Fleischer, 127, 332 ; Flint, 287 ; Flugge, 189 ; Forster, 154 ; Fort, 249 ; Foster (B. W.), 234, 270, 330, 347; Foster (M.), 229, 232; Fowler, 288 ; Foxwell, 289 ; Francotti, 202 ; Frank, 379 ; Frankland, 361 ; Franks (Ken- dal), 390; Frerichs, 30,66, 127, 231, 248, 253, 263, 266, 273, 277. 336, 337.. 338, 339. 347; Frew, 246 ; Frison, 274 ; Fiir- bringer, 87, 403 ; Futterer, 264 Face in diabetes . . . . 285, 306 Faecal masses, hardened, in in- testines . . . . . . . . 276 Fat embolism . . . . . . 335 — in blood . . . . . . 270 urine . . . . . . 202 Fatty degeneration of liver . . 271 renal epithelium . . 280 — heart . . . . . . 269, 286 — liver . . . . . . . . 273 Febrile urobilin . . . . . . 181 426 INDEX. Fehling's solution. . Fermentation in the bladder Ferments in normal urine Ferric chloride reaction . . Ferro-cyanide of potassium Fibrin cylinders . . Filaria sanguinis hominis Florador, analysis of Fluid in renal dropsy Food albuminuria Fourth ventricle, sclerosis in floor of Fresh air . . Friedreich's ataxy Fuchsin PAGE .. 289 .. 213 01. 343 . . 206 •• 39 . . 202 .. 361 .. 25 .. 16 or . . 264 366 255 174 Gaillard, fp. 272, 275 ; Galabin, 45) 53 • Galezowski, 71, 304, 386 ; Gamgee, 345 ; Gans, 319 ; Gardner, 370 ; Gar- nerus, 386; Garrod, 89, 119, 192, 209; Gaucher, 93, 249; Gauthier, 67 ; Gavarret, 30 ; Gemmell, 370, 372 ; Gerhardt, 322 ; Germont, 40, 140, 142 ; Gillet, 157 ; Glaser, 92, 120 ; Gley, 229 ; Godlee, 296, 392 ; Gombault, 119 ; Goodhart, 107, 288 ; Goodsir, 6 ; Gowers, 78, 315, 386; Graefe, 305; Gra- ham, 18 ; Grawitz, 44, 51, 54, 85, 109 ; Gregory, 50, 219 ; Grehant, 65 ; Grenier, 255 ; Griesinger, 315,322; Griswold, 257 ; Grooz, 288 ; Grube, 304, 363,372; Griitzner, 9,51, 59, 61 ; Gschleiden, 417 ; Guinon, 304 ; Gull, 8, 44, 48, 84, 295 ; Gunion, 255 ; Gunn (Marcus), 77 ; Gurowitsch, 153 Gangraena bullosa serpiginosa . . 297 Gangrene as a cause of glyco- suria . . . . . . . . 253 — in diabetes . . . . 296, 317 Gastric catarrh, treatment of . . 177 — functions in diabetes 301, 319, 383 Genito-urioary system in diabetes 277, 294 Glaucoma . . . . . . • • T5 Glucose . . . . . . . . 220 Gluten bread, analysis of . . 360 Glycogen . . . . . . . . 221 Glycogenic deposits in the wall of the heart . . . . 269, 336 — infiltration of renal epithelium 279 Glycolytic ferment . . . . 370 Glycosuria, acute febrile . . 28 s PAGE Glycosuria and jaundice 231, 320 — causes of . . . . . . 253 — disappearance of . . . . 299 — experimental . . . . . . 22=5 — from eating sugar . . . . 288 — in healthy persons . . . . 287 — intermittent . . . . . . 289 — of lactation . . . . . . 257 — physiology of . . . . . . 220 — renal . . . . . . . . 233 Gonococcus . . . . . . 212 Gout as a cause of diabetes 256, 377 Gouty kidney .. .. 117,119 Grape sugar . . . . . . 197 Grawitz and Israel, views of . . 85 Guaiacum test for blood . . . . 208 Gull and Sutton, views of . . 84 Gums, affections of, in diabetes 318 Guy's Hospital Reports . . . . 83 Haehner, p. 394; Haig, 51; Hales, 27 ; Hallervorden, 289 ; Hamilton, 54, 232, 255, 271, 335. 342 ; Hanot, 165, 272, 321 ; Hansemann, 274; Harley, 266, 417 ; Harley (Vaughan), 274 ; Harris, 205 ; Harrison, 289 ; Haslund, 154 ; Hassall, 417 ; Haughton, 378 ; Hay, 202, 229; Haycraft, 192 ; Hedon, 227, 228; Heidenhain,5i,6o; Heller, 320; Helmont (Van), 83; Hen- rot, 266; Hensen, 226, 268; Hermanides, 254 ; Hermann, 9, 28, 204; Heusoner, 297; Heynsius, 223 ; Hildebrandt, 370; Hirsch, 218; Hirschberg, 307, 308; Hirschfeld, 320, 337; Hoffmann, 31, 225 ; Holstoi, 72 ; Holvotschiner, 214; Honig- mann, 320; Hoppe-Seyler, 11, 67, 274, 336; Horden, 294; Howard, 152; Huguenenq, 271 ; Humphreys, 401 ; Hunt, 296 ; Huscke, 6 ; Hutinel, 157. Habits as to food and drink . . 92 Hsematemesis in Bright's disease 164 Hasmatoporphyrin . . . . 209 Hsematuria . . . . . . 408 — causes of . . . . . . 408 — - neurotic and vicarious . . 416 — in purpura . . . . . . 415 — toxic . . . . . . . . 416 — treatment of . . . . . . 174 — symptomatic . . . . . . 414 Hsemoglobinuria . . . . 408, 417 — paroxysmal . . . . . . 417 INDEX. 427 Haemoglobinuria, paroxysmal, causes of . . . . . . . . 417 prognosis of . . . . 420 symptoms of . . . . 418 — — treatment of . . . . 420 Haemophilia, renal . . . . 395 Haemorrhage from the bowel in Bright's disease . . . . 164 — choroidal . . . . . . 78 — into brain substance . . . . 264 — — the vitreous . . . . 78 Haemorrhages in Bright's disease 158 — in duodenum . . . . . . 276 — retinal . . . . . . . . 70 — in stomach . . . . . . 276 Haemorrhagic exfoliative derma- titis . . . . . . . . 149 — myocarditis in Bright's disease 160 Haemorrhoids in Bright's disease 165 177 Hard water and uric acid Head or spine, injuries to Health resorts Hearing in diabetes Heart in acute nephritis . . — — ■ chronic nephritis . . — — diabetes . . 268, 318 lithasmic nephritis — — obstructive nephritis — disease and lithasmic kidney — failure in Bright's disease . — — dropsy due to — hypertrophy of Heller's test Hemi-albumose . . Hemiplegia Henle's loop Heredity in diabetes Hilum Hippuric acid Homburg . . Honey urine Hot air bath — sun, exposure to Hunger in diabetes Hyaline casts Hydraemic oedema — plethora Hydrochinon Hydronephrosis — causes of — frequency of — intermittent — treatment of Hydruria . . Hygiene in Bright's disease Hyperesthesia of the skin Brisrht's disease 119 255 169 285 100 no 336 128 143 120 160 26 43. 44 205 9 303 2 246 I 193 364 219 107, 169 379. 386 ■• 383 30 30. 32 196 400 400 400 403 404 376 151 Hypertrophy of the heart 43, 44, 269 heart, concentric and ec- centric . . . . . . . . 44 — — left ventricle . . . . 31 Hypoxanthin . . . . . . 194 Hysteria and diabetes, associa- tion between . . . . . . 255 Imlach, p. 258 ; Israel, 44, 51, 54, 85, 109, 280, 403. Immunity of African and Mongo- lian races from diabetes . . 242 Imperial drink . . . . . . 107 India, incidence of diabetes in 239 Indican .. .. 181, 196, 290 Infective endocarditis in Bright's disease . . . . . . . . 160 — nephritis . . . . 86, 97 etiology of . . . . . . 97 specific micro-organisms of ••97 — processes as a cause of diabetes . 249. 379. 386 Inflammatory complications, treat- ment of . . , . . . . . 177 Influenza as a cause of diabetes 250 Infundibula . . . . . . 6 Injuries as a cause of diabetes 252, 255 — causing laceration of kidney 409 Inosite . . . . . . . - 220 Insanity as a cause of diabetes 377 Insular sclerosis . . . . . . 255 Integumentary system in diabetes 292 Interlobular arteries . . . . 5 Interstitial nephritis . . . . 85 Intestinal catarrh in Bright's disease , . . . . . . . 164 Intestines in diabetes . . . . 276 Iodoform in diabetes . . . . 370 Irido-choroiditis . . . . • • 75 Iritis in diabetes . . . , . . 306 Iron in brain . . . . . . 264 liver.. .. .. .. 273 Irregular tubule . . . . . . 3 Irritability of temper in diabetes 285 Jaccoud, pp. 28, 156; Jackson (Hughlings) 77 ; Jacobi, 379 ; Jacobson, 392 ; Jacoby, 233 ; Jaeckel (von), 154; Jaeger, 307, 315 ; Jaksch (von), 198, 270, 288, ' 332, 336 ; Jensen, 315 ; John- son (G.) II, 47, 48, 50, 60, 84, 85, 87, 120, 128 ; Johnson (G. S.) 220 ; Jones (Bence) 10, 348 ; Jones (Handfield), 274; Jordao, 315- 428 INDEX. Jambul in diabetes PAGE • . 370 Japan, diabetes in .. 241 Jaundice and glycosuria. 231, 320 Jaundiced urine . . 0. 181 Jews, diabetes among • • 243 Johnson, views of.. 84,85 Johnson's test .. 198 — theory . . .. 47 Jones's (Bence) albumen •• 9 229; 223; 381, Kannenberg, p. 211 ; Kaposi, 294,297; Kauffmann, 225, 228, 232, 233, 275 ; Kaulich, 332 ; Kelsch, 40, 41, 85; Kennedy, 370, 387 ; Kidd, 91 ; Kierulf, 28 ; Kinch, 361 ; Kingsbury, 370 ; Kinsey, 239 ; Kirchner, 315 ; Kirk, 197, 230 ; Kirmissen, 297 ; Klebs, 226, 267, 268 ; Klein, 2 ; Klemperer, 230, 233 ; Knutsford (Lord), 238; Kolisch, 229; Kooi, 171; Kormick (von) Kraske, 197; Kuhne, 9, Kiilz, 222, 231, 315, 362, 386; Kiissmaul, 330, 332, 333, 348; Kiister, 403 Keratitis in Diabetes . . . . 306 Kidney, anatomy of . . . . i - — in diabetes insipidus . . . . 380 — gouty . . . . . . . . 117 — miscellaneous diseases of . . 390 — movable . . . . . . 409 — shape of . . . . . . i — weight of .. .. ..1,7 Knee jerks in diabetes . . 285, 304 Kreatinin . . . . . . . . 193 Kiissmaul's coma . . . . 62 Labbe, p. 249; Lacombe, 377, 386 ; Laennec, 84 ; Lancaster (LeCronier), 150; Lancereaux, 273; Landau, 403; Landesburg, 75 ; Landois, 34, 61, 187, 192, 193, 221 ; Langenhans, 274 ; Langhans, 38 ; Lannois, 228 ; Laplane, 387; Larring, 156; Lassar, 10 ; Latham, 219, 334 ; Lawford, 311; Laycock, 386; Leber, 75, 308; Lebert, 417; Leconte, 229; Lecorche, 153, 154, 186, 249, 257, 268, 318; Legg (Wickham), 222, 231 ; Leichtenstein, 50, 127 ; Le Nobel, 200, 201, 291 ; Leo, 232, 233; Lepine, 9, 16, 18, 21,67, 68, 127, 157, 214, 223, 228, 273, 274. 275. 303. 336, 370 ; Leroux, 294 ; Letulle, 249, 272 ; Letzer- ich, 93; Leube, 12, 13, 39,299; Libby, 387 ; Lichtheim, 29 ; Lieben, 200; Lindsay, 252; Litten, 70, 332 ; Livingstone. 400 ; Lobisch, 21 ; Longstreth, 274 ; Lowinsky, 383 ; Lubarsch, 39 ; Lubimoff, 266, 267 ; Ludwig, 19, 47 ; Lustgarten, 211; Lustig, 268, 276; Luys, 263; Lycett, 91, 118 La Bourboule . . . . . . 365 Labyrinth of kidney . . . . 2 Lactation, glycosuria of . . . . 257 Lactic acid . . . . . . 194 effect of . . . . . . 323 Lactose . . . . . . . . 221 Laevulose . . . . . . 220, 362 Lardaceous degeneration . . 87 — disease less common in Bir- mingham . . . . . . 87 Latham's theory of diabetes . . 234 Lead and gouty kidney . . . . 119 Lepine's malt ferment . . . . 370 Leucin . . . . . . . . 195 Lichtheim's experiments . . 29 Life insurance and albuminuria 22 Lightning stroke as a cause of diabetes . . . . . . . . 254 Lipaemia . . . . . . . . 335 Lithaemic nephritis .. ..117 — — blood of 127 — ~- diagnosis of .. .. 132 dropsy in . . . . . . 132 etiology of . . . . . . 117 heart in . . . . . . 128 — — heredity in.. .. .. 118 illustrative cases of . . 135 — — morbid anatomy of . . 121 ophthalmoscopic changes in 130 prognosis of . . . . 133 ■ — — pulse in . . . . . . 129 — — symptoms and course of.. 124 — - temperament in .. ..118 — — urine of . . . . . . 125 Liver in Bright's disease . . 165 diabetes .. .. 271, 321 — diseases as a cause of diabetes 256 Locomotor ataxy . . . . . . 255 Lungs in diabetes. . 270, 286, 317 Lymphatics of the kidney . . 6 McAvoY, p. 373 ; MacBride, 157, 288; Macdonald, 142; Macken- zie (Stephen), 76, 263, 278, 310, 334; Mackenzie (W.), 305, 308, INDEX. 429 314; Mac Munn, 18, 333, 339 ; M'Nish, 253; Madigan, 299; Magendie, 27 ; 268, 290, 31S ; 53, 54. 88. 118; Mannaberg, 93, 203 ; Marcacci, Maguire, 72, Mahomed, 11, Manby, 255 ; 211 ; Manson, 13 ; Marcet, 294; Marchal (de Calvi), 295; Marie, 304, 322 ; Marsh, 254 ; Marshall, 254 ; Martin, 390 ; Masoni, 230; Masterman, 170; Maudsley, 254; Mayer, 269; Meigs, 91 ; Mering (von), 226, 230; Mesnet, 417; Meyer, 221 ; Miley (Miles), 76, 79 ; Minkowski, 226, 227, 229, 230, 273. 334. 369: Miot, 315; Mircoli,98; Mobius, 41 ; Mole- schott, 370 ; Monckton, 370 ; Monin, 370; Moore (Norman), 274 ; Moosdorf, 252 ; Mosca- telli, 194 ; Moxon, 14, 85 ; Miiller, 196, 289 ; Munk, 61, 267; Murchison, 51, 93; Mur- rell, 387 ; Mya, g, 213 Malaria as a cause of diabetes . . Malignant disease as a cause of glycosuria Malpighian bodies Malt ferment Malta, high mortality from dia- betes in . . Martineau's specific Massage in diabetes Masturbation as a cause diabetes . . Mate in diabetes . . Mauritius, diabetes in Mechanical theory of uraemia Medullary layer of kidney — rays Melanin Menstruation in diabetes Mental emotion as a cause of diabetes . . . . . . 255, Micrococcus diphtheriae. . — tetragonus — of ulcerative endocarditis . . Micro-organisms in morbid urine in normal urine . . Microsporon septicum Milk diet . . Millon's reagent Mind in diabetes Mixed diet . . Modified diet Moore's test of 250 253 4 370 242 369 367 258 370 241 64 195 285 379 213 213 213 212 . . 211 .. 213 169, 363 10 285 169 362 Morbid anatomy of diabetes MortaHty from diabetes mel PAGE 262 237. liti Movable kidney . . Moxon's views Mucin Multiple periarteritis Muscular effort — pains, rheumatic Mycotic nephritis Myocarditis Nagel, p. 75 ; Nauwerck, 184 Nedats (de), 362 ; Netter, 157; Nettleship, 305, 308, 310, 311, 312,315; Neuffer, 380; New- man, 60; Noorden (von), 207, 232 ; Norris, 256, 342 ; Noth- nagel, 378; Noyes, 77, 307; Nussbaum, 20 Nephralgia, malarial Nephritis, acute infective — chronic infective — lithsemic Nerves of the kidney Nervous diseases as a cause of diabetes . . — system in diabetes Neuenahr . . Neuralgia, diabetic Neuritis, diabetic . . Neutral phosphate of lime New growths Nitro-glycerine — hydrochloric acid 242 -rog 85 207 79 379 323 98 49 394 98 108 117 6 ..254 263, 299, 379 ..364 • • 299, 372 267, 301 .. 187 •• 325 173. 370 •• 370 Oliver, pp. 299, 370, 378; Ollivier, 50, 119; Opitz, 387; Oppler, 67 ; Ord, 252 ; Otto, 290 Obesity as a cause of diabetes Obstructive nephritis — — diagnosis of — — dropsy in . . — — etiology of . . — — heart of illustrative cases of — — morbid anatomy of — • — ■ prognosis of symptoms and course of . — — treatment of uraemia in . . — — urine of Occupations liable to Bright disease Odour of the breath in diabetes 286 CEdema in acute nephritis 247 86 143 143 140 143 144 141 143 142 147 143 142 92 430 INDEX. PAGE CEdema in diabetes . . 373, 383 — erythematous . . . . . . 294 — of glottis in Bright's disease 160 — — lungs in Bright's disease 161 Oliver's test for bile acids . . 202 Ophthalmia Brightica . . . . 72 Ophthalmoscopic appearances in acute nephritis . . . . . . loi • chronic nephritis . . 1 1 1 lithsemic nephritis . . 130 Opium in diabetes . . . . 367 Optic nerve, atrophy of . . • • 315 — papillitis . . . . . . 70 Otitis media, diabetic . . . . 315 Ouabain in diabetes . . 370, 372 Ovaries in diabetes . . . . 280 Oxalate of lime . . . . . . 194 Oxalic acid . . . . . . 194 Oxaluric acid . . . . . . 194 Paetsch, p. 154 ; Parkes, 17, 18 ; Paton (Noel), 8, 191, 192, 204, 223, 322 ; Pavy, 14, 17, 18, 220, 222, 223, 224, 226, 229, 231, 232, 244, 252, 268, 299, 319, 417 ; Peabody, 65; Peiper, 268, 276 ; Penzoldt, 333 ; Percy, 267 ; Perl, 93 ; Petters, 332 ; Peyrani, 376; Peyraud, 370; Pfiuger, 224 ; Piatkowski, 370 ; Piorry, 65 ; Pisenti, 278 ; Plu- mert, 322 ; Poncet, 72 ; Poniklo, 254; Ponomaroff, 320; Popper, 274 ; Posner. 10, 20, 21, 203 ; Potain, 51 ; Poulet, 257 ; Pri- . bram, 384, 386 ; Prout, 187, 243, 284, 330; Pryce (Davies), 294, 301 ; Purdy, 363 ; Pye- Smith, 150 Pancreas .. .. .. 226,273 — cancer of, as a cause of 253 275 275 320 274 369 4 diabetes . — pigmentary cirrhosis of Pancreatic calculi — colic in diabetes — diabetes, cases of — remedies Papilla Papillary portion of medullary layer Papillomatosis diabetica . . . . 294 Paralysis in diabetes . . . . 300 Paraplegia in diabetes . . . . 301 Parasites of kidney . . . . 413 Parenchymatous theory of albu- minuria . . . . . . 19, 23 Paris, mortality from diabetes in 238 262 PAGE 231 Pathogeny of diabetes . . Pathology of albuminuria — — diabetes • dropsy — • — polyuria uraemia Pelvis Penicillium glaucum Pepsin — ■ in diabetes Periarteritis, general retinal — multiple Pericarditis Peritonitis, acute . . Permanganate of potash in dia betes Persia, diabetes in Phenacetin in diabetes Phenyl-hydrazin test Phloridzin . . Phosphates Phosphorus in diabetes Phthisis, diabetic . . • tubercle bacilli in — non-tubercular Physiology of glycosuria Picric acid . . Pigmentation of the skin Pilocarpine in diabetes . . Piperazin in diabetes Pityriasis rubra . . Pneumococcus Pneumonia in Bright's disease Polarimeter . . Polydipsia . . Polyuria — pathology of . . Portal vein, thrombosis of Potatoes Pregnancy as a cause of diabetes 256, 378 Primary acute infective nephritis 93. 98 380 25 58 62 6 212 9 370 70. 74 7,9 268 320 370 241 370 198 229 185 370. 372 271, 316 316 271 220 205 292 370 370 294 213 163 200 376 376 58 272 362 Prognosis of diabetes Prognostic value of retinal changes in Bright's disease Protocatechuic acid Proximal convoluted tubule Pruritus vulvas Pseudo-tabes Ptomaines . . Ptosis in diabetes Puerperal kidney Pulse in acute nephritis chronic nephritis diabetes — of high tension 294 291 79 196 2 373 301 214 303 140 100 III 286 45 INDEX. 431 Pulse of high tension, sphygmo graphic tracing of Hthsemic nephritis — slow, in uraemia Purpura in diabetes Pus in urine Pyelitis — causes of — symptoms of . . — treatment of . . Pyonephrosis Pyramids of Ferrein Malpighi . . Pyrocatechin 45 129 157 294 209 400, 405 405 405 406 400, 403 196 QuANjER, p. 370; Quincke, 273, 345 ; Quinquaud, 65 Quantitative estimation of sugar 199 acidity of urine . . 184 Quantity of urine in diabetes . . 288 Rademaker,^. 68 ; Ralfe, 8, 186, i8g, 200,378, 394; Ranke, 189 ; Rayer, 50, 84, 128, 153, 299, 322 ; Raymond, 154 ; Raynaud, 315 ; Reale, 229 ; Redard, 253 ; Rees (Owen), 50, 64, 66, 128 ; Rehder, 29 ; Reich, 394 ; Rendu, 51, 249; Renzi (De), 229 ; Reumont, 255 ; Reynolds, 345) 34S ; Ribbert, 20, 21, 39; Richardiere, 157, 255 ; Rick- ards, 331, 391 ; Riess, 62, 332 ; Rilliet, 64 ; Ritter, 67 ; Roberts, 62, 85, 156, 170, 181, 183, 193, 195, 200, 205, 243, 297, 380, 386, 387 ; Roberts (Prescott), 338 ; Robertson, 243 ; Robin- son, 21; Rokitansky, 21, 87; Rollo, 219, 254, 286, 305, 319, 357 ; Rommelaere, 66 ; Roos, 214; Rosenbach, 229; Rosen- blath, 295 ; Rosenstein, 65, 84, 85. 149. i53> 171. 212, 304, 319; Rossbach, 202 ; Routh, 373 ; Rubner, 189 ; Runeberg, 21 ; Rupstein, 332 ; Russell, 200 ; Ryba, 322 Race in diabetes . . . . . . 243 Rayer, views of . . . . . . 84 Reaction of urine in diabetes . . 288 Reduplication of first sound, causes of. . . . . . . . 128 Rehder's experiment . . . . 29 Renal colic, symptoms of . . 392 treatment of . . . . 398 — diseases, miscellaneous . . 390 Renal epithelium, fatty degenera- tion of . . . . . . . . 280 glycogenic infiltration of. . 279 — glycosuria . . . . . . 233 — haemophilia . . . . . . 395- ■ — tumours . . . . . . 403 ■ — vein . . . . . . . . 5 Respiratory system in diabetes 270, 316 Retinal changes in Bright's disease 70 diagnostic value of . . 76 in diabetes . . . . . . 306 in functional albuminuria 79 — • — possibility of cure of . . 81 prognostic value of . . 79 Retinitis centralis punctata dia- betica . . . . . . . . 307 — diabetic. .. .. .. 306 — hsemorrhagic diabetic . . 312 Retractile albumen . . . . g Rheumatism in diabetes . . . . 323 Roberts, views of . . . . . . 85 Rosenstein, views of . . 84, 85 Rubinat water . . . . . . 373 Rubner's test . . . . . . 198 Sainsbury (Harrington), j!>. 400; Salomon, 333 ; Salomonson, 301 ; Salkowski, 9, 10, 39, 194, 209 ; Salzmann, 393 ; Samel- sohn, 305, 315 ; Sanders, 271, 335, 342; Sandmeyer, 265; Saundby, 271, 335 ; Savage, 254, 416; Schachman, 2:2; Schapiro, 379, 380 ; Scherer, 384 ; Scheuplein, 252 ; Schiff, 22, 225, 226, 229, 265 ; Schmidt, 26; Schmiedeberg, 221; Schmitz, 244, 249, 269, 292, 336, 373 ; Scholz, 154 ; Schot- tin, 67 ; Schulter, 9 ; Schultze, 1S6 ; Schulzen, 189, 384 ; Schweiger, 213 ; Scudamore, 243 ; See (Germain), 370 ; See- gen, 223, 224, 232, 270, 286, 289 ; Seifert, 322 ; Semmola, 15, 51, 89, 127; Senator, 9, 10, 13, 20, 22, 44, 46, 62, 196, 2S9, 332, 334. 336. 376, 378. 384. 386, ■ 395 ; Senz, 9 ; Sibson, 45, 128 ; Silbert, 214 ; Simon, 253, 294, 299 ; Sinclair, 257 ; Slater, 289 ; Smith (Bellingham), 252; Smith (Shingleton), 255, 265, 267 ; Smith (W. G ), 182, 196 ; Snyers, 66, 67, 90; Souques, 255; Spencer, 253, 297, 305; 432 INDEX. Squire (Balmanno), 370, 372 ; Stadelmann, 289, 345, 370 ; Steven, 390; Stewart (Grain- ger), 13, 16, 43, 54, 84, 85, 126, 190 ; Stirling, 13, 192, 193, 205, 222 ; Stoffregen, 9 ; Stokvis, 278, 335 ; Strauss, 40, 127, 140, 142, 278, 379, 384 ; Strumpell, 304 ; Sutton, 44, 48, 84 ; Sydenham, 219 Saccharomyces cerevisias . . 212 Salicin in diabetes . . . . 370 Salicylate of sodium in diabetes 369 Salivation in diabetes .. ..319 Sarcin . . . . . . . . 194 Sarcina ventriculi. . .. ..212 Sclerosis in floor of fourth ven- tricle . . . . . . . . 264 Scotoma, central . . . . . . 3x5 Semolina, analysis of . . . . 361 Serum albumen . . . . 8, 204 — globulin . . . . 8, 204 Sex in diabetes . . . . . . 245 Sexual continence as a cause of diabetes . . . . . . . . 258 — indulgence, excessive, as a cause of diabetes . . . . 258 — power, loss of, in diabetes 285, 300 Shape of the kidney . . . . i Singapore, diabetes in . . . . 240 Sinus of the kidney . . . . i Size of liver in diabetes . . . . 271 Skatoxyl-sulphuric acid . . . . 290 Skin in diabetes . . . . . . 285 — eruptions in Bright's disease 149 — diabetes . . . . 292 Smell in diabetes . . .. 285,315 Social condition in diabetes . . 245 Sodium butyrate . . . . . . 334 Soy beans, analysis of . . . . 361 Specific gravity of normal urine 182 — urine in diabetes . . 288 Spectroscopic examination of blood . . . . . . . . 208 Sphygmographic tracing of high tension pulse . . . . . . 45 Spinal cord in diabetes . . . . 265 Spiral tubule . . . . . . 2 Spleen in diabetes . . . . 273 St. Leonards . . . . . . 169 Stewart (Grainger), views of . . 84 Stomach in diabetes . . . . 276 Stone in the kidney . . . 390 • causes of . . . . 390 — — diagnosis of . . 394 ■ geographical distri- bution of, in the British Islands 391 Stone in the kidney, medical treatment of prognosis of — suspected, grounds for operating in — — — — symptoms of — ■ treatment of impaction of varieties of . . Stools in diabetes . . Strabismus in diabetes . . Streptococci Strict diet . . Strontium bromide in diabetes . . Succinic acid Sugar and starchy food, excessive use of . . . . . . 247, 288 — in blood . . . . . . 270 — non-destruction of . . . . 232 — over-production of . . 231, 232 Sulphide of calcium in diabetes 370 Sulpho-carbolate of soda . . 370 Sulphuric acid . . , . . . 187 Sun, diabetes caused by exposure 397 396 393 39T 396 398 390 285 300 212 359 370 194 to 379. 386 . . 140 294. 373 Surgical kidney . . Sweating in diabetes Symmetrical gangrene Sympathetic ganglia . . . . 267 — nerves . . . . . . . . 267 Syntonin Syphilis as a cause of diabetes 252, 377 — of kidney . . . . . . 412 Syzygium jambolanum in dia- betes . . . . . . . . 370 Tait (Lawson), pp. 34, 258, 373 ; Talamon, 154 ; Tardieu, 263 ; Taylor, 335, 348 ; Teissier, 186, 369 ; Tenneson, 156 ; Tesche- macher, 289; Thierfelder, 229; Thiroloix, 228, 233, 264 ; Tho- lozan, 243 ; Thoma, 48, 61 ; Thomson, 9; Thornton (Knowsley), 400; Thudichum, 184 ; Tilden, 270, 333, 343 ; Tirard (Nestor), 394; Tizzoni, 15 ; Todd, 50 ; Toralbo, 289, 363 ; Toynbee, 315 ; Traube, 31,44, 47, 53,64; Treitz, 66; Trousseau, 29, 237, 247, ^05, 383 ; Tuffier, 325 ; Tiirck, 70 ; Turner, 277 ; Tuttle, 154 Tasnia medio-canellata . . 277, 379 Tannate of soda . . . . - • 173 Tanret's test . . . . 9, 206 INDEX. 433 Taste in diabetes .. .. 285, 315 Teeth in diabetes . . . . . . 285 Temperature in diabetes 285, 298, 3S1 diabetic coma . . . . 343 Thickening of the adventitia or lymph sheath . . . . . . 78 — — mucous membrane of stomach . . Thirst in diabetes . . Thrombosis of portal vein Tongue in diabetes Tonic spasm of the whole system arterioles Torquay Torulae Town and country, prevalence of diabetes in Toxic nephritis Traube's hypothesis Tremor, uraemic . . Trimethylamine . . Triple phosphate . . Trommer's test Trypsin . . . . . . 9, Tube casts, pathological relations of Tubercle and diabetes — bacilli . , — of kidney Tubercular diathesis Tubules, uriniferous Tumours, abdominal — of the cord — on nerves — renal Tungstate of soda . . Turkish bath Types of diabetes . . Tyrosin 276 372 272 285 156 47 169 212 242 86 49 156 334 186 198 213 36 247 316 412 111 2 378 265 266 403 206 i6g 284 195 USTIMOWITSCH .. .. 51,61 Ulcer, perforating .. .. 297 Ulceration of the stomach and intestines . . . . . . 320 Ulcerative endocarditis, micro- coccus of . . . . . . 213 Uraemia . . . . . . 149, 335 — in diabetes insipidus . . . . 385 obstructive nephritis . . 143 — pathology of . . . . . . 62 — temperature in .. .. 156 — theories of . . . . . . 64 — three types of . . * . . . . 62 — treatment of . . . . . . 176 UraE'mic amnesia .. .. .. 154 — asthma, triatment of.. .. 177 Uraemic blindness — coma — convulsions — cramps . . — deafness — delirium — dyspnoea — fever — giddiness — headache . . . . 153 — hemiopia — hemiplegia, transient.. -- hiccough — liver in Bright's disease — tvvitchings — vomiting and diarrhoea Uranium nitrate .. Urate of ammonia Urea, detection of . . — estimation of .. Ureter Uric acid . . as cause of Bright's dis ease Urinar}- pigments, normal Urine, the . . — chemical composition of 184, — colour of — in acute nephritis chronic nephritis . . diabetes insipidus . . — — — mellitus.. — — lithasmic nephritis — ■ ^ obstructive nephritis — method of examining, for micro-organisms — odour of — quantitative estimation of the acidity of — quantity of — reaction of Uriniferous tubules Urinometer Urobilin Uroleucic acid Uroxanthic acid . . PAGE 70, 154 156 153 154 152 153 156 154 154 151 165 156 151 370 193 190 190 6 191 93 181 J 79 382, 385 181 lOI III 383 287 125 142 213 180 1S4 179 1S3 2 182 181 1 96 196 Valentine,/. 370; Vergeley,3i8; Vierordt, 66; Villemin, 36S Virchow, 34, 84 ; Vogel, 186 ; Voit, 67, 189, 232, 233; Vonio- vitch, 387; Voss, 381 ; Vulpian, ^5. 127 Valvular disease of the heart in diabetes .. .. .. 268,318 Vapour bath .. .. .. 169 2S 434 INDEX PAGE Vasa recta . . . . . . ... 6 Vascular contraction ■. . . . 48 — theory of albuminuria 20, 23 Vegetable foods, analysis of various . . . . . . 362 Venae rectae . . . . . . 6 — stellatae . . . . • . . 5 Ventnor . . . . . . . . i6g Vichy . . . . . . 170, 365 Virchow, views of .... 84 Vision in diabetes . . . . . . 285 Vomiting, treatment of . . . . 177 Wagner, pp. 28, 71, 93, 117, 154 ; Walter, 334 ; Watson, 297, 299 ; Weber, 249 ; Wecker (de), 308 ; Wedenski, 220 ; Wedl, 75 ; Weeks, 72, 75 ; Weigert, 39, 85 ; Weil, 377 ; Wells, 70 ; Werner, 9 ; West, 127, 370 ; Westphal, 378 ; Weyl, 2721,; White (Hale), 267; Wilde, 305; Wilks, 370; Willan, 305: WilUamson, 265, 274; Willis 219, 376; Wilson (Stacey), Windle, 201, 263, 331, 336, Wittich (von), 19, 222, 255; 341; 231; Wooldridge, 161 ; Worms 292; Wyatt, 231 Waters, mineral . . •• 363 Weigert, views of . . Weigert 's stain . . Weight of the body in diabs .. 85 •• 39 tes.. 286 kidney . . Weston, pedestrian What 13 dropsy ? . . White patches on retina . . Wines, light .. I, 7 36.41 .. 26 .. 70 . . 170 Xanthin . . •• 193 Xanthoma diabeticum •• 295 Yarrow, p. 258 ; Young, 394 ; Yvon, 189 Zaleski, pp. 264, 273 ; Zenner, 387 ; Zinn, 249 ; Zuntz, 230 Ziemssen's theory of diabetes . . 234 m COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the rules of the Library or by special arreinge- ment with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE C2S(i141)mIOO RC902 Saundby Sa8 1897 r.«nal & vtfi^X, Lectures on renal _====^ 0047951443